21 Matching Annotations
  1. Oct 2026
  2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Recessive Mutations in KCNJ13, Encoding an Inwardly Rectifying Potassium Channel Subunit, Cause Leber Congenital Amaurosis
    3
    1. ClingenBaseline 25 Oct 2026
      One such family of Middle-Eastern origin (family A), including two affected family members, aged 34 (subject A-2; V-3 in Figure 1A) and 32 (subject A-3; V-4 in Figure 1A), is the basis of this report. The study was approved by the local research ethics committee, and all investigations were conducted in accordance with the principles of the Declaration of Helsinki; informed consent was obtained from all participating individuals. Both affected siblings in family A were noticed to have nystagmus and were diagnosed with LCA shortly after birth. Poor night vision and difficulty reading print from an early age was reported for both patients A-2 and A-3; gradual progression of visual problems affecting central and peripheral vision was also noted. Both had bilateral cataract surgery in their 20s. No other family history of retinal disease was reported. Visual acuities were 2.0 logMAR (logarithm of the minimal angle of resolution) in each eye of patient A-2 and 1.78 logMAR for the right and 1.48 for the left eye of patient A-3. Fundoscopy revealed significant pigment at the level of the retinal pigment epithelium (RPE) and in a configuration unlike that of typical RP (A-2 and A-3, Figure 2A).

      Case#: Sergouniotis_2011_Proband_A-2, female, age 34 years, family ethnic origin described as Middle Eastern

      CasePresentingHPOs: Congenital nystagmus HP:0006934, Presenile cataracts HP:0007819, Reduced visual acuity HP:0007663, Nyctalopia HP:0000662, Constriction of peripheral visual field HP:00011

      CaseHPOFreeText: The proband received a diagnosis of Leber congenital amaurosis shortly after birth. Fundoscopy results were described as "significant pigment at the level of the retinal pigment epithelium and in a configuration unlike that of typical RP".

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband was initially genotyped by a combination of homozygosity mapping and exome sequencing.

      CaseMethod1: homozygosity mapping and exome sequencing

      CaseMethod2: Sanger sequencing of the proband and family members to confirm the presence of the variant and to test segregation

      CaseGenotypingMethod: The proband was initially genotyped by a combination of homozygosity mapping and exome sequencing. Sanger sequencing of the proband and family members was then performed to confirm the presence of the variant and to test segregation.

      Variant: The individual is homozygous for the NM_002242.4(KCNJ13):c.496C>T (p.Arg166Ter) variant.

      ClinVar: 30331

      gnomAD: The variant was not found in gnomAD version 4.1.0.

      VariantEvidence: NM_002242.4(KCNJ13):c.496C>T (p.Arg166Ter) is a nonsense variant in exon 3 of 3 that is not predicted to trigger nonsense-mediated decay but rather to truncate the C-terminal 54% of the protein product.

      CaseAddInfo: The proband's family history includes consanguinity and a sibling similarly diagnosed with LCA.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 23 Oct 2026
      To assess whether mutations in KCNJ13 are a common cause of autosomal recessive retinal dystrophy, we performed bidirectional Sanger sequencing of the entire coding region and intron-exon boundaries of the gene in 333 additional unrelated patients (primer details are listed in Table S2). Among the patients, 132 were affected with recessive LCA or childhood onset retinal dystrophy; this panel was enriched for mutations in novel genes, as the patients' DNA had been screened and excluded for previously reported LCA-causing variants through a microarray chip (LCA Chip, Asper Biotech; 35% mutation detection rate; D.S.M, unpublished data). The remaining 201 individuals were diagnosed with autosomal recessive adult onset rod-cone or cone-rod dystrophy and had unknown molecular diagnosis. A homozygous missense variant (c.722T>C [p.Leu241Pro]) was identified in a patient of white European descent (subject B-3, III-2 in Figure 1A; proband of family B) with a remarkably similar phenotype to that observed in family A. Segregation analysis confirmed heterozygosity for the p.Leu241Pro change in maternal (subject B-1, II-4 in Figure 1A) and paternal (subject B-2, II-5 in Figure 1A) DNA. This sequence change has not been previously reported (dbSNP and 1000 genomes) and was found to be absent from 382 ethnically matched control chromosomes (Human Random Control DNA Panels, Salisbury, UK). Although the patient is not knowingly consanguineous, his parents originate from the same isolated geographic area. It is therefore likely that the homozygous state at this locus is consequent upon the presence of a recent common ancestor.

      Case#: Sergouniotis_2011_Proband_B-3, male, age 33 years, family ethnic origin described as European

      CasePresentingHPOs: Reduced visual acuity HP:0007663, Constriction of peripheral visual field HP:0001133, Infantile onset HP:0003593, Strabismus HP:0000486, Nystagmus HP:0000639, Progressive night blindness HP:0007675, Moderate myopia HP:0031624, Decreased light- and dark-adapted electroretinogram amplitude HP:0000654, Presenile cataracts HP:0007819, Nummular pigmentation of the fundus HP:0030505, Retinal pigment epithelial loss on macular OCT HP:0030611

      CaseHPOFreeText: The proband received a diagnosis of Leber congenital amaurosis. His phenotype is described as similar to the other affected individuals, including "a distinct and unusual retinal appearance and a similar early onset of visual loss, suggesting both impaired retinal development and progressive retinal degeneration, involving both rod and cone pathways". The disease was described as mildly progressive. OCT showed distorted retinal microanatomy even in areas without cell death, possibly indicating disturbance of the early development of the neurosensory retina.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband was previously genotyped by screening for previously-reported LCA-causing variants by microarray chip, with no molecular diagnosis.

      CaseMethod1: screening for previously-reported LCA-causing variants by microarray chip

      CaseMethod2: Sanger sequencing of the KCNJ13 exons and intron-exon boundaries

      CaseGenotypingMethod: The proband was previously genotyped by screening for previously-reported LCA-causing variants by microarray chip, with no molecular diagnosis. Sanger sequencing of the KCNJ13 exons and intron-exon boundaries was subsequently performed.

      Variant: The individual is homozygous for the NM_002242.4(KCNJ13):c.722T>C (p.Leu241Pro) variant.

      ClinVar: 30332

      gnomAD: The variant was not found in gnomAD version 4.1.0.

      VariantEvidence: NM_002242.4(KCNJ13):c.722T>C (p.Leu241Pro) is a missense variant that has no experimental evidence in this study but has separately been shown to severely decrease expression and abolish complex glycosylation of KCNJ13 (PMID: 30257863, Figure 10).

      CaseAddInfo: The proband's family history is not known to include consanguinity but heterozygous parents originate from the same isolated geographic area.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    3. ClingenBaseline 21 Oct 2026
      Recessive Mutations in KCNJ13, Encoding an Inwardly Rectifying Potassium Channel Subunit, Cause Leber Congenital Amaurosis

      PMID: 21763485

      Gene: KCNJ13

      HGNC: 6259

      Disease: Leber congenital amaurosis 16

      MONDO: 0013613

      InheritancePattern: autosomal recessive

      Prevalence: The overall prevalence of Leber congenital amaurosis is between 1 in 33,000 and 1 in 100,000 newborns (PMID: 10951519), while the proportion of Leber congenital amaurosis caused by KCNJ13 variants is unknown.

      Penetrance: Known disease-causing alleles appear to be completely penetrant.

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC3135807/
  3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Nonviral base editing of KCNJ13 mutation preserves vision in a model of inherited retinal channelopathy
    1
    1. ClingenBaseline 25 Oct 2026
      In our Kcnj13W53X/+ΔR mice, we used ABE8e mRNA, sgRNA packaged in SNC-PEG-ATRA, and administered subretinally to edit the mutant allele. Full-field ERG measurements were performed at weeks 2, 6, and 10 to monitor longitudinal rescue in phenotype (Figure 6F). At week 10, multifocal ERG (mfERG) was performed on injected eyes to determine whether functional recovery was regionalized based on localized delivery of the base-editor complex. For the control group, Kcnj13W53X/+ΔR was injected with a base editor and a nontargeting guide. The nontargeted guide–injected mice exhibited a progressive decrease in c wave amplitude as well as depressed mfERG waveforms in almost the entire retina. On the other hand, the base-edited eyes showed an increase in the c wave amplitude at all measured time points (Figure 6, G–J). mfERG showed localized waveforms (Figure 6H and Supplemental Figure 11A) that perhaps correlated with the site of injection (Figure 6C). On the second week following the injection, the normalized c wave amplitude (to that before the therapy) in eyes receiving the nontargeted guide was 0.8 ± 0.1, practically indistinguishable to that of the eyes injected with the targeted guide, 0.9 ± 0.2 (P = 0.9). At 10 weeks after injection, the c wave was reduced (0.7 ± 0.1) for the nontargeted retina compared with an increasing trend (1.6 ± 0.1, P = 0.01) (Figure 6K) for the targeted guide–delivered retina. This increase of 55% in amplitude and intact retinal structure, as evaluated by OCT (Figure 6, H and J), demonstrates that inherited retinal channelopathies could be mitigated using base editors. As a further preclinical validation, we determined whether the SNC used to deliver the base editor triggers an immune response. The RPE cells in culture were transduced with either lentivirus, AAV7m8, or AAV5 or were incubated with SNC. Expression of inflammatory cytokines, including IFN-γ, IL-1α, IL-1β, IL-6, CD-8, and Iba1, was assessed by quantitative PCR (qPCR). CD8 and Iba1 showed increased expression in virally transduced RPE cells, but not in cells exposed to SNCs (Supplemental Figure 11B).

      ExperimentName: CRISPR/Cas9-based rescue of patient variant in the mouse RPE

      RescueModel: Mus musculus

      GeneAlteration: The Kcnj13W53X/+ΔR model has been generated from Kcnj13W53X/+ mice by retinal pigment epithelium-specific introduction of the variant encoding the p.Trp53Ter nonsense variant.

      RescueVariant: Rescue was performed by editing the variant to restore wild-type KCNJ13, not by introducing an additional human variant.

      RescuePhenotype: The rescued phenotypes are full-field electroretinogram responses measured at week 10 post-injection and retinal thickness by optical coherence tomography.

      RescueMethod: This rescue model has subretinally injected sgRNA to edit the W53X allele and restore the wild-type by CRISPR/Cas9 base editing.

      RescueEvidence: The ERG c-wave from the RPE layer shows 55% higher amplitude for the edited/targeted retina relative to the non-targeted control (Figures 6J and 6K) and is accompanied by intact retinal structure by OCT (Figures 6H and 6I).

      ModelVariant: NM_002242.4(KCNJ13):c.158G>A (p.Trp53Ter), ClinVarID: 224857

      Experimental Rescue RescueModelOrganism Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC10541187/
  4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Mutations in KCNJ13 Cause Autosomal-Dominant Snowflake Vitreoretinal Degeneration
    2
    1. ClingenBaseline 24 Oct 2026
      Mutations in KCNJ13 Cause Autosomal-Dominant Snowflake Vitreoretinal Degeneration

      PMID: 18179896

      Gene: KCNJ13

      HGNC: 6259

      Disease: snowflake vitreoretinal degeneration

      MONDO: 0008663

      InheritancePattern: autosomal dominant

      Prevalence: The overall prevalence of snowflake vitreoretinal degeneration is ~1 in 1,000,000 (https://www.orpha.net/en/disease/detail/91496).

      Penetrance: Known disease-causing alleles appear to be completely penetrant (PMID: 14644728).

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 22 Oct 2026
      However, sequencing of KCNJ13 (genomic accession CH471063, mRNA-NM_002242) showed a heterozygous c.484C > T transition, changing a CGG codon to TGG and resulting in an R162W change in the amino acid sequence (Figure 1A). This sequence change is present in all affected individuals in the family and not present in unaffected family members or 210 unrelated ethnically matched control individuals (420 chromosomes, providing a power of more than 95% to detect a polymorphism with a frequency of 0.01).

      Case#: Hejtmancik_2008_Family_55001_Proband, sex and age not specified, family origin described as American of European ancestry

      CasePresentingHPOs: Snowflake vitreoretinal degeneration HP:0011533, Corneal guttata HP:0012038, Presenile cataracts HP:0007819, Abnormal vitreous humor morphology HP:0004327, Retinal detachment HP:0000541

      CaseHPOFreeText: All family members have been diagnosed with Snowflake vitreoretinal degeneration between the ages of 12 and 85 years of age. Please note that detailed phenotypes were found in PMID: 14644728, and included fibrillar vitreous degeneration.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: Orofacial features, early-onset hearing loss, and arthritis were absent.

      CasePreviousTesting: The proband was previously subjected to linkage analysis mapping the causal locus to chromosome 2 (PMID: 15557460).

      CaseMethod1: linkage analysis

      CaseMethod2: Sanger sequencing of KCNJ13, COL4A3, SLC19A3, DNER, SLC17, 16A14, LOC646839, CAB39, PSMD1, ARMC9, NCL, PTMA, PDE6D, COPS7B, ECEL1, EFHD1, TNRC15, ATG16L1, SAG, USP40, and CENTG2

      CaseGenotypingMethod: The family was previously genotyped by linkage analysis mapping the causal locus to chromosome 2 (PMID: 15557460), followed by Sanger sequencing of KCNJ13, COL4A3, SLC19A3, DNER, SLC17, 16A14, LOC646839, CAB39, PSMD1, ARMC9, NCL, PTMA, PDE6D, COPS7B, ECEL1, EFHD1, TNRC15, ATG16L1, SAG, USP40, and CENTG2.

      Variant: The individual harbors the NM_002242.4(KCNJ13):c.484C>T (p.Arg162Trp) variant in the heterozygous state.

      ClinVar: 6585

      gnomAD: The variant is found in gnomAD version 4.1.0 at a frequency of 0.0000008536 (1 / 1,171,470) in the European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr2-232768790-G-A?dataset=gnomad_r4

      VariantEvidence:NM_002242.4(KCNJ13):c.484C>T (p.Arg162Trp) is a missense variant that has functional evidence of electrophysiological abnormalities and loss of sensitivity to different K+ concentrations, when exogenously expressed in CHO cells (Figure 2).

      CaseAddInfo: The proband's family includes 12 other affected individuals carrying the variant, and 14 unaffected individuals (as well as 4 unaffected spouses) without the variant.

      CasePMIDs: PMID: 15557460, PMID: 14644728

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC2253967/
  5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Retinal Development and Pathophysiology in Kcnj13 Knockout Mice
    2
    1. ClingenBaseline 24 Oct 2026
      A Kcnj13 knockout mouse line was constructed by inserting a gene trap cassette expressing beta-galactosidase flanked by FRT sites in intron 1 with LoxP sites flanking exon two and converted to a conditional knockout by FLP recombination followed by crossing with C57BL/6J mice having Cre driven by the VMD2 promoter. Lentiviral replacement of Kcnj13 was driven by the EF1a or VMD2 promoters. Results: Blue-Gal expression is evident in E12.5 brain ventricular choroid plexus, lens, neural retina layer, and anterior RPE. In the adult eye expression is seen in the ciliary body, RPE and choroid. Adult conditional Kcnj13 ko mice show loss of photoreceptors in the outer nuclear layer, inner nuclear layer thinning with loss of bipolar cells, and thinning and disruption of the outer plexiform layer, correlating with Cre expression in the overlying RPE which, although preserved, shows morphological disruption. Fundoscopy and OCT show signs of retinal degeneration consistent with the histology, and photopic and scotopic ERGs are decreased in amplitude or extinguished. Lentiviral based replacement of Kcnj13 resulted in increased ERG c- but not a- or b- wave amplitudes.

      ExperimentName: Conditional Kcnj13 knockout in mice

      NonHumanModel: Mus musculus

      GeneAlteration: Conditional knockout was generated by inserting a cassette into exon 2 of 3 in the presence of Cre driven by the VMD2 (RPE-specific) promoter.

      ModelPhenotype: Photoreceptor layer loss on macular OCT HP:0030609, Retinal degeneration HP:0000546, Abnormality of retinal pigmentation HP:0007703, Attenuation of retinal blood vessels HP:0007843, Decreased light- and dark-adapted electroretinogram amplitude HP:0000654

      HumanPhenotype: Reduced visual acuity HP:0007663, Constriction of peripheral visual field HP:00011, Infantile onset HP:0003593, Strabismus HP:0000486, Nystagmus HP:0000639, Progressive night blindness HP:0007675, Moderate myopia HP:0031624, Decreased light- and dark-adapted electroretinogram amplitude HP:0000654, Presenile cataracts HP:0007819, Nummular pigmentation of the fundus HP:0030505, Retinal pigment epithelial loss on macular OCT HP:0030611

      ModelEvidence: The 6-month-old mouse with induced Cre recombinase shows loss of photoreceptor cell layers (Figure 4F) and severe retinal degeneration (Figure 4G) relative to the control lacking Cre (Figure 4E), but with relative preservation of retinal morphology near the optic nerve. The RPE layer in the Cre-positive knockout cells shows irregular and flattened cell shapes with abnormal nuclear and cytoskeletal morphology relative to the control (Figure 5D). The knockout mouse fundus shows distinct inclusions, especially in the outer segment, as well as some attenuation of retinal blood vessels (Figure 6). ERG a-waves and b-waves are also extinguished (Figure 7A), consistent with loss of the entire photoreceptor layer (Figures 4F, 5B). There was also low amplitude of c-waves originating from the RPE cells (Figure 7C) that could be restored by lentiviral transduction of the functional KCNJ13 gene (Figures 7C, 7D).

      ModelVariant: The model features knockout of the endogenous mouse Kcnj13 rather than knock-in of a mutation equivalent to a variant from a human patient.

      Experimental ModelSystems ModelOrganism Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 23 Oct 2026
      Retinal Development and Pathophysiology in Kcnj13 Knockout Mice

      PMID: 35096838

      Gene: KCNJ13

      HGNC: 6259

      Disease: Leber congenital amaurosis 16

      MONDO: 0013613

      InheritancePattern: autosomal recessive

      Prevalence: The overall prevalence of Leber congenital amaurosis is between 1 in 33,000 and 1 in 100,000 newborns (PMID: 10951519), while the proportion of Leber congenital amaurosis caused by KCNJ13 variants is unknown.

      Penetrance: Known disease-causing alleles appear to be completely penetrant.

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC8790323/
  6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16)
    2
    1. ClingenBaseline 23 Oct 2026
      Herein, we report the identification of a novel nonsense mutation in the second exon of the KCNJ13 gene that leads to a premature stop codon in association with LCA16. We have determined that the mutation results in a severe truncation of the Kir7.1 C-terminus, alters protein localization, and disrupts potassium currents. Coexpression of the mutant and wild-type channel has no negative influence on the wild-type channel function, consistent with the normal clinical phenotype of carrier individuals.

      Case#: Pattnaik_2015_Proband, male, age 10 years, family national origin described as Jordanian

      CasePresentingHPOs: Nyctalopia HP:0000662, Childhood onset HP:0011463, Severely reduced visual acuity HP:0001141, Granular macular appearance HP:0007793, Retinal arteriolar constriction HP:0008043, Retinal degeneration HP:0000546, Abnormal choroid morphology (hypertrophy) HP:0000610

      CaseHPOFreeText: The proband has been diagnosed at different times with Stargardt disease, retinitis pigmentosa, cone-rod dystrophy, and Leber congenital amaurosis, first presenting with night vision difficulties at age 2 years. Small focal sub-RPE deposits were observed.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband was initially genotyped by PCR-based screening for known LCA-associated variants and next-generation sequencing focused on a 19-gene LCA panel.

      CaseMethod1: PCR-based screening for known LCA-associated variants as well as next-generation sequencing of a 19-gene LCA panel

      CaseMethod2: Sanger sequencing of gaps and low-coverage regions as well as for confirmation of the variants detected by other methods.

      CaseGenotypingMethod: The proband was initially genotyped by PCR-based screening for known LCA-associated variants and next-generation sequencing focused on a 19-gene LCA panel. Sanger sequencing of gaps and low-coverage regions as well as for confirmation of the variants detected by other methods.

      Variant: The individual is homozygous for the NM_002242.4(KCNJ13):c.158G>A (p.Trp53Ter) variant.

      ClinVar: 224857

      gnomAD: The variant is not found in gnomAD version 4.1.0.

      VariantEvidence: Heterologous expression of the NM_002242.4(KCNJ13):c.158G>A (p.Trp53Ter) variant in CHO-K1 cells revealed that the variant channel retained very little ability to enable the flow of current, with the measurement of -68.8pA more comparable to the negative control (-42.4pA) than to the wild-type control (-588.7pA).

      CaseAddInfo: The family history does not reportedly indicate consanguinity.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 21 Oct 2026
      A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16)

      PMID: 25921210

      Gene: KCNJ13

      HGNC: 6259

      Disease: Leber congenital amaurosis 16

      MONDO: 0013613

      InheritancePattern: autosomal recessive

      Prevalence: The overall prevalence of Leber congenital amaurosis is between 1 in 33,000 and 1 in 100,000 newborns (PMID: 10951519), while the proportion of Leber congenital amaurosis caused by KCNJ13 variants is unknown.

      Penetrance: Known disease-causing alleles appear to be completely penetrant.

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/25921210/
  7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Phenotypic expansion of KCNJ13- associated snowflake vitreoretinal degeneration
    2
    1. ClingenBaseline 23 Oct 2026
      An 18-year old highly myopic woman presented with bilateral retinoschisis associated with a unilateral macular hole in the right eye and vitreomacular traction in the left eye. Methods: Genetic studies disclosed a heterozygous pathogenic variant in the KCNJ13 gene was identified (c.484C>T (p.Arg162Trp)), consistent with a diagnosis of snowflake vitreoretinal degeneration (SVD). Results: While there were no corneal guttata, juvenile cataracts, or perivascular sheathing in this case, salient features of SVD included a fibrillar vitreous structure, crystalline retinopathy, and flattened optic nerves. The patient developed a FTMH in the left eye at 17 months follow up, followed by a rhegmatogenous retinal detachment (RRD) requiring 2 surgical repairs.

      Case#: Ashkenazy_2023_Proband, female, age 18 at time of report, family origin unknown due to adoption but reported in the United States

      CasePresentingHPOs: Snowflake vitreoretinal degeneration HP:0011533, High myopia HP:0011003, Retinoschisis HP:0030502, Rhegmatogenous retinal detachment HP:0012230, Abnormal vitreous humor morphology HP:0004327, Full-thickness macular hole HP:0031152

      CaseHPOFreeText: The patient exhibited fibrillar vitreous structure, crystalline retinopathy, and optic nerve flattening.

      CaseNotHPOs: Corneal guttata HP:0012038, Presenile cataracts HP:0007819

      CaseNotHPOFreeText: Perivascular sheathing was absent.

      CasePreviousTesting: Genotyping of the proband was not described in detail, but reportedly did not include whole exome sequencing, due to the specificity of the phenotype. Genes implied to have been possibly examined were COL2A1, COL11A1, and CSPG2.

      CaseMethod1: Sanger sequencing of KCNJ13

      CaseMethod2: N/A

      CaseGenotypingMethod: Genotyping of the proband was not described in detail, but reportedly did not include whole exome sequencing, due to the specificity of the phenotype. Genes implied to have been possibly examined were COL2A1, COL11A1, and CSPG2. Sanger sequencing of KCNJ13 was performed.

      Variant: The individual harbors the NM_002242.4(KCNJ13):c.484C>T (p.Arg162Trp) variant in the heterozygous state.

      ClinVar: 6585

      gnomAD: The variant is found in gnomAD version 4.1.0 at a frequency of 0.0000008536 (1 / 1,171,470) in the European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr2-232768790-G-A?dataset=gnomad_r4

      VariantEvidence:NM_002242.4(KCNJ13):c.484C>T (p.Arg162Trp) is a missense variant that has functional evidence of electrophysiological abnormalities and loss of sensitivity to different K+ concentrations, when exogenously expressed in CHO cells (PMID: 18179896, Figure 2).

      CaseAddInfo: The proband may or may not be a relative of the family previously reported with the same variant in PMID: 18179896, as both appear to have received medical care in the United States.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 21 Oct 2026
      Phenotypic expansion of KCNJ13- associated snowflake vitreoretinal degeneration

      PMID: 36440807

      Gene: KCNJ13

      HGNC: 6259

      Disease: snowflake vitreoretinal degeneration

      MONDO: 0008663

      InheritancePattern: autosomal dominant

      Prevalence: The overall prevalence of snowflake vitreoretinal degeneration is ~1 in 1,000,000 (https://www.orpha.net/en/disease/detail/91496).

      Penetrance: Known disease-causing alleles appear to be completely penetrant (PMID: 14644728).

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/36440807/
  8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Abnormal Electroretinogram after Kir7.1 Channel Suppression Suggests Role in Retinal Electrophysiology
    1
    1. ClingenBaseline 22 Oct 2026
      shRNA targeting of Kir7.1 inhibited mRNA expression and reduced ERG After demonstrating that Kir7.1 protein is primarily expressed in RPE cells, we sought to determine whether the RPE Kir7.1 channel contributes to the ERG. We delivered a specific shRNA lentiviral particle to the mouse vitreal chamber by micro injection to inhibit Kcnj13 gene expression. Seven days after shRNA injection, eyes were harvested and RPE cells isolated. PCR amplification of Kcnj13 in RPE cells did not reveal a product from the shRNA injected mouse eye (Fig. 3A Lanes 3), whereas in the contralateral eye that received saline injection, a 653 bp band corresponding to the Kcnj13 transcript was present (Fig. 3A Lane 5). Housekeeping gene ß-actin transcript was detected as a 248 bp band in both samples (Fig. 3A Lanes 4 &6). We did not detect either Kir7.1 or actin in negative control experiments (Fig. 3A Lanes 7 & 8). Kir7.1 shRNA inhibition was able to reduce Kcnj13 mRNA expression by an average of 73.62 ± 14.47% (Fig. 3B).

      Mouse model based on ERG defects induced by Kcnj13 shRNA injection (packaged in lentiviral particles)

      Experimental ModelSystems ModelOrganism Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC5587531/
  9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    A distinct vitreo-retinal dystrophy with early-onset cataract from recessive KCNJ13 mutations
    2
    1. ClingenBaseline 22 Oct 2026
      A distinct vitreo-retinal dystrophy with early-onset cataract from recessive KCNJ13 mutations

      PMID: 25475713

      Gene: KCNJ13

      HGNC: 6259

      Disease: Leber congenital amaurosis 16

      MONDO: 0013613

      InheritancePattern: autosomal recessive

      Prevalence: The overall prevalence of Leber congenital amaurosis is between 1 in 33,000 and 1 in 100,000 newborns (PMID: 10951519), while the proportion of Leber congenital amaurosis caused by KCNJ13 variants is unknown.

      Penetrance: Known disease-causing alleles appear to be completely penetrant.

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 22 Oct 2026
      A 12-year-old Saudi Arabian girl with nystagmus since birth was referred because of recent decreased vision. Parents were first cousins and a younger sister had been diagnosed with retinal dystrophy. Examination revealed total white cataract in the right eye. In the left eye, there were posterior cortical lenticular opacities and an unusual retina fundus dystrophic appearance notable for fibrosis over the optic disc and clumped pigmentation. After right eye cataract surgery, the posterior pole of the left eye was seen as similar to that of the right eye and electroretinography revealed severe cone-rod dysfunction, with only subnormal scotopic tracings recordable in both eyes. Next-generation sequencing of retinal dystrophy genes revealed homozygosity for a novel missense mutation in KCNJ13 (c.359T > C; p.Ile120Thr [NM_002242.4]), which co-segregated with the disease.

      Case#: Khan_2015_Proband, female, age 12 years, family national origin described as Saudi

      CasePresentingHPOs: Congenital nystagmus HP:0006934, Juvenile cataract HP:0001118, Reduced visual acuity HP:0007663, Posterior cortical cataract HP:0010924, Abnormal optic disc morphology (fibrosis over the optic disc) HP:0012795, Pigmentary retinopathy HP:0000580, Undetectable light-adapted electroretinogram HP:0030465, Abnormal dark-adapted electroretinogram (decreased amplitude) HP:0030469

      CaseHPOFreeText: The proband's overall phenotype was summarized as "juvenile cataract in the setting of a congenital vitreo-retinal dystrophy notable for fibrosis over the disc and clumped pigmentation in the posterior pole". The authors comment that the phenotype should be described as; "early-onset vitreo-retinal degeneration (with early-onset cataract)" rather than as LCA, due to the presence of vitreous degenerative changes as well as the ERG being recordable in patients in the second decade of life and beyond.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband was initially genotyped by next-generation sequencing focused on a panel of 27 LCA genes and 60 recessive retinitis pigmentosa genes.

      CaseMethod1: next-generation sequencing focused on a panel of 27 LCA genes and 60 recessive retinitis pigmentosa genes

      CaseMethod2: Sanger sequencing of the proband and family members to confirm the presence of the variant and to test segregation

      CaseGenotypingMethod: The proband was initially genotyped by next-generation sequencing focused on a panel of 27 LCA genes and 60 recessive retinitis pigmentosa genes. Sanger sequencing of the proband and family members was then performed to confirm the presence of the variant and to test segregation.

      Variant: The individual is homozygous for the NM_002242.4(KCNJ13):c.359T>C (p.Ile120Thr) variant.

      ClinVar: 191155

      gnomAD: The variant is found in gnomAD version 4.1.0 at a frequency of 0.00001562 (1 allele / 64034 total alleles) in the European (Finnish) population https://gnomad.broadinstitute.org/variant/2-232771004-A-G?dataset=gnomad_r4

      VariantEvidence: NM_002242.4(KCNJ13):c.359T>C (p.Ile120Thr) is a missense variant that has not been studied at the functional level.

      CaseAddInfo: The proband's family history includes consanguinity and a sibling similarly diagnosed with retinal dystrophy.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/25475713/
  10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    The genetic landscape of inherited eye disorders in 74 consecutive families from the United Arab Emirates
    2
    1. ClingenBaseline 22 Oct 2026
      The genetic landscape of inherited eye disorders in 74 consecutive families from the United Arab Emirates

      PMID: 32783370

      Gene: KCNJ13

      HGNC: 6259

      Disease: Leber congenital amaurosis 16

      MONDO: 0013613

      InheritancePattern: autosomal recessive

      Prevalence: The overall prevalence of Leber congenital amaurosis is between 1 in 33,000 and 1 in 100,000 newborns (PMID: 10951519), while the proportion of Leber congenital amaurosis caused by KCNJ13 variants is unknown.

      Penetrance: Known disease-causing alleles appear to be completely penetrant.

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 22 Oct 2026
      In family 6, two affected patients 6‐1 (8 years old) and 6‐2 (4 years old) with a severe EORD were homozygous for a novel missense variant c.431T>C p.(Leu144Pro) in KCNJ13, predicted to be disease‐causing and found only twice in a heterozygous state in 125,455 people (allele frequency = 0.0007971%) from multiple origins (gnomAD). This variant is localized to the conserved transmembrane M2 protein domain, close to the missense variant c.458C>T p.(Thr153Ile) previously reported to cause Leber congenital amaurosis 16 (OMIM #614186) with retinovascular changes in late adolescence. The fundal appearance was consistent with KCNJ13‐retinopathy and regular fundus examinations are required to mitigate any signs of neovascularization with age (Toms et al., 2019).

      Case#: Méjécase_2020_Family_6_Proband_6-1, sex not specified, age 8 years, family national origin described as from the United Arab Emirates

      CasePresentingHPOs: N/A

      CaseHPOFreeText: The proband received a diagnosis of severe early onset retinal dystrophy. The fundus appearance was described as consistent with KCNJ13-retinopathy.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband was previously genotyped by a next-generation sequencing panel.

      CaseMethod1: next-generation sequencing panel

      CaseMethod2: Sanger sequencing of KCNJ13

      CaseGenotypingMethod: The proband was previously genotyped by a next-generation sequencing panel, followed by Sanger sequencing-based confirmation.

      Variant: The individual harbors the NM_002242.4(KCNJ13):c.431T>C (p.Leu144Pro) variant in the homozygous state.

      ClinVar: 916717

      gnomAD: The variant is found in gnomAD version 4.1.0 at a frequency of 0.00001667 (1 / 59998) in the African / African-American population https://gnomad.broadinstitute.org/variant/chr2-232770932-A-G?dataset=gnomad_r4

      VariantEvidence: NM_002242.4(KCNJ13):c.431T>C (p.Leu144Pro) is a missense variant that has no experimental evidence in this study

      CaseAddInfo: The proband's family history includes a similarly affected 4-year-old sibling with the same homozygous genotype.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pmc.ncbi.nlm.nih.gov/articles/PMC8432150/
  11. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    LEBER CONGENITAL AMAUROSIS WITH LARGE RETINAL PIGMENT CLUMPS CAUSED BY COMPOUND HETEROZYGOUS MUTATIONS IN KCNJ13
    2
    1. ClingenBaseline 22 Oct 2026
      A 31-year-old man with Leber congenital amaurosis. Results: Patient had nystagmus since childhood, best-corrected visual acuity limited to 20/400 OD and 20/200 OS, and had cataracts extracted in both eyes. There were clumpy pigment deposits mostly in macular area, causing an uneven line of retinal pigment epithelium on spectral domain optical coherence tomography. In retinal parts devoid of pigment deposits around the optic disk and in periphery, retinal thickness was increased and hyperreflective formations were present either in the inner nuclear layer or in the outer nuclear layer. The patient was compound heterozygous for new mutations in KCNJ13 which encodes the Kir 7.1 potassium channel, c.314G>T (p.Ser105Ile) in exon 2 and c.655C>T (p.Gln219*) in exon 3. Both mutations were absent from databases.

      Case#: Perez-Roustit_2017_Proband, male, age 31 years, family ethnic origin not reported

      CasePresentingHPOs: Nystagmus HP:0000639, Childhood onset HP:0011463, Reduced visual acuity HP:0007663, Presenile cataracts HP:0007819, Pigmentary retinopathy HP:0000580, Patchy atrophy of the retinal pigment epithelium HP:0007791, Undetectable light- and dark-adapted electroretinogram HP:0007688

      CaseHPOFreeText: The proband received a diagnosis of Leber congenital amaurosis. His phenotype included increased retinal thickness and presence of hyper-reflective formations around the optic disc and periphery. Visual impairment was severe but did not evolve significantly during the first 30 years of age.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband was previously genotyped by screening for ABCA4 variants.

      CaseMethod1: Sanger sequencing of the ABCA4 gene

      CaseMethod2: Sanger sequencing of the KCNJ13 exons and intron-exon boundaries

      CaseGenotypingMethod: The proband was previously genotyped by screening for ABCA4 variants, followed by Sanger sequencing of the KCNJ13 exons and intron-exon boundaries.

      Variant: The individual is compound heterozygous with the maternal NM_002242.4(KCNJ13):c.314G>T (p.Ser105Ile) and paternal NM_002242.4(KCNJ13):c.655C>T (p.Gln219Ter) variants.

      ClinVar: 978434, 978433

      gnomAD: The NM_002242.4(KCNJ13):c.314G>T (p.Ser105Ile) variant was not found in gnomAD version 4.1.0. The NM_002242.4(KCNJ13):c.655C>T (p.Gln219Ter) variant is found in gnomAD version 4.1.0 at a frequency of 0.00002669 (2/74924) in the African / African-American population https://gnomad.broadinstitute.org/variant/2-232768619-G-A?dataset=gnomad_r4

      VariantEvidence: NM_002242.4(KCNJ13):c.314G>T (p.Ser105Ile) is a missense variant that has no experimental evidence in this study. NM_002242.4(KCNJ13):c.655C>T (p.Gln219Ter) is a nonsense variant in exon 3 of 3 that is not predicted to trigger NMD but rather to truncate the C-terminal 39% of the protein product.

      CaseAddInfo: The proband's family history is not known to include parental consanguinity or history of retinal disease.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 21 Oct 2026
      LEBER CONGENITAL AMAUROSIS WITH LARGE RETINAL PIGMENT CLUMPS CAUSED BY COMPOUND HETEROZYGOUS MUTATIONS IN KCNJ13

      PMID: 27203561

      Gene: KCNJ13

      HGNC: 6259

      Disease: Leber congenital amaurosis 16

      MONDO: 0013613

      InheritancePattern: autosomal recessive

      Prevalence: The overall prevalence of Leber congenital amaurosis is between 1 in 33,000 and 1 in 100,000 newborns (PMID: 10951519), while the proportion of Leber congenital amaurosis caused by KCNJ13 variants is unknown.

      Penetrance: Known disease-causing alleles appear to be completely penetrant.

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/27203561/
  12. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    A novel phenotype associated with the R162W variant in the KCNJ13 gene
    2
    1. ClingenBaseline 21 Oct 2026
      Four affected members of a Swedish family were included. Three of them were examined with best corrected visual acuity, Goldmann perimetry, full-field-and multifocal electroretinography, optical coherence tomography, fundus color photographs, fundus autofluorescence images, slit lamp inspection, and genetic testing. The fourth subject only managed genetic testing. Results: All subjects carry the pathogenic missense variant; c.484C>T (NM_002242.4), R162W, in KCNJ13. ERG measurements revealed reduced macular-as well as general retinal function. Two of the subjects had a history of retinal detachment and the two younger subjects demonstrated early onset cataract. They all had structural macular changes and slightly gliotic optic discs.

      Case#: Schroeder_2022_Proband, female, age 32 at time of diagnosis, family national origin reported as Swedish

      CasePresentingHPOs: Optic disc pallor HP:0000543, Retinal detachment HP:0000541, Presenile cataracts HP:0007819, Decreased light- and dark-adapted electroretinogram amplitude HP:0000654, Retinal hole HP:0011530, Abnormal fundus autofluorescence imaging HP:0030602

      CaseHPOFreeText: The patient optic discs were described as slightly gliotic. OCT showed lacunar retinal substance losses in the fovea and attenuation in all segments of the macula. FAF showed a paracentral ring of fine granular increase of autofluorescence around the fovea in the posterior pole.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: Genotyping of the proband was performed by whole genome sequencing.

      CaseMethod1: whole genome sequencing

      CaseMethod2: Sanger sequencing of KCNJ13

      CaseGenotypingMethod: Genotyping of the proband was performed by whole genome sequencing, followed by Sanger sequencing of KCNJ13.

      Variant: The individual harbors the NM_002242.4(KCNJ13):c.484C>T (p.Arg162Trp) variant in the heterozygous state.

      ClinVar: 6585

      gnomAD: The variant is found in gnomAD version 4.1.0 at a frequency of 0.0000008536 (1 / 1,171,470) in the European (non-Finnish) population https://gnomad.broadinstitute.org/variant/chr2-232768790-G-A?dataset=gnomad_r4

      VariantEvidence:NM_002242.4(KCNJ13):c.484C>T (p.Arg162Trp) is a missense variant that has functional evidence of electrophysiological abnormalities and loss of sensitivity to different K+ concentrations, when exogenously expressed in CHO cells (PMID: 18179896, Figure 2).

      CaseAddInfo: The proband has three affected family members who also harbored the variant in the heterozygous state. Consanguinity was not reported.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 21 Oct 2026
      A novel phenotype associated with the R162W variant in the KCNJ13 gene

      PMID: 35477418

      Gene: KCNJ13

      HGNC: 6259

      Disease: snowflake vitreoretinal degeneration

      MONDO: 0008663

      InheritancePattern: autosomal dominant

      Prevalence: The overall prevalence of snowflake vitreoretinal degeneration is ~1 in 1,000,000 (https://www.orpha.net/en/disease/detail/91496).

      Penetrance: Known disease-causing alleles appear to be completely penetrant (PMID: 14644728).

      General ClinGen Gene:KCNJ13 HGNC:6259 inferred_gene_hgnc:6259 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/35477418/