18 Matching Annotations
  1. Oct 2026
  2. iovs.arvojournals.org iovs.arvojournals.org
    CORD9 a New Locus for arCRD: Mapping to 8p11, Estimation of Frequency, Evaluation of a Candidate Gene
    3
    1. ClingenBaseline 24 Oct 2026
      Four-point linkage analysis gave a maximum lod score of approximately 7.6 at both D8S1769 and GATA101H09 in the large consanguineous family. Recombination events defined an interval of 8.7 cM between D8S1820 and D8S532 within which the gene must lie. This 8p11 locus (CORD9) is immediately distal to but distinct from the RP1 autosomal dominant RP (adRP) locus.

      FamilyLabel: Danciger_2001_Family

      Family#PresentingHPOs: HP:0011463 (Childhood onset), HP:0007663 (Reduced visual acuity), HP:0001141 (Severely reduced visual acuity), HP:0007994 (Peripheral visual field loss), HP:0000545 (Myopia), HP:0000483 (Astigmatism), HP:0000523 (Subcapsular cataract)

      FamilyPresentingHPOFreeText: The affected family members have been diagnosed with severe cone-rod dystrophy segregating with an autosomal recessive mode of inheritance.

      FamilyNotHPOs: N/A

      FamilyNotHPOFreeText: N/A

      CountryOrigin: Brazil

      Ethnicity: Brazilian

      Race: Not described

      Family#PreviousTesting: Linkage mapping has been performed in affected and unaffected family members using short tandem repeat markers across the genome.

      Family#Method1: Linkage mapping using short tandem repeat markers

      Family#Method2: Haplotype analysis with markers within an 8-cM region of chromosome 8p11.

      Family#GenotypingMethod: Linkage mapping has been performed in affected and unaffected family members using short tandem repeat markers across the genome, followed by haplotype analysis within the linkage region. A subsequent publication sequenced 10 out of 34 genes within the linkage region and found homozygous variants in ADAM9 in particular (PMID: 19409519).

      Affected: 5

      Unaffected: 7

      Segregations: 7 segregations are shown by the pedigree in Figure 1.

      PublishedLOD: 7.6 (associated with the D8S1769 and GATA101H09 short tandem repeat markers on chromosome 8p11)

      eLOD: N/A

      AddSegregationInfo: N/A

      ProbandLabel: Danciger_2001_Family_Patient_A

      Variant: The affected family members harbor the NM_003816.3(ADAM9):c.1130+1G>A variant in the homozygous state.

      ClinVar: 6876

      gnomAD: This variant was not found in gnomAD v2.1.1.

      VariantEvidence: The NM_003816.3(ADAM9):c.1130+1G>A variant is predicted to disrupt a canonical splice site in intron 11.

      FamilyAddInfo: The family is known to be consanguineous, with the parents of affected individuals being second cousins.

      FamilyPMIDs: PMID: 19409519

      Case Family FamilyInfo Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 23 Oct 2026
      Affected members of this family had childhood-onset visual acuity impairment. The disease progressed over decades to major loss of central and then peripheral visual function. At late stages of disease, patients retained only islands of vision in the midperiphery. Funduscopic appearance (Fig. 2) and visual function test results (Fig. 3) in two affected family members in the fifth decade of life are shown. Visual acuities in both patients were 20/200 or worse, and the refractive error was modest myopia with astigmatism. There were small posterior subcapsular cataracts.  In the central retina of the right eye of patient A (Fig. 2A) , there was a large area of discoloration, suggesting retinal pigmented epithelial disturbances. Patient B showed a macular coloboma-like lesion with a central atrophic scar surrounded by a ring of pigmentary change (Fig. 2B) . The central retinal area was discolored as in patient A; there were, in addition, small, discrete, white-yellow patches. In both patients, the fundus temporal to the macula was less pathologic appearing (Figs. 2C 2D) . Both patients had attenuated retinal vessels. Patient B showed temporal pallor of the optic nerve head, whereas this was not as evident in patient A.  Visual function test results are shown in Figure 3 . Compared with ERGs of a representative normal subject, all waveforms of the two patients were severely abnormal (Fig. 3A) . Patient A showed reduced amplitudes but normal timing of both rod and cone ERGs. Patient B had greater reductions in amplitude. Figure 3B shows kinetic perimetry (top panels) and static threshold perimetry in the dark-adapted (middle panels) and light-adapted (bottom panels) states. Sensitivity losses for rods (500-nm stimulus, dark-adapted) and long- (L) and middle (M)-wavelength cones (600-nm stimulus, light-adapted) were calculated from locus-specific normal values and are shown as gray-scale maps (0–3 log units). The psychophysical tests were conducted to position the anatomic fovea at the central fixation target (central scotoma thus truly “central”). Patients otherwise used eccentric fixation loci of approximately 20° from the fovea. By kinetic perimetry, both patients retained midperipheral islands of vision and could see both a large bright target (V-4e) and a smaller bright target (I-4e). Static perimetry also indicated detectable rod and cone sensitivity mainly in the nasal midperiphery. Some loci had no loss of rod or cone sensitivity, whereas other loci showed losses of 1 to 3 log units. 

      Case#: Danciger_2001_Family_Patient_A, gender not specified, age 48 years at the time of the report, family origin reported to be Brazilian

      CasePresentingHPOs: HP:0011463 (Childhood onset), HP:0001141 (Severely reduced visual acuity), HP:0007994 (Peripheral visual field loss), HP:0000545 (Myopia), HP:0007703 (Abnormality of retinal pigmentation), HP:0007843 (Attenuation of retinal blood vessels), HP:0000654 (Decreased light- and dark-adapted electroretinogram amplitude), HP:0000483 (Astigmatism), HP:0000523 (Subcapsular cataract)

      CaseHPOFreeText: The proband was diagnosed with severe cone-rod dystrophy.

      CaseNotHPOs: HP:0000543 (Optic disc pallor)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband and his family have been initially genotyped by linkage mapping using short tandem repeat markers across the genome.

      CaseMethod1: Linkage mapping using short tandem repeat markers

      CaseMethod2: Sanger sequencing

      CaseGenotypingMethod: The proband and his family have been initially genotyped by linkage mapping using short tandem repeat markers across the genome. Haplotype analysis was then performed within the linkage region. Finally, a subsequent publication on the same family sequenced 10 out of 34 genes within the linkage region and found homozygous variants in ADAM9 in particular (PMID: 19409519).

      Variant: The affected family members harbor the NM_003816.3(ADAM9):c.1130+1G>A variant in the homozygous state.

      ClinVar: 6876

      gnomAD: This variant was not found in gnomAD v2.1.1.

      VariantEvidence: The NM_003816.3(ADAM9):c.1130+1G>A variant is predicted to disrupt a canonical splice site in intron 11.

      CaseAddInfo: The proband's family is known to be consanguineous, with the parents being second cousins.

      CasePMIDs: PMID: 19409519

      Case Individual CaseInfo Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    3. ClingenBaseline 22 Oct 2026
      CORD9 a New Locus for arCRD: Mapping to 8p11, Estimation of Frequency, Evaluation of a Candidate Gene

      PMID: 11581183

      Gene: ADAM9

      HGNC: 216

      Disease: cone-rod dystrophy 9

      MONDO: MONDO:0013002

      InheritancePattern: autosomal recessive

      Prevalence: The prevalence of cone-rod dystrophy in general is estimated to be 1 in 40,000 (PMID: 17270046), however, the specific prevalence of cone-rod dystrophy 9 is unknown.

      Penetrance: Penetrance appears to be complete in reported families, but it is possible that incomplete penetrance may be associated with some variants.

      General ClinGen Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    iovs.arvojournals.org/article.aspx
  3. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice
    5
    1. ClingenBaseline 24 Oct 2026
      In MOL0277, a homozygous intronic change (c.411-8A→G) was the only potentially pathogenic change identified. Sequence of cDNA derived from patients' peripheral blood lymphocyte mRNA demonstrated that this mutation activated a cryptic splice acceptor site giving rise only to an aberrant transcript (Figure 2B). The mutant transcript has seven additional base pairs of sequence added to the beginning of exon 6 and is predicted to introduce a frameshift resulting in premature termination (R137SfsX16).

      Case#: Parry_2009_Family_MOL0277_patient_IV:2, male, age not specified, family origin reported to be Arab Muslim

      CasePresentingHPOs: HP:0410280 (Pediatric onset), HP:0007663 (Reduced visual acuity), HP:0007401 (Macular atrophy), HP:0000580 (Pigmentary retinopathy), HP:0007769 (Peripheral retinal degeneration), HP:0008323 (Abnormal light- and dark-adapted electroretinogram)

      CaseHPOFreeText: The proband was diagnosed with cone-rod dystrophy, with family showing autosomal recessive mode of inheritance. Most affected members of the proband's family had white patches around the optic disc and in the posterior pole.

      CaseNotHPOs: HP:0000639 (Nystagmus), HP:0000613 (Photophobia)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband and his family have been initially genotyped by autozygosity mapping with both 10k and 250k Affymetrix SNP arrays and microsatellite markers.

      CaseMethod1: Autozygosity mapping

      CaseMethod2: Sanger sequencing

      CaseGenotypingMethod: The proband and his family have been initially genotyped by autozygosity mapping with both 10k and 250k Affymetrix SNP arrays and microsatellite markers. Sanger sequencing of the ADAM9 locus then identified the variants.

      Variant: The proband harbors the NM_003816.3(ADAM9):c.411-8A>G variant in the homozygous state.

      ClinVar: 6879

      gnomAD: This variant was not found in gnomAD v2.1.1.

      VariantEvidence: NM_003816.3(ADAM9):c.411-8A>G is a variant in intron 5 that has been shown to trigger aberrant splicing and abolish normal splicing by activating use of a cryptic splice acceptor site (Figure 2B). The predicted result is to add 7 bp to the 5' end of exon 6 and introduce a frameshift causing premature termination. Since this affects exon 6 of 21, the predicted result is nonsense-mediated decay or truncation of the C-terminal 83% of the protein product (p.Arg137SerfsX16).

      CaseAddInfo: The proband's family is known to be consanguineous, with the parents being first cousins (pedigree shown in Figure 2).

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 24 Oct 2026
      Loss of the Metalloprotease ADAM9 Leads to Cone-Rod Dystrophy in Humans and Retinal Degeneration in Mice

      PMID: 19409519

      Gene: ADAM9

      HGNC: 216

      Disease: cone-rod dystrophy 9

      MONDO: MONDO:0013002

      InheritancePattern: autosomal recessive

      Prevalence: The prevalence of cone-rod dystrophy in general is estimated to be 1 in 40,000 (PMID: 17270046), however, the specific prevalence of cone-rod dystrophy 9 is unknown.

      Penetrance: Penetrance appears to be complete in reported families, but it is possible that incomplete penetrance may be associated with some variants.

      General ClinGen Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    3. ClingenBaseline 23 Oct 2026
      We also found reduced photoreceptor responses in Adam9 knockout mice, previously reported to be asymptomatic. In 12-month-old knockout mice, photoreceptors appear normal, but the apical processes of the retinal pigment epithelium (RPE) cells are disorganized and contact between photoreceptor outer segments (POSs) and the RPE apical surface is compromised. In 20-month-old mice, there is clear evidence of progressive retinal degeneration with disorganized POS and thinning of the outer nuclear layer (ONL) in addition to the anomaly at the POS-RPE junction. RPE basal deposits and macrophages were also apparent in older mice.

      ExperimentName: Mouse model of Adam9 loss-of-function

      NonHumanModel: Mus musculus

      GeneAlteration: The mice harbor homozygous knockout of the Adam9 gene by an insertion of a neomycin selection cassette in to the exon encoding amino acids 32 to 66 of Adam9 (PMID: 11839819).

      ModelPhenotype: HP:0000546 (Retinal degeneration), HP:0007703 (Abnormality of retinal pigmentation), HP:0030610 (Photoreceptor outer segment loss on macular OCT), HP:0030483 (Reduced amplitude of dark-adapted bright flash electroretinogram a-wave), HP:0007984 (Electronegative electroretinogram), HP:0008323 (Abnormal light- and dark-adapted electroretinogram)

      HumanPhenotype: HP:0410280 (Pediatric onset), HP:0007663 (Reduced visual acuity), HP:0007401 (Macular atrophy), HP:0000580 (Pigmentary retinopathy), HP:0007769 (Peripheral retinal degeneration), HP:0008323 (Abnormal light- and dark-adapted electroretinogram), HP:0000548 (Cone/cone-rod dystrophy), HP:0007994 (Peripheral visual field loss), HP:0000545 (Myopia)

      ModelEvidence: The affected mice exhibit an abnormal gap between the RPE and the photoreceptor outer segment, which would normally be in contact (Figure 5B). The gap contains macrophages (Figure 5L). Outer nuclear layer thinning is observed (Figure 5D), as well as material deposited between the RPE and Bruch's membrane, which may be analogous to drusen deposits in humans (Figure 5K). These findings collectively show an adhesion defect at the interface between the photoreceptor outer segment and the RPE. This evidence of retinal degeneration was complemented by abnormalities in both rod- and cone-driven ERG responses (Figure 4), matching a feature of the human patients.

      ModelVariant: The model harbors a targeted disruption that does not have an equivalent / orthologous variant reported in human patients.

      Experimental ModelSystems ModelOrganism Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    4. ClingenBaseline 23 Oct 2026
      Direct sequencing of ADAM9 in MEP49 revealed a homozygous point mutation in exon 9, creating a premature stop codon (c.766C→T; p.R256X) (Figure 2A).

      Case#: Parry_2009_Family_MEP49_patient_IV:5, male, age not specified, family origin reported to be Pakistani

      CasePresentingHPOs: HP:0410280 (Pediatric onset), HP:0007663 (Reduced visual acuity), HP:0007401 (Macular atrophy), HP:0000580 (Pigmentary retinopathy), HP:0007769 (Peripheral retinal degeneration), HP:0008323 (Abnormal light- and dark-adapted electroretinogram)

      CaseHPOFreeText: The proband was diagnosed with cone-rod dystrophy, with family showing autosomal recessive mode of inheritance. Most affected members of the proband's family had white patches around the optic disc and in the posterior pole.

      CaseNotHPOs: HP:0000639 (Nystagmus), HP:0000613 (Photophobia)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband and his family have been initially genotyped by autozygosity mapping with both 10k and 250k Affymetrix SNP arrays and microsatellite markers.

      CaseMethod1: Autozygosity mapping

      CaseMethod2: Sanger sequencing

      CaseGenotypingMethod: The proband and his family have been initially genotyped by autozygosity mapping with both 10k and 250k Affymetrix SNP arrays and microsatellite markers. Sanger sequencing of the ADAM9 locus then identified the variants.

      Variant: The proband harbors the NM_003816.3(ADAM9):c.766C>T (p.Arg256Ter) variant in the homozygous state.

      ClinVar: 6877

      gnomAD: This variant is found in gnomAD v2.1.1 at a frequency of 0.00003267 (1/30608) in the South Asian population, with no homozygotes. https://gnomad.broadinstitute.org/variant/8-38880696-C-T

      VariantEvidence: NM_003816.3(ADAM9):c.766C>T (p.Arg256Ter) is a nonsense variant in exon 9 of 21, and is therefore predicted to result in nonsense-mediated decay.

      CaseAddInfo: The proband's family is known to be consanguineous, with the parents being first cousins (pedigree shown in Figure 2).

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    5. ClingenBaseline 22 Oct 2026
      A second homozygous stop codon was identified in MOL0172 (c.490C→T; p.R164X) (Figure 2A).

      Case#: Parry_2009_Family_MOL0172_patient_IV:3, male, age not specified, family origin reported to be Tunisian Jewish

      CasePresentingHPOs: HP:0410280 (Pediatric onset), HP:0007663 (Reduced visual acuity), HP:0007401 (Macular atrophy), HP:0000580 (Pigmentary retinopathy), HP:0007769 (Peripheral retinal degeneration), HP:0008323 (Abnormal light- and dark-adapted electroretinogram)

      CaseHPOFreeText: The proband was diagnosed with cone-rod dystrophy, with family showing autosomal recessive mode of inheritance. Most affected members of the proband's family had white patches around the optic disc and in the posterior pole.

      CaseNotHPOs: HP:0000639 (Nystagmus), HP:0000613 (Photophobia)

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband and his family have been initially genotyped by autozygosity mapping with both 10k and 250k Affymetrix SNP arrays and microsatellite markers.

      CaseMethod1: Autozygosity mapping

      CaseMethod2: Sanger sequencing

      CaseGenotypingMethod: The proband and his family have been initially genotyped by autozygosity mapping with both 10k and 250k Affymetrix SNP arrays and microsatellite markers. Sanger sequencing of the ADAM9 locus then identified the variants.

      Variant: The proband harbors the NM_003816.3(ADAM9):c.490C>T (p.Arg164Ter) variant in the homozygous state.

      ClinVar: 6878

      gnomAD: This variant was not found in gnomAD v2.1.1.

      VariantEvidence: NM_003816.3(ADAM9):c.490C>T (p.Arg164Ter) is a nonsense variant in exon 6 of 21, and is therefore predicted to result in nonsense-mediated decay.

      CaseAddInfo: The proband's family is known to be consanguineous, with the father being the mother's uncle (pedigree shown in Figure 2).

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    ncbi.nlm.nih.gov/pmc/articles/PMC2681008/
  4. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Next-Generation Sequencing–Based Molecular Diagnosis of a Chinese Patient Cohort With Autosomal Recessive Retinitis Pigmentosa
    2
    1. ClingenBaseline 24 Oct 2026
      Next-Generation Sequencing–Based Molecular Diagnosis of a Chinese Patient Cohort With Autosomal Recessive Retinitis Pigmentosa

      PMID: 23661369

      Gene: ADAM9

      HGNC: 216

      Disease: cone-rod dystrophy 9

      MONDO: MONDO:0013002

      InheritancePattern: autosomal recessive

      Prevalence: The prevalence of cone-rod dystrophy in general is estimated to be 1 in 40,000 (PMID: 17270046), however, the specific prevalence of cone-rod dystrophy 9 is unknown.

      Penetrance: Penetrance appears to be complete in reported families, but it is possible that incomplete penetrance may be associated with some variants.

      General ClinGen Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 22 Oct 2026
      In our study, a patient from arRP family 4263 was identified to carry a novel homozygous nonsense variant, 1786C>T:p.(R596*), in ADAM9 ({"type":"entrez-nucleotide","attrs":{"text":"NM_003816.2","term_id":"54292119","term_text":"NM_003816.2"}}NM_003816.2), which introduces a premature stop in exon16, resulting in a truncated protein or nonsense-mediated decay. A segregation test indicated that the nonsense variant cosegregated with the disease phenotype (Fig. 5C). To clarify the ambiguity between the molecular and clinical diagnosis, we reevaluated the clinical information for this patient. Patient 4263_1 was a 9-year-old boy from a consanguineous family. Initially, he experienced severe night blindness but no significant loss in daylight vision. His vision acuity was 0.3/0.3 (decimal Snellen) at first clinical visit and decreased rapidly to 0.08/0.1 (decimal Snellen). Full-field ERG showed both rod and cone functions were impaired. However, the amplitude of b-wave in dark-adapted rod response was more severely decreased compared with cone responses. Fundus image and OCT are shown in Supplementary Figure S3. Based on these clinical phenotypes and the ADAM9 mutation identified in the family, the patients were rediagnosed to have CRD with early-onset retinal dystrophy.

      Case#: Fu_2013_Patient_4263_1, male, age 9 at time of report, family origin reported to be Chinese

      CasePresentingHPOs: HP:0030534 (Abnormal best corrected visual acuity test), HP:0000662 (Nyctalopia), HP:0007663 (Reduced visual acuity), HP:0000654 (Decreased light- and dark-adapted electroretinogram amplitude), HP:0007984 (Electronegative electroretinogram), HP:0410280 (Pediatric onset)

      CaseHPOFreeText: The proband was initially diagnosed with retinitis pigmentosa with an autosomal recessive pattern of inheritance, and subsequently re-diagnosed with cone-rod dystrophy with early-onset retinal dystrophy.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband was initially genotyped by next-generation sequencing focusing on a panel of 163 known retinal disease genes.

      CaseMethod1: Next-generation sequencing panel (163 genes)

      CaseMethod2: Sanger sequencing of ADAM9

      CaseGenotypingMethod: The proband was initially genotyped by next-generation sequencing focusing on a panel of 163 known retinal disease genes, followed by Sanger sequencing of ADAM9.

      Variant: The proband harbors the NM_003816.3(ADAM9):c.1786C>T (p.Arg596Ter) variant in the homozygous state.

      CAID: CA370746588

      gnomAD: This variant was not found in gnomAD v2.1.1.

      VariantEvidence: NM_003816.3(ADAM9):c.1786C>T (p.Arg596Ter) is a nonsense variant in exon 16 of 21, which is predicted to trigger NMD or to truncate the C-terminal ~27% of the protein product.

      CaseAddInfo: The proband's parents are consanguineous and are each heterozygous for the variant, while his unaffected sister does not carry the variant.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    ncbi.nlm.nih.gov/pmc/articles/PMC3684217/
  5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin
    2
    1. ClingenBaseline 24 Oct 2026
      MDC-9 (ADAM-9/Meltrin gamma) functions as an adhesion molecule by binding the alpha(v)beta(5) integrin

      PMID: 11162558

      Gene: ADAM9

      HGNC: 216

      Disease: cone-rod dystrophy 9

      MONDO: MONDO:0013002

      InheritancePattern: autosomal recessive

      Prevalence: The prevalence of cone-rod dystrophy in general is estimated to be 1 in 40,000 (PMID: 17270046), however, the specific prevalence of cone-rod dystrophy 9 is unknown.

      Penetrance: Penetrance appears to be complete in reported families, but it is possible that incomplete penetrance may be associated with some variants.

      General ClinGen Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 21 Oct 2026
      The disintegrin domain of MDC-9 lacks an RGD motif but has recently been reported to bind the alpha(6)beta(1) integrin; however, it is unclear whether MDC-9 can bind other integrins. In the present study myeloma cells, but not lymphoblastoid cells, were shown to bind to immobilised, recombinantly expressed MDC-9 disintegrin domain (A9dis). Binding was divalent cation-dependent, being supported by Mn(2+) and Ca(2+). Adhesion of myeloma cells to A9dis was completely inhibited by an antibody to the alpha(v)beta(5) integrin but not by antibodies to other subunits. RGD-containing peptides had no effect on binding, suggesting that MDC-9 interacts with alpha(v)beta(5) in an RGD-independent manner. Flow cytometric analyses demonstrated that myeloma cells, but not lymphoblastoid cells, expressed alpha(v)beta(5) on the cell membrane. These data indicated that the disintegrin domain of MDC-9 can function as an adhesion molecule by interacting with an alpha(v)beta(5) integrin.

      Selection B- Gene function is consistent with phenotype.

      Title: ADAM9 (MDC-9) functions as an adhesion molecule by interacting with integrins.

      GOterm: GO:0033630 (positive regulation of cell adhesion mediated by integrin)

      FunctionalEvidence: Melanoma cells bind to they the immobilized recombinant ADAM9 disintegrin domain in a manner that is dependent on divalent cations (Mn2+ or Ca2+). The interaction can also be disrupted by an antibody to the alpha(v)beta(5) integrin, indicating that the cell-cell adhesion function of ADAM9 is mediated by an interaction with this molecule.

      FunctionalHPO: HP:0000546 (Retinal degeneration), HP:0007703 (Abnormality of retinal pigmentation), HP:0030610 (Photoreceptor outer segment loss on macular OCT

      PhenotypeEvidence: This evidence is consistent with evidence that Adam9 knockout mice exhibit a gap between the photoreceptor outer nuclear segment and the retinal pigment epithelium, indicating that loss of this adhesion molecule may impair the integrity of retinal organization.

      Experimental Function BiochemicalFunction Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/11162558/
  6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Novel ADAM9 homozygous mutation in a consanguineous Egyptian family with severe cone-rod dystrophy and cataract
    2
    1. ClingenBaseline 23 Oct 2026
      Novel ADAM9 homozygous mutation in a consanguineous Egyptian family with severe cone-rod dystrophy and cataract

      PMID: 25091951

      Gene: ADAM9

      HGNC: 216

      Disease: cone-rod dystrophy 9

      MONDO: MONDO:0013002

      InheritancePattern: autosomal recessive

      Prevalence: The prevalence of cone-rod dystrophy in general is estimated to be 1 in 40,000 (PMID: 17270046), however, the specific prevalence of cone-rod dystrophy 9 is unknown.

      Penetrance: Penetrance appears to be complete in reported families, but it is possible that incomplete penetrance may be associated with some variants.

      General ClinGen Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 22 Oct 2026
      arCRD was diagnosed in the mother and two of her children. Bilateral anterior polar and posterior subcapsular cataract was observed in the mother and bilateral dot cataract was diagnosed in three of the four children not affected with arCRD, one of whom also had glaucoma. The characteristics of the arCRD were childhood-onset visual impairment, reorganisation of the retinal pigment epithelium with mid-periphery greyish-white discolouration, attenuated retinal vasculatur and optic disc pallor. A coloboma-like macular lesion was observed in one of the arCRD-affected children. IROme analysis identified a c.1396-2A>G homozygous mutation in the splice acceptor site of intron 13 of ADAM9. This mutation was homozygous in the two children affected by arCRD and in their affected mother. This mutation was heterozygous in the unaffected father and the four unaffected children.

      Case#: El-Haig_2014_Proband, female, age not specified, family origin reported to be Egyptian

      CasePresentingHPOs: HP:0011463 (Childhood onset), HP:0000548 (Cone/cone-rod dystrophy), HP:0007787 (Posterior subcapsular cataract), HP:0010923 (Anterior subcapsular cataract), HP:0000505 (Visual impairment), HP:0007703 (Abnormality of retinal pigmentation), HP:0007843 (Attenuation of retinal blood vessels), HP:0000543 (Optic disc pallor)

      CaseHPOFreeText: The proband and her affected family members have been diagnosed with cone-rod dystrophy, with the family showing an autosomal recessive mode of inheritance.

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: The proband and her family were initially genotyped by IROme, which generates a hybridization-based DNA library of the 64 most frequently mutated genes in retinal dystrophy, then analyzes it by high-throughput sequencing.

      CaseMethod1: Next-generation sequencing panel

      CaseMethod2: Sanger sequencing of ADAM9 exon 14 and flanking exon-intron junctions

      CaseGenotypingMethod: The proband and her family were initially genotyped by IROme, which generates a hybridization-based DNA library of the 64 most frequently mutated genes in retinal dystrophy, then analyzes it by high-throughput sequencing. Sanger sequencing of ADAM9 exon 14 and flanking exon-intron junctions was then performed.

      Variant: The proband harbors the NM_003816.3(ADAM9):c.1396-2A>G variant in the homozygous state.

      ClinVar: 189795

      gnomAD: This variant was not found in gnomAD v2.1.1.

      VariantEvidence: NM_003816.3(ADAM9):c.1396-2A>G is a variant disrupting a canonical splice site in intron 13, which is predicted but not confirmed to disrupt mRNA splicing.

      CaseAddInfo: The proband is from a consanguineous family and has two affected sons who are also homozygous for the variant, as well as five unaffected heterozygous family members.

      CasePMIDs: N/A

      Case Individual CaseInfo Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/25091951/
  7. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    ADAM9 Is Involved in Pathological Retinal Neovascularization
    2
    1. ClingenBaseline 22 Oct 2026
      ADAM9 Is Involved in Pathological Retinal Neovascularization

      PMID: 19273593

      Gene: ADAM9

      HGNC: 216

      Disease: cone-rod dystrophy 9

      MONDO: MONDO:0013002

      InheritancePattern: autosomal recessive

      Prevalence: The prevalence of cone-rod dystrophy in general is estimated to be 1 in 40,000 (PMID: 17270046), however, the specific prevalence of cone-rod dystrophy 9 is unknown.

      Penetrance: Penetrance appears to be complete in reported families, but it is possible that incomplete penetrance may be associated with some variants.

      General ClinGen Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 21 Oct 2026
      In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR.

      Selection B- Gene function is consistent with phenotype.

      Title: ADAM9 enhances protelytic shedding of membrane protein ectodomains.

      GOterm: GO:0006509 (membrane protein ectodomain proteolysis), GO:0045765 (regulation of angiogenesis)

      FunctionalEvidence: ADAM9 over-expression in COS-7 cells enhances proteolytic shedding of membrane proteins involved in angiogenesis (Figure 5). This effect is further enhanced by reactive oxygen species (Figures 6, 7).

      FunctionalHPO: HP:0007843 (Attenuation of retinal blood vessels), HP:0000546 (Retinal degeneration)

      PhenotypeEvidence: This evidence is consistent with attenuation of retinal blood vessels observed in human patients as well as the finding from this same paper that Adam9 knockout mice exhibit reduced ocular neovascularization (Figures 1, 3).

      Experimental Function BiochemicalFunction Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    ncbi.nlm.nih.gov/pmc/articles/PMC2682031/
  8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Generalized progressive retinal atrophy in the Irish Glen of Imaal Terrier is associated with a deletion in the ADAM9 gene
    2
    1. ClingenBaseline 21 Oct 2026
      Sequence analysis of ADAM9 in affected and carrier GITs revealed a deletion of exons 15 and 16 which alters the reading frame leading to a premature stop codon. This mutation was absent from 34 other dog breeds. A variable and, at times, very late onset of gPRA was confirmed in GITs by a relatively mild retinal degeneration at an advanced age. Hence, the identification of the genetic defect underlying gPRA in the GIT represents a suitable model for cone-rod dystrophy of humans, with superior potential to elucidate functional consequences of the recently described null mutations in the human ADAM9 gene.

      ExperimentName: Canine model of Adam9 loss-of-function

      NonHumanModel: Canis lupus familiaris

      GeneAlteration: The affected dogs have homozygous disruption of the Adam9 gene by a deletion of regions from exons 15 and 16.

      ModelPhenotype: HP:0001105 (Retinal atrophy), HP:0000529 (Progressive visual loss), HP:0000580 (Pigmentary retinopathy), HP:0000662 (Nyctalopia)

      HumanPhenotype: HP:0011463 (Childhood onset), HP:0000548 (Cone/cone-rod dystrophy), HP:0007663 (Reduced visual acuity), HP:0001141 (Severely reduced visual acuity), HP:0007994 (Peripheral visual field loss), HP:0000545 (Myopia), HP:0000483 (Astigmatism), HP:0000523 (Subcapsular cataract)

      ModelEvidence: The affected dogs have been described as having generalized progressive retinal atrophy. Complete loss of all retinal layers was observed in affected animals (Figures 1H-1P). This matches the mode of inheritance and progressive nature of the human disease state, as well as the retinal abnormalities and visual defects.

      ModelVariant: The model harbors a targeted deletion that does not have an equivalent / orthologous variant reported in human patients.

      Experimental ModelSystems ModelOrganism Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    2. ClingenBaseline 21 Oct 2026

      PMID: 20691256

      Gene: ADAM9

      HGNC: 216

      Disease: cone-rod dystrophy 9

      MONDO: MONDO:0013002

      InheritancePattern: autosomal recessive

      Prevalence: The prevalence of cone-rod dystrophy in general is estimated to be 1 in 40,000 (PMID: 17270046), however, the specific prevalence of cone-rod dystrophy 9 is unknown.

      Penetrance: Penetrance appears to be complete in reported families, but it is possible that incomplete penetrance may be associated with some variants.

      General ClinGen Gene:ADAM9 HGNC:216 inferred_gene_hgnc:216 inferred_gene_source:hgnc_tag Retina GCEP
    Visit annotations in context

    Tags

    Annotators

    URL

    pubmed.ncbi.nlm.nih.gov/20691256/