11 Matching Annotations
  1. Last 7 days
  2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    A Comprehensive Survey of Sequence Variation in the ABCA4 (ABCR) Gene in Stargardt Disease and Age-Related Macular Degeneration
    1
    1. Vibhor 21 Aug 2026
      STGD113 L541P-A1038V 2588G→C Yes

      Case#: STGD113, 20-24yo at onset, German

      DiseaseAssertion: STGD

      FamilyInfo: segregation in family

      CasePresentingHPOs:

      CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

      PreviouslyPublished: n/a

      Variant: L541P-A1038V; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

      ClinVar: 7879

      CAID: CA119128

      SupplementalData: n/a

      CaseInfo Individual CAID:CA119128 ClinVarID:7879 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC1287885/
  3. www.nature.com www.nature.com
    Biochemical defects in ABCR protein variants associated with human retinopathies
    1
    1. Vibhor 18 Aug 2026
      The two codon 863 variants, G863A and delG863, show a decrease in both basal and retinal-stimulated ATPase, with G863A showing the greater decrease (Fig. 4d).

      In HEK293 cells, G863A was purified, reconstituted into membranes, and tested for basal and retinal-stimulated ATPase activities. G863A was shown to have reduced basal and retinal-stimulated ATPase (Fig 4d)

      ExperimentalAssay:ATPaseActivity ExperimentalAssay ClinVarID:7879 CAID:CA119128 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    nature.com/articles/ng1000_242
  4. Aug 2026
  5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Correlation of Outer Retinal Degeneration and Choriocapillaris Loss in Stargardt disease using en face OCT and OCT Angiography
    1
    1. Vibhor 16 Aug 2026
      10 F 19 c.2588G>C c.1222C>T

      Case#: Patient 10, female, age 19

      DiseaseAssertion: STGD

      FamilyInfo: diagnosis of autosomal recessive STGD based on the pedigree and clinical phenotype of fleck deposits with or without genetic testing

      CasePresentingHPOs: HP:0000608, HP:0000007, HP:0030610, HP:0030500

      CaseHPOFreeText: Macular degeneration. autosomal recessive, Photoreceptor outer segment loss on macular OCT, Yellow/white lesions of the macula

      CaseNotHPOs: n/a

      CaseNotHPOFreeText: n/a

      Genotyping Method: n/a

      PreviouslyPublished: n/a

      Variant: Allele 1: NM_000350.3:c.2588G>C Allele 2: NM_000350.3:c.1222C>T

      ClinVar: Allele 1: NM_000350.3(ABCA4):c.2588G>C (p.Gly863Ala) Allele 2: NM_000350.3(ABCA4):c.1222C>T (p.Arg408Ter)

      CAID: Allele 1: CA119128 Allele 2: CA179692

      SupplementalData: composite mask analysis shown in figure 3 for patient 10

      CAID:CA119128 CAID:CA179692 InheritancePattern:AutosomalRecessive (1) MacularFlecks (6) DiseaseEntity:STGD1 Gene:ABCA4 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC6548611/
  6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    A Comprehensive Survey of Sequence Variation in the ABCA4 (ABCR) Gene in Stargardt Disease and Age-Related Macular Degeneration
    3
    1. Vibhor 16 Aug 2026
      STGD138 IVS13+1GA 2588G→C Yes

      Case#: STGD138, 15-19yo at onset, German

      DiseaseAssertion: STGD

      FamilyInfo: segregation in family

      CasePresentingHPOs:

      CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

      PreviouslyPublished: n/a

      Variant: IVS13+1G→A; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

      ClinVar: 7879

      CAID: CA119128

      SupplementalData: n/a

      CaseInfo Individual ClinVarID:7879 CAID:CA119128 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
    2. Vibhor 09 Aug 2026
      STGD87 2588G→C Q1750X Yes

      Case#: STGD87, 10-14yo at onset, German

      DiseaseAssertion: STGD

      FamilyInfo: segregation in family

      CasePresentingHPOs:

      CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

      PreviouslyPublished: n/a

      Variant: Q1750X; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

      ClinVar: 7879

      CAID: CA119128

      SupplementalData: n/a

      CaseInfo Individual ClinVarID:7879 CAID:CA119128 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
    3. Vibhor 04 Aug 2026
      STGD47/164 IVS13+1G→A 2588G→C Yes

      Case#: STGD47/164, 10-14yo at onset, German

      DiseaseAssertion: STGD

      FamilyInfo: segregation in family

      CasePresentingHPOs:

      CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

      PreviouslyPublished: n/a

      Variant: IVS13+1G→A; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

      ClinVar: 7879

      CAID: CA119128

      SupplementalData: n/a

      CaseInfo Individual ClinVarID:7879 CAID:CA119128 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC1287885/
  7. www.nature.com www.nature.com
    Biochemical defects in ABCR protein variants associated with human retinopathies
    1
    1. Vibhor 01 Aug 2026
      Over 200 ABCA4 sequence variants have been reported so far in patients with STGD and other retinopathies1,5,6,7,8,9,10,11,12,13,14,15,16,17. We have examined 33 missense mutations, 3 small in-frame deletions and 1 frameshift near the carboxy terminus (Table 1 and Fig. 2), including those mutations most commonly encountered in STGD patients1,5,6,7,8,9,10,11 and several that were reported in AMD patients15. As an initial step in assessing protein folding and stability, we analysed each ABCR variant by immunoblotting and azido-ATP labelling (Fig. 3). Mutations that cause small deletions (delVVAIC1681 and delPAL1761) or introduce charged amino acids into predicted transmembrane domains (G851D and G1886E) produce greatly reduced amounts of protein. Among the ABCR variants that are expressed with normal or nearly normal yield, azido-ATP labelling revealed a subset that is defective in ATP binding. A variety of mutations that lie outside of the nucleotide-binding domains (NBDs) can impair azido-ATP labelling, including L541P, predicted to reside adjacent to a transmembrane domain, and W1408R, which resides between the homologous halves of ABCR (Fig. 2). These data suggest that ATP binding to the NBDs is allosterically coupled to conformational changes in or near the transmembrane regions. Moreover, some mutations within either of the two NBDs abolish or nearly abolish all azido-ATP labelling, as seen, for example, with variants T971N, L1971R, G1977S and E2096K, implying allosteric coupling between the two NBDs, as described for P-glycoprotein22,23.Table 1 Naturally occurring ABCR variants produced in transfected 293 cellsFull size tableFigure 2: Locations of 37 naturally occurring ABCR sequence variants and 4 synthetic mutations.The predicted transmembrane topography and domain structure of ABCR is based on the hydropathy profile and sequence alignment with other ABC transporters. The cytosolic face of the membrane is downward. NBD, nucleotide binding domain; HH, highly hydrophobic domain shared with other members of the ABC1/ABCR subfamily of ABC transporters. A, B and C indicate the sequence motifs characteristic of nucleotide binding folds. Asterisks denote the four synthetic mutations.Full size imageFigure 3: Protein yield and ATP-binding capacity of 37 naturally occurring ABCR variants produced in transiently transfected 293 cells.Membranes were analysed by immunoblotting with affinity-purified anti-ABCR antibodies (top) and photoaffinity labelling with α-32P azido-ATP (bottom). We loaded 1 μg (immunoblotting) or 2.5 μg (azido-ATP labelling) of total membrane protein, as determined by Bradford assay, per track. The mutations that reside in NBD-1 and NBD-2 are indicated above the corresponding lanes. The relative levels of the different variant proteins and the extent of azido-ATP labelling were observed to be highly reproducible in multiple independent experiments. ABCR (large arrowhead); an endogenous 55-kD protein (small arrowhead) serves as an internal control for azido-ATP labelling. Molecular mass standards are shown on the left in kD.Full size imageThe combination of immunoblotting and azido-ATP labelling revealed defects in more than 75% of the variants tested. Among the variants with reduced yield and/or ATP binding are G863A and delG863, the two protein products of a guanosine2588→cytosine mutation that both generates a glycine-to-alanine substitution at codon 863 and activates a cryptic splice acceptor site in exon 17 that results in the removal of codon 863 from approximately 50% of the transcripts10. This is the most common allele among STGD patients in Northern Europe, representing roughly 20% of disease-associated alleles. It is also present at a frequency of approximately 3% in the general population in Northern Europe and approximately 1% in the United States population7,9,10. Genotype-phenotype correlations suggest that it is a mild allele and that it leads to STGD only when paired with a more severe allele10. Relative to wild type, the G863A variant is subtantially impaired and the delG863 variant is mildly impaired (Fig. 3).

      This variant was transfected into HEK 293 cells and appears to show reduced expression and ATP-binding capacity, but no quantities were provided

      ExperimentalAssay ExperimentalAssay:ABCA4Expression ClinVarID:7879 CAID:CA119128 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    nature.com/articles/ng1000_242
  8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    Retinoid Binding Properties of Nucleotide Binding Domain 1 of the Stargardt Disease-associated ATP Binding Cassette (ABC) Transporter, ABCA4
    1
    1. Vibhor 01 Aug 2026
      The plots of fluorescence anisotropy changes of 11-cis-retinal with wild type and mutant NBD1 protein titrations are shown in Fig. 6, A–C. The binding of mutant G863A was significantly attenuated as indicated by the drastic right shift of the binding isotherm as well as its inability to achieve saturation in the presence of a high concentration of protein (Fig. 6A). Nonlinear regression analysis gave Kd of 8.0 ± 1.3 × 10−8 m, 8.0 ± 2.0 × 10−6 m, and 4.0 ± 1.4 × 10−6 m for the wild type and R943Q and P940R mutations, respectively (Fig. 6 and Table 1). As a consequence of Stargardt disease mutations, 100-fold (R943Q) to 50-fold (P940R) decreases in the binding affinity of the NBD1 domain for 11-cis-retinal were observed. The retinal binding of the G863A mutant was severely attenuated, and the Kd was ≥1.0 × 10−5 m.

      The effects of this variant on 11-cis-retinal interaction with the NBD1 was evaluated via fluorescence anisotropy. The binding of mutant G863A was significantly attenuated (Kd was ≥1.0 × 10−5 m) as indicated by the drastic right shift of the binding isotherm as well as its inability to achieve saturation in the presence of a high concentration of protein (Fig. 6A).

      ExperimentalAssay ClinVarID:7879 CAID:CA119128 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    pmc.ncbi.nlm.nih.gov/articles/PMC3531725/
  9. Jul 2026
  10. www.jbc.org www.jbc.org
    Biochemical Defects in Retina-specific Human ATP Binding Cassette Transporter Nucleotide Binding Domain 1 Mutants Associated with Macular Degeneration *
    1
    1. Vibhor 27 Jul 2026
      Analysis of the rates of hydrolysis of ATP and CTP in the mutant protein demonstrated that they were significantly reduced (Fig. 3). The results presented in Fig. 3A indicated that the ATPase function of G863A mutant protein was reduced ∼3-fold as compared with NBD1wt, indicating ∼70% of inhibition of the ATPase activity. TheVmax (ATPase) for G863A mutant was 128 pmol/min/mg and that of the wild-type NBD1 was 584 pmol/min/mg (Table II). A time-course analysis of ATP hydrolysis using 2.5 μg of protein (Fig. 3C) suggested the actual rates of ATP hydrolysis were attenuated 3-fold as a consequence of the mutation. We have earlier reported that the NBD1wt has significantly higher CTPase than ATPase activity (1717.Biswas, E.E.Biochemistry. 2001; 40:8181-8187CrossrefScopus (25)PubMedGoogle Scholar). However, in the mutant G863A protein the CTPase activity was reduced (Fig.3B). In this case, the CTP hydrolysis of G863A was reduced to ∼30% of the activity of NDB1wt. The Vmaxfor G863A mutant was 104 pmol/min/mg and that of the wild-type NBD1 was 376 pmol/min/mg (Table II).

      ATPase function of G863A mutant protein was reduced ∼3-fold as compared with NBD1wt, indicating ∼70% of inhibition of the ATPase activity (Fig. 3). TheVmax (ATPase) for G863A mutant was 128 pmol/min/mg and that of the wild-type NBD1 was 584 pmol/min/mg (Table II).

      ExperimentalAssay ExperimentalAssay:ATPaseActivity CAID:CA119128 ClinVarID:7879 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    jbc.org/article/S0021-9258(20)70434-5/fulltext
  11. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
    A Comprehensive Survey of Sequence Variation in the ABCA4 (ABCR) Gene in Stargardt Disease and Age-Related Macular Degeneration
    2
    1. Vibhor 09 Jul 2026
      STGD87 2588G→C Q1750X Yes

      Case#: STGD87, 10-14yo at onset, German

      DiseaseAssertion: STGD

      FamilyInfo: segregation in family

      CasePresentingHPOs:

      CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

      PreviouslyPublished: n/a

      Variant: Q1750X; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

      ClinVar: 7879

      CAID: CA119128

      SupplementalData: n/a

      CaseInfo Individual ClinVarID:7879 CAID:CA119128 ClinGen ABCA4 Annotations hgnc_imputed:CAID
    2. Vibhor 09 Jul 2026
      STGD47/164 IVS13+1G→A 2588G→C Yes

      Case#: STGD47/164, 10-14yo at onset, German

      DiseaseAssertion: STGD

      FamilyInfo: segregation in family

      CasePresentingHPOs:

      CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

      PreviouslyPublished: n/a

      Variant: IVS13+1G→A; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

      ClinVar: 7879

      CAID: CA119128

      SupplementalData: n/a

      CaseInfo Individual ClinVarID:7879 CAID:CA119128 ClinGen ABCA4 Annotations hgnc_imputed:CAID
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    pmc.ncbi.nlm.nih.gov/articles/PMC1287885/