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UniProtKB/Swiss-Prot P78363: Variant p.Asn965Ser

Retinal-specific phospholipid-transporting ATPase ABCA4
Gene: ABCA4
Variant information

Variant position:  965
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Asparagine (N) to Serine (S) at position 965 (N965S, p.Asn965Ser).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (N) to small size and polar (S)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Stargardt disease 1 (STGD1) [MIM:248200]: A common hereditary macular degeneration. It is characterized by decreased central vision, atrophy of the macula and underlying retinal pigment epithelium, and frequent presence of prominent flecks in the posterior pole of the retina. {ECO:0000269|PubMed:10090887, ECO:0000269|PubMed:10206579, ECO:0000269|PubMed:10612508, ECO:0000269|PubMed:10634594, ECO:0000269|PubMed:10711710, ECO:0000269|PubMed:10746567, ECO:0000269|PubMed:10958763, ECO:0000269|PubMed:11328725, ECO:0000269|PubMed:11385708, ECO:0000269|PubMed:11527935, ECO:0000269|PubMed:11594993, ECO:0000269|PubMed:18977788, ECO:0000269|PubMed:24097981, ECO:0000269|PubMed:24444108, ECO:0000269|PubMed:9054934, ECO:0000269|PubMed:9490294, ECO:0000269|PubMed:9503029, ECO:0000269|PubMed:9781034, ECO:0000269|PubMed:9973280}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In STGD1; reduced retinal-stimulated ATP hydrolysis; moderately decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  965
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2273
The length of the canonical sequence.

Location on the sequence:   AVDRLNITFYENQITAFLGH  N GAGKTTTLSILTGLLPPTSG
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         AVDRLNITFYENQITAFLGHNGAGKTTTLSILTGLLPPTSG

Mouse                         AVDRLNITFYENQITAFLGHNGAGKTTTLSILTGLLPPTSG

Slime mold                    AVNDLSIDMYKNRIHSFLGPNGSGKSTTLSMLTGMIEPTSG

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 2273 Retinal-specific phospholipid-transporting ATPase ABCA4
Topological domain 857 – 1376 Cytoplasmic
Domain 929 – 1160 ABC transporter 1
Nucleotide binding 963 – 970 ATP 1
Mutagenesis 966 – 966 G -> D. Abolishes basal and retinal-stimulated ATP hydrolysis.
Mutagenesis 969 – 969 K -> M. Abolishes basal and retinal-stimulated ATP hydrolysis.
Mutagenesis 969 – 969 K -> M. Inhibits ATPase activity; when associated with M-1978. Decreases translocase activity; when associated with M-1978. Does not affect protein subcellular localization in endoplasmic reticulum; when associated with M-1978.


Literature citations

Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants.
Quazi F.; Molday R.S.;
J. Biol. Chem. 288:34414-34426(2013)
Cited for: CATALYTIC ACTIVITY; ACTIVITY REGULATION; FUNCTION; SUBCELLULAR LOCATION; VARIANTS STGD1 PRO-100; ILE-608; ILE-959; SER-965 AND MET-1537; CHARACTERIZATION OF VARIANTS STGD1 PRO-100; ILE-608; ILE-959; SER-965 AND MET-1537; MUTAGENESIS OF CYS-1502; ARG-2107 AND PRO-2180;

Complex inheritance of ABCR mutations in Stargardt disease: linkage disequilibrium, complex alleles, and pseudodominance.
Shroyer N.F.; Lewis R.A.; Lupski J.R.;
Hum. Genet. 106:244-248(2000)
Cited for: VARIANTS STGD1 ASP-340; GLN-572; ALA-863; SER-965; VAL-1038; ALA-1780 AND HIS-1898; VARIANT GLN-943;

Frequency of ABCA4 mutations in 278 Spanish controls: an insight into the prevalence of autosomal recessive Stargardt disease.
Riveiro-Alvarez R.; Aguirre-Lamban J.; Lopez-Martinez M.A.; Trujillo-Tiebas M.J.; Cantalapiedra D.; Vallespin E.; Avila-Fernandez A.; Ramos C.; Ayuso C.;
Br. J. Ophthalmol. 93:1359-1364(2009)
Cited for: VARIANTS STGD1 VAL-156; CYS-212; LYS-380; ARG-550; PRO-572; TRP-602; ARG-607; CYS-653; ASP-767; ILE-897; ALA-901; MET-931; SER-965; MET-1019; HIS-1108; LEU-1129; LEU-1380; ILE-1433; LEU-1486; TYR-1490; GLN-1640; TRP-1640; ARG-1748; ASP-1799; PRO-1940; GLU-1961; SER-1977; PHE-2027; ARG-2060; HIS-2107; TYR-2150 AND VAL-2241;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.