UniProtKB/Swiss-Prot P78363: Variant p.Asn965Ser

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

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

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

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
Variant description:

In STGD1; reduced retinal-stimulated ATP hydrolysis; moderately decreased protein abundance; highly decreased ATPase activity; highly decreased phospholipid translocase activity; decreases about 60% the N-retinylidene-phosphatidylethanolamine transfer activity; stimulates modestly the retinal-stimulated ATPase activity; does not affect ATP-independent N-retinylidene-phosphatidylethanolamine binding; does not affect ATP-dependent release of N-retinylidene-phosphatidylethanolamine; significantly reduces phosphatidylethanolamine flippase activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs201471607 [ dbSNP | Ensembl ]

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

Bovine                        AVDRLNITFYESQITAFLGHNGAGKTTTLSIMTGLLPPTSG

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.

Type	Positions	Description
Chain	1 – 2273	Retinal-specific phospholipid-transporting ATPase ABCA4
Topological domain	857 – 1376	Cytoplasmic
Domain	929 – 1160	ABC transporter 1
Binding site	963 – 970
Disulfide bond	641 – 1490	Interchain
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. Loss of ATP-dependent all-trans-retinal transport; when associated with M-1978. Loss in N-retinylidene-PE transfer activity. Inhibits ATPase activity with increasing retinal concentration. Does not affect N-retinylidene-PE binding. Impairs ATP-dependent release of N-retinylidene-PE. Significantly reduces PE flippase activity.
Turn	965 – 968

Literature citations
ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer.
Quazi F.; Lenevich S.; Molday R.S.;
Nat. Commun. 3:925-925(2012)
Cited for: FUNCTION; CATALYTIC ACTIVITY; MUTAGENESIS OF LYS-969 AND LYS-1978; VARIANTS STGD1 ALA-863 AND SER-965; CHARACTERIZATION OF VARIANTS STGD1 ALA-863 AND SER-965; 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; Denaturing HPLC profiling of the ABCA4 gene for reliable detection of allelic variations.
Stenirri S.; Fermo I.; Battistella S.; Galbiati S.; Soriani N.; Paroni R.; Manitto M.P.; Martina E.; Brancato R.; Allikmets R.; Ferrari M.; Cremonesi L.;
Clin. Chem. 50:1336-1343(2004)
Cited for: VARIANTS STGD1 TRP-18; LYS-96; VAL-108; LEU-143; GLN-152; GLN-223; SER-230; 245-TYR--ASP-2273 DEL; THR-246; GLU-498; PRO-541; ARG-550; GLN-572; 639-TYR--ASP-2273 DEL; SER-641; CYS-653; VAL-690; 700-TRP--ASP-2273 DEL; ASP-767; ARG-821; ALA-863; 876-GLN--ASP-2273 DEL; ILE-897; ASP-954; SER-965; ASP-978; LYS-1022; VAL-1038; ASP-1050; LYS-1087; CYS-1098; PRO-1099; CYS-1108; HIS-1108; LEU-1129; ARG-1203; ASP-1203; ASN-1204; 1300-ARG--ASP-2273 DEL; GLN-1300; TYR-1490; ARG-1512; MET-1526; ASP-1598; 1652-TYR--ASP-2273 DEL; ASP-1762; ASN-1838; TYR-1838; GLU-1961; PHE-1970; PHE-2027; GLN-2030; LEU-2050; HIS-2107; TRP-2139; LEU-2149; TYR-2150; ASN-2177 AND VAL-2241; VARIANTS HIS-212; ARG-423; GLN-943; LEU-1380; ILE-1868 AND LEU-1948; 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; Novel mutations in of the ABCR gene in Italian patients with Stargardt disease.
Passerini I.; Sodi A.; Giambene B.; Mariottini A.; Menchini U.; Torricelli F.;
Eye 24:158-164(2010)
Cited for: VARIANTS STGD1 21-GLN--ASP-2273 DEL; LEU-68; HIS-96; LYS-96; SER-172; CYS-212; LYS-415; PRO-541; 572-ARG--ASP-2273 DEL; LYS-616; CYS-653; VAL-690; 700-TRP--ASP-2273 DEL; ASP-767; ARG-821; ARG-840; MET-931; SER-965; PRO-970; PRO-977; ASP-978; MET-1019; VAL-1038; TRP-1055; GLU-1078; LYS-1087; CYS-1098; 1099-SER--ASP-2273 DEL; CYS-1108; 1177-CYS--ASP-2273 DEL; 1332-GLN--ASP-2273 DEL; LEU-1380; 1408-TRP--ASP-2273 DEL; ILE-1433; 1461-TRP--ASP-2273 DEL; 1479-TRP--ASP-2273 DEL; SER-1484; MET-1526; ASP-1598; ASN-1696; GLU-1961; PHE-1970; SER-1977; 2030-ARG--ASP-2273 DEL; LYS-2096; GLN-2140 AND PRO-2221; ABCA4 mutational spectrum in Mexican patients with Stargardt disease: Identification of 12 novel mutations and evidence of a founder effect for the common p.A1773V mutation.
Chacon-Camacho O.F.; Granillo-Alvarez M.; Ayala-Ramirez R.; Zenteno J.C.;
Exp. Eye Res. 109:77-82(2013)
Cited for: VARIANTS STGD1 TRP-18; HIS-24; 89-GLU--ASP-2273 DEL; CYS-212; ASP-241; TRP-290; TRP-602; GLU-818; SER-965; ARG-1014; LEU-1129; LEU-1380; PHE-1416 DEL; HIS-1443; TRP-1551 DEL; THR-1556; 1681-VAL--VAL-1685 DEL; GLN-1705; VAL-1773; ASN-1775; HIS-1779; GLN-1942; VAL-2074 AND ARG-2128; VARIANTS GLN-943; ILE-1868 AND ILE-2255; Screening of ABCA4 Gene in a Chinese Cohort With Stargardt Disease or Cone-Rod Dystrophy With a Report on 85 Novel Mutations.
Jiang F.; Pan Z.; Xu K.; Tian L.; Xie Y.; Zhang X.; Chen J.; Dong B.; Li Y.;
Invest. Ophthalmol. Vis. Sci. 57:145-152(2016)
Cited for: VARIANTS STGD1 LYS-14; PRO-18; HIS-24; VAL-72; CYS-97; 185-GLN--ASP-2273 DEL; ARG-240; LEU-291; 326-TYR--ASP-2273 DEL; VAL-328; SER-345; THR-410; CYS-508; CYS-511; ARG-519; 533-GLN--ASP-2273 DEL; CYS-537; ARG-548; ARG-550; LEU-593; TRP-602; CYS-603; ARG-607; ASN-645; HIS-653; SER-754; 808-TYR--ASP-2273 DEL; VAL-816; SER-965; TYR-965; SER-973; MET-1019; GLY-1022; LYS-1036; LEU-1074; THR-1094; HIS-1108; LYS-1122; THR-1130; TRP-1140; SER-1159; HIS-1161; 1300-ARG--ASP-2273 DEL; ASN-1371; 1453-TYR--ASP-2273 DEL; LEU-1503; HIS-1511; MET-1526; ARG-1591; 1724-TRP--ASP-2273 DEL; VAL-1773; LEU-1776; TRP-1843; LYS-1885; GLY-1921; MET-1921; ARG-1961; SER-1977; TYR-2017; THR-2023; 2030-ARG--ASP-2273 DEL; ARG-2032; TRP-2038; 2040-ARG--ASP-2273 DEL; GLN-2040; GLY-2042; THR-2064; GLU-2078; SER-2097; ARG-2150 AND SER-2188; VARIANTS ARG-423; TYR-1102; THR-1209; MET-1428; MET-1572; 1618-TRP--ASP-2273 DEL; VAL-1623; GLN-1640; 1652-TYR--ASP-2273 DEL; ILE-1868 AND ILE-2255; VARIANTS CORD3 53-GLU--ASP-2273 DEL; ARG-55; PRO-63; 107-ARG--ASP-2273 DEL; 218-GLN--ASP-2273 DEL; CYS-320; 339-TRP--ASP-2273 DEL; 605-TRP--ASP-2273 DEL; LYS-636; ARG-661; CYS-1183; CYS-1368; 1479-TRP--ASP-2273 DEL; 1650-GLU--ASP-2273 DEL; ILE-1882; SER-2043; HIS-2107 AND ASP-2146;

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.