UniProtKB/Swiss-Prot P78363: Variant p.Gly863Ala

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

863 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 Glycine (G) to Alanine (A) at position 863 (G863A, p.Gly863Ala). 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 glycine (G) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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, FFM and CORD3; also found in a patient with bull's eye maculopathy; mild alteration probably leading to disease phenotype only in combination with a more severe allele; frequent mutation in northern Europe in linkage disequilibrium with the polymorphic variant Q-943; reduced ATP-binding capacity and retinal-stimulated ATP hydrolysis; significantly attenuates 11-cis-retinal binding; decreases about 80% the N-retinylidene-phosphatidylethanolamine transport activity; stimulates modestely 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 rs76157638 [ dbSNP | Ensembl ]

Sequence information Variant position:

863 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:

MLLDAAVYGLLAWYLDQVFP G DYGTPLPWYFLLQESYWLGG 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                         MLLDAAVYGLLAWYLDQVFPGDYGTPLPWYFLLQESYWLGG

Mouse                         MLLDAALYGLLAWYLDQVFPGDYGTPLPWYFLLQESYWLGG

Bovine                        MLLDAALYGLLAWYLDQVFPGDYGTPLPWYFLLQESYWLGG

Slime mold                    LVFDIFLYILILWYLDNVITGEYGIPKKWYFFLTKNYW---

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
Disulfide bond	641 – 1490	Interchain
Beta strand	863 – 865

Literature citations
Retinoid binding properties of nucleotide binding domain 1 of the Stargardt disease-associated ATP binding cassette (ABC) transporter, ABCA4.
Biswas-Fiss E.E.; Affet S.; Ha M.; Biswas S.B.;
J. Biol. Chem. 287:44097-44107(2012)
Cited for: DOMAIN; FUNCTION; VARIANT STGD1 ALA-863; CHARACTERIZATION OF VARIANT STGD1 ALA-863; MUTAGENESIS OF PRO-940; VARIANT GLN-943; 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; Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration.
Allikmets R.; Shroyer N.F.; Singh N.; Seddon J.M.; Lewis R.A.; Bernstein P.S.; Peiffer A.; Zabriskie N.A.; Li Y.; Hutchinson A.; Dean M.; Lupski J.R.; Leppert M.;
Science 277:1805-1807(1997)
Cited for: REVIEW; VARIANTS ARMD2 LYS-471; LEU-1129; SER-1517; THR-1562; ARG-1578; HIS-1898; PHE-1970 AND ASN-2177; VARIANTS GLY-643; HIS-846; ALA-863; GLN-943; MET-1428; GLU-1961 AND ILE-2255; A novel mutation in the ABCR gene in four patients with autosomal recessive Stargardt disease.
Zhang K.; Garibaldi D.C.; Kniazeva M.; Albini T.; Chiang M.F.; Kerrigan M.; Sunness J.S.; Han M.; Allikmets R.;
Am. J. Ophthalmol. 128:720-724(1999)
Cited for: VARIANT STGD1 TYR-54; VARIANT ALA-863; Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.
Maugeri A.; Klevering B.J.; Rohrschneider K.; Blankenagel A.; Brunner H.G.; Deutman A.F.; Hoyng C.B.; Cremers F.P.M.;
Am. J. Hum. Genet. 67:960-966(2000)
Cited for: VARIANTS CORD3 GLU-65; CYS-212; PRO-541; ALA-863; GLY-863 DEL; VAL-1038; LYS-1122; TYR-1490 AND ASP-1598; 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; An analysis of ABCR mutations in British patients with recessive retinal dystrophies.
Papaioannou M.; Ocaka L.; Bessant D.; Lois N.; Bird A.C.; Payne A.; Bhattacharya S.S.;
Invest. Ophthalmol. Vis. Sci. 41:16-19(2000)
Cited for: VARIANTS GLN-943 AND SER-1948; VARIANTS STGD1 TYR-54; ASP-96; HIS-96; VAL-156; VAL-407; ALA-424; ARG-445; TRP-602; 779-CYS--ASP-2273 DEL; ALA-863; ALA-1429; TRP-1640; GLU-1703; 1779-TYR--ASP-2273 DEL AND ARG-2160; VARIANTS CORD3 VAL-407; 2030-ARG--ASP-2273 DEL AND TYR-2150; VARIANT RP19 ALA-424; Late-onset Stargardt disease is associated with missense mutations that map outside known functional regions of ABCR (ABCA4).
Yatsenko A.N.; Shroyer N.F.; Lewis R.A.; Lupski J.R.;
Hum. Genet. 108:346-355(2001)
Cited for: VARIANTS FFM GLY-339; ALA-863; TRP-943; ARG-991; VAL-1038; CYS-1108; ARG-1488; THR-1562; GLN-1640; PHE-2027; GLN-2030 AND CYS-2106; VARIANTS HIS-212; ARG-423; GLN-943; THR-1148; ILE-1868 AND ILE-2255; Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration.
Briggs C.E.; Rucinski D.; Rosenfeld P.J.; Hirose T.; Berson E.L.; Dryja T.P.;
Invest. Ophthalmol. Vis. Sci. 42:2229-2236(2001)
Cited for: VARIANTS STGD1 13-LYS--TRP-15 DEL; TYR-54; LYS-58; VAL-60; GLU-65; GLU-77; HIS-190; PRO-244; ARG-309; CYS-525; CYS-537; PRO-541; PRO-549; ARG-550; GLN-602; ARG-607; MET-643; ASP-767; PRO-797; ARG-821; THR-824; ALA-863; ALA-935; TRP-943; ALA-989; VAL-1038; CYS-1108; LEU-1108; LYS-1122; ARG-1201; GLN-1300; LEU-1380; PRO-1388; ARG-1408; LEU-1486; ARG-1488; TYR-1490; MET-1526; ASN-1532; THR-1562; TRP-1640; LEU-1776; THR-1846; GLU-1961; SER-1977; PHE-2027; GLN-2030; PRO-2035; LEU-2050; CYS-2107; HIS-2107; TRP-2139; ARG-2150 AND TYR-2150; VARIANTS CORD3 GLN-1640 AND ASP-2146; VARIANTS HIS-212; ARG-423; GLN-943; THR-1637; ILE-1868 AND LEU-1948; 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; Detection rate of pathogenic mutations in ABCA4 using direct sequencing: clinical and research implications.
Downes S.M.; Packham E.; Cranston T.; Clouston P.; Seller A.; Nemeth A.H.;
Arch. Ophthalmol. 130:1486-1490(2012)
Cited for: VARIANTS 219-ARG--ASP-2273 DEL; HIS-576; GLN-943; ARG-1488; MET-1526; CYS-1557; THR-1562; GLU-1773; ASP-1794; 2040-ARG--ASP-2273 DEL AND CYS-2107; VARIANTS STGD1 TYR-54; GLN-152; ARG-184; PHE-184; CYS-212; SER-418; LYS-471; MET-643; CYS-653; 782-TRP--ASP-2273 DEL; ALA-863; ALA-989; ARG-991; MET-1019; LYS-1022; SER-1097; CYS-1108; LYS-1122; LEU-1129; ARG-1201; LEU-1380; LYS-1442; LEU-1486; TYR-1490; ASP-1598; ASP-1754; THR-1846; GLU-1961; PHE-2027; GLN-2030; CYS-2106; LYS-2131; TYR-2150 AND PRO-2237; An augmented ABCA4 screen targeting noncoding regions reveals a deep intronic founder variant in Belgian Stargardt patients.
Bauwens M.; De Zaeytijd J.; Weisschuh N.; Kohl S.; Meire F.; Dahan K.; Depasse F.; De Jaegere S.; De Ravel T.; De Rademaeker M.; Loeys B.; Coppieters F.; Leroy B.P.; De Baere E.;
Hum. Mutat. 36:39-42(2015)
Cited for: VARIANTS CORD3 CYS-440; GLY-643; HIS-1145; GLU-1203; LEU-2050 AND ASN-2177; VARIANTS STGD1 HIS-24; GLU-65; SER-247; 431-TRP--ASP-2273 DEL; PRO-541; ARG-607; HIS-653; ALA-863; 1029-GLN--ASP-2273 DEL; VAL-1038; GLN-1300; MET-1537; TRP-1640; PRO-1763; HIS-1898; GLU-1961; PHE-1970; PHE-2027; GLN-2030 AND ARG-2033; VARIANTS RP19 MET-455 AND ILE-552; VARIANTS 681-ARG--ASP-2273 DEL; ASP-767 AND ARG-1591; VARIANT CORD3 GLU-1961; Homozygous variants in KIAA1549, encoding a ciliary protein, are associated with autosomal recessive retinitis pigmentosa.
de Bruijn S.E.; Verbakel S.K.; de Vrieze E.; Kremer H.; Cremers F.P.M.; Hoyng C.B.; van den Born L.I.; Roosing S.;
J. Med. Genet. 55:705-712(2018)
Cited for: VARIANTS ALA-863; GLY-863 DEL AND ILE-1868;

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.