UniProtKB/Swiss-Prot P78363: Variant p.Gly1961Glu

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

1961 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 Glutamate (E) at position 1961 (G1961E, p.Gly1961Glu). 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 medium size and acidic (E) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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; risk factor for ARMD2; also found in patients with cone dystrophy and with macular dystrophy; inhibition of ATP hydrolysis by retinal. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1800553 [ dbSNP | Ensembl ]

Sequence information Variant position:

1961 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:

HELTKIYPGTSSPAVDRLCV G VRPGECFGLLGVNGAGKTTT 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                         HELTKIYPG----TSSPAVDRLCVGVRPGECFGLLGVNGAGKTTT

Mouse                         NELTKVYSG----SSSPAVDRLCVGVRPGECFGLLGVNGAG

Bovine                        NELTKVYSG----TSSPAVDRLCVGVRPGECFGLLGVNGAG

Slime mold                    NNLYKKFNSVGNYKSKIAVYNSTLAIPTGQTFGLLGLNGCG

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	1895 – 2273	Cytoplasmic
Domain	1938 – 2170	ABC transporter 2
Mutagenesis	1975 – 1975	G -> D. Inhibition of retinal-stimulated ATP hydrolysis.
Mutagenesis	1978 – 1978	K -> M. Inhibits ATPase activity; when associated with M-969. Decreases translocase activity; when associated with M-969. Does not affect protein subcellular localization in endoplasmic reticulum; when associated with M-969. 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 ATP-independent N-retinylidene-PE binding. Does not affect ATP-dependent of N-retinylidene-PE release. Significantly reduces PE flippase activity. Inhibition of retinal-stimulated ATP hydrolysis.

Literature citations
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; Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.
Fishman G.A.; Stone E.M.; Grover S.; Derlacki D.J.; Haines H.L.; Hockey R.R.;
Arch. Ophthalmol. 117:504-510(1999)
Cited for: VARIANTS STGD1 VAL-60; ARG-206; ASN-300; PRO-541; ALA-849; PRO-974; VAL-1038; CYS-1108; LEU-1408; ARG-1488; ASP-1652; PRO-1729; GLU-1961; TRP-2038; TRP-2077; HIS-2107; ARG-2128 AND TYR-2150; Further evidence for an association of ABCR alleles with age-related macular degeneration.
Allikmets R.; Tammur J.; Hutchinson A.; Lewis R.A.; Shroyer N.F.; Dalakishvili K.; Lupski J.R.; Steiner K.; Pauleikhoff D.; Holz F.G.; Weber B.H.F.; Dean M.; Atkinson A.; Gail M.H.; Bernstein P.S.; Singh N.; Peiffer A.; Zabriskie N.A.; Leppert M.; Seddon J.M.; Zhang K.; Sunness J.S.; Udar N.S.; Yelchits S.; Silva-Garcia R.; Small K.W.; Simonelli F.; Testa F.; D'Urso M.; Brancato R.; Rinaldi E.; Ingvast S.; Taube A.; Wadelius C.; Souied E.; Ducroq D.; Kaplan J.; Assink J.J.M.; ten Brink J.B.; de Jong P.T.V.M.; Bergen A.A.B.; Maugeri A.; van Driel M.A.; Hoyng C.B.; Cremers F.P.M.; Paloma E.; Coco R.; Balcells S.; Gonzalez-Duarte R.; Kermani S.; Stanga P.; Bhattacharya S.S.; Bird A.C.;
Am. J. Hum. Genet. 67:487-491(2000)
Cited for: VARIANTS GLU-1961 AND ASN-2177; A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.
Rivera A.; White K.; Stoehr H.; Steiner K.; Hemmrich N.; Grimm T.; Jurklies B.; Lorenz B.; Scholl H.P.N.; Apfelstedt-Sylla E.; Weber B.H.F.;
Am. J. Hum. Genet. 67:800-813(2000)
Cited for: VARIANTS STGD1 GLU-60; THR-60; GLU-65; LEU-68; ARG-72; CYS-212; SER-230; SER-247; VAL-328; LYS-471; PRO-541; GLN-572; ARG-607; LYS-635; CYS-653; TYR-764; ARG-765; ALA-901; ILE-959; LYS-1036; VAL-1038; PRO-1063; ASP-1087; CYS-1097; CYS-1108; LEU-1380; LYS-1399; PRO-1430; VAL-1440; HIS-1443; LEU-1486; TYR-1488; MET-1537; PRO-1689; LEU-1705; THR-1733; ARG-1748; PRO-1763; LYS-1885; HIS-1898; GLU-1961; ARG-1975; SER-1977; GLY-2077; TRP-2077 AND VAL-2241; VARIANTS GLN-152; HIS-212; ARG-423; ILE-552; ARG-914; GLN-943; THR-1562; ILE-1868; MET-1921; LEU-1948; PHE-1970; ALA-2059; ASN-2177 AND VAL-2216; New ABCR mutations and clinical phenotype in Italian patients with Stargardt disease.
Simonelli F.; Testa F.; de Crecchio G.; Rinaldi E.; Hutchinson A.; Atkinson A.; Dean M.; D'Urso M.; Allikmets R.;
Invest. Ophthalmol. Vis. Sci. 41:892-897(2000)
Cited for: VARIANTS STGD1 CYS-212; ASP-767; ILE-897; VAL-1038; LYS-1087; LYS-1399; GLN-1640 AND GLU-1961; VARIANT HIS-212; Variation of codons 1961 and 2177 of the Stargardt disease gene is not associated with age-related macular degeneration.
Guymer R.H.; Heon E.; Lotery A.J.; Munier F.L.; Schorderet D.F.; Baird P.N.; McNeil R.J.; Haines H.L.; Sheffield V.C.; Stone E.M.;
Arch. Ophthalmol. 119:745-751(2001)
Cited for: VARIANTS GLU-1961 AND ASN-2177; 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; 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; 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; Predictors of visual acuity and genotype-phenotype correlates in a cohort of patients with Stargardt disease.
Miraldi Utz V.; Coussa R.G.; Marino M.J.; Chappelow A.V.; Pauer G.J.; Hagstrom S.A.; Traboulsi E.I.;
Br. J. Ophthalmol. 98:513-518(2014)
Cited for: VARIANTS STGD1 CYS-212; PRO-541; LEU-640; ASP-767; VAL-1038; CYS-1108; ARG-1408; GLN-1640; TRP-1640; ASP-1838; GLU-1961 AND HIS-2107; 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;

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.