UniProtKB/Swiss-Prot P78363: Variant p.His423Arg

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

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

LB/B 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 Histidine (H) to Arginine (R) at position 423 (H423R, p.His423Arg). 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 (H) to large size and basic (R) 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
Other resources:

Links to websites of interest for the variant.

Variant rs3112831 [ dbSNP | Ensembl ]

Sequence information Variant position:

423 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:

DSPAARRILKNANSTFEELE H VRKLVKAWEEVGPQIWYFFD 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                         DSPAARRILKNANSTFEELEHVRKLVKAWEEVGPQIWYFFD

Mouse                         DSPAARRIMKNANSTFEELDRVRKLVKAWEEVGPQIWYFFE

Bovine                        DSPATRRILKNANSTFEELERVRKLVKVWEEVGPQIWYFFD

Slime mold                    ---------------FKDIESMDE-------------YFHD

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	43 – 646	Extracellular
Glycosylation	415 – 415	N-linked (GlcNAc...) asparagine
Disulfide bond	370 – 519
Helix	416 – 429

Literature citations
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; Analysis of the ABCR (ABCA4) gene in 4-aminoquinoline retinopathy: is retinal toxicity by chloroquine and hydroxychloroquine related to Stargardt disease?
Shroyer N.F.; Lewis R.A.; Lupski J.R.;
Am. J. Ophthalmol. 131:761-766(2001)
Cited for: VARIANTS RETINAL TOXICITY CYS-1129; ARG-1201 AND HIS-2107; VARIANTS HIS-212; ARG-423; ILE-1868 AND ILE-2255; 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; Catalog of 605 single-nucleotide polymorphisms (SNPs) among 13 genes encoding human ATP-binding cassette transporters: ABCA4, ABCA7, ABCA8, ABCD1, ABCD3, ABCD4, ABCE1, ABCF1, ABCG1, ABCG2, ABCG4, ABCG5, and ABCG8.
Iida A.; Saito S.; Sekine A.; Mishima C.; Kitamura Y.; Kondo K.; Harigae S.; Osawa S.; Nakamura Y.;
J. Hum. Genet. 47:285-310(2002)
Cited for: VARIANT ARG-423; 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; 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.