Expasy logo

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P78363: Variant p.Asp846His

Retinal-specific phospholipid-transporting ATPase ABCA4
Gene: ABCA4
Feedback?
Variant information Variant position: help 846 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Aspartate (D) to Histidine (H) at position 846 (D846H, p.Asp846His). 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: help Change from medium size and acidic (D) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In STGD1; likely pathogenic; severely decreases solubility; loss of cytoplasmic vesicle localization; decreases basal and N-Ret-PE-stimulated ATPase activity; severely decreased N-all-trans-retinylidenephosphatidylethanolamine binding. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 846 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 2273 The length of the canonical sequence.
Location on the sequence: help NSPTEGDEFSFLLSMQMMLL D AAVYGLLAWYLDQVFPGDYG 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         NSPTEGDEFSFLLSMQMMLLDAAVYGLLAWYLDQVFPGDYG

Mouse                         KSPLEGDEFSFLLSMKMMLLDAALYGLLAWYLDQVFPGDYG

Bovine                        NSPMEGDEFSFLMSMKMMLLDAALYGLLAWYLDQVFPGDYG

Slime mold                    INVNMVNEYEII---GMLVFDIFLYILILWYLDNVITGEYG
Sequence annotation in neighborhood: help 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
Transmembrane 836 – 856 Helical
Disulfide bond 641 – 1490 Interchain
Mutagenesis 863 – 863 Missing. Reduced retinal-stimulated ATP hydrolysis.
Helix 837 – 860



Literature citations
A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy.
Allikmets R.; Singh N.; Sun H.; Shroyer N.F.; Hutchinson A.; Chidambaram A.; Gerrard B.; Baird L.; Stauffer D.; Peiffer A.; Rattner A.; Smallwood P.M.; Li Y.; Anderson K.L.; Lewis R.A.; Nathans J.; Leppert M.; Dean M.; Lupski J.R.;
Nat. Genet. 15:236-246(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; INVOLVEMENT IN STGD1; VARIANTS GLN-943 AND ASP-1817; VARIANTS STGD1 GLU-818; HIS-846; ALA-863; MET-931; VAL-1028; ALA-1072; LYS-1087 AND TRP-2038; 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: VARIANTS ARMD2 LYS-471; LEU-1129; SER-1517; THR-1562; ARG-1578; HIS-1898 AND PHE-1970; VARIANTS STGD1 HIS-846 AND ALA-863; VARIANTS GLY-643; GLN-943; MET-1428; GLU-1961; ASN-2177 AND ILE-2255; Genotype/phenotype analysis of a photoreceptor-specific ATP-binding cassette transporter gene, ABCR, in Stargardt disease.
Lewis R.A.; Shroyer N.F.; Singh N.; Allikmets R.; Hutchinson A.; Li Y.; Lupski J.R.; Leppert M.; Dean M.;
Am. J. Hum. Genet. 64:422-434(1999)
Cited for: VARIANTS STGD1 ARG-68; GLY-75; GLY-249; CYS-336; GLU-523; ILE-608; ARG-821; HIS-846; ASP-851; VAL-1038; LEU-1071; ALA-1072; CYS-1129; LEU-1129; TYR-1406; LEU-1408; ASP-1439; SER-1440; ARG-1488; ASN-1696; 1761-PRO--LEU-1763 DEL; PRO-1820; TYR-1838; TRP-1843; GLU-1886 AND GLU-1961; REVIEW; Functional Characterization of ABCA4 Missense Variants Linked to Stargardt Macular Degeneration.
Garces F.A.; Scortecci J.F.; Molday R.S.;
Int. J. Mol. Sci. 22:0-0(2020)
Cited for: CHARACTERIZATION OF VARIANTS STGD1 CYS-653; HIS-653; ARG-661; SER-686; VAL-690; MET-716; TYR-764; ARG-765; ASN-765; ASP-767; PRO-797; GLU-818; ARG-821; THR-824; ARG-840; ALA-849; ASP-851; THR-854; LEU-1380; LYS-1399; ASN-1696; GLU-1703; LYS-1703; LEU-1705; VAL-1773; ASP-1794; PRO-1794; ASP-1805; ASN-1838; ASP-1838; TYR-1838; TRP-1843 AND HIS-1898; CHARACTERIZATION OF VARIANTS HIS-846; GLU-1773; ILE-1868 AND CYS-1898; MUTAGENESIS OF GLN-1703 AND HIS-1838; FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION;
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.