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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P78363: Variant p.Thr959Ile

Retinal-specific phospholipid-transporting ATPase ABCA4
Gene: ABCA4
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Variant information Variant position: help 959 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 Threonine (T) to Isoleucine (I) at position 959 (T959I, p.Thr959Ile). 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 polar (T) to medium size and hydrophobic (I) 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; highly decreased ATPase activity; highly decreased phospholipid translocase activity. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 959 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 EPCGRPAVDRLNITFYENQI T AFLGHNGAGKTTTLSILTGL 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                         EP--CGRPAVDRLNITFYENQITAFLGHNGAGKTTTLSILTGL

Mouse                         EP--SGRPAVDRLNITFYENQITAFLGHNGAGKTTTLSILT

Bovine                        EP--YGRPAVDRLNITFYESQITAFLGHNGAGKTTTLSIMT

Slime mold                    KTGDGNRIAVNDLSIDMYKNRIHSFLGPNGSGKSTTLSMLT
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
Topological domain 857 – 1376 Cytoplasmic
Domain 929 – 1160 ABC transporter 1
Binding site 966 – 966
Binding site 969 – 969
Binding site 970 – 970
Binding site 971 – 971
Disulfide bond 641 – 1490 Interchain
Mutagenesis 940 – 940 P -> R. Decreases 11-cis-Retinal binding affinity by 50%.
Mutagenesis 965 – 965 N -> A. No significant effect on basal ATPase activity. Decreased N-Ret-PE-stimulated ATPase activity.
Mutagenesis 965 – 965 N -> DK. Decreased N-Ret-PE binding to 50%-63% of wild-type values.
Mutagenesis 965 – 965 N -> DK. Results in minimal, if any, basal ATPase activity. Loss of N-Ret-PE-stimulated ATPase activity.
Mutagenesis 965 – 965 N -> Q. Decreased basal ATPase activity. Loss of N-Ret-PE-stimulated ATPase activity.
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.
Beta strand 956 – 960



Literature citations
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; LEU-608; ILE-959; SER-965 AND MET-1537; CHARACTERIZATION OF VARIANTS STGD1 PRO-100; LEU-608; ILE-959; SER-965 AND MET-1537; MUTAGENESIS OF CYS-1502; ARG-2107 AND PRO-2180; 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;
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.