UniProtKB/Swiss-Prot P78363: Variant p.Leu541Pro

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

541 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 Leucine (L) to Proline (P) at position 541 (L541P, p.Leu541Pro). 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:

Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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; reduced ATP-binding capacity; abolishes retinal-stimulated ATP hydrolysis; does not affect solubility; does not affect intracellular vesicle localization; significantly reduces substrate binding; drastically reduces basal ATPase activity with little or no substrate stimulation. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs61751392 [ dbSNP | Ensembl ]

Sequence information Variant position:

541 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:

VLDKFESYNDETQLTQRALS L LEENMFWAGVVFPDMYPWTS 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                         VLDKFESYNDETQLTQRALSLLEENMFWAGVVFPDMYPWTS

Mouse                         VLDKFESYDDEVQLTQRALSLLEENRFWAGVVFPGMYPWAS

Bovine                        ILDKFESYDDEFQLTQRALSLLEENRFWAGVVFPDMHPWTS

Slime mold                    ----------------------------GGVWFPD----DS

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
Helix	537 – 543

Literature citations
Spectrum of ABCR gene mutations in autosomal recessive macular dystrophies.
Rozet J.-M.; Gerber S.; Souied E.; Perrault I.; Chatelin S.; Ghazi I.; Leowski C.; Dufier J.-L.; Munnich A.; Kaplan J.;
Eur. J. Hum. Genet. 6:291-295(1998)
Cited for: VARIANTS STGD1 TRP-18; CYS-212; HIS-636; MET-1019; VAL-1038; CYS-1108; TRP-1640; SER-1977 AND HIS-2107; VARIANTS FFM PRO-11; PRO-541; VAL-1038; GLU-1091; CYS-1508; PHE-1970 AND ARG-1971; 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; 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; 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; 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; 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; 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; Correlating the Expression and Functional Activity of ABCA4 Disease Variants With the Phenotype of Patients With Stargardt Disease.
Garces F.; Jiang K.; Molday L.L.; Stoehr H.; Weber B.H.; Lyons C.J.; Maberley D.; Molday R.S.;
Invest. Ophthalmol. Vis. Sci. 59:2305-2315(2018)
Cited for: VARIANTS STGD1 ARG-72; PRO-541; VAL-1038; GLU-1091; PRO-1794 AND TRP-2077; CHARACTERIZATION OF VARIANTS STGD1 ARG-72; PRO-541; VAL-1038; GLU-1091; PRO-1794 AND TRP-2077; MUTAGENESIS OF ALA-1357; FUNCTION; 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.