UniProtKB/Swiss-Prot O94823: Variant p.Leu1421Phe

Phospholipid-transporting ATPase VB
Gene: ATP10B
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Variant information Variant position:

1421 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Phenylalanine (F) at position 1421 (L1421F, p.Leu1421Phe). 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 hydrophobic (L) to large size and aromatic (F) 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
Variant description:

Found in patients with Parkinson disease; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs61734664 [ dbSNP | Ensembl ]

Sequence information Variant position:

1421 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1461 The length of the canonical sequence.
Location on the sequence:

QRCGTECMRDDSCSGDSSAQ L SSGEHLLGPNRIMAYSRGQT 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                         QRCGTECMRDDSCSGDSSAQLSSGEHLLGPNRIM---AYSRGQT

Mouse                         PRCSREHSRDDTCTVDTLAKLSSGECLLDPNRTVAPTAYSR

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 – 1461	Phospholipid-transporting ATPase VB
Topological domain	1317 – 1461	Cytoplasmic
Alternative sequence	530 – 1461	Missing. In isoform B and isoform C.

Literature citations
Mutated ATP10B increases Parkinson's disease risk by compromising lysosomal glucosylceramide export.
Martin S.; Smolders S.; Van den Haute C.; Heeman B.; van Veen S.; Crosiers D.; Beletchi I.; Verstraeten A.; Gossye H.; Gelders G.; Pals P.; Hamouda N.N.; Engelborghs S.; Martin J.J.; Eggermont J.; De Deyn P.P.; Cras P.; Baekelandt V.; Vangheluwe P.; Van Broeckhoven C.;
Acta Neuropathol. 139:1001-1024(2020)
Cited for: FUNCTION; CATALYTIC ACTIVITY; TISSUE SPECIFICITY; SUBCELLULAR LOCATION; PTM; ACTIVE SITE; VARIANTS SER-105; 153-ARG--ILE-1461 DEL; ASN-161; TRP-393; VAL-558; ARG-648; ARG-671; LEU-748; LYS-865; ALA-993; THR-1038; THR-1222 AND PHE-1421; MUTAGENESIS OF GLU-210 AND ASP-433; Segregation of ATP10B variants in families with autosomal recessive parkinsonism.
Tesson C.; Lohmann E.; Devos D.; Bertrand H.; Lesage S.; Brice A.;
Acta Neuropathol. 140:783-785(2020)
Cited for: VARIANTS MET-219; THR-540; ARG-671; LYS-865 AND PHE-1421;

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.