UniProtKB/SwissProt variant VAR

Variant information

Variant position:

53

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 53 (L53P, p.Leu53Pro).

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 HLD5; induces misfolding and degradation, leading to destabilization of the PI4K complex.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs72549407 [ dbSNP | Ensembl ]

Sequence information

Variant position:

53

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

521

The length of the canonical sequence.

Location on the sequence:

DKSSLVSSLYKVIQEPQSEL L EPVCHQLFEFYRSGEEQLLQ

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                         DKSSLVSSLYKVIQEPQSELLEPVCHQLFEFYRSGEEQLLQ

Mouse                         DKSSLVTSLYKVIQEPQSELLEPVCHQLFEFYRSGEEQLLR

Chicken                       DKTALISSLYKVIQEPQSELLEPVCHQLFEFYRSGEEQLLR

Zebrafish                     EKGSLVPALYKVIRENYSDLLEPVCHQLFEFYRSGEPRLQR

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 – 521	Hyccin
Alternative sequence	1 – 341	Missing. In isoform 2.

Literature citations

The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane.
Baskin J.M.; Wu X.; Christiano R.; Oh M.S.; Schauder C.M.; Gazzerro E.; Messa M.; Baldassari S.; Assereto S.; Biancheri R.; Zara F.; Minetti C.; Raimondi A.; Simons M.; Walther T.C.; Reinisch K.M.; De Camilli P.;
Nat. Cell Biol. 18:132-138(2016)
Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 12-271 IN COMPLEX WITH TTC7B; FUNCTION; SUBCELLULAR LOCATION; INTERACTION WITH TTC7B; IDENTIFICATION IN THE PI4K COMPLEX; CHARACTERIZATION OF VARIANTS HLD5 PRO-53 AND ARG-57;

Deficiency of hyccin, a newly identified membrane protein, causes hypomyelination and congenital cataract.
Zara F.; Biancheri R.; Bruno C.; Bordo L.; Assereto S.; Gazzerro E.; Sotgia F.; Wang X.B.; Gianotti S.; Stringara S.; Pedemonte M.; Uziel G.; Rossi A.; Schenone A.; Tortori-Donati P.; van der Knaap M.S.; Lisanti M.P.; Minetti C.;
Nat. Genet. 38:1111-1113(2006)
Cited for: VARIANT HLD5 PRO-53; FUNCTION; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9BYI3: Variant p.Leu53Pro