UniProtKB/SwissProt variant VAR

Variant information

Variant position:

375

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 Tyrosine (Y) to Cysteine (C) at position 375 (Y375C, p.Tyr375Cys).

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 large size and aromatic (Y) to medium size and polar (C)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-2

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 PS and BSTVS.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121913478 [ dbSNP | Ensembl ]

Sequence information

Variant position:

375

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

Protein sequence length:

821

The length of the canonical sequence.

Location on the sequence:

AWLTVLPAPGREKEITASPD Y LEIAIYCIGVFLIACMVVTV

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                         AWLTVL----PAPGREKEITASPDYLEIAIYCIGVFLIACMVVTV

Mouse                         AWLTVL----PAPVREKEITASPDYLEIAIYCIGVFLIACM

Chicken                       AWLTVL----PAPEKEKEFPTSPDYLEIAIYCIGVFLIACM

Xenopus laevis                AWLTVH----PAPVNPLEDNPVPYYMEIGIYSTGIFIIFCM

Zebrafish                     AWLTVH----PAETNPIETDYPPDYVEIAIYCIGVFLIACM

Drosophila                    VYLRVVSPLPPLEIYALLHAHPLGFTLAAITIVALFLLGSA

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	22 – 821	Fibroblast growth factor receptor 2
Topological domain	22 – 377	Extracellular
Alternative sequence	255 – 821	Missing. In isoform 8.
Alternative sequence	314 – 429	Missing. In isoform 9.
Alternative sequence	361 – 361	P -> PKQQ. In isoform 3, isoform 4, isoform 11, isoform 12, isoform 13 and isoform 16.
Alternative sequence	366 – 821	Missing. In isoform 13.

Literature citations

Fibroblast growth factor receptor 2 mutations in Beare-Stevenson cutis gyrata syndrome.
Przylepa K.A.; Paznekas W.A.; Zhang M.; Golabi M.; Bias W.; Bamshad M.J.; Carey J.C.; Hall B.D.; Stevenson R.; Orlow S.J.; Cohen M.M. Jr.; Jabs E.W.;
Nat. Genet. 13:492-494(1996)
Cited for: VARIANTS BSTVS CYS-372 AND CYS-375;

Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis.
Kan S.-H.; Elanko N.; Johnson D.; Cornejo-Roldan L.R.; Cook J.; Reich E.W.; Tomkins S.; Verloes A.; Twigg S.R.F.; Rannan-Eliya S.; McDonald-McGinn D.M.; Zackai E.H.; Wall S.A.; Muenke M.; Wilkie A.O.M.;
Am. J. Hum. Genet. 70:472-486(2002)
Cited for: VARIANTS CS CYS-105; PRO-267; VAL-276; CYS-281; PRO-289; ARG-338; HIS-340; PHE-342; TRP-342; CYS-347; CYS-354; HIS-549 AND GLY-678; VARIANTS PS PHE-172; 252-PHE-SER-253; CYS-290; CYS-340; PRO-341; ARG-342; SER-342; CYS-375; GLY-565; ARG-641 AND GLU-663; VARIANTS APRS TRP-252 AND ARG-253; VARIANTS CS/PS PHE-278 AND TYR-342; VARIANT CRANIOSYNOSTOSIS ASN-659; VARIANTS THR-186 AND SER-315;

Mutation in the FGFR2 gene in a Taiwanese patient with Beare-Stevenson cutis gyrata syndrome.
Wang T.-J.; Huang C.-B.; Tsai F.-J.; Wu J.-Y.; Lai R.-B.; Hsiao M.;
Clin. Genet. 61:218-221(2002)
Cited for: VARIANT BSTVS CYS-375;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P21802: Variant p.Tyr375Cys