UniProtKB/Swiss-Prot P22455: Variant p.Gly388Arg

Fibroblast growth factor receptor 4
Gene: FGFR4
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Variant information Variant position:

388 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 Glycine (G) to Arginine (R) at position 388 (G388R, p.Gly388Arg). 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 glycine (G) to large size and basic (R) 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 cancer cells, may be associated with accelerated disease progression and increased tumor cell motility, possibly due to increased stability of the protease MMP14; leads to phosphorylation at residue Y-390, resulting in prolonged FGFR4 activity; increases interaction with STAT3, resulting in STAT3 phosphorylation and signaling activation.. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs351855 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

TDIILYASGSLALAVLLLLA G LYRGQALHGRHPRPPATVQK 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                         TDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQK

Mouse                         TDIILYVSGSLVLLVLLLLAGVYHRQVIRGHYSRQPVTIQK

Rat                           TDIILYVSGSLALVLLLLLAGVYHRQAIHGHHSRQPVTVQK

Xenopus laevis                MDIIIYTSGFLAVAMAIMIVILCRMQTPHSKQTLQTPTVHK

Zebrafish                     TDIIIYASGFLALVMAIVIVVLCRMQVHPSREPFDTLPVQK

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 – 802	Fibroblast growth factor receptor 4
Transmembrane	370 – 390	Helical
Modified residue	390 – 390	Phosphotyrosine; in variant R-388
Alternative sequence	353 – 416	EEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLAR -> GTGRIPHLTCDSLTPAGRTKSPTL. In isoform 2.

Literature citations
PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma.
Marshall A.D.; van der Ent M.A.; Grosveld G.C.;
Mol. Carcinog. 51:807-815(2012)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANTS ILE-10 AND LEU-136; INVOLVEMENT IN CANCER; VARIANT ARG-388; Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS ILE-10; LEU-136 AND ARG-388; Polymorphisms of fibroblast growth factor receptor 4 have association with the development of prostate cancer and benign prostatic hyperplasia and the progression of prostate cancer in a Japanese population.
Ma Z.; Tsuchiya N.; Yuasa T.; Inoue T.; Kumazawa T.; Narita S.; Horikawa Y.; Tsuruta H.; Obara T.; Saito M.; Satoh S.; Ogawa O.; Habuchi T.;
Int. J. Cancer 123:2574-2579(2008)
Cited for: INVOLVEMENT IN CANCER; VARIANT ARG-388; Altered fibroblast growth factor receptor 4 stability promotes prostate cancer progression.
Wang J.; Yu W.; Cai Y.; Ren C.; Ittmann M.M.;
Neoplasia 10:847-856(2008)
Cited for: CATALYTIC ACTIVITY; FUNCTION AS FGF2 RECEPTOR AND IN STIMULATION OF CELL PROLIFERATION; SUBCELLULAR LOCATION; INTERACTION WITH FGF2 AND HIP1; PHOSPHORYLATION AT TYR-642 AND TYR-643; INVOLVEMENT IN CANCER; CHARACTERIZATION OF VARIANT ARG-388; FGFR4 Gly388Arg polymorphism contributes to prostate cancer development and progression: a meta-analysis of 2618 cases and 2305 controls.
Xu B.; Tong N.; Chen S.Q.; Hua L.X.; Wang Z.J.; Zhang Z.D.; Chen M.;
BMC Cancer 11:84-84(2011)
Cited for: INVOLVEMENT IN CANCER; VARIANT ARG-388; Germline variant FGFR4 p.G388R exposes a membrane-proximal STAT3 binding site.
Ulaganathan V.K.; Sperl B.; Rapp U.R.; Ullrich A.;
Nature 528:570-574(2015)
Cited for: INTERACTION WITH STAT3; INVOLVEMENT IN CANCER; CHARACTERIZATION OF VARIANT ARG-388; PHOSPHORYLATION AT TYR-390; Fibroblast growth factor receptor 4 regulates tumor invasion by coupling fibroblast growth factor signaling to extracellular matrix degradation.
Sugiyama N.; Varjosalo M.; Meller P.; Lohi J.; Hyytiainen M.; Kilpinen S.; Kallioniemi O.; Ingvarsen S.; Engelholm L.H.; Taipale J.; Alitalo K.; Keski-Oja J.; Lehti K.;
Cancer Res. 70:7851-7861(2010)
Cited for: CHARACTERIZATION OF VARIANT ARG-388; FUNCTION IN TUMOR CELL INVASION;

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.