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UniProtKB/Swiss-Prot P22455: Variant p.Gly388Arg

Fibroblast growth factor receptor 4
Gene: FGFR4
Variant information

Variant position:  388
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 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 PC; also found in other types of cancer; associated with increased disease susceptibility, accelerated cancer progression and poor prognosis; results in prolonged FGFR4 activity; causes increased cell motility and tumor cell invasion possibly due to increased stability of the protease MMP14; increased interaction with STAT3; results in STAT3 phosphorylation and signaling activation.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



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.

TypePositionsDescription
Chain 22 – 802 Fibroblast growth factor receptor 4
Transmembrane 370 – 390 Helical
Alternative sequence 353 – 416 EEDPTWTAAAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLAR -> GTGRIPHLTCDSLTPAGRTKSPTL. In isoform 2.


Literature citations

Targeted expression of a human pituitary tumor-derived isoform of FGF receptor-4 recapitulates pituitary tumorigenesis.
Ezzat S.; Zheng L.; Zhu X.F.; Wu G.E.; Asa S.L.;
J. Clin. Invest. 109:69-78(2002)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3); SUBCELLULAR LOCATION (ISOFORM 3); INVOLVEMENT IN CANCER; VARIANT PC ARG-388;

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 PC 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 PC; VARIANT PC 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 PC; CHARACTERIZATION OF VARIANT PC 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 PC; VARIANT PC 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 PC ARG-388;

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 PC 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.