FGFR4 (fibroblast growth factor receptor 4)

Gene

• Entrez ID: 2264
• Gene name: Fibroblast growth factor receptor 4
• Gene symbol: FGFR4
• Synonyms: CD334, JTK2, TKF
• Chromosome: 5
• Chromosome location: 5q35.2
• Summary: The protein encoded by this gene is a tyrosine kinase and cell surface receptor for fibroblast growth factors. The encoded protein is involved in the regulation of several pathways, including cell proliferation, cell differentiation, cell migration, lipid

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs351855	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant
rs1057519792	C>A,G	Likely-pathogenic	Missense variant, coding sequence variant
rs1057519793	T>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1057520036	A>G	Likely-pathogenic	Missense variant, coding sequence variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT460224	hsa-miR-15a-5p	PAR-CLIP	23592263
MIRT460223	hsa-miR-15b-5p	PAR-CLIP	23592263
MIRT460222	hsa-miR-16-5p	PAR-CLIP	23592263
MIRT460221	hsa-miR-195-5p	PAR-CLIP	23592263
MIRT460220	hsa-miR-424-5p	PAR-CLIP	23592263
MIRT460219	hsa-miR-497-5p	PAR-CLIP	23592263
MIRT460217	hsa-miR-6838-5p	PAR-CLIP	23592263
MIRT460218	hsa-miR-6510-5p	PAR-CLIP	23592263
MIRT460216	hsa-miR-4716-3p	PAR-CLIP	23592263
MIRT460215	hsa-miR-6794-5p	PAR-CLIP	23592263
MIRT460214	hsa-miR-214-3p	PAR-CLIP	23592263
MIRT460212	hsa-miR-3619-5p	PAR-CLIP	23592263
MIRT460213	hsa-miR-761	PAR-CLIP	23592263
MIRT460211	hsa-miR-6798-5p	PAR-CLIP	23592263
MIRT460210	hsa-miR-1909-3p	PAR-CLIP	23592263
MIRT460209	hsa-miR-6722-3p	PAR-CLIP	23592263
MIRT460208	hsa-miR-6799-5p	PAR-CLIP	23592263
MIRT460207	hsa-miR-6825-5p	PAR-CLIP	23592263
MIRT460206	hsa-miR-4723-5p	PAR-CLIP	23592263
MIRT460205	hsa-miR-5698	PAR-CLIP	23592263
MIRT460204	hsa-miR-6870-5p	PAR-CLIP	23592263
MIRT460203	hsa-miR-7111-5p	PAR-CLIP	23592263
MIRT460202	hsa-miR-491-5p	PAR-CLIP	23592263
MIRT460201	hsa-miR-3151-5p	PAR-CLIP	23592263
MIRT460199	hsa-miR-4447	PAR-CLIP	23592263
MIRT460200	hsa-miR-4472	PAR-CLIP	23592263
MIRT460198	hsa-miR-6742-5p	PAR-CLIP	23592263
MIRT460197	hsa-miR-6796-5p	PAR-CLIP	23592263
MIRT736364	hsa-miR-486-3p	Luciferase reporter assay, Western blotting, Immunohistochemistry (IHC), qRT-PCR	32313144
MIRT460224	hsa-miR-15a-5p	PAR-CLIP	23592263
MIRT460223	hsa-miR-15b-5p	PAR-CLIP	23592263
MIRT460222	hsa-miR-16-5p	PAR-CLIP	23592263
MIRT460221	hsa-miR-195-5p	PAR-CLIP	23592263
MIRT460220	hsa-miR-424-5p	PAR-CLIP	23592263
MIRT460219	hsa-miR-497-5p	PAR-CLIP	23592263
MIRT460217	hsa-miR-6838-5p	PAR-CLIP	23592263
MIRT460218	hsa-miR-6510-5p	PAR-CLIP	23592263
MIRT460216	hsa-miR-4716-3p	PAR-CLIP	23592263
MIRT460215	hsa-miR-6794-5p	PAR-CLIP	23592263
MIRT460214	hsa-miR-214-3p	PAR-CLIP	23592263
MIRT460212	hsa-miR-3619-5p	PAR-CLIP	23592263
MIRT460213	hsa-miR-761	PAR-CLIP	23592263
MIRT460211	hsa-miR-6798-5p	PAR-CLIP	23592263
MIRT460210	hsa-miR-1909-3p	PAR-CLIP	23592263
MIRT460209	hsa-miR-6722-3p	PAR-CLIP	23592263
MIRT460208	hsa-miR-6799-5p	PAR-CLIP	23592263
MIRT460207	hsa-miR-6825-5p	PAR-CLIP	23592263
MIRT460206	hsa-miR-4723-5p	PAR-CLIP	23592263
MIRT460205	hsa-miR-5698	PAR-CLIP	23592263
MIRT460204	hsa-miR-6870-5p	PAR-CLIP	23592263
MIRT460203	hsa-miR-7111-5p	PAR-CLIP	23592263
MIRT460202	hsa-miR-491-5p	PAR-CLIP	23592263
MIRT460201	hsa-miR-3151-5p	PAR-CLIP	23592263
MIRT460199	hsa-miR-4447	PAR-CLIP	23592263
MIRT460200	hsa-miR-4472	PAR-CLIP	23592263
MIRT460198	hsa-miR-6742-5p	PAR-CLIP	23592263
MIRT460197	hsa-miR-6796-5p	PAR-CLIP	23592263
MIRT996188	hsa-miR-138	CLIP-seq
MIRT996189	hsa-miR-15a	CLIP-seq
MIRT996190	hsa-miR-15b	CLIP-seq
MIRT996191	hsa-miR-16	CLIP-seq
MIRT996192	hsa-miR-1827	CLIP-seq
MIRT996193	hsa-miR-1909	CLIP-seq
MIRT996194	hsa-miR-195	CLIP-seq
MIRT996195	hsa-miR-1976	CLIP-seq
MIRT996196	hsa-miR-2110	CLIP-seq
MIRT996197	hsa-miR-214	CLIP-seq
MIRT996198	hsa-miR-3151	CLIP-seq
MIRT996199	hsa-miR-3153	CLIP-seq
MIRT996200	hsa-miR-3177-3p	CLIP-seq
MIRT996201	hsa-miR-3612	CLIP-seq
MIRT996202	hsa-miR-3689a-3p	CLIP-seq
MIRT996203	hsa-miR-3689c	CLIP-seq
MIRT996204	hsa-miR-3689d	CLIP-seq
MIRT996205	hsa-miR-370	CLIP-seq
MIRT996206	hsa-miR-424	CLIP-seq
MIRT996207	hsa-miR-4271	CLIP-seq
MIRT996208	hsa-miR-4660	CLIP-seq
MIRT996209	hsa-miR-4725-3p	CLIP-seq
MIRT996210	hsa-miR-4728-5p	CLIP-seq
MIRT996211	hsa-miR-4731-5p	CLIP-seq
MIRT996212	hsa-miR-4774-5p	CLIP-seq
MIRT996213	hsa-miR-497	CLIP-seq
MIRT996214	hsa-miR-564	CLIP-seq
MIRT996215	hsa-miR-650	CLIP-seq
MIRT996216	hsa-miR-940	CLIP-seq
MIRT996217	hsa-miR-1247	CLIP-seq
MIRT996218	hsa-miR-1266	CLIP-seq
MIRT996189	hsa-miR-15a	CLIP-seq
MIRT996190	hsa-miR-15b	CLIP-seq
MIRT996191	hsa-miR-16	CLIP-seq
MIRT996193	hsa-miR-1909	CLIP-seq
MIRT996194	hsa-miR-195	CLIP-seq
MIRT996196	hsa-miR-2110	CLIP-seq
MIRT996197	hsa-miR-214	CLIP-seq
MIRT996219	hsa-miR-24	CLIP-seq
MIRT996198	hsa-miR-3151	CLIP-seq
MIRT996220	hsa-miR-3155	CLIP-seq
MIRT996221	hsa-miR-3155b	CLIP-seq
MIRT996222	hsa-miR-3157-5p	CLIP-seq
MIRT996204	hsa-miR-3689d	CLIP-seq
MIRT996223	hsa-miR-3925-3p	CLIP-seq
MIRT996206	hsa-miR-424	CLIP-seq
MIRT996207	hsa-miR-4271	CLIP-seq
MIRT996224	hsa-miR-4518	CLIP-seq
MIRT996225	hsa-miR-4524	CLIP-seq
MIRT996208	hsa-miR-4660	CLIP-seq
MIRT996226	hsa-miR-4691-3p	CLIP-seq
MIRT996209	hsa-miR-4725-3p	CLIP-seq
MIRT996211	hsa-miR-4731-5p	CLIP-seq
MIRT996227	hsa-miR-4755-3p	CLIP-seq
MIRT996228	hsa-miR-484	CLIP-seq
MIRT996213	hsa-miR-497	CLIP-seq
MIRT996229	hsa-miR-503	CLIP-seq
MIRT996230	hsa-miR-646	CLIP-seq
MIRT996231	hsa-miR-766	CLIP-seq
MIRT996189	hsa-miR-15a	CLIP-seq
MIRT996190	hsa-miR-15b	CLIP-seq
MIRT996191	hsa-miR-16	CLIP-seq
MIRT996193	hsa-miR-1909	CLIP-seq
MIRT996194	hsa-miR-195	CLIP-seq
MIRT996197	hsa-miR-214	CLIP-seq
MIRT996204	hsa-miR-3689d	CLIP-seq
MIRT996206	hsa-miR-424	CLIP-seq
MIRT996213	hsa-miR-497	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
IKZF1	Activation	11981041

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0004714	Function	Transmembrane receptor protein tyrosine kinase activity	IBA	21873635
GO:0005007	Function	Fibroblast growth factor-activated receptor activity	IBA	21873635
GO:0005007	Function	Fibroblast growth factor-activated receptor activity	IDA	8663044, 18480409, 21653700
GO:0005007	Function	Fibroblast growth factor-activated receptor activity	IGI	10525310
GO:0005515	Function	Protein binding	IPI	17627937, 20798051
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005768	Component	Endosome	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA	20683963
GO:0005794	Component	Golgi apparatus	IDA	18061161
GO:0005886	Component	Plasma membrane	IDA	18061161
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0005887	Component	Integral component of plasma membrane	IDA	20683963
GO:0005911	Component	Cell-cell junction	IDA	20798051
GO:0007169	Process	Transmembrane receptor protein tyrosine kinase signaling pathway	IBA	21873635
GO:0007275	Process	Multicellular organism development	IBA	21873635
GO:0008201	Function	Heparin binding	IDA	18480409
GO:0008284	Process	Positive regulation of cell population proliferation	IDA	8663044
GO:0008284	Process	Positive regulation of cell population proliferation	IGI	8663044
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IDA	21653700
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IGI	8663044
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	IPI	10525310
GO:0008543	Process	Fibroblast growth factor receptor signaling pathway	TAS
GO:0010628	Process	Positive regulation of gene expression	IMP	19085950
GO:0010715	Process	Regulation of extracellular matrix disassembly	IMP	20876804
GO:0016477	Process	Cell migration	IMP	20876804
GO:0017134	Function	Fibroblast growth factor binding	IBA	21873635
GO:0017134	Function	Fibroblast growth factor binding	IDA	8663044, 18480409
GO:0017134	Function	Fibroblast growth factor binding	IPI	10525310, 17627937
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IDA	18480409, 20683963
GO:0019216	Process	Regulation of lipid metabolic process	ISS
GO:0030133	Component	Transport vesicle	IDA	18061161
GO:0033674	Process	Positive regulation of kinase activity	IBA	21873635
GO:0042593	Process	Glucose homeostasis	ISS
GO:0042632	Process	Cholesterol homeostasis	ISS
GO:0043085	Process	Positive regulation of catalytic activity	IMP	20798051
GO:0043235	Component	Receptor complex	IBA	21873635
GO:0045862	Process	Positive regulation of proteolysis	IMP	20798051
GO:0046777	Process	Protein autophosphorylation	IDA	20798051
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0055062	Process	Phosphate ion homeostasis	ISS
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IBA	21873635
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IMP	21653700
GO:0070857	Process	Regulation of bile acid biosynthetic process	IBA	21873635
GO:0070857	Process	Regulation of bile acid biosynthetic process	IMP	17623664, 20683963
GO:1903412	Process	Response to bile acid	IMP	19085950
GO:2000573	Process	Positive regulation of DNA biosynthetic process	IMP	21653700

Other IDs

• MIM: 134935
• HGNC: 3691
• e!Ensembl: ENSG00000160867

Protein

• UniProt ID: P22455
• Protein name: Fibroblast growth factor receptor 4 (FGFR-4) (EC 2.7.10.1) (CD antigen CD334)
• Protein function: Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, gl
• PDB: 4QQ5, 4QQC, 4QQJ, 4QQT, 4QRC, 4R6V, 4TYE, 4TYG, 4TYI, 4TYJ, 4UXQ, 4XCU, 5JKG, 5NUD, 5NWZ, 5XFF, 5XFJ, 6IUO, 6IUP, 6J6Y, 6JPE, 6JPJ, 6NVG, 6NVH, 6NVI, 6NVJ, 6NVK, 6V9C, 6YI8, 7DTZ, 7F3M, 7N1J, 7TYD, 7V29, 7VJL, 7WCT, 7WCW, 7WCX, 7YBO, 7YBP, 7YBX, 7YC1, 7YC3, 7YSW, 8KH6, 8KH7, 8KH8, 8KH9, 8W5C, 8XLQ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07679	I-set	154 → 241	Immunoglobulin I-set domain	Domain
  PF13927	Ig_3	248 → 337		Domain
  PF07714	PK_Tyr_Ser-Thr	467 → 743	Protein tyrosine and serine/threonine kinase	Domain

• Sequence:

  MRLLLALLGVLLSVPGPPVLSLEASEEVELEPCLAPSLEQQEQELTVALGQPVRLCCGRA
  ERGGHWYKEGSRLAPAGRVRGWRGRLEIASFLPEDAGRYLCLARGSMIVLQNLTLITGDS
  LTSSNDDEDPKSHRDPSNRHSYPQQAPYWTHPQRMEKKLHAVPAGNTVKFRCPAAGNPTP
  TIRWLKDGQAFHGENRIGGIRLRHQHWSLVMESVVPSDRGTYTCLVENAVGSIRYNYLLD
  VLERSPHRPILQAGLPANTTAVVGSDVELLCKVYSDAQPHIQWLKHIVINGSSFGADGFP
  YVQVLKTADINSSEVEVLYLRNVSAEDAGEYTCLAGNSIGLSYQSAWLTVLPEEDPTWTA
  AAPEARYTDIILYASGSLALAVLLLLAGLYRGQALHGRHPRPPATVQKLSRFPLARQFSL
  ESGSSGKSSSSLVRGVRLSSSGPALLAGLVSLDLPLDPLWEFPRDRLVLGKPLGEGCFGQ
  VVRAEAFGMDPARPDQASTVAVKMLKDNASDKDLADLVSEMEVMKLIGRHKNIINLLGVC
  TQEGPLYVIVECAAKGNLREFLRARRPPGPDLSPDGPRSSEGPLSFPVLVSCAYQVARGM
  QYLESRKCIHRDLAARNVLVTEDNVMKIADFGLARGVHHIDYYKKTSNGRLPVKWMAPEA
  LFDRVYTHQSDVWSFGILLWEIFTLGGSPYPGIPVEELFSLLREGHRMDRPPHCPPELYG
  LMRECWHAAPSQRPTFKQLVEALDKVLLAVSEEYLDLRLTFGPYSPSGGDASSTCSSSDS
  VFSHDPLPLGSSSFPFGSGVQT

• Sequence length: 802

Pathways

KEGG:

MAPK signaling pathway
Ras signaling pathway
Rap1 signaling pathway
Calcium signaling pathway
Endocytosis
PI3K-Akt signaling pathway
Signaling pathways regulating pluripotency of stem cells
Regulation of actin cytoskeleton
Pathways in cancer

Reactome:

PI3K Cascade
PIP3 activates AKT signaling
betaKlotho-mediated ligand binding
FGFR4 mutant receptor activation
FGFR4 ligand binding and activation
Constitutive Signaling by Aberrant PI3K in Cancer
Phospholipase C-mediated cascade; FGFR4
FRS-mediated FGFR4 signaling
SHC-mediated cascade:FGFR4
PI-3K cascade:FGFR4
Negative regulation of FGFR4 signaling
Signaling by FGFR4 in disease
RAF/MAP kinase cascade
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Adenocarcinoma	Adenoid Cystic Carcinoma	rs121913530, rs886039394, rs121913474	23685749
Lung adenocarcinoma	Adenocarcinoma of lung (disorder)	rs28934576, rs121913530, rs397516975, rs587776805, rs121913469, rs121913364, rs121913351, rs121913366, rs397516896, rs397516977, rs397516981, rs397517127, rs121913344, rs727504233, rs121913370, rs760043106, rs1057519788, rs1131692238, rs1131692237, rs1554350382
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	21349172, 15448004, 18756523, 18670643, 20876804
Rhabdomyosarcoma	Rhabdomyosarcoma	rs137854557, rs121909224, rs63751466, rs11540652, rs28934874, rs104894229, rs104894230, rs267606708, rs80357867, rs276174889, rs80359011, rs80358556, rs80359391, rs80357989, rs886037650, rs886037651, rs201744589, rs587780067, rs587781462, rs587782144, rs55863639, rs768638173, rs864622639, rs875989784, rs876657714, rs878855246, rs199474742, rs879253942, rs886037721, rs1057519989, rs750380279, rs1131691211, rs1202793339, rs1567611375	24124571, 19809159

Unknown
Disease name	Disease term	dbSNP ID	References
Mammary neoplasms	Mammary Neoplasms		19946327
Prostatic neoplasms	Prostatic Neoplasms		15448004
Respiratory distress syndrome	Respiratory Distress Syndrome, Adult		25070658