FGF19

Summary

FGF19 (fibroblast growth factor 19, HGNC:3675) is a protein-coding gene on chromosome 11q13.3, encoding Fibroblast growth factor 19 (O95750). Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. In precision oncology, FGF19 Overexpression confers sensitivity to Fisogatinib in Hepatocellular Carcinoma (CIViC Level B); 2 further curated variant–drug associations are listed below.

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes including embryonic development cell growth, morphogenesis, tissue repair, tumor growth and invasion. This growth factor is a high affinity, heparin dependent ligand for FGFR4. Expression of this gene was detected only in fetal but not adult brain tissue. Synergistic interaction of the chick homolog and Wnt-8c has been shown to be required for initiation of inner ear development.

Source: NCBI Gene 9965 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 28 total
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• MANE Select transcript: NM_005117

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3675
Approved symbol	FGF19
Name	fibroblast growth factor 19
Location	11q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000162344
Ensembl biotype	protein_coding
OMIM	603891
Entrez	9965

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000294312, ENST00000911903

RefSeq mRNA: 1 — MANE Select: NM_005117 NM_005117

CCDS: CCDS8193

Canonical transcript exons

ENST00000294312 — 3 exons

Exon	Start	End
ENSE00001064292	69703645	69704022
ENSE00001064293	69703261	69703364
ENSE00001064294	69698238	69699576

Expression profiles

Bgee: expression breadth broad, 28 present calls, max score 99.05.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.0945 / max 1172.7437, expressed in 142 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121052	2.0945	142

Top tissues by expression

240 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gall bladder	UBERON:0002110	99.05	gold quality
epithelial cell of pancreas	CL:0000083	85.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.88	gold quality
ileal mucosa	UBERON:0000331	70.12	silver quality
islet of Langerhans	UBERON:0000006	69.16	gold quality
pancreatic ductal cell	CL:0002079	68.33	silver quality
sperm	CL:0000019	62.76	gold quality
jejunal mucosa	UBERON:0000399	55.02	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
quadriceps femoris	UBERON:0001377	53.05	gold quality
vastus lateralis	UBERON:0001379	51.63	gold quality
cerebellar vermis	UBERON:0004720	50.94	gold quality
myocardium	UBERON:0002349	50.25	gold quality
Brodmann (1909) area 46	UBERON:0006483	50.05	gold quality
deltoid	UBERON:0001476	49.86	gold quality
tibialis anterior	UBERON:0001385	49.30	silver quality
jejunum	UBERON:0002115	48.25	gold quality
sural nerve	UBERON:0015488	47.40	silver quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
lateral globus pallidus	UBERON:0002476	45.90	gold quality
small intestine	UBERON:0002108	45.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	44.90	gold quality
body of tongue	UBERON:0011876	44.02	gold quality
thymus	UBERON:0002370	43.78	gold quality
subthalamic nucleus	UBERON:0001906	43.68	gold quality
pharyngeal mucosa	UBERON:0000355	43.61	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	1400.71
E-GEOD-109979	no	99.01
E-ANND-3	no	1.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
ASCL1	Activation
CYP7A1	Repression
NEUROG2	Activation

Upstream regulators (CollecTRI, top): ATF4, FOXC1, GLI1, GLI2, NR1H4, NR1I2, PAX6, PBX1, SREBF2

miRNA regulators (miRDB)

58 targeting FGF19, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-188-3P	100.00	68.76	1240
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766

Literature-anchored findings (GeneRIF, showing 40)

• FGF19 transgenic mice had a significant and specific reduction in fat mass that resulted from an increase in energy expenditure. FGF19 transgenic mice did not become obese or diabetic on a high fat diet. (PMID:11956156)
• The formation of liver tumors in transgenic mice overexpressing human fibroblast growth factor 19 (FGF19) in skeletal muscle (PMID:12057932)
• demonstrated that FGF-19, acting as an FXR-induced signaling molecule, represses expression of the CYP7A1 gene; this signaling cascade defines a novel mechanism for feedback repression of bile acid biosynthesis (PMID:12815072)
• The crystal structure of FGF19 is reported and a model proposed for the interaction of FGF19 with its sole receptor, fibroblast growth factor receptor 4. (PMID:14730967)
• FGF19 is able to increase metabolic rate concurrently with an increase in fatty acid oxidation. (PMID:14976145)
• This study reveals an important role for FOXC1 in the direct regulation of the FGF19-FGFR4-MAPK pathway to promote both the development and maintenance of anterior segment structures within the eye. (PMID:17000708)
• Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors (PMID:17339340)
• FGF19 is coexpressed with its cognate receptor FGFR4 in primary human liver, lung, and colon tumors and in a subset of human colon cancer cell lines, where their interactions are important for tumor growth. (PMID:17599042)
• a functional FGF19 receptor may consist of FGF receptor (FGFR) and heparan sulfate complexed with either alphaKlotho or betaKlotho (PMID:17711860)
• Circulating levels of FGF21 but not FGF19 are strongly related to body weight and serum levels of leptin, adiponectin, and insulin in both anorectic and normal-weight women. (PMID:18559909)
• Both FGF23 and FGF21 require intact alpha or betaKlotho for signaling, respectively, whereas FGF19 can signal through a Klotho chimera consisting of the N terminus of alphaKlotho and the C terminus of betaKlotho. (PMID:18829467)
• The liver expresses FGF19 under conditions of extrahepatic cholestasis. (PMID:19185005)
• the inhibitory effect of FGF-19 on insulin activation of hepatic fatty acid synthesis constitutes a mechanism that would explain the beneficial effect of FGF-19 on metabolic syndrome. (PMID:19233843)
• FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action (PMID:19237543)
• Plasma FGF19 did not significantly differ between controls, and subjects with obesity or Cushing’s syndrome. (PMID:19681655)
• FGF19 is associated with a beneficial metabolic profile in both control and chronic hemodialysis patients. (PMID:20013647)
• activation of FGFR4 is the mechanism whereby FGF19 can increase hepatocyte proliferation and induce hepatocellular carcinoma formation. (PMID:20018895)
• Patients with nonalcoholic fatty liver disease (NAFLD) show an unimpaired intestinal FGF19 production. However, the hepatic response to FGF19 is impaired in NAFLD patients with insulin resistance (HOMA score > or =2.5). (PMID:20093562)
• A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis between fasting serum 7alphaC4 and FGF19 levels. (PMID:20691689)
• Data established that FGF19 is an important driver gene in HCC. (PMID:21397858)
• findings show that FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism (PMID:21436455)
• FGFR4 activation mediates the induction of hepatocyte proliferation and the suppression of bile acid biosynthesis by FGF19. (PMID:21437243)
• Baseline serum FGF-19 levels are significantly lower in obese patients with type 2 diabetes and is at least partially dependent upon nutritional status, but is not related to glucose metabolism or insulin sensitivity parameters. (PMID:21574752)
• Sulfated glycosaminoglycans are required for specific and sensitive fibroblast growth factor (FGF) 19 signaling via FGF receptor 4 and betaKlotho. (PMID:21653700)
• The serum bile salts were slightly but significantly elevated, and the levels of the endocrine-acting fibroblast growth factor 19 (FGF19) and FGF21 were increased. (PMID:21691104)
• Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and mice (PMID:21747170)
• found to activate signaling pathways in cell lines of cholangiocytic, enteroendocrine, and enterocytic origin (PMID:21953282)
• FGF-19 levels are low in type 2 diabetic patients with metabolic syndrome. (PMID:22166511)
• The FGF19 effect on APOA was attenuated by transfection of primary hepatocytes with siRNA against the FGF19 receptor 4 (FGFR4). (PMID:22267484)
• Mouse Fgf15 and human FGF19 play key roles in enterohepatic signaling, regulation of liver bile acid biosynthesis, gallbladder motility and metabolic homeostasis (PMID:22396169)
• Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB. (PMID:22442730)
• These results suggest that FGF19 is transcriptionally activated through multiple Farnesoid X receptor-responsive elements in the promoter region (PMID:22561792)
• HNF4alpha and LRH-1 promote active transcription histone marks on the Cyp7a1 promoter that are reversed by FGF19 in a SHP-dependent manner (PMID:23038264)
• The specificity of hFGF19 signaling is greatly altered in a mouse model system. (PMID:23064887)
• FGF19 (fibroblast growth factor 19) as a novel target gene for activating transcription factor 4 in response to endoplasmic reticulum stress (PMID:23205607)
• A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents. (PMID:23329754)
• FGF19 protein expression might be an effective predictor of early recurrence and a marker for poor prognosis of hepatocellular carcinoma. (PMID:23456506)
• Fasting serum FGF19 levels were decreased in Chinese subjects with IFG and inversely associated with fasting glucose levels. (PMID:23628619)
• FGF19 expression is not associated with lymph node metastasis and locally invasive characteristics of the tumor in colorectal cancers (PMID:23803094)
• serum FGF19 and FGF21 and hepatic Klotho expression are inversely associated with hepatic damage in children with NAFLD (PMID:23840612)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgf19	ENSDARG00000098663
mus_musculus	Fgf15	ENSMUSG00000031073
rattus_norvegicus	Fgf19	ENSRNOG00000020899

Paralogs (21): FGF10 (ENSG00000070193), FGF22 (ENSG00000070388), FGF4 (ENSG00000075388), FGF20 (ENSG00000078579), FGF14 (ENSG00000102466), FGF9 (ENSG00000102678), FGF21 (ENSG00000105550), FGF8 (ENSG00000107831), FGF6 (ENSG00000111241), FGF1 (ENSG00000113578), FGF12 (ENSG00000114279), FGF23 (ENSG00000118972), FGF13 (ENSG00000129682), FGF5 (ENSG00000138675), FGF2 (ENSG00000138685), FGF7 (ENSG00000140285), FGF18 (ENSG00000156427), FGF17 (ENSG00000158815), FGF11 (ENSG00000161958), FGF3 (ENSG00000186895), FGF16 (ENSG00000196468)

Protein

Protein identifiers

Fibroblast growth factor 19 — O95750 (reviewed: O95750)

All UniProt accessions (2): A0A7U3L4E7, O95750

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades. Stimulates glucose uptake in adipocytes. Activity requires the presence of KLB and FGFR4.

Subunit / interactions. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by KL, KLB and heparan sulfate glycosaminoglycans that function as coreceptors. Interacts with KL; this interaction is direct. Interacts with KLB; this interaction is direct. Interacts with FGFR4 in the presence of heparin, KL or KLB. Interacts with MALRD1.

Subcellular location. Secreted.

Tissue specificity. Expressed in fetal brain, cartilage, retina, and adult gall bladder.

Induction. Induced by the bile acids receptor NR1H4 that binds and activates a NR1H4-responsive element within intron 2.

Miscellaneous. Contrarily to other members of the family that can bind several FGF receptors FGF19 is specific for FGFR4.

Similarity. Belongs to the heparin-binding growth factors family.

RefSeq proteins (1): NP_005108* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002209	Fibroblast_GF_fam	Family
IPR008996	IL1/FGF	Homologous_superfamily
IPR035444	FGF15/19/21	Family

Pfam: PF00167

UniProt features (21 total): strand 10, helix 5, turn 2, disulfide bond 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1PWA	X-RAY DIFFRACTION	1.3
2P23	X-RAY DIFFRACTION	1.8
6KTR	X-RAY DIFFRACTION	2.6
6NFJ	X-RAY DIFFRACTION	3.19

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95750-F1	80.10	0.54

Antibody-complex structures (SAbDab): 2 — 6KTR, 6NFJ

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 58–70, 102–120

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-109704	PI3K Cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1307965	betaKlotho-mediated ligand binding
R-HSA-190322	FGFR4 ligand binding and activation
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654228	Phospholipase C-mediated cascade; FGFR4
R-HSA-5654712	FRS-mediated FGFR4 signaling
R-HSA-5654719	SHC-mediated cascade:FGFR4
R-HSA-5654720	PI-3K cascade:FGFR4
R-HSA-5654733	Negative regulation of FGFR4 signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 201 (showing top): REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_ETHANOL, GOBP_CARBOHYDRATE_TRANSPORT, WWTAAGGC_UNKNOWN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, NKX25_02, KEGG_MAPK_SIGNALING_PATHWAY, REACTOME_SIGNALING_BY_FGFR, GOBP_NEGATIVE_REGULATION_OF_STEROID_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY, LHX3_01

GO Biological Process (16): neural crest cell migration (GO:0001755), positive regulation of protein phosphorylation (GO:0001934), nervous system development (GO:0007399), heart development (GO:0007507), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), response to bacterium (GO:0009617), negative regulation of gene expression (GO:0010629), neurogenesis (GO:0022008), regulation of cell migration (GO:0030334), positive regulation of MAPK cascade (GO:0043410), response to ethanol (GO:0045471), positive regulation of D-glucose import across plasma membrane (GO:0046326), positive regulation of JNK cascade (GO:0046330), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of bile acid biosynthetic process (GO:0070858)

GO Molecular Function (3): fibroblast growth factor receptor binding (GO:0005104), growth factor activity (GO:0008083), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Downstream signaling of activated FGFR4	4
Signaling by FGFR4	2
IRS-mediated signalling	1
Intracellular signaling by second messengers	1
FGFR4 ligand binding and activation	1
PI3K/AKT Signaling in Cancer	1
MAPK1/MAPK3 signaling	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of MAPK cascade	2
cellular anatomical structure	2
neural crest cell development	1
mesenchymal cell migration	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
system development	1
animal organ development	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to fibroblast growth factor stimulus	1
response to other organism	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
nervous system development	1
cell differentiation	1
cell migration	1
regulation of cell motility	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
response to alcohol	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
JNK cascade	1
regulation of JNK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
bile acid biosynthetic process	1
negative regulation of steroid biosynthetic process	1
negative regulation of small molecule metabolic process	1
regulation of bile acid biosynthetic process	1
growth factor receptor binding	1

Protein interactions and networks

STRING

1623 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGF19	KLB	Q86Z14	998
FGF19	FGFR4	P22455	998
FGF19	KL	Q9UEF7	962
FGF19	LTO1	Q8WV07	908
FGF19	FGFR1	P11362	884
FGF19	SLC51A	Q86UW1	873
FGF19	CYP7A1	P22680	847
FGF19	NR1H4	Q96RI1	818
FGF19	FGF17	O60258	798
FGF19	FGFR3	P22607	790
FGF19	FGF8	P55075	760
FGF19	FGF4	P08620	740
FGF19	GPBAR1	Q8TDU6	719
FGF19	EGF	P01133	718
FGF19	SLC51B	Q86UW2	675

IntAct

26 interactions, top by confidence:

A	B	Type	Score
FGF19	AKT1	psi-mi:“MI:2364”(proximity)	0.470
AKT1	FGF19	psi-mi:“MI:0915”(physical association)	0.470
FGF19	FGFR4	psi-mi:“MI:0407”(direct interaction)	0.440
FGFR1	FGF19	psi-mi:“MI:0915”(physical association)	0.400
FGF19	UBR3	psi-mi:“MI:0915”(physical association)	0.400
NPTX1	NPTXR	psi-mi:“MI:0914”(association)	0.350
BRAF	FGF19	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	FGF19	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	FGF19	psi-mi:“MI:2364”(proximity)	0.270
FGF19	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	FGF19	psi-mi:“MI:2364”(proximity)	0.270
SPOP	FGF19	psi-mi:“MI:2364”(proximity)	0.270
FGF19	SPOP	psi-mi:“MI:2364”(proximity)	0.270
EGFR	FGF19	psi-mi:“MI:2364”(proximity)	0.270
FGF19	TP53	psi-mi:“MI:2364”(proximity)	0.270
FGF19	PTPN11	psi-mi:“MI:2364”(proximity)	0.270
FGF19	PTEN	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (3): FGFR4 (Reconstituted Complex), UBR3 (Affinity Capture-MS), FGF19 (Affinity Capture-MS)

ESM2 similar proteins: A0MTF4, A4Q9F4, M3X9S6, O15520, O35565, O43189, O43320, O54693, O54769, O73754, O95750, P05524, P08620, P11487, P12034, P15656, P31371, P36364, P36386, P48801, P48802, P48803, P48804, P48807, P54130, P70492, P97401, P98172, Q20FD0, Q2HXK8, Q3ZFI5, Q5RF67, Q5T6S3, Q5XI70, Q91875, Q92765, Q92838, Q95117, Q95L12, Q96GD3

Diamond homologs: A0MTF4, A6P7H6, M3X9S6, O15520, O35565, O35622, O43320, O54769, O95750, P03968, P03969, P05230, P05524, P08620, P09038, P10767, P11487, P12034, P12226, P13109, P15655, P15656, P19596, P20002, P20003, P21658, P21781, P31371, P34004, P36363, P36364, P36386, P41444, P48798, P48799, P48800, P48801, P48802, P48803, P48804

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ATF4	“up-regulates quantity by expression”	FGF19	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	40.3×	3e-05
PIP3 activates AKT signaling	5	27.8×	9e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of ERK1 and ERK2 cascade	5	30.4×	8e-05
positive regulation of gene expression	5	13.8×	1e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

28 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

380 predictions. Top by Δscore:

Variant	Effect	Δscore
11:69703254:CACTT:C	donor_loss	1.0000
11:69703255:ACTT:A	donor_loss	1.0000
11:69703256:CTTA:C	donor_loss	1.0000
11:69703257:TTA:T	donor_loss	1.0000
11:69703258:TAC:T	donor_loss	1.0000
11:69703259:A:AC	donor_gain	1.0000
11:69703259:A:AT	donor_loss	1.0000
11:69703259:ACCAG:A	donor_gain	1.0000
11:69703260:C:CT	donor_gain	1.0000
11:69703260:C:G	donor_loss	1.0000
11:69703260:CCAG:C	donor_gain	1.0000
11:69703260:CCAGC:C	donor_gain	1.0000
11:69703643:A:AC	donor_gain	1.0000
11:69703644:C:CC	donor_gain	1.0000
11:69699575:AG:A	acceptor_gain	0.9900
11:69699577:C:CC	acceptor_gain	0.9900
11:69699577:CTGC:C	acceptor_loss	0.9900
11:69703260:CCA:C	donor_gain	0.9900
11:69703638:CACT:C	donor_loss	0.9900
11:69703641:TCA:T	donor_loss	0.9900
11:69703642:CA:C	donor_loss	0.9900
11:69703643:ACTG:A	donor_loss	0.9900
11:69703644:CT:C	donor_gain	0.9900
11:69703644:CTGTG:C	donor_gain	0.9900
11:69699572:TGAAG:T	acceptor_gain	0.9800
11:69699573:GAAG:G	acceptor_gain	0.9800
11:69699574:AAG:A	acceptor_gain	0.9800
11:69703259:AC:A	donor_gain	0.9800
11:69703260:CC:C	donor_gain	0.9800
11:69703276:G:A	donor_gain	0.9800

AlphaMissense

1406 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:69699548:A:C	F122C	0.999
11:69699548:A:G	F122S	0.998
11:69699419:A:C	F165C	0.997
11:69699513:A:C	Y134D	0.997
11:69699418:G:C	F165L	0.996
11:69699418:G:T	F165L	0.996
11:69699419:A:G	F165S	0.996
11:69699420:A:G	F165L	0.996
11:69699485:A:T	V143D	0.996
11:69699547:G:C	F122L	0.996
11:69699547:G:T	F122L	0.996
11:69699549:A:G	F122L	0.996
11:69703322:A:T	I92N	0.996
11:69703700:G:C	F59L	0.996
11:69703700:G:T	F59L	0.996
11:69703702:A:G	F59L	0.996
11:69699553:A:C	C120W	0.995
11:69699554:C:T	C120Y	0.995
11:69703291:G:C	C102W	0.995
11:69703322:A:G	I92T	0.995
11:69703295:A:T	L101H	0.994
11:69699513:A:G	Y134H	0.993
11:69699513:A:T	Y134N	0.993
11:69699554:C:G	C120S	0.993
11:69699555:A:T	C120S	0.993
11:69703292:C:T	C102Y	0.993
11:69703322:A:C	I92S	0.993
11:69703326:C:G	A91P	0.993
11:69703763:C:A	W38C	0.993
11:69703763:C:G	W38C	0.993

dbSNP variants (sampled 300 via entrez): RS1000080485 (11:69697978 C>G,T), RS1000225393 (11:69702431 TGTGAGGCCTGCGCGG>T), RS1001040128 (11:69702619 C>G,T), RS1001323860 (11:69702442 C>T), RS1001352049 (11:69703207 G>A), RS1001475615 (11:69706000 A>C), RS1001989958 (11:69699702 G>A), RS1001998520 (11:69703873 G>A,T), RS1002113100 (11:69703607 G>A,T), RS1002241180 (11:69697744 T>C), RS1002914055 (11:69700211 A>T), RS1003175809 (11:69704840 C>A,G), RS1003679604 (11:69704730 G>A,T), RS1003778832 (11:69698671 T>C), RS1003847322 (11:69698716 C>G)

Disease associations

OMIM: gene MIM:603891 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000678_13	Breast cancer	3.000000e-15
GCST004412_6	Craniofacial microsomia	4.000000e-17
GCST008053_187	Height	1.000000e-06
GCST008053_56	Height	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
FGF19 Overexpression	Fisogatinib	Hepatocellular Carcinoma	Sensitivity/Response	CIViC B	EID7636
FGF19 Overexpression	FGFR4 Inhibitor H3B-6527	Hepatocellular Carcinoma	Sensitivity/Response	CIViC D	EID7518
FGF19 Overexpression	Sorafenib	Hepatocellular Carcinoma	Resistance	CIViC D	EID7519

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Chenodeoxycholic Acid	increases expression, affects binding, increases activity	5
sodium arsenite	decreases expression, increases expression	3
Deoxycholic Acid	increases activity, increases expression, affects binding	3
Lithocholic Acid	increases activity, increases expression, increases reaction	3
entinostat	increases expression, affects cotreatment	2
GW 4064	affects binding, increases activity, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Heparin	affects binding, increases reaction	2
Ursodeoxycholic Acid	increases expression, increases reaction	2
Cadmium Chloride	increases expression	2
Cholic Acid	increases activity, increases expression, affects binding	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
sotorasib	affects cotreatment, decreases expression	1
bisphenol A	increases methylation	1
gallium arsenide	increases expression	1
pyrazolanthrone	decreases expression, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
obeticholic acid	increases expression, increases secretion	1
ICG 001	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Dasatinib	decreases reaction, increases phosphorylation, increases export, increases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation	1
Bile Acids and Salts	affects chemical synthesis, affects secretion, affects uptake	1
Cholesterol	increases phosphorylation, increases reaction, decreases reaction, increases export	1
Diethylhexyl Phthalate	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8L7	Ubigene HCT 116 FGF19 KO	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.