FGF22

Summary

FGF22 (fibroblast growth factor 22, HGNC:3679) is a protein-coding gene on chromosome 19p13.3, encoding Fibroblast growth factor 22 (Q9HCT0). Plays a role in the fasting response, glucose homeostasis, lipolysis and lipogenesis.

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. The mouse homolog of this gene was found to be preferentially expressed in the inner root sheath of the hair follicle, which suggested a role in hair development. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 27006 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 61 total
• Druggable target: yes
• MANE Select transcript: NM_020637

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3679
Approved symbol	FGF22
Name	fibroblast growth factor 22
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000070388
Ensembl biotype	protein_coding
OMIM	605831
Entrez	27006

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000215530, ENST00000586042, ENST00000591390

RefSeq mRNA: 2 — MANE Select: NM_020637 NM_001300812, NM_020637

CCDS: CCDS12037, CCDS74241

Canonical transcript exons

ENST00000215530 — 3 exons

Exon	Start	End
ENSE00000892314	643235	643338
ENSE00001183756	643410	644373
ENSE00003929435	639879	640139

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 81.33.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	81.33	gold quality
skin of abdomen	UBERON:0001416	78.35	gold quality
zone of skin	UBERON:0000014	75.80	gold quality
right frontal lobe	UBERON:0002810	73.82	gold quality
anterior cingulate cortex	UBERON:0009835	72.81	gold quality
cingulate cortex	UBERON:0003027	72.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	72.33	gold quality
prefrontal cortex	UBERON:0000451	69.47	gold quality
left ovary	UBERON:0002119	69.14	gold quality
putamen	UBERON:0001874	69.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	68.26	gold quality
nucleus accumbens	UBERON:0001882	68.17	gold quality
amygdala	UBERON:0001876	67.89	gold quality
frontal cortex	UBERON:0001870	67.67	gold quality
upper arm skin	UBERON:0004263	67.63	gold quality
neocortex	UBERON:0001950	67.50	gold quality
right ovary	UBERON:0002118	67.40	gold quality
caudate nucleus	UBERON:0001873	66.69	gold quality
tibial nerve	UBERON:0001323	66.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.02	gold quality
hypothalamus	UBERON:0001898	65.78	gold quality
cerebellar hemisphere	UBERON:0002245	65.44	gold quality
cerebellar cortex	UBERON:0002129	65.38	gold quality
telencephalon	UBERON:0001893	65.27	gold quality
cerebral cortex	UBERON:0000956	65.09	gold quality
substantia nigra	UBERON:0002038	64.39	gold quality
gingival epithelium	UBERON:0001949	64.28	gold quality
apex of heart	UBERON:0002098	64.22	gold quality
forebrain	UBERON:0001890	64.18	gold quality
sural nerve	UBERON:0015488	64.14	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.92

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• This study showed that serum FGF22 levels in depressive patients were negatively correlated with serum IL-1beta levels. In animal and cell experiments, enhancing the levels of FGF22 in rat hippocampus was demonstrated to alleviate the chronic unpredictable mild stress-induced depression. The increase in FGF22 was found to be associated with reduced IL-1beta expression and hippocampal apoptosis. (PMID:28948716)
• FGF22 displays protective, antioxidant, and mitogenic effect on mammalian cells. (PMID:29627393)
• High FGF22 expression is associated with Lung Adenocarcinoma. (PMID:30803369)
• FGFBP1-mediated crosstalk between fibroblasts and pancreatic cancer cells via FGF22/FGFR2 promotes invasion and metastasis of pancreatic cancer. (PMID:34117747)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgf22	ENSDARG00000076510
mus_musculus	Fgf22	ENSMUSG00000020327
rattus_norvegicus	Fgf22	ENSRNOG00000071745

Paralogs (21): FGF10 (ENSG00000070193), 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), FGF19 (ENSG00000162344), FGF3 (ENSG00000186895), FGF16 (ENSG00000196468)

Protein

Protein identifiers

Fibroblast growth factor 22 — Q9HCT0 (reviewed: Q9HCT0)

All UniProt accessions (3): Q9HCT0, A0A7U3JVZ9, K7ELB9

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the fasting response, glucose homeostasis, lipolysis and lipogenesis. Can stimulate cell proliferation (in vitro). May be involved in hair development.

Subunit / interactions. Interacts with FGFR1 and FGFR2. Interacts with FGFBP1.

Subcellular location. Secreted.

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

RefSeq proteins (2): NP_001287741, NP_065688* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002209	Fibroblast_GF_fam	Family
IPR008996	IL1/FGF	Homologous_superfamily

Pfam: PF00167

UniProt features (2 total): signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCT0-F1	88.48	0.78

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-109704	PI3K Cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-190370	FGFR1b ligand binding and activation
R-HSA-190377	FGFR2b ligand binding and activation
R-HSA-2033519	Activated point mutants of FGFR2
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654219	Phospholipase C-mediated cascade: FGFR1
R-HSA-5654221	Phospholipase C-mediated cascade; FGFR2
R-HSA-5654687	Downstream signaling of activated FGFR1
R-HSA-5654688	SHC-mediated cascade:FGFR1
R-HSA-5654689	PI-3K cascade:FGFR1
R-HSA-5654693	FRS-mediated FGFR1 signaling
R-HSA-5654695	PI-3K cascade:FGFR2
R-HSA-5654699	SHC-mediated cascade:FGFR2
R-HSA-5654700	FRS-mediated FGFR2 signaling
R-HSA-5654726	Negative regulation of FGFR1 signaling
R-HSA-5654727	Negative regulation of FGFR2 signaling
R-HSA-5655253	Signaling by FGFR2 in disease
R-HSA-5658623	FGFRL1 modulation of FGFR1 signaling
R-HSA-5673001	RAF/MAP kinase cascade
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 137 (showing top): REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, KEGG_MAPK_SIGNALING_PATHWAY, REACTOME_SIGNALING_BY_FGFR, REACTOME_FGFR1_LIGAND_BINDING_AND_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, KEGG_PATHWAYS_IN_CANCER, GOBP_RESPONSE_TO_FIBROBLAST_GROWTH_FACTOR, GOBP_SYNAPTIC_SIGNALING, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION

GO Biological Process (9): positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), neurogenesis (GO:0022008), cell differentiation (GO:0030154), regulation of cell migration (GO:0030334), positive regulation of MAPK cascade (GO:0043410), regulation of synapse maturation (GO:0090128), trans-synaptic signaling (GO:0099537), signal transduction (GO:0007165)

GO Molecular Function (2): fibroblast growth factor receptor binding (GO:0005104), growth factor activity (GO:0008083)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleolus (GO:0005730), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cell surface (GO:0009986), glutamatergic synapse (GO:0098978), GABA-ergic synapse (GO:0098982), extrinsic component of postsynaptic density membrane (GO:0099147), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Downstream signaling of activated FGFR1	4
Downstream signaling of activated FGFR2	4
Signaling by FGFR1	3
IRS-mediated signalling	1
Intracellular signaling by second messengers	1
FGFR1 ligand binding and activation	1
FGFR2 ligand binding and activation	1
FGFR2 mutant receptor activation	1
PI3K/AKT Signaling in Cancer	1
Signaling by FGFR2	1
Signaling by FGFR in disease	1
MAPK1/MAPK3 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
synapse	3
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
nervous system development	1
cell differentiation	1
cellular developmental process	1
cell migration	1
regulation of cell motility	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
regulation of developmental process	1
regulation of synapse organization	1
synapse maturation	1
synaptic signaling	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
growth factor receptor binding	1
receptor ligand activity	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
postsynaptic density membrane	1
extrinsic component of postsynaptic specialization membrane	1

Protein interactions and networks

STRING

3580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGF22	FGFR1	P11362	995
FGF22	FGFR2	P18443	990
FGF22	EGF	P01133	989
FGF22	KL	Q9UEF7	987
FGF22	FGFBP1	Q14512	976
FGF22	FGFR4	P22455	970
FGF22	HSPG2	P98160	948
FGF22	DCN	P07585	939
FGF22	HGF	P14210	881
FGF22	CDH2	P19022	881
FGF22	FGFR3	P22607	876
FGF22	CD44	P16070	875
FGF22	FGF23	Q9GZV9	849
FGF22	KLB	Q86Z14	847
FGF22	NRP1	O14786	823
FGF22	SHH	Q15465	823

IntAct

1 interactions, top by confidence:

A	B	Type	Score
	FGF22	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (1): PTX3 (Reconstituted Complex)

ESM2 similar proteins: A0MTF4, M3X9S6, O12972, O15520, O43189, O43320, O54769, O54951, O70141, O95750, P05524, P08620, P10767, P11403, P11487, P12034, P15656, P21658, P31371, P36364, P36386, P48801, P48802, P48803, P48804, P48807, P54130, P70492, Q0GA42, Q20FD0, Q2HXK8, Q2KJ92, Q3ZFI5, Q5BK01, Q5JXM2, Q6ZRP7, Q86VR8, Q8BQB4, Q8CCB5, Q91875

Diamond homologs: A0MTF4, A6P7H6, M3X9S6, O15520, O35565, O43320, O54769, P03968, P03969, P05230, P05524, P08620, P09038, P10767, P11403, P11487, P12034, P12226, P13109, P15655, P15656, P19596, P20002, P20003, P21658, P21781, P31371, P34004, P36363, P36364, P36386, P48798, P48799, P48800, P48801, P48802, P48803, P48804, P48805, P48806

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

683 predictions. Top by Δscore:

Variant	Effect	Δscore
19:640135:GGACA:G	donor_gain	1.0000
19:640136:GACAG:G	donor_gain	1.0000
19:640140:G:GG	donor_gain	1.0000
19:640136:GACA:G	donor_gain	0.9900
19:640137:A:T	donor_gain	0.9900
19:640138:CA:C	donor_gain	0.9900
19:640137:ACA:A	donor_gain	0.9800
19:643335:GTCG:G	donor_gain	0.9800
19:643427:CTGCA:C	acceptor_loss	0.9800
19:643428:TGCA:T	acceptor_loss	0.9800
19:643429:GCA:G	acceptor_loss	0.9800
19:643430:CAGGT:C	acceptor_loss	0.9800
19:643431:A:AC	acceptor_loss	0.9800
19:643432:G:T	acceptor_loss	0.9800
19:643233:A:AG	acceptor_gain	0.9700
19:643234:G:GG	acceptor_gain	0.9700
19:643339:G:GG	donor_gain	0.9700
19:640138:CAG:C	donor_loss	0.9600
19:640139:AG:A	donor_loss	0.9600
19:640140:GTG:G	donor_loss	0.9600
19:640141:T:A	donor_loss	0.9600
19:640142:GAGT:G	donor_loss	0.9600
19:643234:GGC:G	acceptor_gain	0.9600
19:643337:CGG:C	donor_loss	0.9600
19:643339:GTG:G	donor_loss	0.9600
19:643340:TGAG:T	donor_loss	0.9600
19:643341:GAGT:G	donor_loss	0.9600
19:640143:AGTG:A	donor_loss	0.9500
19:640144:G:GG	donor_gain	0.9500
19:643229:CCCCA:C	acceptor_loss	0.9500

AlphaMissense

1062 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:643435:T:C	F115S	0.995
19:643435:T:G	F115C	0.991
19:643582:T:C	F164S	0.988
19:643247:T:C	I76T	0.987
19:643509:T:C	F140L	0.986
19:643511:C:A	F140L	0.986
19:643511:C:G	F140L	0.986
19:643581:T:C	F164L	0.984
19:643582:T:G	F164C	0.984
19:643583:C:A	F164L	0.984
19:643583:C:G	F164L	0.984
19:643334:G:A	G105E	0.983
19:643322:G:T	G101V	0.982
19:640079:T:C	F52L	0.981
19:640081:C:A	F52L	0.981
19:640081:C:G	F52L	0.981
19:643442:G:C	E117D	0.981
19:643442:G:T	E117D	0.981
19:643430:C:G	C113W	0.978
19:643510:T:G	F140C	0.977
19:643333:G:T	G105W	0.975
19:643441:A:T	E117V	0.975
19:643247:T:G	I76S	0.974
19:643277:T:A	I86N	0.973
19:643277:T:G	I86S	0.973
19:643307:C:A	A96D	0.972
19:643434:T:C	F115L	0.971
19:643436:C:A	F115L	0.971
19:643436:C:G	F115L	0.971
19:643277:T:C	I86T	0.970

dbSNP variants (sampled 300 via entrez): RS1000370286 (19:638263 T>TC), RS1000477211 (19:639031 G>T), RS1000513711 (19:642015 C>T), RS1000672869 (19:638252 C>T), RS1000826064 (19:641266 C>A,T), RS1000880123 (19:641940 CTCAGG>C), RS1001270053 (19:644084 C>T), RS1001655165 (19:639318 T>G), RS1001851646 (19:638520 C>T), RS1002301892 (19:642726 C>T), RS1002389166 (19:638339 G>T), RS1002416562 (19:642081 C>T), RS1002909690 (19:640585 G>C), RS1003082281 (19:644003 G>A,C), RS1003108764 (19:639860 G>A)

Disease associations

OMIM: gene MIM:605831 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362983 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
butyraldehyde	decreases expression	1
licochalcone B	increases expression	1
Letrozole	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Diazinon	increases methylation	1
Malathion	decreases expression	1
Valproic Acid	increases methylation	1
S-Nitrosoglutathione	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 4 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2354256	Functional	PubChem BioAssay. Small Molecule Inhibitors of FGF22-Mediated Excitatory Synaptogenesis & Epilepsy Measured in Biochemical System Using RT-PCR - 7012-01_Inhibitor_Dose_CherryPick_Activity. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL3214941	Binding	PubChem BioAssay. Small Molecule Inhibitors of FGF22-Mediated Excitatory Synaptogenesis & Epilepsy Measured in Biochemical System Using RT-PCR - 7012-04_Inhibitor_Dose_CherryPick_Activity. (absACnn = the concentration at which the curve cro	PubChem BioAssay data set

Clinical trials (associated diseases)

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