FGF18

Summary

FGF18 (fibroblast growth factor 18, HGNC:3674) is a protein-coding gene on chromosome 5q35.1, encoding Fibroblast growth factor 18 (O76093). Plays an important role in the regulation of cell proliferation, cell differentiation and cell migration.

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. It has been shown in vitro that this protein is able to induce neurite outgrowth in PC12 cells. Studies of the similar proteins in mouse and chick suggested that this protein is a pleiotropic growth factor that stimulates proliferation in a number of tissues, most notably the liver and small intestine. Knockout studies of the similar gene in mice implied the role of this protein in regulating proliferation and differentiation of midline cerebellar structures.

Source: NCBI Gene 8817 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 30 total
• MANE Select transcript: NM_003862

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3674
Approved symbol	FGF18
Name	fibroblast growth factor 18
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	FGF-18, ZFGF5
Ensembl gene	ENSG00000156427
Ensembl biotype	protein_coding
OMIM	603726
Entrez	8817

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000274625, ENST00000966519

RefSeq mRNA: 1 — MANE Select: NM_003862 NM_003862

CCDS: CCDS4378

Canonical transcript exons

ENST00000274625 — 5 exons

Exon	Start	End
ENSE00001026386	171449147	171449253
ENSE00001084443	171420407	171420443
ENSE00001084450	171436093	171436273
ENSE00001351537	171456539	171457626
ENSE00001383119	171419647	171420231

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 88.90.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9098 / max 83.3762, expressed in 377 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60182	0.8061	350
203791	0.1037	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	88.90	silver quality
heart right ventricle	UBERON:0002080	87.49	gold quality
vena cava	UBERON:0004087	85.97	silver quality
left ventricle myocardium	UBERON:0006566	85.64	gold quality
cartilage tissue	UBERON:0002418	85.01	gold quality
apex of heart	UBERON:0002098	84.82	gold quality
buccal mucosa cell	CL:0002336	83.02	silver quality
cardiac ventricle	UBERON:0002082	82.73	gold quality
heart left ventricle	UBERON:0002084	82.52	gold quality
parietal pleura	UBERON:0002400	79.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.62	gold quality
heart	UBERON:0000948	75.77	gold quality
pleura	UBERON:0000977	75.66	gold quality
endothelial cell	CL:0000115	73.28	silver quality
cortical plate	UBERON:0005343	72.65	gold quality
tendon	UBERON:0000043	72.06	gold quality
synovial joint	UBERON:0002217	71.87	silver quality
visceral pleura	UBERON:0002401	71.36	gold quality
myocardium	UBERON:0002349	70.97	silver quality
pericardium	UBERON:0002407	70.60	silver quality
omental fat pad	UBERON:0010414	70.14	gold quality
peritoneum	UBERON:0002358	70.10	gold quality
adipose tissue of abdominal region	UBERON:0007808	69.33	gold quality
right coronary artery	UBERON:0001625	69.17	gold quality
germinal epithelium of ovary	UBERON:0001304	69.08	silver quality
type B pancreatic cell	CL:0000169	68.05	gold quality
right atrium auricular region	UBERON:0006631	67.49	gold quality
hair follicle	UBERON:0002073	66.88	silver quality
cardiac atrium	UBERON:0002081	66.55	gold quality
tibial nerve	UBERON:0001323	66.08	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10283	yes	314.65
E-ANND-3	yes	3.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOXP1, GLIS3, HNF4A, LEF1, RUNX2, TCF7L2, ZNF91

miRNA regulators (miRDB)

91 targeting FGF18, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-369-3P	99.85	70.52	2264

Literature-anchored findings (GeneRIF, showing 31)

• mRNA expression examined by in situ hybridization in whole human embryos at 30 days and 8 weeks of gestation. (PMID:15749088)
• analysis of FGF18 and FGFR5 expression in primary endothelial cells and vascular smooth muscle cells (PMID:16019430)
• FGF18 is wildly expressed in the cardiovascular tissue. It enhanced cell migration in response to mechanical damage. we detected FGF18 expression in liver vascular and liver sinusoidal endothelial cells (LSECs), but not in hepatic parenchymal cells. (PMID:16756958)
• FGF18 may play a prominent role in chondrogenesis and osteogenesis during skeletal development and growth (review) (PMID:17128416)
• FGF3, FGF7, FGF10, FGF18, and FGFR1 may have roles in nonsyndromic cleft lip and palate (PMID:17360555)
• FGF18 is almost generally over-expressed in colon cancer and exerts pro-tumorigenic effects both in the epithelial and the stromal compartments by stimulating growth and survival of tumour cells, migration of fibroblasts and neovascularization (PMID:17890768)
• There was an association between gene FGF18 rs4043716 and nonsyndromic cleft lip with or without palate in Chinese population. (PMID:19727229)
• fibroblast growth factor 18 seems to play a role in maintenance of chondrocyte properties, although its expression was rather high in dedifferentiated chondrocytes. (PMID:19909293)
• FGF2 and -18 bind to discrete structures on the heparan sulfate chains attached to chondrocyte-derived perlecan which modulate the growth factor activities (PMID:20507176)
• FGF8, FGF17, and FGF18 are involved in autocrine and paracrine signaling in HCC and enhance the survival of tumor cells under stress conditions, malignant behavior, and neoangiogenesis. (PMID:21319186)
• role for FGF-18 in chondrogenic and osteogenic events which drive discal development and ossification of the vertebral bodies. (PMID:23397188)
• Tumors from ovarian cancer patients had increased FGF18 expression levels with microvessel density and M2 macrophage infiltration. (PMID:24018557)
• Fgf18 as a molecule that protects articular cartilage by gene expression profiling, and the anticatabolic effects may at least partially be mediated by the Timp1 expression. (PMID:24577103)
• The position of sulfate ions bound to FGF18 provides insight into the putative HS-binding site and allows comparison with the prototypical FGFs, FGF1, and FGF2. (PMID:24668462)
• Data suggest that the combination of FIGO stage, ovarian carcinoma type, and/or fibroblast growth factor 18 (FGF18) score could predict poor prognosis among ovarian carcinoma patients. (PMID:26427667)
• FGF9 and FGF18 increased the migratory capacities of human lung fibroblasts, and FGF9 actively modulated matrix metalloproteinase activity in idiopathic pulmonary fibrosis. (PMID:26773067)
• significantly increased in endometrioid adenocarinoma (PMID:27267714)
• FGF18 serves an essential role in the growth and migration of non-small cell lung cancer cells by regulating the ERK, p38 signaling pathways and MMP26 protein levels. (PMID:27959447)
• the suppressive effect of miR-139 on FGF18 and in turn on proliferation, apoptosis, invasion, migration and tumor-induced angiogenesis of HCC cells was investigated. FGF18 was suggested as a prognostic biomarker and therapeutic target in HCC patients and miR-139 may be a promising strategy used in HCC treatment via the suppression of FGF18 (PMID:28765917)
• the results suggest that FGF18 may be involved in MC3T3E1 cell proliferation and osteoblastic differentiation. (PMID:28765932)
• we genotyped rs9313548 and performed case-control-based association analysis with developmental dyslexia in a Chinese population. Our results were in consistent with previous studies as we did not observe significant association of rs9313548 with developmental dyslexia. (PMID:29240020)
• High FGF18 expression is associated with angiogenesis in hepatocellular carcinoma. (PMID:29242604)
• EGR1 is a major upstream component of FGF signaling in theca cells and that it directs cell fate toward proliferation. (PMID:29723542)
• FGF18 played an important role in the growth and metastasis of breast cancer. (PMID:29901199)
• In primary gastric cancer samples, FGF18 was overexpressed in genomically stable and chromosomal instability subtypes of GC. Overexpression was associated with poor survival. FGF18 knockdown inhibited tumor formation abilities, induced G1 phase cell cycle arrest, enhanced anti-cancer drug sensitivity, activated ATM pathway but quenched TGF-beta pathway. FGF18 was a direct target of tumor suppressor, miR-590-5p. (PMID:30082912)
• The halo-recombinant human FGF18 promotes chondrocyte differentiation through ERK signaling pathway. (PMID:30416101)
• The FGF18 is promising candidates for prognostic factors in adenocarcinomas of the esophago-gastric junction and new potential targets for new anti-cancer therapies. (PMID:31527546)
• Identification of a genetic polymorphism in FGF18 significantly associated with the risk of Knee osteoarthritis based on samples with Chinese Han ancestry. (PMID:32109713)
• FGF18-FGFR2 signaling triggers the activation of c-Jun-YAP1 axis to promote carcinogenesis in a subgroup of gastric cancer patients and indicates translational potential. (PMID:32934314)
• FGF18 promotes human lung branching morphogenesis through regulating mesenchymal progenitor cells. (PMID:36791060)
• Circulating FGF18 is decreased in pleural mesothelioma but not correlated with disease prognosis. (PMID:37340889)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgf18b	ENSDARG00000043962
danio_rerio	fgf18a	ENSDARG00000088048
mus_musculus	Fgf18	ENSMUSG00000057967
rattus_norvegicus	Fgf18	ENSRNOG00000048389

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), FGF17 (ENSG00000158815), FGF11 (ENSG00000161958), FGF19 (ENSG00000162344), FGF3 (ENSG00000186895), FGF16 (ENSG00000196468)

Protein

Protein identifiers

Fibroblast growth factor 18 — O76093 (reviewed: O76093)

Alternative names: zFGF5

All UniProt accessions (2): O76093, A0A7U3JVY7

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the regulation of cell proliferation, cell differentiation and cell migration. Required for normal ossification and bone development. Stimulates hepatic and intestinal proliferation.

Subunit / interactions. Interacts with FGFR3 and FGFR4.

Subcellular location. Secreted.

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

RefSeq proteins (1): NP_003853* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002209	Fibroblast_GF_fam	Family
IPR008996	IL1/FGF	Homologous_superfamily

Pfam: PF00167

UniProt features (23 total): strand 10, helix 4, turn 2, glycosylation site 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4CJM	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76093-F1	87.50	0.62

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 (1): 109–127

Glycosylation sites (2): 39, 137

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-109704	PI3K Cascade
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1839130	Signaling by activated point mutants of FGFR3
R-HSA-190322	FGFR4 ligand binding and activation
R-HSA-190371	FGFR3b ligand binding and activation
R-HSA-190372	FGFR3c ligand binding and activation
R-HSA-190375	FGFR2c ligand binding and activation
R-HSA-2033519	Activated point mutants of FGFR2
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-5654221	Phospholipase C-mediated cascade; FGFR2
R-HSA-5654227	Phospholipase C-mediated cascade; FGFR3
R-HSA-5654228	Phospholipase C-mediated cascade; FGFR4
R-HSA-5654695	PI-3K cascade:FGFR2
R-HSA-5654699	SHC-mediated cascade:FGFR2
R-HSA-5654700	FRS-mediated FGFR2 signaling
R-HSA-5654704	SHC-mediated cascade:FGFR3
R-HSA-5654706	FRS-mediated FGFR3 signaling
R-HSA-5654710	PI-3K cascade:FGFR3
R-HSA-5654712	FRS-mediated FGFR4 signaling
R-HSA-5654719	SHC-mediated cascade:FGFR4
R-HSA-5654720	PI-3K cascade:FGFR4
R-HSA-5654727	Negative regulation of FGFR2 signaling
R-HSA-5654732	Negative regulation of FGFR3 signaling
R-HSA-5654733	Negative regulation of FGFR4 signaling
R-HSA-5655253	Signaling by FGFR2 in disease
R-HSA-5655332	Signaling by FGFR3 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: 340 (showing top): BROWNE_HCMV_INFECTION_4HR_UP, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_CHEMOTAXIS, GOBP_CARTILAGE_DEVELOPMENT, MORF_MSH3, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, BROWNE_HCMV_INFECTION_8HR_UP, PEREZ_TP63_TARGETS, KEGG_MAPK_SIGNALING_PATHWAY, REACTOME_FGFR2C_LIGAND_BINDING_AND_ACTIVATION, REACTOME_SIGNALING_BY_FGFR

GO Biological Process (25): angiogenesis (GO:0001525), intramembranous ossification (GO:0001957), endochondral ossification (GO:0001958), chondrocyte development (GO:0002063), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), anatomical structure morphogenesis (GO:0009653), neurogenesis (GO:0022008), lung development (GO:0030324), regulation of cell migration (GO:0030334), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), positive regulation of chondrocyte differentiation (GO:0032332), positive regulation of MAP kinase activity (GO:0043406), positive regulation of MAPK cascade (GO:0043410), positive regulation of blood vessel endothelial cell migration (GO:0043536), positive regulation of angiogenesis (GO:0045766), vascular endothelial growth factor receptor signaling pathway (GO:0048010), ERK1 and ERK2 cascade (GO:0070371), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of endothelial cell chemotaxis to fibroblast growth factor (GO:2000546), ossification (GO:0001503), chondrocyte differentiation (GO:0002062)

GO Molecular Function (3): type 1 fibroblast growth factor receptor binding (GO:0005105), type 2 fibroblast growth factor receptor binding (GO:0005111), growth factor activity (GO:0008083)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleolus (GO:0005730), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Downstream signaling of activated FGFR2	4
Downstream signaling of activated FGFR3	4
Downstream signaling of activated FGFR4	3
FGFR3 ligand binding and activation	2
IRS-mediated signalling	1
Intracellular signaling by second messengers	1
FGFR3 mutant receptor activation	1
Signaling by FGFR4	1
FGFR2 ligand binding and activation	1
FGFR2 mutant receptor activation	1
PI3K/AKT Signaling in Cancer	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chondrocyte differentiation	2
cell communication	2
cellular process	2
signaling	2
cell surface receptor protein tyrosine kinase signaling pathway	2
fibroblast growth factor receptor binding	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
direct ossification	1
replacement ossification	1
endochondral bone morphogenesis	1
cell development	1
regulation of cellular process	1
cellular response to stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cellular response to fibroblast growth factor stimulus	1
developmental process	1
anatomical structure development	1
nervous system development	1
cell differentiation	1
respiratory tube development	1
animal organ development	1
respiratory system development	1
cell migration	1
regulation of cell motility	1
positive regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
regulation of chondrocyte differentiation	1
positive regulation of cell differentiation	1
positive regulation of cartilage development	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of MAPK cascade	1
positive regulation of protein serine/threonine kinase activity	1
MAPK cascade	1
regulation of MAPK cascade	1

Protein interactions and networks

STRING

3764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGF18	FGFR1	P11362	996
FGF18	FGFR3	P22607	994
FGF18	FGFR2	P18443	992
FGF18	FGFR4	P22455	990
FGF18	EGF	P01133	989
FGF18	KL	Q9UEF7	987
FGF18	HSPG2	P98160	970
FGF18	FGFBP1	Q14512	946
FGF18	DCN	P07585	937
FGF18	CDH2	P19022	880
FGF18	HGF	P14210	874
FGF18	CD44	P16070	874
FGF18	KLB	Q86Z14	855
FGF18	FGF23	Q9GZV9	845
FGF18	TGFB1	P01137	825

IntAct

3 interactions, top by confidence:

A	B	Type	Score
	FGF18	psi-mi:“MI:0407”(direct interaction)	0.440
FGF18	LYAR	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (2): PTX3 (Reconstituted Complex), LYAR (Two-hybrid)

ESM2 similar proteins: A6P7H6, O35622, O57341, O76093, O88182, O89101, P03968, P03969, P12226, P13109, P15655, P19596, P20003, P21781, P36363, P37237, P41444, P48798, P48800, P48808, P61150, P61328, P61329, P70377, P70378, P70379, P79150, Q02195, Q0VCA0, Q5D0X0, Q5MK86, Q5MPA9, Q5RAY8, Q5RDS9, Q60487, Q6DTM3, Q6GLR6, Q6PGN3, Q6SJP8, Q7M303

Diamond homologs: A0MTF4, A6P7H6, M3X9S6, O15520, O35565, O35622, O43320, O54769, O76093, O88182, O89101, O95750, P03968, P03969, P05230, P05524, P08620, P09038, P10767, P11403, P11487, P12034, P12226, P13109, P15655, P15656, P19596, P20002, P20003, P21658, P21781, P31371, P34004, P36363, P36364, P36386, P41444, P48798, P48799, P48800

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FGF18	up-regulates	FGFR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

863 predictions. Top by Δscore:

Variant	Effect	Δscore
5:171420228:GCCT:G	donor_gain	1.0000
5:171436089:CCAG:C	acceptor_loss	1.0000
5:171436090:CAG:C	acceptor_loss	1.0000
5:171436091:A:AG	acceptor_gain	1.0000
5:171436091:A:AT	acceptor_loss	1.0000
5:171436091:AG:A	acceptor_gain	1.0000
5:171436091:AGGT:A	acceptor_gain	1.0000
5:171436092:G:GT	acceptor_gain	1.0000
5:171436092:GG:G	acceptor_gain	1.0000
5:171436092:GGT:G	acceptor_gain	1.0000
5:171436092:GGTG:G	acceptor_gain	1.0000
5:171436092:GGTGC:G	acceptor_gain	1.0000
5:171436269:G:GG	donor_gain	1.0000
5:171436269:GTATG:G	donor_loss	1.0000
5:171436271:ATGGT:A	donor_loss	1.0000
5:171436274:G:A	donor_loss	1.0000
5:171436274:G:GG	donor_gain	1.0000
5:171436275:T:G	donor_loss	1.0000
5:171449135:T:A	acceptor_gain	1.0000
5:171449142:C:A	acceptor_gain	1.0000
5:171449145:A:AG	acceptor_gain	1.0000
5:171449146:G:GG	acceptor_gain	1.0000
5:171449146:GCCC:G	acceptor_gain	1.0000
5:171449146:GCCCA:G	acceptor_gain	1.0000
5:171449251:AAG:A	donor_loss	1.0000
5:171449252:AGG:A	donor_loss	1.0000
5:171449255:T:G	donor_loss	1.0000
5:171456535:GCA:G	acceptor_loss	1.0000
5:171456537:A:AG	acceptor_gain	1.0000
5:171456537:AGCCC:A	acceptor_gain	1.0000

AlphaMissense

1346 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:171436193:T:C	L57P	1.000
5:171436195:T:G	Y58D	1.000
5:171436198:A:C	S59R	1.000
5:171436200:C:A	S59R	1.000
5:171436200:C:G	S59R	1.000
5:171436202:G:C	R60P	1.000
5:171436207:A:C	S62R	1.000
5:171436209:T:A	S62R	1.000
5:171436209:T:G	S62R	1.000
5:171436223:A:C	Q67P	1.000
5:171436247:C:A	A75D	1.000
5:171449153:T:A	L86H	1.000
5:171449153:T:C	L86P	1.000
5:171449173:T:C	F93L	1.000
5:171449174:T:C	F93S	1.000
5:171449174:T:G	F93C	1.000
5:171449175:C:A	F93L	1.000
5:171449175:C:G	F93L	1.000
5:171449186:T:A	V97D	1.000
5:171449189:G:C	R98P	1.000
5:171449192:T:A	I99N	1.000
5:171449192:T:C	I99T	1.000
5:171449192:T:G	I99S	1.000
5:171449197:G:C	G101R	1.000
5:171449215:T:G	Y107D	1.000
5:171449221:T:C	C109R	1.000
5:171449222:G:A	C109Y	1.000
5:171449222:G:T	C109F	1.000
5:171449223:C:G	C109W	1.000
5:171449236:G:C	G114R	1.000

dbSNP variants (sampled 300 via entrez): RS1000029617 (5:171430719 C>T), RS1000036535 (5:171436678 AGT>A), RS1000295335 (5:171441757 A>G), RS1000381030 (5:171430956 C>T), RS1000418964 (5:171443323 G>T), RS1000426171 (5:171449936 C>T), RS1000645929 (5:171441992 T>G), RS1000706415 (5:171437957 C>T), RS1000745052 (5:171444561 C>T), RS1000808793 (5:171449603 C>T), RS1000843018 (5:171434277 T>G), RS1000881404 (5:171428018 T>A,C,G), RS1000896856 (5:171453845 T>C), RS1001032958 (5:171437879 G>A), RS1001067594 (5:171421485 G>A)

Disease associations

OMIM: gene MIM:603726 | disease phenotypes: MIM:236600

GenCC curated gene-disease

Mondo (1): congenital hydrocephalus (MONDO:0016349)

Orphanet (1): Congenital hydrocephalus (Orphanet:2185)

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST002647_127	Height	1.000000e-18
GCST007430_34	Peak expiratory flow	2.000000e-06
GCST007431_48	Lung function (FEV1/FVC)	2.000000e-42
GCST007432_68	FEV1	4.000000e-08
GCST007692_104	Chronic obstructive pulmonary disease	1.000000e-09
GCST008163_165	Height	8.000000e-08
GCST008839_137	Height	4.000000e-31
GCST008839_412	Height	1.000000e-15
GCST008839_462	Height	3.000000e-11
GCST010320_128	PR interval	5.000000e-13
GCST010321_5	PR interval	1.000000e-12
GCST010396_41	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06
GCST010702_141	Subcortical volume (MOSTest)	9.000000e-14
GCST010703_175	Brain morphology (MOSTest)	4.000000e-11
GCST012224_1	Cocaine dependence (time to event)	5.000000e-07
GCST012227_197	Hip circumference adjusted for BMI	6.000000e-09
GCST012334_7	Multisite chronic pain	3.000000e-08
GCST90000025_501	Appendicular lean mass	6.000000e-34
GCST90020028_1004	Hip circumference adjusted for BMI	3.000000e-11
GCST90020028_1005	Hip circumference adjusted for BMI	3.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0004462	PR interval
EFO:0007874	gut microbiome measurement
EFO:0004346	neuroimaging measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0010100	multisite chronic pain
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects expression, increases expression, affects cotreatment, decreases expression	3
Valproic Acid	affects expression, increases expression	3
entinostat	increases expression, affects cotreatment	2
Vorinostat	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Progesterone	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases expression, affects expression	2
Cyclosporine	decreases expression, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
taxifolin	decreases expression	1
methylmercuric chloride	increases expression	1
bisphenol A	affects expression	1
trichostatin A	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
ochratoxin A	increases expression	1
potassium chromate(VI)	increases expression, affects cotreatment	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
pentanal	increases expression	1
3-nitrobenzanthrone	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
nutlin 3	increases expression, affects cotreatment	1
abrine	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1S6	SEES3-1V human FGF18, clone1	Embryonic stem cell	Male
CVCL_A1S7	SEES3-1V human FGF18, clone2	Embryonic stem cell	Male
CVCL_A1S8	SEES3-1V human FGF18, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06664372	Not specified	NOT_YET_RECRUITING	Insertion of Frontal Ventricular Catheter of VP Shunt in Congenital Hydrocephalus Guided by Trans Fontanelle Ultrasound