FGF10

Summary

FGF10 (fibroblast growth factor 10, HGNC:3666) is a protein-coding gene on chromosome 5p12, encoding Fibroblast growth factor 10 (O15520). Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. It is haploinsufficient (ClinGen: sufficient evidence).

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 protein exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. Studies of the mouse homolog of suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of lim bud formation. This gene is also implicated to be a primary factor in the process of wound healing.

Source: NCBI Gene 2255 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lacrimoauriculodentodigital syndrome 3 (Definitive, GenCC) — +5 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 131 total — 15 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 74
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004465

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3666
Approved symbol	FGF10
Name	fibroblast growth factor 10
Location	5p12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000070193
Ensembl biotype	protein_coding
OMIM	602115
Entrez	2255

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000264664, ENST00000513107, ENST00000912799

RefSeq mRNA: 1 — MANE Select: NM_004465 NM_004465

CCDS: CCDS3950

Canonical transcript exons

ENST00000264664 — 3 exons

Exon	Start	End
ENSE00001002257	44388358	44389420
ENSE00001082046	44310427	44310530
ENSE00001148778	44300247	44305192

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 95.66.

FANTOM5 (CAGE): breadth broad, TPM avg 0.4676 / max 38.8154, expressed in 190 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61587	0.3289	155
61588	0.0683	33
61583	0.0269	7
61584	0.0200	4
61586	0.0123	2
61585	0.0113	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	95.66	gold quality
synovial joint	UBERON:0002217	84.96	gold quality
endocervix	UBERON:0000458	82.41	gold quality
ectocervix	UBERON:0012249	80.14	gold quality
omental fat pad	UBERON:0010414	79.98	gold quality
peritoneum	UBERON:0002358	79.87	gold quality
adipose tissue of abdominal region	UBERON:0007808	78.92	gold quality
layer of synovial tissue	UBERON:0007616	78.81	gold quality
uterine cervix	UBERON:0000002	77.67	gold quality
left uterine tube	UBERON:0001303	77.58	gold quality
vagina	UBERON:0000996	76.38	gold quality
mucosa of stomach	UBERON:0001199	76.29	gold quality
caput epididymis	UBERON:0004358	76.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.00	gold quality
left ovary	UBERON:0002119	74.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.92	gold quality
adipose tissue	UBERON:0001013	72.40	gold quality
right ovary	UBERON:0002118	72.26	gold quality
body of pancreas	UBERON:0001150	71.93	gold quality
ovary	UBERON:0000992	71.68	gold quality
calcaneal tendon	UBERON:0003701	71.67	gold quality
colonic epithelium	UBERON:0000397	71.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	70.73	gold quality
right lobe of thyroid gland	UBERON:0001119	70.58	gold quality
prostate gland	UBERON:0002367	70.19	gold quality
thoracic mammary gland	UBERON:0005200	70.09	gold quality
mammary gland	UBERON:0001911	69.63	gold quality
gall bladder	UBERON:0002110	69.59	gold quality
tibial nerve	UBERON:0001323	69.09	gold quality
tibial artery	UBERON:0007610	68.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	862.02
E-ANND-3	yes	7.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETV1, ETV4, EWSR1, GATA3, GATA4, GLI2, ISL1, LITAF, NFKB, NKX2-5, NR2C2, PAX9, PBX1, RELA, RUNX2, SIX1, SP1, SP3, TBX1, TBX20, TBX4, TBX5, TCF3, TWIST1

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• FGF10 upregulates Na(+)-K(+)-exchanging ATPase via the MAPK pathway. (PMID:12804770)
• TGFbeta1 caused a rapid and transient decrease in Fgf10 mRNA levels in primary prostatic cells. Deletion analysis of the Fgf10 promoter identified a region that mediated a proportion of promoter activity as well as promoter down-regulation by TGFbeta1. (PMID:14726452)
• FGF-10 attenuates H2O2-induced alveolar epithelium DNA damage by mechanisms that involve activation of Grb2-SOS/Ras/RAF-1/ERK1/2 pathway and DNA repair. (PMID:14975937)
• Fgf10 mRNA is overexpressed in a subset of human breast carcinomas. (PMID:15208658)
• Data validate the symmetric two-end model of fibroblast growth factor (FGF) receptor (FGFR) dimerization and FGF binding and argue against the asymmetric model of FGFR dimerization. (PMID:15632068)
• We suggest that haploinsufficiency for FGF10 during a crucial stage of development results in ALSG. (PMID:15654336)
• in psoriatic lesions activated lymphocytes can stimulate fibroblasts to produce KGF and FGF-10, which in turn contribute to sustain the hyperproliferative status of the keratinocytes (PMID:15679583)
• Human embryonic pancreatic mesenchyme expresses FGF10, which might be used used to expand human embryonic pancreatic epithelial cells. (PMID:15690149)
• Human recombinant FGF10 maintains murine Notch activation and induces the expansion of murine pancreatic precursors while blocking their differentiation. (PMID:16323074)
• Localization of the FGF-10 receptor to the urothelial layer is clinically significant because intravesical administration of FGF-10 may provide a means to control the turnover of transitional epithelium in bladder disorders such as interstitial cystitis. (PMID:16597614)
• Activation of Toll-like receptor 2 (TLR2) or Toll-like receptor 4 (TLR4) inhibited FGF-10 expression, leading to abnormal saccular airway morphogenesis. (PMID:17071719)
• R80S and G138E mutations are associated with aplasia of the lacrimal and salivary glands. (PMID:17213838)
• These results indicate that mutations are rare in FGF8 and FGFR2 in hypospadias, but gene variants may influence the risk. (PMID:17264867)
• FGF3, FGF7, FGF10, FGF18, and FGFR1 may have roles in nonsyndromic cleft lip and palate (PMID:17360555)
• a nuclear localization signal-like motif of FGF-10 is a partial determinant of its intracellular distribution and is necessary for its mitogenic activity (PMID:17471512)
• Trophoblast outgrowth and invasion (part of placental villi sprouting) at the fetal maternal interface is in part under delicate control of FGF 10 and Sprouty 2. (PMID:17496316)
• FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction; however, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group (PMID:17609292)
• Results suggest that Lacrimo-auriculo-dento-digital syndrome is caused by reduced activity of the fibroblast growth factor 10 (FGF10)-FGF receptor 2 signaling pathway. (PMID:17682060)
• KGFR internalization triggered by either KGF or FGF10 occurs through clathrin-coated pits (PMID:17944804)
• Expression in diverse niches of adult brain of Fgf10-lacZ reporter mice implicates Fgf10 in control of neurogenesis and/or conservation of neurogenic potential. (PMID:18329286)
• It cannot be ruled out that other genes involved in the signalling pathway of FGF10 may contribute to the formation of these congenital malformations. (PMID:18587586)
• Stromal FGF10 induces migration and invasion in pancreatic cancer cells through interaction with FGFR2, resulting in a poor prognosis. (PMID:18594526)
• An analysis of the distribution and fate of Fgf10-expressing cells in the adult mouse brain suggests that Fgf10 may have critical regulatory roles in stem cell function and generation of new neurons in diverse areas of the adult brain. (PMID:18773495)
• Fgf10 is a strong causative candidate for defects observed in Apert syndrome since its genetic knockdown in a mouse model of Apert syndrome results in the rescue of the skeletal and visceral defects associated with this congenital disease. (PMID:18773495)
• family-based approach revealed an intronic variation of the FGF10 gene causing aplasia of lacrimal and salivary glands-syndrome (PMID:19102732)
• Disruption of localized pattern of mesenchymal fibroblast growth factor 10 expression results in impairment of lung branching morphogenesis, which progresses to emphysematous airspaces in adults. (PMID:19115389)
• There was no association among gene FGFR1 rs13317, p. E467K, p. M369I, p. S393S and gene FGF10 rs1448037 and nonsyndromic cleft lip with or without palate in Chinese population. (PMID:19727229)
• FGF10 can promote the adipogenesis effect in situ. (PMID:19915940)
• These results suggested that Thr-114 is a crucial functional residue for FGF10, and mutating Thr-114 to Ala or Arg would lead to great decrease in receptor-binding affinity and biological activity of FGF10. (PMID:20036575)
• Gremlin-mediated BMP inhibition results in activation of epithelial cells and transient fibrosis, but also induction of epithelium-protective FGF10 (PMID:20705941)
• FGF2 and FGF10 regulate migratory activity of ovine trophoblast cells through MAPK-dependent pathways. (PMID:21310815)
• [review] FGF10 mediates biological responses by activating FGF receptor 2b (FGFR2b) in a paracrine manner. (PMID:21696361)
• Investigation of the pulmonary functions of COPD patients heterozygous for loss of function mutations in the FGF10 gene was performed. The patients show a significant decrease in lung function parameters when compared to control values. (PMID:21742743)
• The relationship between human ISL1 and FGF10 within the embryonic time window during which the linear heart tube remodels into four chambers, was examined. (PMID:22303449)
• Identification of FGF-10 at both protein and mRNA levels in ovaries from fetuses, girls, and women suggests that FGF-10 contributes to preantral follicle development; FGF-10 is expressed in both granulosa cells and oocytes. (PMID:22877940)
• Our data suggest that common variants in FGF10 increase the risk for a wide range of non-syndromic limb deficiencies. (PMID:22965740)
• tooth agenesis had increased risk of a family history of cancer. tooth agenesis was associated with positive self-reported family history of cancer and variants in FGF10. (PMID:23169889)
• the posttranslational and transcriptional mechanisms underlying stimulation of P-glycoprotein function and expression by keratinocyte growth factor-2 (KGF2) that may contribute to the beneficial effects of KGF2 in intestinal inflammatory disorders (PMID:23328208)
• The sclera of myopic eyes had higher FGF10 levels. The risk G allele of SNP rs339501 was associated with extreme myopia in human and caused a higher gene expression in the luciferase assay. (PMID:23599340)
• FGF-10 expression during the development of the human hindgut and anorectum suggests that it may play a role in hindgut and anorectal morphogenesis. (PMID:23774963)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fgf10a	ENSDARG00000030932
danio_rerio	fgf10b	ENSDARG00000100475
mus_musculus	Fgf10	ENSMUSG00000021732
rattus_norvegicus	Fgf10	ENSRNOG00000012278

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

Protein

Protein identifiers

Fibroblast growth factor 10 — O15520 (reviewed: O15520)

Alternative names: Keratinocyte growth factor 2

All UniProt accessions (3): O15520, A0A7U3JW18, D6RG33

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. May play a role in wound healing.

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

Subcellular location. Secreted.

Disease relevance. Aplasia of lacrimal and salivary glands (ALSG) [MIM:180920] A rare condition characterized by dry conjunctival mucosae, irritable eyes, epiphora (constant tearing), and xerostomia (dryness of the mouth), which increases risk of dental erosion, dental caries, periodontal disease, and oral infections. ALSG has variable expressivity, and affected individuals may have aplasia or hypoplasia of the lacrimal, parotid, submandibular, and sublingual glands and absence of the lacrimal puncta. The disease is caused by variants affecting the gene represented in this entry. Lacrimo-auriculo-dento-digital syndrome 3 (LADD3) [MIM:620193] A form of lacrimo-auriculo-dento-digital syndrome, an autosomal dominant disease characterized by aplastic/hypoplastic lacrimal and salivary glands and ducts, cup-shaped ears, hearing loss, hypodontia and enamel hypoplasia, and distal limb segments anomalies. In addition to these cardinal features, facial dysmorphism, malformations of the kidney and respiratory system and abnormal genitalia have been reported. Craniosynostosis and severe syndactyly are not observed. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_004456* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002209	Fibroblast_GF_fam	Family
IPR008996	IL1/FGF	Homologous_superfamily

Pfam: PF00167

UniProt features (24 total): strand 11, helix 3, sequence conflict 3, glycosylation site 2, sequence variant 2, signal peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8YQ1	X-RAY DIFFRACTION	2.56
1NUN	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15520-F1	81.12	0.64

Functional residue map

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

Glycosylation sites (2): 51, 196

Function

Pathways and Gene Ontology

Reactome pathways

24 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-210747	Regulation of gene expression in early pancreatic precursor cells
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
R-HSA-9937080	Developmental Lineage of Multipotent Pancreatic Progenitor Cells
R-HSA-9938206	Developmental Lineage of Mammary Stem Cells

MSigDB gene sets: 662 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_DIGESTION, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MAMMARY_GLAND_MORPHOGENESIS, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GOBP_EPIDERMIS_MORPHOGENESIS, GOBP_AXIS_SPECIFICATION, GOBP_GLAND_MORPHOGENESIS

GO Biological Process (134): establishment of mitotic spindle orientation (GO:0000132), angiogenesis (GO:0001525), metanephros development (GO:0001656), organ induction (GO:0001759), mesonephros development (GO:0001823), endothelial cell proliferation (GO:0001935), positive regulation of endothelial cell proliferation (GO:0001938), blood vessel remodeling (GO:0001974), metanephros morphogenesis (GO:0003338), determination of left/right symmetry (GO:0007368), salivary gland development (GO:0007431), positive regulation of cell population proliferation (GO:0008284), fibroblast growth factor receptor signaling pathway (GO:0008543), regulation of smoothened signaling pathway (GO:0008589), embryonic pattern specification (GO:0009880), positive regulation of epithelial cell migration (GO:0010634), positive regulation of keratinocyte proliferation (GO:0010838), Wnt signaling pathway (GO:0016055), pituitary gland development (GO:0021983), neurogenesis (GO:0022008), actin cytoskeleton organization (GO:0030036), regulation of cell migration (GO:0030334), embryonic genitalia morphogenesis (GO:0030538), negative regulation of epithelial cell differentiation (GO:0030857), thyroid gland development (GO:0030878), otic vesicle formation (GO:0030916), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), pancreas development (GO:0031016), hair follicle morphogenesis (GO:0031069), embryonic camera-type eye development (GO:0031076), response to estradiol (GO:0032355), response to lipopolysaccharide (GO:0032496), positive regulation of ATP-dependent activity (GO:0032781), lacrimal gland development (GO:0032808), regulation of activin receptor signaling pathway (GO:0032925), protein localization to cell surface (GO:0034394), somatic stem cell population maintenance (GO:0035019), wound healing (GO:0042060), tissue regeneration (GO:0042246), odontogenesis of dentin-containing tooth (GO:0042475)

GO Molecular Function (6): fibroblast growth factor receptor binding (GO:0005104), type 2 fibroblast growth factor receptor binding (GO:0005111), growth factor activity (GO:0008083), heparin binding (GO:0008201), chemoattractant activity (GO:0042056), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986)

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
Regulation of beta-cell development	1
PI3K/AKT Signaling in Cancer	1
Signaling by FGFR2	1
Signaling by FGFR in disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
kidney development	2
positive regulation of epithelial cell proliferation	2
gland development	2
receptor ligand activity	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of animal organ formation	1
specification of animal organ identity	1
developmental induction	1
positive regulation of animal organ morphogenesis	1
epithelial cell proliferation	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
tissue remodeling	1
metanephros development	1
kidney morphogenesis	1
determination of bilateral symmetry	1
left/right pattern formation	1
exocrine 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
smoothened signaling pathway	1
regulation of signal transduction	1
pattern specification process	1
embryo development	1
epithelial cell migration	1
regulation of epithelial cell migration	1
positive regulation of cell migration	1
regulation of keratinocyte proliferation	1
keratinocyte proliferation	1
cell surface receptor signaling pathway	1
diencephalon development	1
endocrine system development	1

Protein interactions and networks

STRING

4193 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGF10	FGFR2	P18443	998
FGF10	FGFR1	P11362	997
FGF10	EGF	P01133	990
FGF10	KL	Q9UEF7	987
FGF10	FGFR4	P22455	982
FGF10	FGFBP1	Q14512	974
FGF10	DCN	P07585	940
FGF10	FGFR3	P22607	932
FGF10	HSPG2	P98160	930
FGF10	SHH	Q15465	924
FGF10	CD44	P16070	922
FGF10	HGF	P14210	886
FGF10	BMP4	P12644	884
FGF10	CDH2	P19022	881
FGF10	KLB	Q86Z14	845

IntAct

18 interactions, top by confidence:

A	B	Type	Score
FGF10	FGFR2	psi-mi:“MI:0407”(direct interaction)	0.570
FGF10	FGFR2	psi-mi:“MI:2364”(proximity)	0.570
FGF10	THAP1	psi-mi:“MI:0915”(physical association)	0.560
FGF10	SREK1IP1	psi-mi:“MI:0915”(physical association)	0.560
FGF10	ITIH2	psi-mi:“MI:0914”(association)	0.530
FGF10	rl26_rl26l_human	psi-mi:“MI:0915”(physical association)	0.500
FGF10	MANF	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350
FGF10	EGFR	psi-mi:“MI:2364”(proximity)	0.270
PTEN	FGF10	psi-mi:“MI:2364”(proximity)	0.270
FGF10	PTPN11	psi-mi:“MI:2364”(proximity)	0.270
FGF10	AKT1	psi-mi:“MI:2364”(proximity)	0.270
FGF10	THAP1	psi-mi:“MI:0915”(physical association)	0.000
SREK1IP1	FGF10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): HIST1H1A (Affinity Capture-MS), RPL26L1 (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), ITIH2 (Affinity Capture-MS), HBD (Affinity Capture-MS), FGF10 (Co-localization), FGF10 (Protein-peptide), FGF10 (Protein-peptide), HIST1H1A (Affinity Capture-MS), ITIH2 (Affinity Capture-MS), RPL26L1 (Affinity Capture-MS), SIRT1 (Affinity Capture-MS), FGF10 (Biochemical Activity), THAP1 (Two-hybrid), SREK1IP1 (Two-hybrid)

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, 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

3 interactions.

A	Effect	B	Mechanism
TBX5	“up-regulates quantity by expression”	FGF10	“transcriptional regulation”
FGF10	up-regulates	FGFR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	14
Uncertain significance	63
Likely benign	20
Benign	11

Top pathogenic / likely-pathogenic (29)

Variant ID	HGVS	Classification
1064421	NC_000005.9:g.44300489_44312646del	Pathogenic
1322898	NM_004465.2(FGF10):c.190G>T (p.Gly64Ter)	Pathogenic
1368007	NM_004465.2(FGF10):c.198_199insA (p.Val67fs)	Pathogenic
1527161	GRCh37/hg19 5p12-11(chr5:43855245-46389339)	Pathogenic
1527162	GRCh37/hg19 5p12-11(chr5:43972062-46101844)	Pathogenic
2009733	NM_004465.2(FGF10):c.101del (p.Pro34fs)	Pathogenic
2431095	NM_004465.2(FGF10):c.*1093A>G	Pathogenic
2664283	NM_004465.2(FGF10):c.237G>A (p.Trp79Ter)	Pathogenic
2691789	NM_004465.2(FGF10):c.234dup (p.Trp79fs)	Pathogenic
3062821	GRCh37/hg19 5p12-11(chr5:43949281-46116307)x1	Pathogenic
7530	NC_000005.10:g.(44304226_44304232)_(44357318_44357323)del	Pathogenic
7531	NM_004465.2(FGF10):c.317G>T (p.Cys106Phe)	Pathogenic
7532	NM_004465.2(FGF10):c.467T>G (p.Ile156Arg)	Pathogenic
7533	NM_004465.2(FGF10):c.409A>T (p.Lys137Ter)	Pathogenic
7535	NM_004465.2(FGF10):c.413G>A (p.Gly138Glu)	Pathogenic
1801340	NM_004465.2(FGF10):c.374C>A (p.Ala125Asp)	Likely pathogenic
2575897	NM_004465.2(FGF10):c.355G>A (p.Gly119Arg)	Likely pathogenic
3254622	NM_004465.2(FGF10):c.1_31delinsGCAGCCTTTCAGTTTCAG (p.Met1fs)	Likely pathogenic
3370503	NM_004465.2(FGF10):c.626A>G (p.Ter209Trp)	Likely pathogenic
4072334	NM_004465.2(FGF10):c.324C>A (p.Tyr108Ter)	Likely pathogenic
451206	NM_004465.2(FGF10):c.267dup (p.Leu90fs)	Likely pathogenic
452864	NM_004465.2(FGF10):c.526del (p.Met176fs)	Likely pathogenic
4759488	NM_004465.2(FGF10):c.245T>A (p.Leu82Gln)	Likely pathogenic
547371	NM_004465.2(FGF10):c.1A>G (p.Met1Val)	Likely pathogenic
547372	NM_004465.2(FGF10):c.232del (p.Arg78fs)	Likely pathogenic
547373	NM_004465.2(FGF10):c.256del (p.Thr86fs)	Likely pathogenic
547374	NM_004465.2(FGF10):c.356del (p.Gly119fs)	Likely pathogenic
547375	NM_004465.2(FGF10):c.401T>A (p.Met134Lys)	Likely pathogenic
547377	NM_004465.2(FGF10):c.550G>A (p.Gly184Arg)	Likely pathogenic

SpliceAI

703 predictions. Top by Δscore:

Variant	Effect	Δscore
5:44310418:AATAC:A	donor_loss	1.0000
5:44310419:ATACT:A	donor_loss	1.0000
5:44310420:TACTT:T	donor_loss	1.0000
5:44310421:AC:A	donor_loss	1.0000
5:44310422:CTTAC:C	donor_loss	1.0000
5:44310423:TTACT:T	donor_loss	1.0000
5:44310424:TA:T	donor_loss	1.0000
5:44310425:A:AC	donor_gain	1.0000
5:44310425:A:C	donor_loss	1.0000
5:44310426:C:CT	donor_gain	1.0000
5:44310426:CT:C	donor_gain	1.0000
5:44310426:CTG:C	donor_gain	1.0000
5:44310426:CTGA:C	donor_gain	1.0000
5:44310426:CTGAG:C	donor_gain	1.0000
5:44388352:A:AC	donor_gain	1.0000
5:44388353:C:CC	donor_gain	1.0000
5:44388353:CTTA:C	donor_gain	1.0000
5:44388354:TTA:T	donor_loss	1.0000
5:44388355:TACTG:T	donor_loss	1.0000
5:44388356:A:AC	donor_gain	1.0000
5:44388356:AC:A	donor_loss	1.0000
5:44388357:C:A	donor_loss	1.0000
5:44388357:C:CA	donor_gain	1.0000
5:44388357:CT:C	donor_gain	1.0000
5:44388357:CTG:C	donor_gain	1.0000
5:44388357:CTGT:C	donor_gain	1.0000
5:44388357:CTGTA:C	donor_gain	1.0000
5:44305189:CTTT:C	acceptor_gain	0.9900
5:44305191:TTC:T	acceptor_loss	0.9900
5:44305192:TC:T	acceptor_loss	0.9900

AlphaMissense

1363 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:44305019:A:C	F201L	1.000
5:44305019:A:T	F201L	1.000
5:44305020:A:G	F201S	1.000
5:44305021:A:G	F201L	1.000
5:44388443:T:A	R80S	1.000
5:44388443:T:G	R80S	1.000
5:44305014:G:T	P203Q	0.999
5:44305020:A:C	F201C	0.999
5:44305056:C:T	G189E	0.999
5:44305071:C:T	G184E	0.999
5:44305083:A:G	L180S	0.999
5:44305129:C:G	A165P	0.999
5:44305132:A:G	Y164H	0.999
5:44305136:A:C	N162K	0.999
5:44305136:A:T	N162K	0.999
5:44305160:C:A	E154D	0.999
5:44305160:C:G	E154D	0.999
5:44305167:A:G	L152P	0.999
5:44305172:A:C	C150W	0.999
5:44305173:C:T	C150Y	0.999
5:44310431:C:T	G142D	0.999
5:44310443:C:A	G138V	0.999
5:44310443:C:T	G138E	0.999
5:44310444:C:A	G138W	0.999
5:44310444:C:G	G138R	0.999
5:44310444:C:T	G138R	0.999
5:44310458:G:T	A133D	0.999
5:44310461:A:G	L132S	0.999
5:44310488:A:T	V123D	0.999
5:44310492:C:G	A122P	0.999

dbSNP variants (sampled 300 via entrez): RS1000009019 (5:44374472 G>A), RS1000040334 (5:44374890 T>C), RS1000058715 (5:44343863 A>G), RS1000127474 (5:44308323 G>A), RS1000196023 (5:44308917 G>A,C,T), RS1000235169 (5:44381174 G>C,T), RS1000248994 (5:44301026 A>T), RS1000265296 (5:44351747 T>C), RS1000286217 (5:44353451 C>T), RS1000322725 (5:44300740 C>T), RS1000334379 (5:44389616 C>A,T), RS1000381595 (5:44347616 C>T), RS1000382647 (5:44381636 T>C), RS1000386363 (5:44387476 T>G), RS1000429546 (5:44306627 A>C,G)

Disease associations

OMIM: gene MIM:602115 | disease phenotypes: MIM:149730, MIM:265430, MIM:180920, MIM:620193, MIM:119530

GenCC curated gene-disease

Disease	Classification	Inheritance
lacrimoauriculodentodigital syndrome 3	Definitive	Autosomal dominant
congenital alveolar dysplasia due to FGF10	Strong	Autosomal dominant
LADD syndrome	Supportive	Autosomal dominant
aplasia of lacrimal and salivary glands	Supportive	Autosomal dominant
congenital heart defects, multiple types	Limited	Autosomal dominant
craniosynostosis	Limited	Autosomal dominant

Mondo (11): developmental and epileptic encephalopathy (MONDO:0100620), LADD syndrome (MONDO:0007872), familial primary pulmonary hypoplasia (MONDO:0009936), aplasia of lacrimal and salivary glands (MONDO:0008397), lacrimoauriculodentodigital syndrome 3 (MONDO:0859578), lung adenocarcinoma (MONDO:0005061), orofacial cleft 1 (MONDO:0007335), interstitial lung disease specific to childhood (MONDO:0017014), congenital heart defects, multiple types (MONDO:0000119), craniosynostosis (MONDO:0015469), congenital alveolar dysplasia due to FGF10 (MONDO:0100090)

Orphanet (5): Primary pulmonary hypoplasia (Orphanet:2257), Lacrimoauriculodentodigital syndrome (Orphanet:2363), Aplasia of lacrimal and salivary glands (Orphanet:86815), Interstitial lung disease specific to childhood (Orphanet:264656), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

74 total (30 of 74 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000076	Vesicoureteral reflux
HP:0000089	Renal hypoplasia
HP:0000126	Hydronephrosis
HP:0000164	Abnormality of the dentition
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000217	Xerostomia
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000378	Cupped ear
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000453	Choanal atresia
HP:0000458	Anosmia
HP:0000478	Abnormality of the eye
HP:0000495	Recurrent corneal erosions
HP:0000508	Ptosis
HP:0000522	Alacrima
HP:0000561	Absent eyelashes
HP:0000565	Esotropia
HP:0000577	Exotropia
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001148_7	Prostate cancer	4.000000e-08
GCST003059_10	Parkinson’s disease	1.000000e-06
GCST003427_203	Alzheimer disease and age of onset	2.000000e-07
GCST004166_5	Nonsyndromic cleft lip with cleft palate	1.000000e-08
GCST004988_262	Breast cancer	6.000000e-73
GCST006054_7	High altitude adaptation	2.000000e-08
GCST007429_9	Lung function (FVC)	9.000000e-17
GCST007432_135	FEV1	3.000000e-13
GCST008058_264	Estimated glomerular filtration rate	3.000000e-08
GCST008295_37	Number of decayed, missing and filled tooth surfaces or use of dentures	1.000000e-13
GCST008306_41	Dentures	3.000000e-12
GCST008870_87	Keratinocyte cancer (MTAG)	2.000000e-07
GCST008871_35	Basal cell carcinoma	9.000000e-10
GCST009665_3	Breast cancer	2.000000e-10
GCST010002_24	Refractive error	1.000000e-13
GCST012496_3	Lung function (FVC)	2.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0003959	cleft lip
EFO:0009105	high altitude adaptation
EFO:0004312	vital capacity
EFO:0004314	forced expiratory volume
EFO:0010078	dentures
EFO:0010176	keratinocyte carcinoma

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
C538132	Lacrimoauriculodentodigital syndrome (supp.)
C566121	Orofacial Cleft 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
U 0126	increases activity, increases expression, increases phosphorylation, decreases reaction	2
Chondroitin Sulfates	affects binding	2
Colforsin	decreases reaction, increases phosphorylation	2
Tretinoin	affects cotreatment, increases expression	2
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
FTI 277	decreases reaction, increases activity, increases expression	1
Chir 99021	affects cotreatment, increases expression	1
incobotulinumtoxinA	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Allergens	decreases expression	1
Arsenates	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Asbestos	decreases expression	1
Atrazine	affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Dermatan Sulfate	affects binding	1
Dust	increases secretion	1
Heparin	affects binding, increases reaction	1
Lipopolysaccharides	increases expression, decreases reaction	1
N-Nitrosopyrrolidine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases 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_A1S3	SEES3-1V human FGF10, clone1	Embryonic stem cell	Male
CVCL_A1S4	SEES3-1V human FGF10, clone2	Embryonic stem cell	Male
CVCL_A1S5	SEES3-1V human FGF10, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT03347526	PHASE3	SUSPENDED	A Novel Approach to Infantile Spasms
NCT03421496	PHASE3	TERMINATED	A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT02229968	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118144	PHASE2	COMPLETED	Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
NCT00126581	PHASE2	COMPLETED	Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer
NCT00334815	PHASE2	ACTIVE_NOT_RECRUITING	Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT00368992	PHASE2	COMPLETED	S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
NCT00511485	PHASE2	COMPLETED	Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03)
NCT00950365	PHASE2	COMPLETED	Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer
NCT00955305	PHASE2	TERMINATED	Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
NCT01218516	PHASE2	COMPLETED	A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung