FGF10

fibroblast growth factor 10, the group of Receptor ligands|Fibroblast growth factor family

Basic information

Region (hg38): 5:44300246-44389706

Links

ENSG00000070193 ∙ NCBI:2255 ∙ OMIM:602115 ∙ HGNC:3666 ∙ Uniprot:O15520 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• LADD syndrome 1 (Definitive), mode of inheritance: AD
• LADD syndrome (Supportive), mode of inheritance: AD
• aplasia of lacrimal and salivary glands (Supportive), mode of inheritance: AD
• lacrimoauriculodentodigital syndrome 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lacrimoauriculodentodigital syndrome 3	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Dental; Endocrine; Musculoskeletal	15654336; 16501574; 16630169; 17213838

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGF10 gene.

• not provided (37 variants)
• Congenital absence of salivary gland (14 variants)
• Levy-Hollister syndrome (12 variants)
• Inborn genetic diseases (6 variants)
• FGF10-related condition (3 variants)
• not specified (2 variants)
• Levy-Hollister syndrome;Congenital absence of salivary gland (2 variants)
• Lung adenocarcinoma (2 variants)
• Orofacial cleft 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGF10 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	6	2	10
missense	1	4	16	2		23
nonsense	1	1				2
start loss		1				1
frameshift	2	5				7
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding	1		1	5	8	15
Total	5	11	20	13	10

Highest pathogenic variant AF is 0.0000460

Variants in FGF10

This is a list of pathogenic ClinVar variants found in the FGF10 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-44303902-T-C		Lung adenocarcinoma	Pathogenic (Jun 06, 2022)
5-44304272-G-T		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)
5-44304990-T-A		Congenital absence of salivary gland • Levy-Hollister syndrome	Benign/Likely benign (Jun 12, 2021)
5-44304998-T-C		Congenital absence of salivary gland • Levy-Hollister syndrome	Conflicting classifications of pathogenicity (Jan 19, 2024)
5-44305002-T-G		Congenital absence of salivary gland • not specified • Congenital absence of salivary gland;Levy-Hollister syndrome • FGF10-related disorder	Benign/Likely benign (Dec 11, 2023)
5-44305009-C-T			Uncertain significance (Oct 24, 2022)
5-44305012-T-C		Congenital absence of salivary gland	Conflicting classifications of pathogenicity (Oct 24, 2022)
5-44305031-G-A		Congenital absence of salivary gland	Benign (Jan 12, 2024)
5-44305041-C-T			Uncertain significance (Jan 14, 2023)
5-44305045-G-A		Congenital absence of salivary gland	Pathogenic/Likely pathogenic (Oct 26, 2018)
5-44305069-C-T		Inborn genetic diseases	Uncertain significance (Jun 30, 2022)
5-44305072-C-T		Levy-Hollister syndrome	Likely pathogenic (Nov 01, 2016)
5-44305081-T-G		Levy-Hollister syndrome • FGF10-related disorder	Uncertain significance (Aug 03, 2023)
5-44305083-A-G			Uncertain significance (Feb 14, 2023)
5-44305095-A-G			Uncertain significance (Nov 20, 2023)
5-44305095-AT-A			Likely pathogenic (Aug 19, 2020)
5-44305155-A-C		Lacrimoauriculodentodigital syndrome 3	Pathogenic (Apr 01, 2006)
5-44305169-C-G		Inborn genetic diseases	Uncertain significance (May 03, 2023)
5-44305207-C-G		Congenital absence of salivary gland	Benign (Jan 31, 2024)
5-44305272-C-T			Likely benign (Apr 20, 2019)
5-44305283-TTC-T			Likely benign (Mar 06, 2019)
5-44305413-T-A			Benign (Nov 08, 2018)
5-44310147-G-A			Likely benign (Feb 11, 2019)
5-44310216-TG-T			Likely benign (Aug 06, 2019)
5-44310390-A-T			Benign (Nov 08, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGF10	protein_coding	protein_coding	ENST00000264664	3	86163

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.938	0.0620	125641	0	1	125642	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.850	80	104	0.766	0.00000485	1360
Missense in Polyphen		14	39.392	0.3554		504
Synonymous	-0.448	46	42.3	1.09	0.00000207	396
Loss of Function	2.75	0	8.82	0.00	4.76e-7	117

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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. {ECO:0000269|PubMed:16597617}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:15654336}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Lacrimo-auriculo-dento-digital syndrome (LADDS) [MIM:149730]: An autosomal dominant ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Lacrimo-auriculo-dento-digital syndrome is 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. {ECO:0000269|PubMed:16501574, ECO:0000269|PubMed:16630169}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Melanoma - Homo sapiens (human);Breast cancer - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Heart Development;Differentiation Pathway;MAPK Signaling Pathway;BMP Signaling Pathway in Eyelid Development;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PTF1A related regulatory pathway;PI3K-Akt Signaling Pathway;Regulation of Actin Cytoskeleton;FGFR2b ligand binding and activation;FGFR2 ligand binding and activation;FRS-mediated FGFR2 signaling;Negative regulation of FGFR2 signaling;Signaling by FGFR2;Phospholipase C-mediated cascade; FGFR2;SHC-mediated cascade:FGFR2;PI-3K cascade:FGFR2;Downstream signaling of activated FGFR2;Disease;Signal Transduction;Signaling by FGFR;PI3K Cascade;IRS-mediated signalling;Insulin receptor signalling cascade;Activated point mutants of FGFR2;Signaling by Insulin receptor;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;FGF;Signaling by FGFR2 in disease;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;FGFR2 mutant receptor activation;Signaling by FGFR in disease;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;GPCR signaling-G alpha i;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Phospholipase C-mediated cascade: FGFR1;Diseases of signal transduction;FGFR1b ligand binding and activation;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);FGFR1 ligand binding and activation;FGFRL1 modulation of FGFR1 signaling;FRS-mediated FGFR1 signaling;SHC-mediated cascade:FGFR1;PI-3K cascade:FGFR1;Negative regulation of FGFR1 signaling;Signaling by FGFR1 (Consensus)

Recessive Scores

• pRec: 0.452

Intolerance Scores

• rvis_EVS: 0.41
• rvis_percentile_EVS: 76.67

Haploinsufficiency Scores

• pHI: 0.610
• hipred: Y
• hipred_score: 0.830
• ghis: 0.399

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.831

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fgf10
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; reproductive system phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype; cellular phenotype; skeleton phenotype; renal/urinary system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: fgf10b
• Affected structure: exocrine pancreas
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: establishment of mitotic spindle orientation;MAPK cascade;activation of MAPK activity;angiogenesis;metanephros development;organ induction;mesonephros development;blood vessel remodeling;metanephros morphogenesis;determination of left/right symmetry;salivary gland development;negative regulation of cell population proliferation;fibroblast growth factor receptor signaling pathway;regulation of smoothened signaling pathway;embryonic pattern specification;regulation of signaling receptor activity;epithelial cell migration;positive regulation of epithelial cell migration;positive regulation of keratinocyte proliferation;peptidyl-tyrosine phosphorylation;pituitary gland development;embryonic genitalia morphogenesis;thyroid gland development;otic vesicle formation;positive regulation of vascular endothelial growth factor receptor signaling pathway;pancreas development;hair follicle morphogenesis;embryonic camera-type eye development;actin cytoskeleton reorganization;response to estradiol;response to lipopolysaccharide;positive regulation of ATPase activity;lacrimal gland development;regulation of activin receptor signaling pathway;protein localization to cell surface;somatic stem cell population maintenance;phosphatidylinositol-3-phosphate biosynthetic process;wound healing;tissue regeneration;odontogenesis of dentin-containing tooth;muscle cell fate commitment;positive regulation of MAPK cascade;keratinocyte proliferation;negative regulation of cell differentiation;positive regulation of DNA repair;positive regulation of DNA replication;positive regulation of Notch signaling pathway;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of Ras protein signal transduction;phosphatidylinositol phosphorylation;regulation of saliva secretion;positive regulation of fibroblast proliferation;spleen development;thymus development;embryonic digestive tract morphogenesis;branching morphogenesis of an epithelial tube;female genitalia morphogenesis;male genitalia morphogenesis;positive regulation of lymphocyte proliferation;epithelial cell proliferation;urothelial cell proliferation;positive regulation of urothelial cell proliferation;positive regulation of epithelial cell proliferation;positive regulation of peptidyl-tyrosine phosphorylation;white fat cell differentiation;positive chemotaxis;induction of positive chemotaxis;smooth muscle cell differentiation;positive regulation of keratinocyte migration;positive regulation of protein kinase B signaling;radial glial cell differentiation;positive regulation of epithelial cell proliferation involved in wound healing;limb bud formation;lung epithelium development;lung saccule development;bronchiole morphogenesis;bud outgrowth involved in lung branching;bud elongation involved in lung branching;mesenchymal-epithelial cell signaling involved in lung development;type II pneumocyte differentiation;prostatic bud formation;fibroblast growth factor receptor signaling pathway involved in mammary gland specification;mammary gland bud formation;submandibular salivary gland formation;epithelial cell proliferation involved in salivary gland morphogenesis;regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling;branch elongation involved in salivary gland morphogenesis;semicircular canal fusion;mesenchymal cell differentiation involved in lung development;secretion by lung epithelial cell involved in lung growth;lung proximal/distal axis specification;tear secretion;positive regulation of white fat cell proliferation;ERK1 and ERK2 cascade;positive regulation of ERK1 and ERK2 cascade;Harderian gland development;negative regulation of cell cycle arrest;positive regulation of hair follicle cell proliferation;positive regulation of canonical Wnt signaling pathway;positive regulation of G1/S transition of mitotic cell cycle;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: extracellular region;extracellular space;nucleus;plasma membrane;cell surface;collagen-containing extracellular matrix
• Molecular function: protein tyrosine kinase activity;Ras guanyl-nucleotide exchange factor activity;fibroblast growth factor receptor binding;type 2 fibroblast growth factor receptor binding;protein binding;growth factor activity;heparin binding;1-phosphatidylinositol-3-kinase activity;chemoattractant activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity