FGF3

fibroblast growth factor 3, the group of Receptor ligands|Fibroblast growth factor family

Basic information

Region (hg38): 11:69809968-69819416

Previous symbols: [ "INT2" ]

Links

ENSG00000186895 ∙ NCBI:2248 ∙ OMIM:164950 ∙ HGNC:3681 ∙ Uniprot:P11487 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• deafness with labyrinthine aplasia, microtia, and microdontia (Strong), mode of inheritance: AR
• deafness with labyrinthine aplasia, microtia, and microdontia (Definitive), mode of inheritance: AR
• deafness with labyrinthine aplasia, microtia, and microdontia (Strong), mode of inheritance: AR
• deafness with labyrinthine aplasia, microtia, and microdontia (Supportive), mode of inheritance: AR
• deafness with labyrinthine aplasia, microtia, and microdontia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, congenital with inner ear agenesis, microtia, and microdontia	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental	17236138; 18435799; 18701883; 21480479
The condition may typically be recognizable from physical examination

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGF3 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGF3 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			1	17	2	20
missense		3	38	1	1	43
nonsense	1	2				3
start loss						0
frameshift		2				2
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region					1	1
non coding				13	8	21
Total	1	8	40	31	11

Highest pathogenic variant AF is 0.00000656

Variants in FGF3

This is a list of pathogenic ClinVar variants found in the FGF3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-69810045-C-T			Likely benign (Dec 12, 2018)
11-69810334-C-T		Inborn genetic diseases	Uncertain significance (Apr 28, 2022)
11-69810342-G-A		Inborn genetic diseases	Uncertain significance (Oct 20, 2021)
11-69810352-C-T			Uncertain significance (Aug 29, 2022)
11-69810353-G-A			Likely benign (Sep 22, 2023)
11-69810366-A-C			Uncertain significance (Jun 20, 2019)
11-69810374-C-T		FGF3-related disorder	Likely benign (Nov 26, 2019)
11-69810377-G-A			Benign/Likely benign (Jun 30, 2023)
11-69810390-C-T		Inborn genetic diseases	Uncertain significance (Nov 08, 2022)
11-69810396-C-T		FGF3-related disorder	Benign/Likely benign (Dec 22, 2023)
11-69810400-G-A			Likely pathogenic (Apr 18, 2018)
11-69810400-G-T			Likely benign (Jan 19, 2018)
11-69810408-AC-A		Deafness with labyrinthine aplasia, microtia, and microdontia	Pathogenic (Feb 01, 2007)
11-69810435-C-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
11-69810455-C-T		Inborn genetic diseases	Uncertain significance (Oct 12, 2021)
11-69810458-C-T			Likely benign (Sep 22, 2023)
11-69810474-T-A		Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
11-69810481-C-T		Inborn genetic diseases	Uncertain significance (Feb 07, 2023)
11-69810502-A-T			Uncertain significance (Jul 10, 2023)
11-69810513-C-T			Uncertain significance (Aug 04, 2023)
11-69810516-C-T		not specified	Uncertain significance (May 04, 2022)
11-69810518-G-C			Likely benign (Oct 05, 2022)
11-69810527-G-A			Likely benign (Nov 17, 2022)
11-69810541-G-T			Conflicting classifications of pathogenicity (Aug 25, 2023)
11-69810545-C-T			Likely benign (Sep 06, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGF3	protein_coding	protein_coding	ENST00000334134	3	8801

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000931	0.355	125733	0	13	125746	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.118	140	136	1.03	0.0000101	1467
Missense in Polyphen		69	72.347	0.95373		686
Synonymous	-0.00372	60	60.0	1.00	0.00000421	527
Loss of Function	-0.0156	6	5.96	1.01	3.53e-7	71

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000791	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.000100	0.0000980
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 ear development. {ECO:0000269|PubMed:8663044}.
• Disease: DISEASE: Deafness with labyrinthine aplasia, microtia and microdontia (LAMM) [MIM:610706]: Unique autosomal recessive syndrome characterized by type I microtia, microdontia, and profound congenital deafness associated with a complete absence of inner ear structures (Michel aplasia). {ECO:0000269|PubMed:17236138, ECO:0000269|PubMed:18435799}. 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);MECP2 and Associated Rett Syndrome;MAPK Signaling Pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling 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: 0.415

Haploinsufficiency Scores

• pHI: 0.819
• hipred: Y
• hipred_score: 0.800
• ghis: 0.433

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.710

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgf3
• Phenotype: growth/size/body region phenotype; embryo phenotype; skeleton phenotype; immune system phenotype; limbs/digits/tail 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); hearing/vestibular/ear phenotype; normal 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: fgf3
• Affected structure: pharyngeal arch 3-7
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: MAPK cascade;signal transduction;cell-cell signaling;multicellular organism development;positive regulation of cell population proliferation;fibroblast growth factor receptor signaling pathway;anatomical structure morphogenesis;regulation of signaling receptor activity;peptidyl-tyrosine phosphorylation;cell differentiation;phosphatidylinositol-3-phosphate biosynthetic process;phosphatidylinositol phosphorylation;positive regulation of cell division;positive regulation of protein kinase B signaling;negative regulation of cardiac muscle tissue development
• Cellular component: extracellular region
• Molecular function: protein tyrosine kinase activity;Ras guanyl-nucleotide exchange factor activity;fibroblast growth factor receptor binding;protein binding;growth factor activity;1-phosphatidylinositol-3-kinase activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity