FGF9

fibroblast growth factor 9, the group of Receptor ligands|Fibroblast growth factor family

Basic information

Region (hg38): 13:21671073-21704498

Links

ENSG00000102678 ∙ NCBI:2254 ∙ OMIM:600921 ∙ HGNC:3687 ∙ Uniprot:P31371 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple synostoses syndrome 3 (Strong), mode of inheritance: AD
• multiple synostoses syndrome 3 (Moderate), mode of inheritance: AD
• multiple synostoses syndrome (Supportive), mode of inheritance: AD
• multiple synostoses syndrome 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple synostoses syndrome 3	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	19589401

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGF9 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGF9 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				17	4	21
missense	1	1	14	1	1	18
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	1		2
non coding			65	5	37	107
Total	1	1	80	23	42

Variants in FGF9

This is a list of pathogenic ClinVar variants found in the FGF9 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-21671084-C-T		Multiple synostoses syndrome 3	Uncertain significance (Jan 12, 2018)
13-21671117-C-T		Multiple synostoses syndrome 3	Uncertain significance (Jan 13, 2018)
13-21671136-G-T		Multiple synostoses syndrome 3	Uncertain significance (Jan 12, 2018)
13-21671146-G-C		Multiple synostoses syndrome 3	Uncertain significance (Jan 12, 2018)
13-21671187-C-T		Multiple synostoses syndrome 3	Benign (Jan 12, 2018)
13-21671201-C-T		Multiple synostoses syndrome 3	Benign (Jan 13, 2018)
13-21671210-C-T		Multiple synostoses syndrome 3	Uncertain significance (Jan 13, 2018)
13-21671322-A-AT		Symphalangism-brachydactyly syndrome	Uncertain significance (Jun 14, 2016)
13-21671461-A-T		Multiple synostoses syndrome 3	Uncertain significance (Jan 13, 2018)
13-21671484-G-A		Multiple synostoses syndrome 3	Benign (Jan 12, 2018)
13-21671499-C-T		Multiple synostoses syndrome 3	Benign (Jan 12, 2018)
13-21671570-AT-A		Symphalangism-brachydactyly syndrome	Uncertain significance (Jun 14, 2016)
13-21671657-G-A		Multiple synostoses syndrome 3	Uncertain significance (Jan 12, 2018)
13-21671742-A-G		Multiple synostoses syndrome 3	Benign (Jan 13, 2018)
13-21671762-G-T		Multiple synostoses syndrome 3	Uncertain significance (Jan 13, 2018)
13-21671788-C-CT		Symphalangism-brachydactyly syndrome	Benign (Jun 14, 2016)
13-21671788-C-CTT		Symphalangism-brachydactyly syndrome	Benign (Jun 14, 2016)
13-21671795-T-TC		Symphalangism-brachydactyly syndrome	Likely benign (Jun 14, 2016)
13-21671796-T-TC		Symphalangism-brachydactyly syndrome	Uncertain significance (Jun 14, 2016)
13-21671868-C-T		Multiple synostoses syndrome 3	Uncertain significance (Jan 12, 2018)
13-21671875-T-TA		Symphalangism-brachydactyly syndrome	Uncertain significance (Jun 14, 2016)
13-21671923-T-C		Multiple synostoses syndrome 3	Likely pathogenic (May 06, 2021)
13-21671945-C-T			Likely benign (May 23, 2023)
13-21671950-T-A			Uncertain significance (Oct 20, 2021)
13-21671954-G-C			Benign (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGF9	protein_coding	protein_coding	ENST00000382353	3	33116

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.947	0.0528	125746	0	2	125748	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.54	70	117	0.599	0.00000600	1345
Missense in Polyphen		12	39.883	0.30088		436
Synonymous	-0.00622	51	50.9	1.00	0.00000274	415
Loss of Function	2.82	0	9.27	0.00	5.45e-7	107

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.00000881	0.00000879
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, cell differentiation and cell migration. May have a role in glial cell growth and differentiation during development, gliosis during repair and regeneration of brain tissue after damage, differentiation and survival of neuronal cells, and growth stimulation of glial tumors. {ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:8663044}.
• Disease: DISEASE: Multiple synostoses syndrome 3 (SYNS3) [MIM:612961]: A bone disease characterized by multiple progressive joint fusions that commonly involve proximal interphalangeal, tarsal-carpal, humeroradial and cervical spine joints. Additional features can include progressive conductive deafness and facial dysmorphism. {ECO:0000269|PubMed:19589401}. 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);MAPK Signaling Pathway;ESC Pluripotency Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Regulation of Actin Cytoskeleton;FGFR2c ligand binding and activation;FGFR2 ligand binding and activation;FRS-mediated FGFR2 signaling;Negative regulation of FGFR2 signaling;Signaling by FGFR2;FGFR3b ligand binding and activation;Phospholipase C-mediated cascade; FGFR2;FGFR3c ligand binding and activation;SHC-mediated cascade:FGFR2;FRS-mediated FGFR3 signaling;PI-3K cascade:FGFR2;Downstream signaling of activated FGFR2;SHC-mediated cascade:FGFR3;PI-3K cascade:FGFR4;PI-3K cascade:FGFR3;Downstream signaling of activated FGFR3;Disease;Negative regulation of FGFR3 signaling;Signaling by FGFR3;FGFR4 ligand binding and activation;Signal Transduction;FRS-mediated FGFR4 signaling;SHC-mediated cascade:FGFR4;Downstream signaling of activated FGFR4;Negative regulation of FGFR4 signaling;Signaling by FGFR4;Signaling by FGFR;FGFR3 ligand binding and activation;FGFR3 mutant receptor activation;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;Signaling by activated point mutants of FGFR3;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 FGFR3 point mutants in cancer;Signaling by FGFR3 in disease;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 activated point mutants of FGFR1;FGFR1 mutant receptor activation;Signaling by FGFR1 in disease;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Phospholipase C-mediated cascade: FGFR1;Diseases of signal transduction;Downstream signaling of activated FGFR1;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);FGFR1c ligand binding and activation;FGFR1 ligand binding and activation;FRS-mediated FGFR1 signaling;SHC-mediated cascade:FGFR1;PI-3K cascade:FGFR1;Negative regulation of FGFR1 signaling;Signaling by FGFR1;Phospholipase C-mediated cascade; FGFR3;Phospholipase C-mediated cascade; FGFR4 (Consensus)

Recessive Scores

• pRec: 0.315

Intolerance Scores

• rvis_EVS: 0.17
• rvis_percentile_EVS: 65.33

Haploinsufficiency Scores

• pHI: 0.903
• hipred: Y
• hipred_score: 0.875
• ghis: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.454

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgf9
• 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); endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; skeleton phenotype; embryo phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); reproductive 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; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; immune system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;MAPK cascade;angiogenesis;osteoblast differentiation;eye development;positive regulation of mesenchymal cell proliferation;chondrocyte differentiation;protein import into nucleus;signal transduction;cell-cell signaling;positive regulation of cell population proliferation;fibroblast growth factor receptor signaling pathway;male gonad development;regulation of signaling receptor activity;positive regulation of gene expression;peptidyl-tyrosine phosphorylation;substantia nigra development;negative regulation of Wnt signaling pathway;male sex determination;embryonic limb morphogenesis;positive regulation of vascular endothelial growth factor receptor signaling pathway;positive regulation of activin receptor signaling pathway;phosphatidylinositol-3-phosphate biosynthetic process;inner ear morphogenesis;positive regulation of MAPK cascade;positive regulation of smoothened signaling pathway;phosphatidylinositol phosphorylation;regulation of timing of cell differentiation;embryonic digestive tract development;embryonic skeletal system development;positive regulation of epithelial cell proliferation;positive regulation of cell division;positive regulation of protein kinase B signaling;positive regulation of cardiac muscle cell proliferation;lung-associated mesenchyme development;positive regulation of canonical Wnt signaling pathway;positive regulation of vascular smooth muscle cell proliferation;positive regulation of vascular associated smooth muscle cell migration;negative regulation of vascular smooth muscle cell differentiation involved in phenotypic switching
• Cellular component: extracellular region;basement membrane;extracellular space;cytoplasm
• Molecular function: protein tyrosine kinase activity;Ras guanyl-nucleotide exchange factor activity;fibroblast growth factor receptor binding;growth factor activity;heparin binding;1-phosphatidylinositol-3-kinase activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity