FGF17

fibroblast growth factor 17, the group of Fibroblast growth factor family

Basic information

Region (hg38): 8:22042397-22048809

Links

ENSG00000158815 ∙ NCBI:8822 ∙ OMIM:603725 ∙ HGNC:3673 ∙ Uniprot:O60258 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Kallmann syndrome (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism (Supportive), mode of inheritance: AD
• hypogonadotropic hypogonadism 20 with or without anosmia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypogonadotropic hypogonadism 20, with or without anosmia	AD/Multigenic	Endocrine	In Hypogonadotropic hypogonadism, surveillance in adolescence related to sexual maturation is indicated, as is monitoring of bone mineral density in order to allow early detection and treatment of disease; In order to induce and maintain secondary sex characteristics, gradually increasing doses of gonadal steroids (females: estrogen/progestin; males: testosterone/hCG) can be beneficial; Related to fertility, endocrinologic therapy (females: recombinant hCG or pulsatile GnRH therapy; males: hCG/HMG/recombinant FSH or pulsatile GnRH therapy) may be effective, though IVF may be required	Craniofacial; Endocrine; Musculoskeletal; Neurologic	6881209; 23643382
Relatively complex genetic models of disease have been described (eg, involving variants in other FGF8-network-associated genes)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FGF17 gene.

• not provided (31 variants)
• Inborn genetic diseases (6 variants)
• not specified (1 variants)
• FGF17-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGF17 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				8	3	11
missense			10	1		11
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding				6	6	12
Total	0	0	10	15	9

Variants in FGF17

This is a list of pathogenic ClinVar variants found in the FGF17 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-22042640-T-A			Benign (Oct 05, 2018)
8-22042891-G-A			Likely benign (Nov 08, 2018)
8-22042940-C-A			Likely benign (May 25, 2018)
8-22042941-C-T		not specified	Uncertain significance (May 06, 2022)
8-22042942-G-A		not specified	Uncertain significance (Aug 08, 2022)
8-22042978-T-A			Likely benign (Oct 08, 2022)
8-22042994-C-G			Benign (Apr 09, 2019)
8-22043188-G-A			Benign (Dec 31, 2019)
8-22043238-C-T			Likely benign (Jun 28, 2019)
8-22043246-A-G			Benign (Aug 09, 2018)
8-22045805-G-A			Benign (Aug 30, 2018)
8-22045924-C-T			Likely benign (Jun 28, 2019)
8-22046107-C-T			Likely benign (Sep 13, 2022)
8-22046108-G-A			Likely benign (Nov 02, 2023)
8-22046128-G-T			Likely benign (Feb 07, 2018)
8-22046173-C-T			Likely benign (May 11, 2022)
8-22046200-C-T			Benign (Dec 31, 2019)
8-22046248-C-T			Likely benign (Jun 02, 2022)
8-22046253-G-A		not specified	Uncertain significance (Oct 26, 2022)
8-22046263-C-T			Benign (Mar 15, 2022)
8-22046278-C-T			Likely benign (Apr 12, 2023)
8-22046282-A-G		not specified	Uncertain significance (Aug 19, 2023)
8-22046298-G-A			Benign (Aug 17, 2023)
8-22046518-C-A			Likely benign (Oct 11, 2023)
8-22046533-T-C		not specified	Uncertain significance (Jul 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGF17	protein_coding	protein_coding	ENST00000359441	5	6412

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.956	0.0438	125574	0	3	125577	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.85	89	154	0.579	0.0000101	1416
Missense in Polyphen		18	61.693	0.29177		519
Synonymous	-0.207	65	62.9	1.03	0.00000418	419
Loss of Function	2.90	0	9.79	0.00	4.17e-7	110

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	0.00	0.00
European (Non-Finnish)	0.0000269	0.0000264
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 and as signaling molecule in the induction and patterning of the embryonic brain. Required for normal brain development. {ECO:0000269|PubMed:16597617}.
• Disease: DISEASE: Hypogonadotropic hypogonadism 20 with or without anosmia (HH20) [MIM:615270]: A disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic- pituitary axis. In some cases, it is associated with non- reproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss. Anosmia or hyposmia is related to the absence or hypoplasia of the olfactory bulbs and tracts. Hypogonadism is due to deficiency in gonadotropin-releasing hormone and probably results from a failure of embryonic migration of gonadotropin-releasing hormone-synthesizing neurons. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism is referred to as Kallmann syndrome, whereas in the presence of a normal sense of smell, it has been termed normosmic idiopathic hypogonadotropic hypogonadism (nIHH). {ECO:0000269|PubMed:23643382}. Note=The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FGF17 also have a mutation in another HH-associated gene including FGFR1, HS6ST1 and FLRT3 (PubMed:23643382). {ECO:0000269|PubMed:23643382}.
• 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;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;Phospholipase C-mediated cascade; FGFR3;Phospholipase C-mediated cascade; FGFR4 (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.0960
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.980
• hipred: Y
• hipred_score: 0.809
• ghis: 0.705

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.394

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgf17
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: MAPK cascade;signal transduction;cell-cell signaling;nervous system development;positive regulation of cell population proliferation;fibroblast growth factor receptor signaling pathway;regulation of signaling receptor activity;peptidyl-tyrosine phosphorylation;phosphatidylinositol-3-phosphate biosynthetic process;phosphatidylinositol phosphorylation;positive regulation of protein kinase B signaling
• Cellular component: extracellular region;extracellular space
• Molecular function: protein tyrosine kinase activity;Ras guanyl-nucleotide exchange factor activity;type 1 fibroblast growth factor receptor binding;type 2 fibroblast growth factor receptor binding;growth factor activity;1-phosphatidylinositol-3-kinase activity;phosphatidylinositol-4,5-bisphosphate 3-kinase activity