Hypogonadotropic hypogonadism 20 with or without anosmia

Summary

Hypogonadotropic hypogonadism 20 with or without anosmia (MONDO:0014106) is a disease caused by FGF17 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FGF17 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypogonadotropic hypogonadism 20 with or without anosmia
Mondo ID	MONDO:0014106
OMIM	615270
DOID	DOID:0090082
UMLS	C3808983
MedGen	815313
GARD	0015932
Is cancer (heuristic)	no

Also known as: FGF17 hypogonadotropic hypogonadism · HH20 · hypogonadotropic hypogonadism 20 with or without anosmia · hypogonadotropic hypogonadism caused by mutation in FGF17

Data availability: 3 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Kallmann syndrome › hypogonadotropic hypogonadism 20 with or without anosmia

Related subtypes (17): hypogonadotropic hypogonadism 2 with or without anosmia, hypogonadotropic hypogonadism 3 with or without anosmia, hypogonadotropic hypogonadism 1 with or without anosmia, hypogonadotropic hypogonadism 4 with or without anosmia, hypogonadotropic hypogonadism 5 with or without anosmia, hypogonadotropic hypogonadism 6 with or without anosmia, hypogonadotropic hypogonadism 8 with or without anosmia, hypogonadotropic hypogonadism 9 with or without anosmia, hypogonadotropic hypogonadism 11 with or without anosmia, hypogonadotropic hypogonadism 14 with or without anosmia, hypogonadotropic hypogonadism 15 with or without anosmia, hypogonadotropic hypogonadism 16 with or without anosmia, hypogonadotropic hypogonadism 17 with or without anosmia, hypogonadotropic hypogonadism 18 with or without anosmia, hypogonadotropic hypogonadism 19 with or without anosmia, hypogonadotropic hypogonadism 21 with or without anosmia, hypogonadotropic hypogonadism 22 with or without anosmia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
50858	NM_003867.4(FGF17):c.323T>C (p.Ile108Thr)	FGF17	risk factor	no assertion criteria provided
4072421	NM_003867.4(FGF17):c.359C>T (p.Pro120Leu)	FGF17	Uncertain significance	criteria provided, single submitter
50860	NM_003867.4(FGF17):c.560A>G (p.Asn187Ser)	FGF17	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FGF17	Strong	Autosomal dominant	hypogonadotropic hypogonadism 20 with or without anosmia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGF17	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGF17	Orphanet:478	Kallmann syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGF17	HGNC:3673	ENSG00000158815	O60258	Fibroblast growth factor 17	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FGF17	Fibroblast growth factor 17	Plays an important role in the regulation of embryonic development and as signaling molecule in the induction and patterning of the embryonic brain.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGF17	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGF17	154	tissue_specific	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGF17	3,908

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FGF17	O60258	86.39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
FGFR3b ligand binding and activation	1	1631.4×	0.003	FGF17
Signaling by activated point mutants of FGFR1	1	951.7×	0.003	FGF17
Signaling by activated point mutants of FGFR3	1	951.7×	0.003	FGF17
FGFR3c ligand binding and activation	1	878.5×	0.003	FGF17
FGFR2c ligand binding and activation	1	878.5×	0.003	FGF17
Phospholipase C-mediated cascade; FGFR3	1	878.5×	0.003	FGF17
FGFRL1 modulation of FGFR1 signaling	1	878.5×	0.003	FGF17
FGFR4 ligand binding and activation	1	815.7×	0.003	FGF17
FGFR1c ligand binding and activation	1	761.3×	0.003	FGF17
Phospholipase C-mediated cascade; FGFR4	1	761.3×	0.003	FGF17
Activated point mutants of FGFR2	1	671.8×	0.003	FGF17
Phospholipase C-mediated cascade: FGFR1	1	671.8×	0.003	FGF17
Phospholipase C-mediated cascade; FGFR2	1	634.4×	0.003	FGF17
PI-3K cascade:FGFR3	1	634.4×	0.003	FGF17
SHC-mediated cascade:FGFR3	1	601.0×	0.003	FGF17
PI-3K cascade:FGFR4	1	571.0×	0.003	FGF17
Downstream signaling of activated FGFR1	1	543.8×	0.003	FGF17
FRS-mediated FGFR3 signaling	1	543.8×	0.003	FGF17
SHC-mediated cascade:FGFR4	1	543.8×	0.003	FGF17
PI-3K cascade:FGFR1	1	519.1×	0.003	FGF17
SHC-mediated cascade:FGFR1	1	496.5×	0.003	FGF17
PI-3K cascade:FGFR2	1	496.5×	0.003	FGF17
FRS-mediated FGFR4 signaling	1	496.5×	0.003	FGF17
Signaling by FGFR3 in disease	1	496.5×	0.003	FGF17
SHC-mediated cascade:FGFR2	1	475.8×	0.003	FGF17
FRS-mediated FGFR1 signaling	1	456.8×	0.003	FGF17
FRS-mediated FGFR2 signaling	1	439.2×	0.003	FGF17
Negative regulation of FGFR3 signaling	1	439.2×	0.003	FGF17
Negative regulation of FGFR4 signaling	1	407.9×	0.003	FGF17
Negative regulation of FGFR1 signaling	1	368.4×	0.003	FGF17

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast growth factor receptor signaling pathway	1	285.6×	0.017	FGF17
neurogenesis	1	208.1×	0.017	FGF17
regulation of cell migration	1	157.5×	0.017	FGF17
positive regulation of MAPK cascade	1	80.6×	0.023	FGF17
cell-cell signaling	1	69.6×	0.023	FGF17
nervous system development	1	45.9×	0.029	FGF17
positive regulation of cell population proliferation	1	33.6×	0.034	FGF17
signal transduction	1	16.1×	0.062	FGF17

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGF17	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	FGF17

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FGF17	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.