Hypogonadotropic hypogonadism 17 with or without anosmia

disease

On this page

Also known as HH17hypogonadotropic hypogonadism caused by mutation in SPRY4SPRY4 hypogonadotropic hypogonadism

Summary

Hypogonadotropic hypogonadism 17 with or without anosmia (MONDO:0014102) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypogonadotropic hypogonadism 17 with or without anosmia
Mondo ID	MONDO:0014102
OMIM	615266
DOID	DOID:0090079
UMLS	C3808971
MedGen	815301
GARD	0015928
Is cancer (heuristic)	no

Also known as: HH17 · hypogonadotropic hypogonadism 17 with or without anosmia · hypogonadotropic hypogonadism caused by mutation in SPRY4 · SPRY4 hypogonadotropic hypogonadism

Data availability: 8 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Kallmann syndrome › hypogonadotropic hypogonadism 17 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

8 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 conflicting classifications of pathogenicity, 1 benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
50875	NM_001127496.3(SPRY4):c.46G>A (p.Val16Ile)	SPRY4	Pathogenic	no assertion criteria provided
50872	NM_001127496.3(SPRY4):c.461A>G (p.Lys154Arg)	SPRY4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
50874	NM_001127496.3(SPRY4):c.653C>A (p.Ser218Tyr)	SPRY4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2582723	NM_001127496.3(SPRY4):c.278G>A (p.Ser93Asn)	SPRY4	Uncertain significance	criteria provided, single submitter
3169424	NM_001127496.3(SPRY4):c.478G>A (p.Glu160Lys)	SPRY4	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892541	NM_001127496.3(SPRY4):c.766G>A (p.Gly256Ser)	SPRY4	Uncertain significance	criteria provided, single submitter
4813425	NM_001127496.3(SPRY4):c.541del (p.Val181fs)	SPRY4	Uncertain significance	criteria provided, single submitter
50873	NM_001127496.3(SPRY4):c.841G>A (p.Val281Ile)	SPRY4	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 3 · 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
SPRY4	Moderate	Autosomal dominant	hypogonadotropic hypogonadism 17 with or without anosmia	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SPRY4	Orphanet:363494	Non-seminomatous germ cell tumor of testis
SPRY4	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
SPRY4	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
SPRY4	HGNC:15533	ENSG00000187678	Q9C004	Protein sprouty homolog 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SPRY4	Protein sprouty homolog 4	Suppresses the insulin receptor and EGFR-transduced MAPK signaling pathway, but does not inhibit MAPK activation by a constitutively active mutant Ras.

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)
SPRY4	Other/Unknown	no		Sprouty, Sprouty_domain

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
ascending aorta	1
left coronary artery	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SPRY4	219	ubiquitous	marker	left coronary artery, right lung, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SPRY4	1,118

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SPRY4	Q9C004	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
negative regulation of substrate adhesion-dependent cell spreading	1	1123.5×	0.002	SPRY4
negative regulation of fibroblast growth factor receptor signaling pathway	1	1053.2×	0.002	SPRY4
animal organ development	1	732.7×	0.002	SPRY4
negative regulation of Ras protein signal transduction	1	674.1×	0.002	SPRY4
negative regulation of ERK1 and ERK2 cascade	1	216.1×	0.006	SPRY4
cellular response to leukemia inhibitory factor	1	159.0×	0.006	SPRY4

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
SPRY4	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	SPRY4

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)
SPRY4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: SPRY4