Hypogonadotropic hypogonadism 19 with or without anosmia

disease

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Also known as DUSP6 hypogonadotropic hypogonadismHH19hypogonadotropic hypogonadism caused by mutation in DUSP6

Summary

Hypogonadotropic hypogonadism 19 with or without anosmia (MONDO:0014105) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypogonadotropic hypogonadism 19 with or without anosmia
Mondo ID	MONDO:0014105
OMIM	615269
DOID	DOID:0090090
UMLS	C3808981
MedGen	815311
GARD	0015931
Is cancer (heuristic)	no

Also known as: DUSP6 hypogonadotropic hypogonadism · HH19 · hypogonadotropic hypogonadism 19 with or without anosmia · hypogonadotropic hypogonadism caused by mutation in DUSP6

Data availability: 7 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 19 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

7 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1033462	NM_001946.4(DUSP6):c.117C>A (p.Cys39Ter)	DUSP6	Pathogenic	criteria provided, single submitter
50854	NM_001946.4(DUSP6):c.566A>G (p.Asn189Ser)	DUSP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
50855	NM_001946.4(DUSP6):c.545C>T (p.Ser182Phe)	DUSP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029551	NM_001946.4(DUSP6):c.169G>A (p.Ala57Thr)	DUSP6	Uncertain significance	criteria provided, multiple submitters, no conflicts
50857	NM_001946.4(DUSP6):c.229T>A (p.Phe77Ile)	DUSP6	Uncertain significance	criteria provided, multiple submitters, no conflicts
802882	NM_001946.4(DUSP6):c.340G>T (p.Val114Leu)	DUSP6	Benign	criteria provided, multiple submitters, no conflicts
50856	NM_001946.4(DUSP6):c.1037C>T (p.Thr346Met)	POC1B-DUSP6	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
DUSP6	Supportive	Autosomal dominant	hypogonadotropic hypogonadism	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DUSP6	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
DUSP6	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
DUSP6	HGNC:3072	ENSG00000139318	Q16828	Dual specificity protein phosphatase 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DUSP6	Dual specificity protein phosphatase 6	Dual specificity protein phosphatase, which mediates dephosphorylation and inactivation of MAP kinases.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DUSP6	Phosphatase	yes	3.1.3.16	Dual-sp_phosphatase_cat-dom, Tyr_Pase_dom, Rhodanese-like_dom

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
monocyte	1
parotid gland	1
pericardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DUSP6	296	ubiquitous	marker	parotid gland, pericardium, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DUSP6	2,421

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DUSP6	Q16828	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Signaling by MAPK mutants	1	1631.4×	0.002	DUSP6
ERKs are inactivated	1	878.5×	0.002	DUSP6
RAF-independent MAPK1/3 activation	1	634.4×	0.002	DUSP6
Negative regulation of MAPK pathway	1	265.6×	0.004	DUSP6

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of heart growth	1	8426.0×	0.001	DUSP6
response to nitrosative stress	1	4213.0×	0.001	DUSP6
response to growth factor	1	1404.3×	0.003	DUSP6
peptidyl-tyrosine dephosphorylation	1	887.0×	0.003	DUSP6
ERK1 and ERK2 cascade	1	318.0×	0.007	DUSP6
negative regulation of MAPK cascade	1	300.9×	0.007	DUSP6
negative regulation of ERK1 and ERK2 cascade	1	216.1×	0.008	DUSP6
MAPK cascade	1	153.2×	0.010	DUSP6
response to xenobiotic stimulus	1	69.1×	0.019	DUSP6
positive regulation of apoptotic process	1	56.7×	0.021	DUSP6
cell differentiation	1	29.1×	0.037	DUSP6
signal transduction	1	16.1×	0.062	DUSP6

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DUSP6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
DUSP6	38	Binding:37, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DUSP6	3.1.3.16, 3.1.3.48	protein-serine/threonine phosphatase, protein-tyrosine-phosphatase

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	1	DUSP6
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
DUSP6	38	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: DUSP6