Hypogonadotropic hypogonadism 13 with or without anosmia

disease

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Also known as HH13hypogonadotropic hypogonadism caused by mutation in KISS1KISS1 hypogonadotropic hypogonadism

Summary

Hypogonadotropic hypogonadism 13 with or without anosmia (MONDO:0013915) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypogonadotropic hypogonadism 13 with or without anosmia
Mondo ID	MONDO:0013915
OMIM	614842
DOID	DOID:0090073
UMLS	C3541462
MedGen	762090
GARD	0018601
Is cancer (heuristic)	no

Also known as: HH13 · hypogonadotropic hypogonadism 13 with or without anosmia · hypogonadotropic hypogonadism caused by mutation in KISS1 · KISS1 hypogonadotropic hypogonadism

Data availability: 5 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › gonadal disorder › hypogonadism › hypogonadotropic hypogonadism › hypogonadotropic hypogonadism 13 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

5 retrieved; paginated sample, class counts are floors:

2 benign, 1 pathogenic, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
30349	NM_002256.4(KISS1):c.339C>G (p.Asn113Lys)	KISS1	Pathogenic	no assertion criteria provided
3381872	NM_002256.4(KISS1):c.345C>G (p.Asn115Lys)	KISS1	Likely pathogenic	criteria provided, single submitter
1174871	NM_002256.4(KISS1):c.242C>G (p.Pro81Arg)	KISS1	Benign	criteria provided, multiple submitters, no conflicts
403018	NM_002256.4(KISS1):c.417del (p.Ter139TrpextTer?)	KISS1	Benign	criteria provided, multiple submitters, no conflicts
501504	NM_002256.4(KISS1):c.268C>G (p.His90Asp)	KISS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
KISS1	Moderate	Autosomal recessive	hypogonadotropic hypogonadism 13 with or without anosmia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KISS1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
KISS1	Orphanet:650097	Genetic central precocious puberty in male

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
KISS1	HGNC:6341	ENSG00000170498	Q15726	Metastasis-suppressor KiSS-1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KISS1	Metastasis-suppressor KiSS-1	Kisspeptins are ligands for the G-protein coupled receptor KISS1R/GPR54.

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)
KISS1	Other/Unknown	no		Metastasis-suppressor_KiSS-1

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
epithelium of bronchus	1
placenta	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KISS1	105	tissue_specific	marker	placenta, right lobe of liver, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KISS1	2,056

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KISS1	Q15726	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Class A/1 (Rhodopsin-like receptors)	1	74.2×	0.029	KISS1
Peptide ligand-binding receptors	1	74.2×	0.029	KISS1
GPCR ligand binding	1	64.2×	0.029	KISS1
G alpha (q) signalling events	1	57.4×	0.029	KISS1
GPCR downstream signalling	1	43.4×	0.029	KISS1
Signaling by GPCR	1	40.1×	0.029	KISS1
Signal Transduction	1	10.2×	0.098	KISS1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of luteinizing hormone secretion	1	3370.4×	9e-04	KISS1
cytoskeleton organization	1	132.7×	0.011	KISS1
G protein-coupled receptor signaling pathway	1	36.2×	0.028	KISS1

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
KISS1	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	KISS1

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)
KISS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: KISS1