Hypogonadotropic hypogonadism 18 with or without anosmia

disease

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Also known as HH18hypogonadotropic hypogonadism 18 with or without anosmia, Autosomal recessive, Autosomal dominant, Digenic dominanthypogonadotropic hypogonadism caused by mutation in IL17RDIL17RD hypogonadotropic hypogonadism

Summary

Hypogonadotropic hypogonadism 18 with or without anosmia (MONDO:0014103) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypogonadotropic hypogonadism 18 with or without anosmia
Mondo ID	MONDO:0014103
OMIM	615267
DOID	DOID:0090076
UMLS	C3808975
MedGen	815305
GARD	0015929
Is cancer (heuristic)	no

Also known as: HH18 · hypogonadotropic hypogonadism 18 with or without anosmia · hypogonadotropic hypogonadism 18 with or without anosmia, Autosomal recessive, Autosomal dominant, Digenic dominant · hypogonadotropic hypogonadism caused by mutation in IL17RD · IL17RD hypogonadotropic hypogonadism

Data availability: 15 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 18 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

15 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 4 benign, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4277795	NM_017563.5(IL17RD):c.1358C>T (p.Ala453Val)	IL17RD	Likely pathogenic	criteria provided, single submitter
1029472	NM_017563.5(IL17RD):c.1373C>G (p.Ala458Gly)	IL17RD	Uncertain significance	criteria provided, multiple submitters, no conflicts
1305375	NM_017563.5(IL17RD):c.715G>A (p.Glu239Lys)	IL17RD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2370394	NM_017563.5(IL17RD):c.1705C>T (p.Pro569Ser)	IL17RD	Uncertain significance	criteria provided, multiple submitters, no conflicts
2509425	NM_017563.5(IL17RD):c.56A>G (p.Asn19Ser)	IL17RD	Uncertain significance	criteria provided, multiple submitters, no conflicts
3731393	NM_017563.5(IL17RD):c.8C>G (p.Pro3Arg)	IL17RD	Uncertain significance	criteria provided, single submitter
3891379	NM_017563.5(IL17RD):c.1645A>G (p.Met549Val)	IL17RD	Uncertain significance	criteria provided, single submitter
3891380	NM_017563.5(IL17RD):c.2101G>A (p.Gly701Ser)	IL17RD	Uncertain significance	criteria provided, single submitter
3891381	NM_017563.5(IL17RD):c.826A>G (p.Thr276Ala)	IL17RD	Uncertain significance	criteria provided, single submitter
4538414	NM_017563.5(IL17RD):c.439T>C (p.Ser147Pro)	IL17RD	Uncertain significance	no assertion criteria provided
1183074	NM_017563.5(IL17RD):c.764C>T (p.Thr255Met)	IL17RD	Benign	criteria provided, multiple submitters, no conflicts
1224839	NM_017563.5(IL17RD):c.1531T>C (p.Leu511=)	IL17RD	Benign	criteria provided, multiple submitters, no conflicts
1243386	NM_017563.5(IL17RD):c.660T>C (p.His220=)	IL17RD	Benign	criteria provided, multiple submitters, no conflicts
1292703	NM_017563.5(IL17RD):c.868+29T>C	IL17RD	Benign	criteria provided, multiple submitters, no conflicts
3242533	NM_017563.5(IL17RD):c.1992C>G (p.Ile664Met)	IL17RD	Likely benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
IL17RD	Limited	Autosomal dominant	hypogonadotropic hypogonadism 18 with or without anosmia	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IL17RD	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
IL17RD	HGNC:17616	ENSG00000144730	Q8NFM7	Interleukin-17 receptor D	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IL17RD	Interleukin-17 receptor D	Feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation.

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)
IL17RD	Other/Unknown	no		SEFIR_dom, IL17R_D_N, Toll_tir_struct_dom_sf

Expression context

Cohort genes with no expression data: 0.

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
mammary duct	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IL17RD	236	broad	yes	secondary oocyte, oocyte, mammary duct

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL17RD	981

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IL17RD	Q8NFM7	69.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
MAP2K and MAPK activation	1	285.5×	0.004	IL17RD

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of epithelial to mesenchymal transition	1	411.0×	0.005	IL17RD
negative regulation of transforming growth factor beta receptor signaling pathway	1	173.7×	0.006	IL17RD

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
IL17RD	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	IL17RD

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)
IL17RD	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: IL17RD