Hypogonadotropic hypogonadism 15 with or without anosmia

disease

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Also known as HH15HS6ST1 hypogonadotropic hypogonadismhypogonadotropic hypogonadism caused by mutation in HS6ST1

Summary

Hypogonadotropic hypogonadism 15 with or without anosmia (MONDO:0013946) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypogonadotropic hypogonadism 15 with or without anosmia
Mondo ID	MONDO:0013946
OMIM	614880
DOID	DOID:0090075
UMLS	C3553977
MedGen	766891
GARD	0015872
Is cancer (heuristic)	no

Also known as: HH15 · HS6ST1 hypogonadotropic hypogonadism · hypogonadotropic hypogonadism 15 with or without anosmia · hypogonadotropic hypogonadism caused by mutation in HS6ST1

Data availability: 6 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 15 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

6 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2572171	NC_000002.12:g.128262169_128275055dup	HS6ST1	Uncertain significance	criteria provided, single submitter
3891358	NM_004807.3(HS6ST1):c.568C>T (p.Arg190Cys)	HS6ST1	Uncertain significance	criteria provided, single submitter
3891359	NM_004807.3(HS6ST1):c.650C>A (p.Thr217Lys)	HS6ST1	Uncertain significance	criteria provided, single submitter
930865	NM_004807.3(HS6ST1):c.955T>A (p.Tyr319Asn)	HS6ST1	Uncertain significance	criteria provided, single submitter
180161	NM_004807.3(HS6ST1):c.1144C>T (p.Arg382Trp)	HS6ST1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
770340	NM_004807.3(HS6ST1):c.745C>A (p.Arg249Ser)	HS6ST1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
HS6ST1	Supportive	Autosomal dominant	hypogonadotropic hypogonadism	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HS6ST1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
HS6ST1	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
HS6ST1	HGNC:5201	ENSG00000136720	O60243	Heparan-sulfate 6-O-sulfotransferase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HS6ST1	Heparan-sulfate 6-O-sulfotransferase 1	6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.

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)
HS6ST1	Other/Unknown	no		Sulfotransferase, Heparan_SO4-6-sulfoTrfase, P-loop_NTPase

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
ganglionic eminence	1
kidney epithelium	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HS6ST1	258	ubiquitous	marker	kidney epithelium, pancreatic ductal cell, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HS6ST1	807

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HS6ST1	O60243	87.28

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
HS-GAG biosynthesis	1	346.1×	0.003	HS6ST1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
labyrinthine layer blood vessel development	1	802.5×	0.004	HS6ST1
heparan sulfate proteoglycan biosynthetic process	1	561.7×	0.004	HS6ST1
lung alveolus development	1	351.1×	0.005	HS6ST1
neuron development	1	255.3×	0.005	HS6ST1
angiogenesis	1	62.4×	0.016	HS6ST1

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
HS6ST1	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	HS6ST1

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)
HS6ST1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: HS6ST1