Heterotaxy, visceral, 9, autosomal, with male infertility

Summary

Heterotaxy, visceral, 9, autosomal, with male infertility (MONDO:0030070) is a disease caused by MNS1 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: MNS1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	heterotaxy, visceral, 9, autosomal, with male infertility
Mondo ID	MONDO:0030070
OMIM	618948
DOID	DOID:0051023
UMLS	C5394551
MedGen	1717772
GARD	0025522
Is cancer (heuristic)	no

Also known as: HETEROTAXY, VISCERAL, 9, AUTOSOMAL, WITH MALE INFERTILITY · heterotaxy, visceral, 9, autosomal, with male infertility · HTX9

Data availability: 12 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › visceral heterotaxy › heterotaxy, visceral, 9, autosomal, with male infertility

Related subtypes (18): right atrial isomerism, situs inversus, heterotaxy, visceral, 1, X-linked, laterality defects, autosomal dominant, heterotaxy, visceral, 2, autosomal, heterotaxy, visceral, 3, autosomal, heterotaxy, visceral, 4, autosomal, heterotaxy, visceral, 6, autosomal, heterotaxy, visceral, 7, autosomal, heterotaxy, visceral, 8, autosomal, dextrocardia, levocardia, heterotaxy, visceral, 10, autosomal, with male infertility, heterotaxy, visceral, 11, autosomal, with male infertility, heterotaxy, visceral, 5, autosomal, heterotaxy, visceral, 12, autosomal, heterotaxy, visceral, 13, autosomal, heterotaxy, visceral, 14, autosomal

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

12 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 likely pathogenic, 2 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3024123	NM_018365.4(MNS1):c.605dup (p.Gln203fs)	MNS1	Pathogenic	no assertion criteria provided
3024124	NM_018365.4(MNS1):c.68_69delinsAG (p.Cys23Ter)	MNS1	Pathogenic	no assertion criteria provided
973691	NM_018365.4(MNS1):c.724C>T (p.Arg242Ter)	TEX9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1709310	NM_018365.4(MNS1):c.538C>T (p.Arg180Ter)	MNS1	Likely pathogenic	criteria provided, single submitter
2775454	NM_018365.4(MNS1):c.675AGA[1] (p.Glu226del)	MNS1	Likely pathogenic	criteria provided, single submitter
3779883	NM_018365.4(MNS1):c.508dup (p.Ile170fs)	MNS1	Likely pathogenic	criteria provided, single submitter
635005	NM_018365.4(MNS1):c.407_410del (p.Glu136fs)	MNS1	Likely pathogenic	criteria provided, single submitter
1709309	NM_018365.4(MNS1):c.375G>T (p.Glu125Asp)	MNS1	Uncertain significance	criteria provided, single submitter
2582460	NM_018365.4(MNS1):c.1163G>A (p.Arg388Gln)	MNS1	Uncertain significance	criteria provided, single submitter
3242214	NM_018365.4(MNS1):c.1391C>T (p.Pro464Leu)	MNS1	Uncertain significance	criteria provided, single submitter
4079282	NM_018365.4(MNS1):c.217A>C (p.Ile73Leu)	MNS1	Uncertain significance	criteria provided, single submitter
4532208	NM_018365.4(MNS1):c.10A>T (p.Lys4Ter)	MNS1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 0 · 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
MNS1	Strong	Autosomal recessive	heterotaxy, visceral, 9, autosomal, with male infertility	2

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MNS1	HGNC:29636	ENSG00000138587	Q8NEH6	Meiosis-specific nuclear structural protein 1	gencc,clinvar
TEX9	HGNC:29585	ENSG00000151575	Q8N6V9	Testis-expressed protein 9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MNS1	Meiosis-specific nuclear structural protein 1	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MNS1	Other/Unknown	no		MNS1, TPH_dom
TEX9	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	2
right uterine tube	2
epithelium of bronchus	1
calcaneal tendon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MNS1	227	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, right uterine tube
TEX9	192	ubiquitous	marker	calcaneal tendon, right uterine tube, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MNS1	1,669
TEX9	574

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MNS1	Q8NEH6	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TEX9	Q8N6V9	78.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
left/right axis specification	1	1203.7×	0.003	MNS1
positive regulation of cilium assembly	1	766.0×	0.003	MNS1
cilium organization	1	601.9×	0.003	MNS1
sperm axoneme assembly	1	468.1×	0.003	MNS1
meiotic cell cycle	1	244.2×	0.005	MNS1
flagellated sperm motility	1	117.0×	0.009	MNS1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MNS1	0	0
TEX9	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MNS1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	MNS1, TEX9

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MNS1	1	—
TEX9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.