Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction

Summary

Central hypoventilation syndrome, congenital, 2, and autonomic dysfunction (MONDO:0030537) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	central hypoventilation syndrome, congenital, 2, and autonomic dysfunction
Mondo ID	MONDO:0030537
OMIM	619482
UMLS	C5561963
MedGen	1794173
Is cancer (heuristic)	no

Also known as: CCHS2 · central hypoventilation syndrome, congenital, 2, and autonomic dysfunction

Data availability: 14 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › central hypoventilation syndrome, congenital › central hypoventilation syndrome, congenital, 2, and autonomic dysfunction

Related subtypes (2): central hypoventilation syndrome, congenital, 3, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease

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

14 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 likely benign, 2 likely pathogenic, 1 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1210289	NM_001101421.4(MYO1H):c.2572del (p.Arg858fs)	MYO1H	Pathogenic	no assertion criteria provided
1701926	NM_001101421.4(MYO1H):c.2454+1G>A	MYO1H	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4292641	NM_001101421.4(MYO1H):c.2427G>A (p.Trp809Ter)	MYO1H	Likely pathogenic	criteria provided, single submitter
4688041	NM_001101421.4(MYO1H):c.263del (p.Val88fs)	MYO1H	Likely pathogenic	criteria provided, single submitter
2227557	NM_001101421.4(MYO1H):c.2234G>A (p.Arg745His)	MYO1H	Uncertain significance	criteria provided, multiple submitters, no conflicts
2433967	NM_001101421.4(MYO1H):c.1036-1G>T	MYO1H	Uncertain significance	criteria provided, multiple submitters, no conflicts
3065502	NM_001101421.4(MYO1H):c.2965_2967del (p.Glu989del)	MYO1H	Uncertain significance	criteria provided, single submitter
3779998	NM_001101421.4(MYO1H):c.1528C>T (p.Arg510Ter)	MYO1H	Uncertain significance	criteria provided, single submitter
3779999	NM_001101421.4(MYO1H):c.2538+3A>T	MYO1H	Uncertain significance	criteria provided, single submitter
4278440	NM_001101421.4(MYO1H):c.3094-1G>T	MYO1H	Uncertain significance	criteria provided, single submitter
4292853	NM_001101421.4(MYO1H):c.1695_1697del (p.Glu566del)	MYO1H	Uncertain significance	criteria provided, single submitter
1341353	NM_001101421.3(MYO1H):c.1784del	MYO1H	Likely benign	criteria provided, single submitter
1341354	NM_001101421.4(MYO1H):c.3067AAAAAT[1] (p.1023KN[1])	MYO1H	Likely benign	criteria provided, single submitter
4681180	NM_001101421.4(MYO1H):c.1300C>T (p.Gln434Ter)	MYO1H	Likely benign	criteria provided, single submitter

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
MYO1H	Supportive	Autosomal dominant	congenital central hypoventilation syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO1H	Orphanet:661	Congenital central hypoventilation 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
MYO1H	HGNC:13879	ENSG00000174527	Q8N1T3	Unconventional myosin-Ih	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYO1H	Unconventional myosin-Ih	Myosins are actin-based motor molecules with ATPase activity.

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)
MYO1H	Other/Unknown	no		Myosin_head_motor_dom-like, Myosin_TH1, 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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYO1H	156		marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYO1H	640

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYO1H	Q8N1T3	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 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
actin filament-based movement	1	802.5×	0.004	MYO1H
actin filament organization	1	118.7×	0.011	MYO1H
endocytosis	1	95.2×	0.011	MYO1H

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
MYO1H	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	MYO1H

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)
MYO1H	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.