Central hypoventilation syndrome, congenital, 3

Summary

Central hypoventilation syndrome, congenital, 3 (MONDO:0030539) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	central hypoventilation syndrome, congenital, 3
Mondo ID	MONDO:0030539
OMIM	619483
UMLS	C5561964
MedGen	1794174
Is cancer (heuristic)	no

Also known as: CCHS3 · central hypoventilation syndrome, congenital, 3

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

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, 3

Related subtypes (2): central hypoventilation syndrome, congenital, 2, and autonomic dysfunction, 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

2 retrieved; paginated sample, class counts are floors:

1 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1283920	LBX1, 1-BP DEL, 697T	LBX1	Pathogenic	no assertion criteria provided
4532288	NM_006562.5(LBX1):c.707del (p.Val236fs)	LBX1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
LBX1	Moderate	Autosomal recessive	central hypoventilation syndrome, congenital, 3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LBX1	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
LBX1	HGNC:16960	ENSG00000138136	P52954	Transcription factor LBX1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LBX1	Transcription factor LBX1	Transcription factor required for the development of GABAergic interneurons in the dorsal horn of the spinal cord and migration and further development of hypaxial muscle precursor cells for limb muscles, diaphragm and hypoglossal cord.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LBX1	Transcription factor	no		HTH_motif, HD, Homeodomain-like_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
gastrocnemius	1
hindlimb stylopod muscle	1
muscle of leg	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LBX1	28		yes	gastrocnemius, muscle of leg, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LBX1	750

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LBX1	P52954	68.61

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
spinal cord association neuron specification	1	16852.0×	2e-04	LBX1
negative regulation of glutamatergic neuron differentiation	1	16852.0×	2e-04	LBX1
glutamatergic neuron differentiation	1	16852.0×	2e-04	LBX1
neuron fate determination	1	2106.5×	0.001	LBX1
spinal cord motor neuron differentiation	1	936.2×	0.002	LBX1
heart looping	1	267.5×	0.007	LBX1
muscle organ development	1	166.8×	0.009	LBX1
anatomical structure morphogenesis	1	139.3×	0.010	LBX1
cell population proliferation	1	102.8×	0.012	LBX1
negative regulation of cell population proliferation	1	42.1×	0.026	LBX1
regulation of transcription by RNA polymerase II	1	11.7×	0.086	LBX1

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
LBX1	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	LBX1

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)
LBX1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.