COACH syndrome

Summary

COACH syndrome (MONDO:0100349) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 48

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		8	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

48 HPO clinical features (Orphanet curated; top 48 by frequency):

HPO ID	Term	Frequency
HP:0000657	Oculomotor apraxia	Very frequent (80-99%)
HP:0001251	Ataxia	Very frequent (80-99%)
HP:0001252	Hypotonia	Very frequent (80-99%)
HP:0001320	Cerebellar vermis hypoplasia	Very frequent (80-99%)
HP:0002104	Apnea	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0002342	Intellectual disability, moderate	Very frequent (80-99%)
HP:0002612	Congenital hepatic fibrosis	Very frequent (80-99%)
HP:0002793	Abnormal pattern of respiration	Very frequent (80-99%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Very frequent (80-99%)
HP:0005248	Intrahepatic biliary atresia	Very frequent (80-99%)
HP:0007360	Aplasia/Hypoplasia of the cerebellum	Very frequent (80-99%)
HP:0000112	Nephropathy	Frequent (30-79%)
HP:0000276	Long face	Frequent (30-79%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000567	Chorioretinal coloboma	Frequent (30-79%)
HP:0000588	Optic disc coloboma	Frequent (30-79%)
HP:0000612	Iris coloboma	Frequent (30-79%)
HP:0000639	Nystagmus	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001347	Hyperreflexia	Frequent (30-79%)
HP:0004422	Biparietal narrowing	Frequent (30-79%)
HP:0008872	Feeding difficulties in infancy	Frequent (30-79%)
HP:0000003	Multicystic kidney dysplasia	Occasional (5-29%)
HP:0000023	Inguinal hernia	Occasional (5-29%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000202	Orofacial cleft	Occasional (5-29%)
HP:0000238	Hydrocephalus	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000369	Low-set ears	Occasional (5-29%)
HP:0000426	Prominent nasal bridge	Occasional (5-29%)
HP:0000463	Anteverted nares	Occasional (5-29%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000864	Abnormality of the hypothalamus-pituitary axis	Occasional (5-29%)
HP:0001162	Postaxial hand polydactyly	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001337	Tremor	Occasional (5-29%)
HP:0001394	Cirrhosis	Occasional (5-29%)
HP:0001409	Portal hypertension	Occasional (5-29%)
HP:0001744	Splenomegaly	Occasional (5-29%)
HP:0002085	Occipital encephalocele	Occasional (5-29%)
HP:0002269	Abnormality of neuronal migration	Occasional (5-29%)
HP:0002553	Highly arched eyebrow	Occasional (5-29%)
HP:0002650	Scoliosis	Occasional (5-29%)
HP:0002896	Neoplasm of the liver	Occasional (5-29%)
HP:0007370	Aplasia/Hypoplasia of the corpus callosum	Occasional (5-29%)
HP:0100626	Chronic hepatic failure	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	COACH syndrome
Mondo ID	MONDO:0100349
MeSH	C536430
Orphanet	1454
DOID	DOID:0111589
SNOMED CT	721847002
UMLS	C1857662
MedGen	387879
GARD	0001410
Is cancer (heuristic)	no

Also known as: cerebellar vermis hypo/aplasia, oligophrenia, ataxia congenital, coloboma, and hepatic fibrosis · cerebellar vermis hypoplasia-oligophrenia-congenital ataxia-coloboma-hepatic fibrosis · gentile syndrome · Joubert syndrome with congenital hepatic fibrosis · Joubert syndrome with hepatic defect · JS-H

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive cerebellar ataxia › autosomal recessive congenital cerebellar ataxia › Joubert syndrome and related disorders › COACH syndrome

Related subtypes (3): Joubert syndrome with oculorenal defect, Joubert syndrome with ocular defect, Joubert syndrome with Jeune asphyxiating thoracic dystrophy

Subtypes (3): COACH syndrome 2, COACH syndrome 3, COACH syndrome 1

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
41142	NM_003611.3(OFD1):c.710del (p.Lys237fs)	OFD1	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OFD1	Orphanet:244	Primary ciliary dyskinesia
OFD1	Orphanet:2750	Orofaciodigital syndrome type 1
OFD1	Orphanet:2754	Orofaciodigital syndrome type 6
OFD1	Orphanet:475	Isolated Joubert syndrome
OFD1	Orphanet:791	Retinitis pigmentosa

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
OFD1	HGNC:2567	ENSG00000046651	O75665	Centriole and centriolar satellite protein OFD1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OFD1	Centriole and centriolar satellite protein OFD1	Component of the centrioles controlling mother and daughter centrioles length.

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)
OFD1	Other/Unknown	no		LisH, OFD1

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
bronchial epithelial cell	1
cervix squamous epithelium	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OFD1	288	ubiquitous	marker	sperm, bronchial epithelial cell, cervix squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OFD1	2,878

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
OFD1	O75665	68.41

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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
Hedgehog ‘off’ state	1	178.4×	0.009	OFD1
Loss of Nlp from mitotic centrosomes	1	158.6×	0.009	OFD1
Loss of proteins required for interphase microtubule organization from the centrosome	1	158.6×	0.009	OFD1
AURKA Activation by TPX2	1	152.3×	0.009	OFD1
Recruitment of mitotic centrosome proteins and complexes	1	135.9×	0.009	OFD1
Regulation of PLK1 Activity at G2/M Transition	1	126.9×	0.009	OFD1
Recruitment of NuMA to mitotic centrosomes	1	116.5×	0.009	OFD1
Anchoring of the basal body to the plasma membrane	1	113.1×	0.009	OFD1

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
obsolete negative regulation of fibroblast growth factor receptor signaling pathway involved in neural plate anterior/posterior pattern formation	1	8426.0×	6e-04	OFD1
embryonic body morphogenesis	1	2106.5×	0.001	OFD1
epithelial cilium movement involved in determination of left/right asymmetry	1	1296.3×	0.001	OFD1
axoneme assembly	1	543.6×	0.002	OFD1
cilium assembly	1	73.6×	0.014	OFD1

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
OFD1	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	OFD1

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)
OFD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.