COACH syndrome 2

Summary

COACH syndrome 2 (MONDO:0030859) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 269

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	COACH syndrome 2
Mondo ID	MONDO:0030859
OMIM	619111
UMLS	C5436837
MedGen	1752166
GARD	0016422
Is cancer (heuristic)	no

Also known as: CC2D2A COACH syndrome 2 · COACH2

Data availability: 269 ClinVar variants.

Disease family

Classification path: 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 › COACH syndrome 2

Related subtypes (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

269 retrieved; paginated sample, class counts are floors:

147 uncertain significance, 38 pathogenic/likely pathogenic, 35 conflicting classifications of pathogenicity, 33 likely pathogenic, 13 pathogenic, 2 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1074596	NM_001378615.1(CC2D2A):c.1538G>A (p.Trp513Ter)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
126242	NM_001378615.1(CC2D2A):c.394C>T (p.Arg132Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1297595	NM_001378615.1(CC2D2A):c.712G>T (p.Glu238Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322034	NM_001378615.1(CC2D2A):c.3763C>T (p.Arg1255Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1395827	NM_001378615.1(CC2D2A):c.3688C>T (p.Arg1230Ter)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts
1427276	NM_001378615.1(CC2D2A):c.4522del (p.Ile1508fs)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456425	NM_001378615.1(CC2D2A):c.121C>T (p.Gln41Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
166801	NM_001378615.1(CC2D2A):c.1017+1G>A	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1904397	NM_001378615.1(CC2D2A):c.3535G>T (p.Glu1179Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210609	NM_001378615.1(CC2D2A):c.2683C>T (p.Gln895Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
210612	NM_001378615.1(CC2D2A):c.4465_4468del (p.Asp1489fs)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217597	NM_001378615.1(CC2D2A):c.3850C>T (p.Arg1284Cys)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217602	NM_001378615.1(CC2D2A):c.3055C>T (p.Arg1019Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217604	NM_001378615.1(CC2D2A):c.2999A>T (p.Glu1000Val)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217607	NM_001378615.1(CC2D2A):c.4667A>T (p.Asp1556Val)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
217618	NM_001378615.1(CC2D2A):c.1558C>T (p.Arg520Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2203534	NM_001378615.1(CC2D2A):c.2581G>A (p.Asp861Asn)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2925185	NM_001378615.1(CC2D2A):c.463C>T (p.Gln155Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2934877	NM_001378615.1(CC2D2A):c.715del (p.Met239fs)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2936760	NM_001378615.1(CC2D2A):c.4522dup (p.Ile1508fs)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2938979	NM_001080522.2(CC2D2A):c.3597_3600del	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2940749	NM_001378615.1(CC2D2A):c.2923-1G>A	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2942128	NM_001378615.1(CC2D2A):c.839del (p.Gln280fs)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2954141	NM_001378615.1(CC2D2A):c.2568del (p.Glu857fs)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382631	NM_001378615.1(CC2D2A):c.3613dup (p.Ile1205fs)	CC2D2A	Pathogenic	criteria provided, single submitter
3590278	NM_001378615.1(CC2D2A):c.1363C>T (p.Gln455Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3590387	NM_001378615.1(CC2D2A):c.3280del (p.Leu1094fs)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
411851	NM_001378615.1(CC2D2A):c.1267C>T (p.Arg423Ter)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56297	NM_001378615.1(CC2D2A):c.1339del (p.Ala447fs)	CC2D2A	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56301	NM_001378615.1(CC2D2A):c.3084del (p.Lys1029fs)	CC2D2A	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CC2D2A	Orphanet:1454	Joubert syndrome with hepatic defect
CC2D2A	Orphanet:2318	Joubert syndrome with oculorenal defect
CC2D2A	Orphanet:564	Meckel syndrome
CC2D2A	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
CC2D2A	HGNC:29253	ENSG00000048342	Q9P2K1	Coiled-coil and C2 domain-containing protein 2A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CC2D2A	Coiled-coil and C2 domain-containing protein 2A	Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CC2D2A	Protease	yes		C2_dom, CC2D2AN-C2, C2_domain_sf

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
bronchus	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CC2D2A	247	ubiquitous	marker	right uterine tube, bronchial epithelial cell, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CC2D2A	899

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CC2D2A	Q9P2K1	69.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Anchoring of the basal body to the plasma membrane	1	113.1×	0.014	CC2D2A
Cilium Assembly	1	108.8×	0.014	CC2D2A
Organelle biogenesis and maintenance	1	66.0×	0.015	CC2D2A

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
protein localization to ciliary transition zone	1	2407.4×	0.005	CC2D2A
embryonic brain development	1	802.5×	0.006	CC2D2A
motile cilium assembly	1	581.1×	0.006	CC2D2A
axoneme assembly	1	543.6×	0.006	CC2D2A
camera-type eye development	1	358.6×	0.007	CC2D2A
non-motile cilium assembly	1	290.6×	0.007	CC2D2A
determination of left/right symmetry	1	255.3×	0.007	CC2D2A
neural tube closure	1	187.2×	0.007	CC2D2A
smoothened signaling pathway	1	181.2×	0.007	CC2D2A
kidney development	1	140.4×	0.009	CC2D2A
heart development	1	78.8×	0.014	CC2D2A
cilium assembly	1	73.6×	0.014	CC2D2A

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
CC2D2A	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	1	CC2D2A
E	Difficult family or no structure, no drug	0

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)
CC2D2A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.