Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4

disease

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Also known as cardioencephalomyopathy, fatal infantile, due to cytochrome C oxidase deficiency type 4CEMCOX4COA6 fatal infantile encephalocardiomyopathyfatal infantile encephalocardiomyopathy caused by mutation in COA6mitochondrial complex IV deficiency, nuclear type 13

Summary

Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 (MONDO:0014668) is a disease caused by COA6 (GenCC Strong), with 2 cohort genes.

At a glance

Causal gene: COA6 (GenCC Strong)
Cohort genes: 2
ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4
Mondo ID	MONDO:0014668
OMIM	616501
DOID	DOID:0080360
UMLS	C4225304
MedGen	905398
GARD	0018573
Is cancer (heuristic)	no

Also known as: cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4 · cardioencephalomyopathy, fatal infantile, due to cytochrome C oxidase deficiency type 4 · CEMCOX4 · COA6 fatal infantile encephalocardiomyopathy · fatal infantile encephalocardiomyopathy caused by mutation in COA6 · mitochondrial complex IV deficiency, nuclear type 13

Data availability: 8 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › familial cardiomyopathy › fatal infantile encephalocardiomyopathy › cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4

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

8 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
144036	NM_001206641.3(COA6):c.267G>C (p.Trp89Cys)	COA6	Pathogenic	no assertion criteria provided
204622	NM_001206641.3(COA6):c.286T>C (p.Trp96Arg)	COA6	Pathogenic	no assertion criteria provided
3767189	NM_001206641.3(COA6):c.415_418dup (p.Lys140fs)	COA6	Likely pathogenic	criteria provided, single submitter
144037	NM_001206641.3(COA6):c.349G>T (p.Glu117Ter)	COA6	Uncertain significance	criteria provided, single submitter
2580902	NM_001206641.3(COA6):c.272C>G (p.Ala91Gly)	COA6	Uncertain significance	criteria provided, single submitter
419305	NM_001206641.3(COA6):c.373-8dup	COA6	Benign	criteria provided, multiple submitters, no conflicts
506397	NM_001206641.3(COA6):c.212+162G>A	COA6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
380009	NM_001206641.3(COA6):c.47G>C (p.Ser16Thr)	COA6-AS1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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
COA6	Strong	Unknown	cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 4	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COA6	Orphanet:1561	Fatal infantile cytochrome C oxidase deficiency

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COA6	HGNC:18025	ENSG00000168275	Q5JTJ3	Cytochrome c oxidase assembly factor 6 homolog	gencc,clinvar
COA6-AS1	HGNC:40825	ENSG00000231663		COA6 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COA6	Cytochrome c oxidase assembly factor 6 homolog	Involved in the maturation of the mitochondrial respiratory chain complex IV subunit MT-CO2/COX2.

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)
COA6	Other/Unknown	no		CX6/COA6-like_sf, COA6, COX6B-like
COA6-AS1	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
gastrocnemius	1
left ventricle myocardium	1
tibialis anterior	1
cerebellar vermis	1
putamen	1
quadriceps femoris	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COA6	247	ubiquitous	marker	left ventricle myocardium, tibialis anterior, gastrocnemius
COA6-AS1	135	ubiquitous	marker	quadriceps femoris, cerebellar vermis, putamen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COA6	1,486
COA6-AS1	0

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COA6	Q5JTJ3	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Mitochondrial protein import	1	167.9×	0.006	COA6

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
respiratory chain complex IV assembly	1	2407.4×	8e-04	COA6
mitochondrial respiratory chain complex IV assembly	1	624.1×	0.002	COA6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
COA6	0	0
COA6-AS1	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	2	COA6, COA6-AS1

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)
COA6	0	—
COA6-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: COA6, COA6-AS1