Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3

Summary

Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3 (MONDO:0014667) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

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 3
Mondo ID	MONDO:0014667
OMIM	616500
DOID	DOID:0080359
UMLS	C4225154
MedGen	903495
GARD	0018572
Is cancer (heuristic)	no

Also known as: cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3 · cardioencephalomyopathy, fatal infantile, due to cytochrome C oxidase deficiency type 3 · CEMCOX3 · COA5 fatal infantile encephalocardiomyopathy · fatal infantile encephalocardiomyopathy caused by mutation in COA5 · mitochondrial complex IV, deficiency, nuclear type 9

Data availability: 1 ClinVar variant · 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 3

Related subtypes (3): cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1, cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 2, 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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
31087	NM_001008215.3(COA5):c.157G>C (p.Ala53Pro)	COA5	Pathogenic	no assertion criteria provided

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
COA5	Limited	Unknown	cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COA5	Orphanet:1561	Fatal infantile cytochrome C oxidase deficiency

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
COA5	HGNC:33848	ENSG00000183513	Q86WW8	Cytochrome c oxidase assembly factor 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COA5	Cytochrome c oxidase assembly factor 5	Assembly factor for cytochrome c oxidase (respiratory chain complex IV).

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)
COA5	Other/Unknown	no		Cyt_c_oxidase_assmbl_Pet191

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
C1 segment of cervical spinal cord	1
left ovary	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COA5	252	ubiquitous	marker	C1 segment of cervical spinal cord, left ovary, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COA5	1,044

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COA5	Q86WW8	82.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Complex IV assembly	1	228.4×	0.004	COA5

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
leukocyte differentiation	1	3370.4×	0.001	COA5
mitochondrial respiratory chain complex IV assembly	1	624.1×	0.004	COA5
spleen development	1	401.2×	0.004	COA5
thymus development	1	337.0×	0.004	COA5
multicellular organism growth	1	137.0×	0.007	COA5

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
COA5	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	COA5

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)
COA5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.