mitochondrial complex IV deficiency, nuclear type 18

Summary

mitochondrial complex IV deficiency, nuclear type 18 (MONDO:0033653) 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	mitochondrial complex IV deficiency, nuclear type 18
Mondo ID	MONDO:0033653
OMIM	619062
DOID	DOID:0070503
UMLS	C5436720
MedGen	1752734
GARD	0016415
Is cancer (heuristic)	no

Also known as: MC4DN18 · mitochondrial complex IV deficiency, nuclear type 18

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

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › inborn mitochondrial metabolism disorder › mitochondrial oxidative phosphorylation disorder › mitochondrial respiratory chain complex deficiency › mitochondrial complex IV deficiency, nuclear-type › mitochondrial complex IV deficiency, nuclear type 18

Related subtypes (21): pancreatic insufficiency-anemia-hyperostosis syndrome, mitochondrial complex IV deficiency, nuclear type 3, mitochondrial complex IV deficiency, nuclear type 4, mitochondrial complex IV deficiency, nuclear type 7, mitochondrial complex IV deficiency, nuclear type 8, mitochondrial complex IV deficiency, nuclear type 10, mitochondrial complex IV deficiency, nuclear type 11, mitochondrial complex IV deficiency, nuclear type 12, mitochondrial complex IV deficiency, nuclear type 14, mitochondrial complex IV deficiency, nuclear type 15, mitochondrial complex IV deficiency, nuclear type 16, mitochondrial complex IV deficiency, nuclear type 17, mitochondrial complex IV deficiency, nuclear type 19, mitochondrial complex IV deficiency, nuclear type 20, mitochondrial complex IV deficiency, nuclear type 21, mitochondrial complex IV deficiency, nuclear type 1, mitochondrial complex IV deficiency, nuclear type 22, mitochondrial complex IV deficiency, nuclear type 23, COX deficiency, benign infantile mitochondrial myopathy, mitochondrial complex IV deficiency, nuclear type 24, mitochondrial complex 4 deficiency, nuclear type 25

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 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
638271	NM_005205.4(COX6A2):c.117C>A (p.Ser39Arg)	COX6A2	Likely pathogenic	criteria provided, single submitter
638272	NM_005205.4(COX6A2):c.127T>C (p.Cys43Arg)	COX6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
COX6A2	Limited	Autosomal recessive	mitochondrial complex IV deficiency, nuclear type 18	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COX6A2	Orphanet:254905	Isolated 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
COX6A2	HGNC:2279	ENSG00000156885	Q02221	Cytochrome c oxidase subunit 6A2, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COX6A2	Cytochrome c oxidase subunit 6A2, mitochondrial	Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.

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)
COX6A2	Other/Unknown	no		Cyt_c_oxidase_su6a, Cyt_c_oxidase_su6a_CS, Cyt_c_oxidase_su6a_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
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COX6A2	180	broad	marker	hindlimb stylopod muscle, apex of heart, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COX6A2	1,590

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COX6A2	Q02221	87.30

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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×	0.010	COX6A2
Cytoprotection by HMOX1	1	184.2×	0.010	COX6A2
TP53 Regulates Metabolic Genes	1	129.8×	0.010	COX6A2
Respiratory electron transport	1	95.2×	0.011	COX6A2

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
mitochondrial electron transport, cytochrome c to oxygen	1	766.0×	0.003	COX6A2
generation of precursor metabolites and energy	1	343.9×	0.003	COX6A2

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
COX6A2	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	COX6A2

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)
COX6A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.