mitochondrial complex IV deficiency, nuclear type 20

Summary

mitochondrial complex IV deficiency, nuclear type 20 (MONDO:0033655) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex IV deficiency, nuclear type 20
Mondo ID	MONDO:0033655
OMIM	619064
DOID	DOID:0070505
UMLS	C5436726
MedGen	1771040
GARD	0016417
Is cancer (heuristic)	no

Also known as: MC4DN20 · mitochondrial complex IV deficiency, nuclear type 20

Data availability: 3 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 20

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 18, mitochondrial complex IV deficiency, nuclear type 19, 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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3028911	NM_004255.4(COX5A):c.266T>G (p.Ile89Ser)	COX5A	Pathogenic	no assertion criteria provided
977933	NM_004255.4(COX5A):c.319C>T (p.Arg107Cys)	COX5A	Pathogenic	no assertion criteria provided
4277769	NM_004255.4(COX5A):c.163C>T (p.Arg55Cys)	COX5A	Uncertain significance	criteria provided, single submitter

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
COX5A	Limited	Autosomal recessive	mitochondrial complex IV deficiency, nuclear type 20	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COX5A	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
COX5A	HGNC:2267	ENSG00000178741	P20674	Cytochrome c oxidase subunit 5A, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COX5A	Cytochrome c oxidase subunit 5A, 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)
COX5A	Other/Unknown	no		Cyt_c_oxidase_su5A/6, Cyt_c_oxidase_su5A/6_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
cardiac ventricle	1
heart left ventricle	1
heart right ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COX5A	295	ubiquitous	marker	heart right ventricle, cardiac ventricle, heart left ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COX5A	2,725

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COX5A	P20674	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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×	0.011	COX5A
Cytoprotection by HMOX1	1	184.2×	0.011	COX5A
TP53 Regulates Metabolic Genes	1	129.8×	0.011	COX5A
Mitochondrial protein degradation	1	114.2×	0.011	COX5A
Respiratory electron transport	1	95.2×	0.011	COX5A

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×	0.002	COX5A
cellular respiration	1	432.1×	0.002	COX5A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COX5A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
COX5A	1	Binding:1

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	COX5A

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)
COX5A	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.