mitochondrial complex IV deficiency, nuclear type 7

Summary

mitochondrial complex IV deficiency, nuclear type 7 (MONDO:0033637) is a disease caused by COX6B1 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: COX6B1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex IV deficiency, nuclear type 7
Mondo ID	MONDO:0033637
OMIM	619051
DOID	DOID:0070494
UMLS	C5436685
MedGen	1754683
GARD	0016406
Is cancer (heuristic)	no

Also known as: MC4DN7 · mitochondrial complex IV deficiency, nuclear type 7

Data availability: 13 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 7

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 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 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

13 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 2 likely benign, 1 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
16875	NM_001863.5(COX6B1):c.59G>A (p.Arg20His)	COX6B1	Likely pathogenic	criteria provided, single submitter
1392701	NM_001863.5(COX6B1):c.200C>T (p.Thr67Ile)	COX6B1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1356406	NM_001863.5(COX6B1):c.157G>A (p.Val53Met)	COX6B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1383648	NM_001863.5(COX6B1):c.250G>A (p.Gly84Arg)	COX6B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1946817	NM_001863.5(COX6B1):c.18G>C (p.Glu6Asp)	COX6B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
214276	NM_001863.5(COX6B1):c.247C>T (p.Pro83Ser)	COX6B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3583638	NM_001863.5(COX6B1):c.208-19T>G	COX6B1	Uncertain significance	criteria provided, single submitter
3583639	NM_001863.5(COX6B1):c.258C>G (p.Ile86Met)	COX6B1	Uncertain significance	criteria provided, single submitter
3583640	NM_001863.5(COX6B1):c.*10A>G	COX6B1	Uncertain significance	criteria provided, single submitter
889433	NM_001863.5(COX6B1):c.212C>T (p.Thr71Ile)	COX6B1	Uncertain significance	criteria provided, multiple submitters, no conflicts
377750	NM_001863.5(COX6B1):c.107-16A>G	COX6B1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
508010	NM_001863.5(COX6B1):c.-11-8G>A	COX6B1	Likely benign	criteria provided, multiple submitters, no conflicts
509612	NM_001863.5(COX6B1):c.243G>A (p.Thr81=)	COX6B1	Likely benign	criteria provided, multiple submitters, no conflicts

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
COX6B1	Definitive	Autosomal recessive	mitochondrial complex IV deficiency, nuclear type 7	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COX6B1	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
COX6B1	HGNC:2280	ENSG00000126267	P14854	Cytochrome c oxidase subunit 6B1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COX6B1	Cytochrome c oxidase subunit 6B1	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)
COX6B1	Other/Unknown	no		Cyt_c_oxidase_su6B, CX6/COA6-like_sf, COX6B-like

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
cardiac ventricle	1
heart left ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COX6B1	295	ubiquitous	marker	apex of heart, cardiac ventricle, heart left ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COX6B1	2,232

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COX6B1	P14854	3

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	COX6B1
Cytoprotection by HMOX1	1	184.2×	0.010	COX6B1
TP53 Regulates Metabolic Genes	1	129.8×	0.010	COX6B1
Respiratory electron transport	1	95.2×	0.011	COX6B1

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	COX6B1
cellular respiration	1	432.1×	0.003	COX6B1
substantia nigra development	1	366.4×	0.003	COX6B1

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
COX6B1	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
COX6B1	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	COX6B1

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)
COX6B1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.