mitochondrial complex III deficiency nuclear type 7

Summary

mitochondrial complex III deficiency nuclear type 7 (MONDO:0014356) is a disease caused by UQCC2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: UQCC2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex III deficiency nuclear type 7
Mondo ID	MONDO:0014356
OMIM	615824
DOID	DOID:0080116
UMLS	C4014408
MedGen	862845
GARD	0016015
Is cancer (heuristic)	no

Also known as: MC3DN7 · mitochondrial complex III deficiency caused by mutation in UQCC2 · mitochondrial complex III deficiency, nuclear type 7 · UQCC2 mitochondrial complex III deficiency

Data availability: 19 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 III deficiency › mitochondrial complex III deficiency, nuclear type › mitochondrial complex III deficiency nuclear type 7

Related subtypes (10): mitochondrial complex III deficiency nuclear type 1, mitochondrial complex III deficiency nuclear type 2, mitochondrial complex III deficiency nuclear type 3, mitochondrial complex III deficiency nuclear type 4, mitochondrial complex III deficiency nuclear type 5, mitochondrial complex III deficiency nuclear type 6, mitochondrial complex III deficiency nuclear type 8, mitochondrial complex III deficiency nuclear type 9, mitochondrial complex III deficiency, nuclear type 10, mitochondrial complex III deficiency, nuclear type 11

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

19 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 3 pathogenic, 2 likely benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
585258	NM_032340.3(UQCC2):c.[23G>C;28C>T]		Pathogenic	no assertion criteria provided
133295	NM_032340.4(UQCC2):c.214-3C>G	UQCC2	Pathogenic	no assertion criteria provided
2499488	NM_032340.4(UQCC2):c.101G>A (p.Arg34Gln)	UQCC2	Pathogenic	no assertion criteria provided
1032949	NM_032340.4(UQCC2):c.37T>C (p.Cys13Arg)	UQCC2	Uncertain significance	criteria provided, single submitter
1220358	NM_032340.4(UQCC2):c.112G>A (p.Ala38Thr)	UQCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1368816	NM_032340.4(UQCC2):c.138G>A (p.Gln46=)	UQCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2980796	NM_032340.4(UQCC2):c.283+3A>C	UQCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3593500	NM_032340.4(UQCC2):c.347C>T (p.Ala116Val)	UQCC2	Uncertain significance	criteria provided, single submitter
3593501	NM_032340.4(UQCC2):c.330del (p.Lys110fs)	UQCC2	Uncertain significance	criteria provided, single submitter
3593502	NM_032340.4(UQCC2):c.214-6G>A	UQCC2	Uncertain significance	criteria provided, single submitter
3593503	NM_032340.4(UQCC2):c.214-9G>A	UQCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3593504	NM_032340.4(UQCC2):c.167T>C (p.Met56Thr)	UQCC2	Uncertain significance	criteria provided, single submitter
3593505	NM_032340.4(UQCC2):c.165G>C (p.Gln55His)	UQCC2	Uncertain significance	criteria provided, single submitter
3593506	NM_032340.4(UQCC2):c.4G>A (p.Ala2Thr)	UQCC2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3593507	NM_032340.4(UQCC2):c.3G>A (p.Met1Ile)	UQCC2	Uncertain significance	criteria provided, single submitter
635828	NM_032340.4(UQCC2):c.28C>T (p.Leu10Phe)	UQCC2	Uncertain significance	criteria provided, single submitter
381205	NM_032340.4(UQCC2):c.321G>A (p.Met107Ile)	UQCC2	Likely benign	criteria provided, multiple submitters, no conflicts
511602	NM_032340.4(UQCC2):c.75G>C (p.Arg25=)	UQCC2	Likely benign	criteria provided, multiple submitters, no conflicts
516964	NM_032340.4(UQCC2):c.225C>A (p.Pro75=)	UQCC2	Benign/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
UQCC2	Strong	Autosomal recessive	mitochondrial complex III deficiency nuclear type 7	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UQCC2	Orphanet:1460	Isolated complex III 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
UQCC2	HGNC:21237	ENSG00000137288	Q9BRT2	Ubiquinol-cytochrome c reductase complex assembly factor 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UQCC2	Ubiquinol-cytochrome c reductase complex assembly factor 2	Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex).

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)
UQCC2	Other/Unknown	no		UQCC2

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
heart left ventricle	1
right atrium auricular region	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UQCC2	251	ubiquitous	marker	apex of heart, right atrium auricular region, heart left ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UQCC2	1,016

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
UQCC2	Q9BRT2	88.94

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 III assembly	1	439.2×	0.002	UQCC2

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
regulation of skeletal muscle cell differentiation	1	2808.7×	0.001	UQCC2
regulation of oxidative phosphorylation	1	1203.7×	0.001	UQCC2
mitochondrial respiratory chain complex III assembly	1	1203.7×	0.001	UQCC2
positive regulation of mitochondrial translation	1	1123.5×	0.001	UQCC2
regulation of insulin secretion	1	391.9×	0.003	UQCC2

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
UQCC2	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	UQCC2

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)
UQCC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.