mitochondrial complex III deficiency nuclear type 4

Summary

mitochondrial complex III deficiency nuclear type 4 (MONDO:0014065) is a disease caused by UQCRQ (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: UQCRQ (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex III deficiency nuclear type 4
Mondo ID	MONDO:0014065
OMIM	615159
DOID	DOID:0080113
UMLS	C3554607
MedGen	767521
GARD	0015912
Is cancer (heuristic)	no

Also known as: MC3DN4 · mitochondrial complex III deficiency caused by mutation in UQCRQ · mitochondrial complex III deficiency, nuclear type 4 · UQCRQ mitochondrial complex III deficiency

Data availability: 50 ClinVar variants · 3 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 4

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 5, mitochondrial complex III deficiency nuclear type 6, mitochondrial complex III deficiency nuclear type 7, 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

50 retrieved; paginated sample, class counts are floors:

36 uncertain significance, 9 conflicting classifications of pathogenicity, 3 benign, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
137891	NM_014402.5(UQCRQ):c.108C>G (p.Pro36=)	LOC126807509	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
350839	NM_014402.5(UQCRQ):c.45C>T (p.Ile15=)	LOC126807509	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
669826	NM_014402.5(UQCRQ):c.90C>T (p.Val30=)	LOC126807509	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
729	NM_014402.5(UQCRQ):c.134C>T (p.Ser45Phe)	LOC126807509	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
904277	NM_014402.5(UQCRQ):c.-16C>T	LOC126807509	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
215349	NM_014402.5(UQCRQ):c.10G>A (p.Glu4Lys)	UQCRQ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
350840	NM_014402.5(UQCRQ):c.*18C>T	UQCRQ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
350842	NM_014402.5(UQCRQ):c.*236C>G	UQCRQ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
350855	NM_014402.5(UQCRQ):c.*970A>C	UQCRQ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1033694	NM_014402.5(UQCRQ):c.22C>A (p.Leu8Met)	LOC126807509	Uncertain significance	criteria provided, multiple submitters, no conflicts
2402585	NM_014402.5(UQCRQ):c.110A>G (p.Asn37Ser)	LOC126807509	Uncertain significance	criteria provided, multiple submitters, no conflicts
350838	NM_014402.5(UQCRQ):c.-18G>C	UQCRQ	Uncertain significance	criteria provided, single submitter
350841	NM_014402.5(UQCRQ):c.*19G>T	UQCRQ	Uncertain significance	criteria provided, single submitter
350843	NM_014402.5(UQCRQ):c.*236C>T	UQCRQ	Uncertain significance	criteria provided, single submitter
350844	NM_014402.5(UQCRQ):c.*249A>G	UQCRQ	Uncertain significance	criteria provided, single submitter
350845	NM_014402.5(UQCRQ):c.*332G>A	UQCRQ	Uncertain significance	criteria provided, single submitter
350847	NM_014402.5(UQCRQ):c.*364C>T	UQCRQ	Uncertain significance	criteria provided, single submitter
350848	NM_014402.5(UQCRQ):c.*545A>C	UQCRQ	Uncertain significance	criteria provided, single submitter
350850	NM_014402.5(UQCRQ):c.*658A>C	UQCRQ	Uncertain significance	criteria provided, single submitter
350853	NM_014402.5(UQCRQ):c.*756C>T	UQCRQ	Uncertain significance	criteria provided, single submitter
350856	NM_014402.5(UQCRQ):c.*971C>A	UQCRQ	Uncertain significance	criteria provided, single submitter
350857	NM_014402.5(UQCRQ):c.*979G>A	UQCRQ	Uncertain significance	criteria provided, single submitter
350858	NM_014402.5(UQCRQ):c.*1026C>G	UQCRQ	Uncertain significance	criteria provided, single submitter
350859	NM_014402.5(UQCRQ):c.*1058A>G	UQCRQ	Uncertain significance	criteria provided, single submitter
350860	NM_014402.5(UQCRQ):c.*1078T>A	UQCRQ	Uncertain significance	criteria provided, single submitter
350861	NM_014402.5(UQCRQ):c.*1086A>C	UQCRQ	Uncertain significance	criteria provided, single submitter
350863	NM_014402.5(UQCRQ):c.*1204G>A	UQCRQ	Uncertain significance	criteria provided, single submitter
904278	NM_014402.5(UQCRQ):c.*102T>C	UQCRQ	Uncertain significance	criteria provided, single submitter
904348	NM_014402.5(UQCRQ):c.*1010C>G	UQCRQ	Uncertain significance	criteria provided, single submitter
904349	NM_014402.5(UQCRQ):c.*1115G>C	UQCRQ	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
UQCRQ	Strong	Autosomal recessive	mitochondrial complex III deficiency nuclear type 4	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UQCRQ	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
UQCRQ	HGNC:29594	ENSG00000164405	O14949	Cytochrome b-c1 complex subunit 8	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UQCRQ	Cytochrome b-c1 complex subunit 8	Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of 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)
UQCRQ	Other/Unknown	no		Cyt_bc1_su8, Cyt_bc1_su8_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
body of tongue	1
cardiac ventricle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UQCRQ	295	ubiquitous	marker	apex of heart, body of tongue, cardiac ventricle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UQCRQ	2,366

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UQCRQ	O14949	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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×	0.007	UQCRQ
Mitochondrial protein degradation	1	114.2×	0.011	UQCRQ
Respiratory electron transport	1	95.2×	0.011	UQCRQ

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
subthalamus development	1	16852.0×	3e-04	UQCRQ
pons development	1	16852.0×	3e-04	UQCRQ
pyramidal neuron development	1	2106.5×	0.001	UQCRQ
cerebellar Purkinje cell layer development	1	1532.0×	0.001	UQCRQ
thalamus development	1	1404.3×	0.001	UQCRQ
mitochondrial electron transport, ubiquinol to cytochrome c	1	1296.3×	0.001	UQCRQ
hypothalamus development	1	1053.2×	0.001	UQCRQ
midbrain development	1	601.9×	0.002	UQCRQ
cellular respiration	1	432.1×	0.003	UQCRQ
hippocampus development	1	230.8×	0.004	UQCRQ

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
UQCRQ	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	UQCRQ

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)
UQCRQ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.