mitochondrial complex III deficiency, nuclear type 10

Summary

mitochondrial complex III deficiency, nuclear type 10 (MONDO:0032909) is a disease caused by UQCRFS1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: UQCRFS1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex III deficiency, nuclear type 10
Mondo ID	MONDO:0032909
OMIM	618775
UMLS	C5394051
MedGen	1719382
GARD	0016377
Is cancer (heuristic)	no

Also known as: MC3DN10

Data availability: 5 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 10

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 7, mitochondrial complex III deficiency nuclear type 8, mitochondrial complex III deficiency nuclear type 9, 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

5 retrieved; paginated sample, class counts are floors:

3 pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
619297	NM_006003.3(UQCRFS1):c.215-1G>C	UQCRFS1	Pathogenic	criteria provided, single submitter
619499	NM_006003.3(UQCRFS1):c.610C>T (p.Arg204Ter)	UQCRFS1	Pathogenic	criteria provided, single submitter
619501	NM_006003.3(UQCRFS1):c.41T>A (p.Val14Asp)	UQCRFS1	Pathogenic	no assertion criteria provided
1684191	NM_006003.3(UQCRFS1):c.24A>G (p.Ser8=)	LOC130064118	Benign	criteria provided, multiple submitters, no conflicts
1684192	NM_006003.3(UQCRFS1):c.16T>G (p.Ser6Ala)	LOC130064118	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
UQCRFS1	Strong	Autosomal recessive	mitochondrial complex III deficiency, nuclear type 10	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UQCRFS1	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
UQCRFS1	HGNC:12587	ENSG00000169021	P47985	Cytochrome b-c1 complex subunit Rieske, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UQCRFS1	Cytochrome b-c1 complex subunit Rieske, mitochondrial	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)
UQCRFS1	Other/Unknown	no		Rieske_TM, Rieske_Fe-S_prot_C, Ubiquinol_cyt_c_Rdtase_Fe-S-su

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
gastrocnemius	1
heart left ventricle	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UQCRFS1	134	ubiquitous	marker	gastrocnemius, heart left ventricle, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UQCRFS1	4,001

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UQCRFS1	P47985	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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×	0.005	UQCRFS1
Respiratory electron transport	1	95.2×	0.011	UQCRFS1

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, ubiquinol to cytochrome c	1	1296.3×	0.001	UQCRFS1
mitochondrial respiratory chain complex III assembly	1	1203.7×	0.001	UQCRFS1
respiratory electron transport chain	1	842.6×	0.001	UQCRFS1

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
UQCRFS1	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	UQCRFS1

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)
UQCRFS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.