mitochondrial complex III deficiency nuclear type 5

Summary

mitochondrial complex III deficiency nuclear type 5 (MONDO:0014066) is a disease caused by UQCRC2 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: UQCRC2 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitochondrial complex III deficiency nuclear type 5
Mondo ID	MONDO:0014066
OMIM	615160
DOID	DOID:0080114
UMLS	C3554608
MedGen	767522
GARD	0015913
Is cancer (heuristic)	no

Also known as: MC3DN5 · mitochondrial complex III deficiency caused by mutation in UQCRC2 · mitochondrial complex III deficiency, nuclear type 5 · UQCRC2 mitochondrial complex III deficiency

Data availability: 17 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 5

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 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

17 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely pathogenic, 1 benign, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177305	NM_003366.4(UQCRC2):c.323G>A (p.Gly108Asp)	PDZD9	Pathogenic	no assertion criteria provided
41880	NM_003366.4(UQCRC2):c.547C>T (p.Arg183Trp)	PDZD9	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4848961	NC_000016.9:g.(?21964681)(21994982_?)del	UQCRC2	Pathogenic	criteria provided, single submitter
996066	NM_003366.4(UQCRC2):c.665G>C (p.Gly222Ala)	UQCRC2	Pathogenic	criteria provided, single submitter
2506293	NM_003366.4(UQCRC2):c.729dup (p.Leu244fs)	PDZD9	Likely pathogenic	criteria provided, single submitter
1254725	NM_003366.4(UQCRC2):c.266T>C (p.Leu89Pro)	PDZD9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
430295	NM_003366.4(UQCRC2):c.361T>C (p.Tyr121His)	PDZD9	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029699	NM_003366.4(UQCRC2):c.1228T>C (p.Ser410Pro)	PDZD9	Uncertain significance	criteria provided, single submitter
1032124	NM_003366.4(UQCRC2):c.661A>T (p.Ile221Phe)	PDZD9	Uncertain significance	criteria provided, single submitter
2444151	NM_003366.4(UQCRC2):c.1254dup (p.Val419fs)	PDZD9	Uncertain significance	criteria provided, single submitter
2446877	NM_003366.4(UQCRC2):c.1189G>A (p.Gly397Arg)	PDZD9	Uncertain significance	no assertion criteria provided
2446878	NM_003366.4(UQCRC2):c.437T>C (p.Phe146Ser)	PDZD9	Uncertain significance	no assertion criteria provided
4846958	NM_003366.4(UQCRC2):c.379C>T (p.Arg127Trp)	PDZD9	Uncertain significance	criteria provided, single submitter
2438492	NM_003366.4(UQCRC2):c.206G>A (p.Ser69Asn)	UQCRC2	Uncertain significance	criteria provided, single submitter
3068275	NM_003366.4(UQCRC2):c.117+1G>T	UQCRC2	Uncertain significance	criteria provided, single submitter
380582	NM_003366.4(UQCRC2):c.548G>A (p.Arg183Gln)	PDZD9	Benign	criteria provided, multiple submitters, no conflicts
775106	NM_003366.4(UQCRC2):c.953A>C (p.Gln318Pro)	PDZD9	Benign/Likely 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
UQCRC2	Strong	Autosomal recessive	mitochondrial complex III deficiency nuclear type 5	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UQCRC2	Orphanet:1460	Isolated complex III deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UQCRC2	HGNC:12586	ENSG00000140740	P22695	Cytochrome b-c1 complex subunit 2, mitochondrial	gencc,clinvar
PDZD9	HGNC:28740	ENSG00000155714	Q8IXQ8	PDZ domain-containing protein 9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UQCRC2	Cytochrome b-c1 complex subunit 2, 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: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Protease	1	18.3×	0.108
Scaffold/PPI	1	8.6×	0.112

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UQCRC2	Protease	yes		Pept_M16_Zn_BS, Peptidase_M16_C, Metalloenz_LuxS/M16
PDZD9	Scaffold/PPI	no		PDZ, PDZ_sf, PDZD9

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of tongue	1
heart right ventricle	1
skeletal muscle tissue of rectus abdominis	1
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UQCRC2	303	ubiquitous	marker	heart right ventricle, body of tongue, skeletal muscle tissue of rectus abdominis
PDZD9	118	tissue_specific	yes	left testis, testis, right testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UQCRC2	4,507
PDZD9	356

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UQCRC2	P22695	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PDZD9	Q8IXQ8	64.69

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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	UQCRC2
Mitochondrial protein degradation	1	114.2×	0.011	UQCRC2
Respiratory electron transport	1	95.2×	0.011	UQCRC2

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
oxidative phosphorylation	1	1404.3×	0.002	UQCRC2
mitochondrial electron transport, ubiquinol to cytochrome c	1	1296.3×	0.002	UQCRC2
cellular respiration	1	432.1×	0.004	UQCRC2
aerobic respiration	1	247.8×	0.005	UQCRC2
proteolysis	1	34.2×	0.029	UQCRC2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UQCRC2	0	0
PDZD9	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
UQCRC2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	UQCRC2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PDZD9

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
UQCRC2	1	—
PDZD9	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.