UQCRH
protein-codingubiquinol-cytochrome c reductase hinge protein, the group of Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits
Gene summary
Enables quinol-cytochrome-c reductase activity. Predicted to be involved in mitochondrial electron transport, ubiquinol to cytochrome c. Located in mitochondrial inner membrane. Implicated in mitochondrial complex III deficiency. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0859321
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0044970
Submitter: ClinGen
The relationship between *UQCRH* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of September 30, 2024. The *UQCRH* gene encodes a structural subunit of complex III of the mitochondrial respiratory chain. The first and only report of *UQCRH* in relation to autosomal recessive primary mitochondrial disease was in 2021 (PMID: 34750991). *UQCRH* has been associated with a single disease entity to date; mitochondrial complex III deficiency, nuclear type 11 [OMIM# 620137]. This is one disease entity according to the ClinGen Lumping and Splitting Framework, and is considered a primary mitochondrial disease. Evidence supporting this gene-disease relationship includes case-level data and experimental data. This curation included one homozygous in-frame deletion identified in one proband and a similarly affected first cousin from one publication (PMID: 34750991). The two affected individuals had recurrent episodic vomiting and metabolic acidosis in the setting of a viral trigger. The mechanism of disease is loss of function. This gene-disease relationship is also supported by a biochemical function shared with other genes associated with primary mitochondrial disease (PMID: 33340416), functional alteration studies and rescue in patient cells (PMID: 34750991), and a *Uqcrh-/-* mouse model (PMID: 34750991). In summary, there is limited evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on September 30, 2024 (SOP Version 10).
Inheritance Pattern: Unknown
Disease ID:MONDO:0859321
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0859321
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Biochemical
Intervention: Biochemical
Rationale: Individuals have been described as having acute metabolic decompensation related to insults such as viral infections, and awareness may allow prompt diagnosis and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to UQCRH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006004.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 17 | 0 | 0 | 17 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005995.2 | 4 | MANE Select | |
| Ensembl | ENSP00000309565.5 | 4 | MANE Select | |
| RefSeq | NP_001284494.1 | 3 | Standard | |
| RefSeq | NP_001284495.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cardiac muscle contraction - Homo sapiens (human)
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
- Alzheimer,s disease - Homo sapiens (human)
- Huntington,s disease - Homo sapiens (human)
- Thermogenesis - Homo sapiens (human)
Biological Process
- oxidative phosphorylation
- mitochondrial electron transport, ubiquinol to cytochrome c
- aerobic respiration
- oxidation-reduction process
Molecular Function
- protein binding
- ubiquinol-cytochrome-c reductase activity
Cellular Component
- mitochondrion
- mitochondrial inner membrane
- mitochondrial respirasome
- mitochondrial respiratory chain complex III
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000311672
- Coding exons
- 4
- Length
- 13146
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 17
- Defined
- 125748
- p
- 0.0000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.167 | 49 | 52.4 | 0.935 | 0.00000311 | 597 |
| Missense (PolyPhen) | 10 | 11.719 | 0.85334 | 151 | ||
| Synonymous | -0.296 | 22 | 20.3 | 1.08 | 0.00000115 | 155 |
| Loss of Function | 0.917 | 5 | 7.76 | 0.645 | 4.96e-7 | 78 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000079 | 0.000079 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This protein may mediate formation of the complex between cytochromes c and c1.;
Recessive Scores
- pRec
- 0.128
Intolerance Scores
- LoFtool
- 0.686
- RVIS EVS
- 0.15
- RVIS percentile EVS
- 64.11
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.920
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |