UQCRB

protein-coding

ubiquinol-cytochrome c reductase binding protein, the group of Mitochondrial complex III: ubiquinol-cytochrome c reductase complex subunits

Gene summary

This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. This protein plays an important role in hypoxia-induced angiogenesis through mitochondrial reactive oxygen species-mediated signaling. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X. [provided by RefSeq, Dec 2011]

Previous symbols:

UQBP

MANE transcript

NM_006294.5

Inheritance

ClinVar variants

P:6U:33B:9

Top phenotype

Mitochondrial complex III deficiency, nuclear type 3

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr8:96,222,947-96,235,546

External References & Databases

Ensembl (ENSG00000156467)

Transcript & Mutation Effects

hg38 • Region Span ~12.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial complex III deficiency nuclear type 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014064

Submitter: PanelApp Australia

mitochondrial complex III deficiency nuclear type 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014064

Submitter: G2P

mitochondrial diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: ClinGen

The relationship between *UQCRB* and primary mitochondrial disease was evaluated using the ClinGen Clinical Validity Framework as of October 7, 2024. The *UQCRB* gene encodes the ubiquinol-cytochrome *c* reductase binding protein, a component of the ubiquinol-cytochrome *c* oxidoreductase (complex III) that binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. The *UQCRB* gene was first reported in relation to autosomal recessive primary mitochondrial disease in 2003 (PMID: 12709789). *UQCRB* has been associated with a single disease entity to date; mitochondrial complex III deficiency, nuclear type 3 [OMIM# 615158]. 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 frameshift variant identified in two unrelated cases from two publications (PMIDs: 12709789, 35221877). Features in the two reported individuals include metabolic acidosis, hypoglycemia, hepatomegaly, and elevated lactate. The mechanism of disease is suspected to be 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). 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 October 7, 2024 (SOP Version 10).

mitochondrial complex III deficiency nuclear type 3LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014064

Submitter: Ambry Genetics

mitochondrial complex III deficiency nuclear type 3LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014064

Submitter: Labcorp Genetics (formerly Invitae)

mitochondrial complex III deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015448

Submitter: Orphanet

Clinical Genomic Database (CGD)

Mitochondrial complex III deficiency, nuclear type 3AR

Manifestation: Biochemical; Gastrointestinal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: Individuals may suffer acute episodes of metabolic crisis; Treatment with Mitochondrial cocktail type therapy may be beneficial

Refs: 12709789

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UQCRB variants in ClinVar

4 Conditions Cataloged

not providedTotal: 53

not specifiedTotal: 23

Mitochondrial complex III deficiency nuclear type 3Total: 6

UQCRB-related disorderTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006294.5. 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				6 clinvar	1 clinvar	7
missense		2 clinvar	27 clinvar	2 clinvar		31
nonsense		1 clinvar	1 clinvar			2
start loss		1 clinvar				1
frameshift	1 clinvar	1 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	5	33	8	1	48

Highest pathogenic variant AF is 0.00002231476

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006294.5	RefSeq	NP_006285.1	4	MANE Select
ENST00000287022.10	Ensembl	ENSP00000287022.5	4	MANE Select
NM_001199975.3	RefSeq	NP_001186904.1	2	Standard
NM_001254752.2	RefSeq	NP_001241681.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
uqcrb	Danio rerio	Structure: angiogenic sprout Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

uqcrb

Danio rerio

Structure: angiogenic sprout

Quality: decreased amount

abnormal

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
mitochondrial respiratory chain complex III assembly
oxidation-reduction process

Molecular Function

protein binding
ubiquinol-cytochrome-c reductase activity

Cellular Component

mitochondrial inner membrane
mitochondrial respirasome
mitochondrial respiratory chain complex III

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000518406
Coding exons: 5
Length: 9715
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125728
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.185	69	73.5	0.939	0.00000366	916
Missense (PolyPhen)		7	12.968	0.53978		189
Synonymous	0.154	23	24.0	0.960	0.00000114	239
Loss of Function	1.43	4	8.50	0.471	5.11e-7	93

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000070	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

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 component is involved in redox-linked proton pumping.;
Disease: DISEASE: Mitochondrial complex III deficiency, nuclear 3 (MC3DN3) [MIM:615158]: A disorder of the mitochondrial respiratory chain resulting in a highly variable phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance. {ECO:0000269|PubMed:12709789}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.183

Intolerance Scores

LoFtool: 0.512
RVIS EVS: 0.15
RVIS percentile EVS: 64.11

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium