UQCRB

Summary

UQCRB (ubiquinol-cytochrome c reductase binding protein, HGNC:12582) is a protein-coding gene on chromosome 8q22.1, encoding Cytochrome b-c1 complex subunit 7 (P14927). Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. It is a selective cancer dependency (DepMap: 45.4% of cell lines).

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.

Source: NCBI Gene 7381 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial complex III deficiency nuclear type 3 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 87 total — 2 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 45.4% of screened cell lines
• MANE Select transcript: NM_006294

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12582
Approved symbol	UQCRB
Name	ubiquinol-cytochrome c reductase binding protein
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	QP-C, QCR7, UQCR6
Ensembl gene	ENSG00000156467
Ensembl biotype	protein_coding
OMIM	191330
Entrez	7381

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay

ENST00000287022, ENST00000517523, ENST00000517603, ENST00000518406, ENST00000518876, ENST00000519322, ENST00000521036, ENST00000521948, ENST00000523920, ENST00000858703, ENST00000858704, ENST00000944300

RefSeq mRNA: 3 — MANE Select: NM_006294 NM_001199975, NM_001254752, NM_006294

CCDS: CCDS59107, CCDS6269

Canonical transcript exons

ENST00000287022 — 4 exons

Exon	Start	End
ENSE00001088080	96222947	96231132
ENSE00001088082	96235512	96235545
ENSE00003557565	96231774	96231940
ENSE00003671126	96233156	96233227

Expression profiles

Bgee: expression breadth ubiquitous, 304 present calls, max score 99.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 257.2157 / max 4749.7343, expressed in 1824 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94025	234.8032	1822
205261	22.4125	1798

Top tissues by expression

304 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.92	gold quality
vena cava	UBERON:0004087	99.84	gold quality
renal medulla	UBERON:0000362	99.83	gold quality
choroid plexus epithelium	UBERON:0003911	99.83	gold quality
right atrium auricular region	UBERON:0006631	99.83	gold quality
pigmented layer of retina	UBERON:0001782	99.81	gold quality
apex of heart	UBERON:0002098	99.80	gold quality
retina	UBERON:0000966	99.78	gold quality
biceps brachii	UBERON:0001507	99.76	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.76	gold quality
body of tongue	UBERON:0011876	99.76	gold quality
diaphragm	UBERON:0001103	99.75	gold quality
superior vestibular nucleus	UBERON:0007227	99.75	gold quality
germinal epithelium of ovary	UBERON:0001304	99.74	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.73	gold quality
pons	UBERON:0000988	99.72	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.71	gold quality
substantia nigra pars compacta	UBERON:0001965	99.69	gold quality
superior surface of tongue	UBERON:0007371	99.69	gold quality
tongue	UBERON:0001723	99.68	gold quality
seminal vesicle	UBERON:0000998	99.67	gold quality
triceps brachii	UBERON:0001509	99.67	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.67	gold quality
inferior vagus X ganglion	UBERON:0005363	99.67	gold quality
ventral tegmental area	UBERON:0002691	99.66	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.66	gold quality
lateral globus pallidus	UBERON:0002476	99.65	gold quality
cranial nerve II	UBERON:0000941	99.64	gold quality
pylorus	UBERON:0001166	99.64	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.64	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	46.45
E-MTAB-8142	yes	46.32
E-HCAD-9	yes	18.71
E-HCAD-10	yes	12.69
E-GEOD-135922	yes	12.12
E-MTAB-10042	yes	6.09
E-MTAB-7316	no	4167.16
E-MTAB-9154	no	2141.97
E-CURD-79	no	2070.41
E-MTAB-8530	no	2006.00
E-HCAD-30	no	605.40
E-CURD-89	no	576.84
E-HCAD-4	no	113.28
E-HCAD-8	no	45.25
E-MTAB-6701	no	27.85

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR5A2

miRNA regulators (miRDB)

138 targeting UQCRB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 45.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• Two SNPs in the 3’ untranslated region of UQCRB (complex III), rs7836698 and rs10504961, were associated with overall survival. (PMID:22545919)
• Studies indicate that mitochondrial oxygen sensor ubiquinol-cytochrome c reductase binding protein (UQCRB) as a terpestacin-binding protein. (PMID:23475074)
• Mitochondrial UQCRB regulates VEGFR2 signaling in endothelial cells. (PMID:23708980)
• a UQCRB mutation promotes angiogenesis through the generation of mitochondrial reactive oxygen species (PMID:25446085)
• UQCRB gene mutation is associated with mitochondrial complex III deficiency in a Chinese family. (PMID:28604960)
• The knockdown of UQCRB gene by UQCRB siRNA significantly inhibited the cancer stem cell-like phenotypes as well as the expression of stemness markers by blocking mitochondrial ROS/HIF1alpha/cMet pathway in U87MG GSCs. (PMID:29115404)
• Our results provide novel insights into the critical role of UQCRB in regulating CRC, supporting UQCRB as a new candidate for the development of diagnostics for CRC patients. (PMID:29147009)
• our present study revealed that hsa-miR-10a-5p is associated with genes involved in the cholesterol synthesis pathway in mutant UQCRB-expressing cells. (PMID:30120311)
• MiR-4435 is an UQCRB-related circulating miRNA in human colorectal cancer. (PMID:32071343)
• Disruption of mitochondrial complex III in cap mesenchyme but not in ureteric progenitors results in defective nephrogenesis associated with amino acid deficiency. (PMID:35341793)
• N-Acetyltransferase 10 represses Uqcr11 and Uqcrb independently of ac4C modification to promote heart regeneration. (PMID:38459019)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	uqcrb	ENSDARG00000011146
mus_musculus	Uqcrb	ENSMUSG00000021520
rattus_norvegicus	Uqcrb	ENSRNOG00000024967
drosophila_melanogaster	UQCR-14	FBGN0030733
drosophila_melanogaster	UQCR-14L	FBGN0039576
caenorhabditis_elegans		WBGENE00020181

Protein

Protein identifiers

Cytochrome b-c1 complex subunit 7 — P14927 (reviewed: P14927)

Alternative names: Complex III subunit 7, Complex III subunit VII, QP-C, Ubiquinol-cytochrome c reductase complex 14 kDa protein

All UniProt accessions (4): P14927, B7Z2R2, E5RHG9, E5RIT7

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c.

Subunit / interactions. Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1. The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Mitochondrial complex III deficiency, nuclear type 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the UQCRB/QCR7 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P14927-1	1	yes
P14927-2	2

RefSeq proteins (3): NP_001186904, NP_001241681, NP_006285* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003197	QCR7	Family
IPR036544	QCR7_sf	Homologous_superfamily

Pfam: PF02271

Enzyme classification (BRENDA):

• EC 7.1.1.8 — quinol-cytochrome-c reductase (BRENDA: 55 organisms, 103 substrates, 130 inhibitors, 45 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

17 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
DECYLUBIQUINOL	0.01–12.4	5
2 FERRICYTOCHROME C	0.004–0.009	4
CYTOCHROME C	0.004–0.025	4
QH2	0.008–0.072	3
UBIQUINOL	0.001–0.02	3
UBIQUINOL-10	0.004–0.038	3
CYTOCHROME C2	0.023–0.03	2
HORSE HEART CYTOCHROME C	0.006–0.025	2
UBIQUINOL-1	0.0064–0.08	2
UBIQUINOL-2	0.002–0.0054	2
2 FERRICYTOCHROME C2	0.001	1
COENZYME Q1H2	0.0046	1
RHODOQUINOL-3	0.005	1
2 FERRICYTOCHROME C1	—	0
2,3-DIMETHOXY-5-METHYL-6-(10-BROMODECYL)-1,4-BEN	—	0

UniProt features (21 total): modified residue 8, helix 7, initiator methionine 1, chain 1, splice variant 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9HZL	ELECTRON MICROSCOPY	2.52
9CG3	ELECTRON MICROSCOPY	2.96
5XTE	ELECTRON MICROSCOPY	3.4
5XTH	ELECTRON MICROSCOPY	3.9
5XTI	ELECTRON MICROSCOPY	17.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14927-F1	93.77	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 2, 12, 12, 19, 78, 78, 83, 96

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-9865881	Complex III assembly

MSigDB gene sets: 249 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MODULE_93, MORF_MBD4, MODULE_151, MODULE_77, MORF_HDAC1, MORF_RAD21, HSIAO_HOUSEKEEPING_GENES, MODULE_149, PATIL_LIVER_CANCER, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MARTINEZ_RB1_TARGETS_UP

GO Biological Process (4): oxidative phosphorylation (GO:0006119), mitochondrial electron transport, ubiquinol to cytochrome c (GO:0006122), aerobic respiration (GO:0009060), cellular respiration (GO:0045333)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), respiratory chain complex III (GO:0045275), respiratory chain complex (GO:0098803), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aerobic respiration	1
proton motive force-driven ATP synthesis	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	1
energy derivation by oxidation of organic compounds	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cytochrome complex	1
respiratory chain complex	1
transmembrane transporter complex	1
oxidoreductase complex	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UQCRB	UQCRQ	O14949	998
UQCRB	MT-CYB	P00156	984
UQCRB	UQCRC2	P22695	979
UQCRB	CYC1	P08574	978
UQCRB	UQCRC1	P31930	964
UQCRB	UQCR10	Q9UDW1	945
UQCRB	UQCRFS1	P47985	913
UQCRB	UQCRH	P07919	905
UQCRB	BCS1L	Q9Y276	897
UQCRB	CYCS	P00001	801
UQCRB	COX7A1	P24310	799
UQCRB	UQCR11	O14957	788
UQCRB	COX5B	P10606	757
UQCRB	NDUFB4	O95168	696
UQCRB	COX5A	P20674	647

IntAct

126 interactions, top by confidence:

A	B	Type	Score
UQCRB	MAGEA4	psi-mi:“MI:0915”(physical association)	0.850
MAGEA4	UQCRB	psi-mi:“MI:0915”(physical association)	0.850
UQCRC1	UQCRQ	psi-mi:“MI:0915”(physical association)	0.740
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
UQCRQ	COX7A2L	psi-mi:“MI:0914”(association)	0.640
UQCRB	COX7A2L	psi-mi:“MI:0914”(association)	0.640
CYC1	UQCRB	psi-mi:“MI:0915”(physical association)	0.640
UQCRB	MAGEA4	psi-mi:“MI:0915”(physical association)	0.560
ACCS	UQCRB	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	ACCS	psi-mi:“MI:0915”(physical association)	0.560
MAGEA4	UQCRB	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	ACAP1	psi-mi:“MI:0915”(physical association)	0.560
MAGEB4	UQCRB	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	ZSWIM7	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	HPCA	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	FYN	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	BECN1	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	KIAA0355	psi-mi:“MI:0915”(physical association)	0.560
LAPTM4A	UQCRB	psi-mi:“MI:0915”(physical association)	0.560
UQCRB	LARP4B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (200): UQCRB (Two-hybrid), ACCS (Two-hybrid), UQCRB (Affinity Capture-MS), UQCRB (Affinity Capture-MS), UQCRB (Two-hybrid), UQCRC2 (Affinity Capture-MS), COX7A2L (Affinity Capture-MS), MYO18A (Affinity Capture-MS), UHRF1 (Affinity Capture-MS), S100A10 (Affinity Capture-MS), PRKCA (Affinity Capture-MS), UQCRC1 (Affinity Capture-MS), CYTB (Affinity Capture-MS), RABL6 (Affinity Capture-MS), UQCR10 (Affinity Capture-MS)

ESM2 similar proteins: A0A0K2GUJ4, A0A1D8PJ73, A3LN78, M9RZ95, O01369, O60169, O74533, P00128, P00129, P0CAB8, P14927, P30815, P33334, P34621, P38231, P46268, P49345, P53733, P82926, P90993, Q04697, Q09375, Q17439, Q22438, Q28GD1, Q54HY7, Q54QG4, Q5ABS1, Q5BJJ8, Q5RC24, Q61SE7, Q6BNL9, Q6BNQ5, Q6C3K7, Q6CTS4, Q6CUZ6, Q6FS31, Q6FSD7, Q6FSJ2, Q6PBR7

Diamond homologs: A0A0K2GUJ4, F4JWS8, M9RZ95, O01369, O01374, O74533, P00128, P00129, P14927, P46268, P48502, P49345, Q5ABS1, Q5RC24, Q6BNQ5, Q6FSJ2, Q751U4, Q871K1, Q9D855, Q9GP40, Q9SUU5, Q54M82, Q6C3K7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
UQCRB	“form complex”	“CoQ-cytochrome c reductase-Mitochondrial respiratory chain complex III”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Complex III assembly	6	41.8×	9e-07
Respiratory electron transport	17	25.7×	2e-17
Complex IV assembly	6	21.8×	4e-05
Cytoprotection by HMOX1	6	17.5×	1e-04
Complex I biogenesis	5	13.1×	2e-03
TP53 Regulates Metabolic Genes	6	12.4×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial electron transport, cytochrome c to oxygen	7	64.6×	3e-09
cellular respiration	10	52.1×	2e-12
mitochondrial electron transport, NADH to ubiquinone	6	25.9×	2e-05
aerobic respiration	7	20.9×	8e-06
proton motive force-driven mitochondrial ATP synthesis	5	15.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

87 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	25
Likely benign	32
Benign	9

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
215348	NM_006294.5(UQCRB):c.274del (p.Glu92fs)	Pathogenic
666435	GRCh37/hg19 8q22.1(chr8:97154645-98155535)x3	Pathogenic
215346	NM_006294.5(UQCRB):c.56A>T (p.Lys19Ile)	Likely pathogenic
444760	NM_006294.5(UQCRB):c.310G>T (p.Glu104Ter)	Likely pathogenic

SpliceAI

737 predictions. Top by Δscore:

Variant	Effect	Δscore
8:96231768:TGCTA:T	donor_loss	1.0000
8:96231769:GCTAC:G	donor_loss	1.0000
8:96231770:CTACC:C	donor_loss	1.0000
8:96231771:TA:T	donor_loss	1.0000
8:96231772:AC:A	donor_loss	1.0000
8:96231773:C:CA	donor_loss	1.0000
8:96231773:CCT:C	donor_gain	1.0000
8:96231775:T:TA	donor_gain	1.0000
8:96231854:T:TA	donor_gain	1.0000
8:96231936:TAACC:T	acceptor_gain	1.0000
8:96231937:AACC:A	acceptor_gain	1.0000
8:96231938:ACC:A	acceptor_gain	1.0000
8:96231939:CC:C	acceptor_gain	1.0000
8:96231939:CCC:C	acceptor_gain	1.0000
8:96231940:CC:C	acceptor_gain	1.0000
8:96231941:C:CC	acceptor_gain	1.0000
8:96231941:C:T	acceptor_gain	1.0000
8:96231941:CTAT:C	acceptor_loss	1.0000
8:96231942:T:C	acceptor_loss	1.0000
8:96235510:ACCGG:A	donor_gain	1.0000
8:96235511:CCGGC:C	donor_gain	1.0000
8:96231047:C:CT	donor_gain	0.9900
8:96231048:T:TT	donor_gain	0.9900
8:96231050:CATGA:C	donor_gain	0.9900
8:96231060:T:TA	donor_gain	0.9900
8:96231732:T:TA	donor_gain	0.9900
8:96231774:C:G	donor_loss	0.9900
8:96231943:A:AC	acceptor_gain	0.9900
8:96235506:ACTT:A	donor_loss	0.9900
8:96235507:CTT:C	donor_loss	0.9900

AlphaMissense

726 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:96233166:G:C	F27L	0.994
8:96233166:G:T	F27L	0.994
8:96233168:A:G	F27L	0.994
8:96231940:C:T	G31E	0.993
8:96231826:A:G	L69P	0.992
8:96231835:G:T	A66E	0.992
8:96231855:C:A	R59S	0.992
8:96231855:C:G	R59S	0.992
8:96231937:A:G	L32S	0.992
8:96233156:C:G	G31R	0.992
8:96233156:C:T	G31R	0.992
8:96231836:C:G	A66P	0.991
8:96231847:C:G	R62P	0.991
8:96231848:G:T	R62S	0.991
8:96231856:C:A	R59M	0.990
8:96231880:A:G	L51P	0.990
8:96231880:A:T	L51H	0.990
8:96231882:T:A	R50S	0.990
8:96231882:T:G	R50S	0.990
8:96231883:C:G	R50T	0.990
8:96231926:C:G	D36H	0.990
8:96231893:C:G	A47P	0.988
8:96233156:C:A	G31W	0.988
8:96231107:A:G	L95P	0.987
8:96231849:A:C	F61L	0.987
8:96231849:A:T	F61L	0.987
8:96231851:A:G	F61L	0.987
8:96231856:C:G	R59T	0.987
8:96231832:A:G	L67P	0.986
8:96231805:A:G	L76S	0.985

dbSNP variants (sampled 300 via entrez): RS1000502694 (8:96223063 G>T), RS1000664450 (8:96229485 C>G,T), RS1000831861 (8:96233599 A>T), RS1000874704 (8:96233282 T>C), RS1001327772 (8:96228791 A>G), RS1001674224 (8:96229113 A>G), RS1002062945 (8:96223939 A>G), RS1002221154 (8:96236264 C>A), RS1002834190 (8:96236702 T>C), RS1003322181 (8:96231291 A>C,G,T), RS1003469803 (8:96231517 T>C,G), RS1003771156 (8:96226472 A>G), RS1003842825 (8:96237386 C>T), RS1005007174 (8:96225718 A>C,T), RS1005020941 (8:96226165 T>C)

Disease associations

OMIM: gene MIM:191330 | disease phenotypes: MIM:615158, MIM:151200

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial complex III deficiency nuclear type 3	Strong	Autosomal recessive
mitochondrial complex III deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (3): mitochondrial complex III deficiency nuclear type 3 (MONDO:0014064), Leri pleonosteosis (MONDO:0007894), mitochondrial complex III deficiency (MONDO:0015448)

Orphanet (1): Leri pleonosteosis (Orphanet:2900)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0002151	Increased circulating lactate concentration
HP:0002240	Hepatomegaly
HP:0003593	Infantile onset
HP:0011924	Decreased activity of mitochondrial complex III
HP:0012759	Neurodevelopmental abnormality
HP:0020078	Alaninuria
HP:0031956	Elevated circulating aspartate aminotransferase concentration
HP:0031964	Elevated circulating alanine aminotransferase concentration

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004691_8	Huntington’s disease progression	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C537118	Leri pleonosteosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1671612 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

5 potent at pChembl≥5 of 8 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.60	IC50	2500	nM	CHEMBL3360259
5.30	IC50	5000	nM	CHEMBL188279
5.30	IC50	5000	nM	CHEMBL3360267
5.10	IC50	8000	nM	CHEMBL185823
5.10	IC50	8000	nM	CHEMBL186268

PubChem BioAssay actives

5 with measured affinity, of 31 total; 5 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(4-hydroxyphenyl)-4-phenylbenzenesulfonamide	1165236: Modulation of UQCRB in human HepG2 cells assessed as inhibition of HIF-1alpha for 4 hrs under 1%O2 by Western blot analysis	ic50	2.5000	uM
potassium 4-[(4-phenylphenyl)sulfonylamino]phenolate	1165236: Modulation of UQCRB in human HepG2 cells assessed as inhibition of HIF-1alpha for 4 hrs under 1%O2 by Western blot analysis	ic50	5.0000	uM
4-tert-butyl-N-(4-hydroxyphenyl)benzenesulfonamide	1165236: Modulation of UQCRB in human HepG2 cells assessed as inhibition of HIF-1alpha for 4 hrs under 1%O2 by Western blot analysis	ic50	5.0000	uM
4-tert-butyl-N-(2-hydroxyphenyl)benzenesulfonamide	1165236: Modulation of UQCRB in human HepG2 cells assessed as inhibition of HIF-1alpha for 4 hrs under 1%O2 by Western blot analysis	ic50	8.0000	uM
4-tert-butyl-N-(3-hydroxyphenyl)benzenesulfonamide	1165236: Modulation of UQCRB in human HepG2 cells assessed as inhibition of HIF-1alpha for 4 hrs under 1%O2 by Western blot analysis	ic50	8.0000	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	7
Atrazine	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
1,2,5,6-dibenzanthracene	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
1-methyl-4-phenyl-2,3-dihydropyridinium	decreases expression	1
epigallocatechin gallate	increases expression, affects cotreatment	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	increases reaction, affects binding	1
corosolic acid	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
ICG 001	decreases expression	1
jinfukang	decreases expression	1
5-hydroxythalidomide	affects binding	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Bilirubin	decreases expression	1
Copper	affects binding, decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1671404	Binding	Binding affinity to UQCRB expressed in T7 phage at 100 uM after 1 hr by competitive binding assay	Identification of a novel small molecule targeting UQCRB of mitochondrial complex III and its anti-angiogenic activity. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_QX48	MCCI0001i-HCM	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.