UQCC6

Summary

UQCC6 (ubiquinol-cytochrome c reductase complex assembly factor 6, HGNC:34450) is a protein-coding gene on chromosome 12q23.3, encoding Ubiquinol-cytochrome c reductase complex assembly factor 6 (Q69YU5). Required for the assembly and stability of the mitochondrial ubiquinol-cytochrome c reductase complex (complex III (CIII) or cytochrome b-c1 complex), a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain (ETC) which drives oxidative pho….

Involved in mitochondrial cytochrome c oxidase assembly and mitochondrial respiratory chain complex III assembly. Located in mitochondrion. Is active in mitochondrial inner membrane.

Source: NCBI Gene 728568 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001135570

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34450
Approved symbol	UQCC6
Name	ubiquinol-cytochrome c reductase complex assembly factor 6
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13975, DKFZp547P055, BR
Ensembl gene	ENSG00000204954
Ensembl biotype	protein_coding
OMIM	618812
Entrez	728568

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000378090, ENST00000543740, ENST00000546540, ENST00000546819, ENST00000547945, ENST00000547975, ENST00000549478, ENST00000549960, ENST00000552460, ENST00000552940, ENST00000553183, ENST00000651157, ENST00000866169, ENST00000920803, ENST00000920804, ENST00000920805

RefSeq mRNA: 1 — MANE Select: NM_001135570 NM_001135570

CCDS: CCDS44964

Canonical transcript exons

ENST00000378090 — 3 exons

Exon	Start	End
ENSE00001476226	103956631	103956748
ENSE00001476228	103957069	103957215
ENSE00002332702	103950194	103951630

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 93.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.9928 / max 165.9154, expressed in 1795 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132985	15.9960	1780
132987	1.8827	1059
132986	0.5932	301
132984	0.5208	289

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vastus lateralis	UBERON:0001379	93.44	gold quality
quadriceps femoris	UBERON:0001377	92.94	gold quality
tibialis anterior	UBERON:0001385	92.38	gold quality
biceps brachii	UBERON:0001507	92.20	gold quality
deltoid	UBERON:0001476	91.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.09	gold quality
left ventricle myocardium	UBERON:0006566	90.76	silver quality
skeletal muscle tissue	UBERON:0001134	90.73	gold quality
endothelial cell	CL:0000115	90.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.63	gold quality
muscle tissue	UBERON:0002385	90.08	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.07	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.02	gold quality
kidney epithelium	UBERON:0004819	89.88	silver quality
cortical plate	UBERON:0005343	89.16	gold quality
muscle of leg	UBERON:0001383	88.76	gold quality
gastrocnemius	UBERON:0001388	88.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.63	gold quality
prefrontal cortex	UBERON:0000451	86.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.55	gold quality
myocardium	UBERON:0002349	85.43	silver quality
heart left ventricle	UBERON:0002084	85.20	gold quality
ganglionic eminence	UBERON:0004023	85.16	gold quality
left ovary	UBERON:0002119	85.14	gold quality
right ovary	UBERON:0002118	85.11	gold quality
right adrenal gland	UBERON:0001233	85.03	gold quality
left adrenal gland cortex	UBERON:0035825	84.90	gold quality
cardiac ventricle	UBERON:0002082	84.89	gold quality
right adrenal gland cortex	UBERON:0035827	84.78	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	22.21
E-CURD-112	yes	7.15
E-ANND-3	yes	5.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

72 targeting UQCC6, 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-656-3P	100.00	72.15	2788
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540

Literature-anchored findings (GeneRIF, showing 2)

• Study demonstrate that BRAWNIN, a 71 a.a. peptide encoded by C12orf73, is essential for respiratory chain complex III (CIII) assembly. In human cells, BRAWNIN is induced by the energy-sensing AMPK pathway, and its depletion impairs mitochondrial ATP production. Findings demonstrate that BRAWNIN is essential for vertebrate oxidative phosphorylation. (PMID:32161263)
• Knockdown of BRAWNIN minimally affect mitochondrial complex III assembly in human cells. (PMID:37769950)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	uqcc6	ENSDARG00000045797
mus_musculus	Uqcc6	ENSMUSG00000063320
rattus_norvegicus	Uqcc6	ENSRNOG00000026982

Protein

Protein identifiers

Ubiquinol-cytochrome c reductase complex assembly factor 6 — Q69YU5 (reviewed: Q69YU5)

Alternative names: Protein BRAWNIN

All UniProt accessions (5): Q69YU5, F8VQR3, F8VS87, F8VXG8, G3V1W1

UniProt curated annotations — full annotation on UniProt →

Function. Required for the assembly and stability of the mitochondrial ubiquinol-cytochrome c reductase complex (complex III (CIII) or cytochrome b-c1 complex), a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain (ETC) which drives oxidative phosphorylation. Mediates early complex III biogenesis. Participates in regulating the levels of electron transport chain proteins, and therefore energy supply, in response to changes in energy demand. Also required for cytochrome c oxidase complex (complex IV) assembly.

Subunit / interactions. Interacts with UQCRC1. Interacts with UQCRQ. Interacts with UQCC5. Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; stabilizes nascent cytochrome b/MT-CYB and promotes its membrane insertion. Forms a complex, named COMA, composed of UQCC1, UQCC2 and UQCC4; activates MT-CYB translation. Forms a complex, named COMC, composed of UQCC1, UQCC2; UQCC3 and UQCC4; mediates MT-CYB hemylation and association with the first nuclear-encoded complex III subunit UQCRQ. Interacts with MT-CYB.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Cardiac and skeletal muscle (at protein level).

Induction. Up-regulated in response to glucose, serum, fatty acid starvation and AMPK activation using 5-aminoimidizole-4-carboxamide-1-beta- D-riboside.

Similarity. Belongs to the UQCC6 family.

RefSeq proteins (1): NP_001129042* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027858	BRAWNIN	Family

Pfam: PF14990

UniProt features (5 total): topological domain 2, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q69YU5-F1	70.99	0.30

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9865881	Complex III assembly

MSigDB gene sets: 134 (showing top): GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, PATIL_LIVER_CANCER, GOCC_MITOCHONDRIAL_ENVELOPE, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, PETRETTO_HEART_MASS_QTL_CIS_UP, GOCC_ORGANELLE_INNER_MEMBRANE, chr12q23, GOCC_ORGANELLE_ENVELOPE, PLASARI_TGFB1_SIGNALING_VIA_NFIC_10HR_DN, GSE14699_NAIVE_VS_ACT_CD8_TCELL_UP, ALKBH3_TARGET_GENES, ATF6_TARGET_GENES

GO Biological Process (2): mitochondrial respiratory chain complex IV assembly (GO:0033617), mitochondrial respiratory chain complex III assembly (GO:0034551)

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

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
mitochondrial respiratory chain complex assembly	2
respiratory chain complex IV assembly	1
respiratory chain complex III assembly	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UQCC6	ZNF583	Q96ND8	478
UQCC6	TMEM247	A6NEH6	473
UQCC6	MTMR8	Q96EF0	449
UQCC6	ANKRD39	Q53RE8	447
UQCC6	CLDND2	Q8NHS1	437
UQCC6	RALGPS1	Q5JS13	425
UQCC6	UQCC5	Q8WVI0	420
UQCC6	SAXO4	Q7Z5V6	419
UQCC6	TMEM223	A0PJW6	418
UQCC6	CCDC81	Q6ZN84	418
UQCC6	SFXN2	Q96NB2	414
UQCC6	DHRS13	Q6UX07	395
UQCC6	SCNM1	Q9BWG6	391
UQCC6	RIPOR1	Q6ZS17	379
UQCC6	DNAJB14	Q8TBM8	374

IntAct

9 interactions, top by confidence:

A	B	Type	Score
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
GHITM	MFN2	psi-mi:“MI:0914”(association)	0.530
SLC25A32	CS	psi-mi:“MI:0914”(association)	0.350
AIFM1	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
SFXN1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
IMMP1L	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
PARL	HAX1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (13): C12orf73 (Affinity Capture-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Proximity Label-MS), C12orf73 (Affinity Capture-MS), C12orf73 (Affinity Capture-MS)

ESM2 similar proteins: A1XQS2, D3Z9R8, E2R4X3, E9PQ53, O14548, O60397, O82067, P14790, P34660, P46269, P46270, P56378, P56379, Q02827, Q1RMH3, Q29259, Q2KI08, Q3SZ13, Q3T061, Q3ZBI7, Q4V8S3, Q56JY4, Q5R987, Q5RDZ8, Q5XFV8, Q5ZML6, Q61387, Q63ZZ0, Q69YU5, Q78IK2, Q7SXI1, Q8BH51, Q8BTC1, Q8C1Q6, Q8N0X7, Q96B49, Q96I36, Q96IX5, Q96KF7, Q99KD6

Diamond homologs: E7EXZ6, Q5RDZ8, Q69YU5, Q8BTC1, B7Z0X7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1961 predictions. Top by Δscore:

Variant	Effect	Δscore
12:103941405:CACAG:C	acceptor_loss	1.0000
12:103941408:A:AG	acceptor_gain	1.0000
12:103941408:A:T	acceptor_loss	1.0000
12:103941408:AG:A	acceptor_gain	1.0000
12:103941409:G:GG	acceptor_gain	1.0000
12:103941409:GG:G	acceptor_gain	1.0000
12:103941409:GGAAA:G	acceptor_gain	1.0000
12:103941543:TTAAG:T	donor_gain	1.0000
12:103941545:AAGGT:A	donor_loss	1.0000
12:103941546:AGGTG:A	donor_loss	1.0000
12:103941547:GGTG:G	donor_loss	1.0000
12:103941548:G:GG	donor_gain	1.0000
12:103941624:TTTA:T	acceptor_loss	1.0000
12:103941627:A:AG	acceptor_gain	1.0000
12:103941627:AGCTC:A	acceptor_loss	1.0000
12:103941628:G:GA	acceptor_gain	1.0000
12:103941628:GC:G	acceptor_gain	1.0000
12:103941628:GCT:G	acceptor_gain	1.0000
12:103941628:GCTC:G	acceptor_gain	1.0000
12:103941628:GCTCT:G	acceptor_gain	1.0000
12:103941702:GTGTG:G	donor_gain	1.0000
12:103941703:TGTG:T	donor_gain	1.0000
12:103941704:GTG:G	donor_gain	1.0000
12:103941704:GTGG:G	donor_gain	1.0000
12:103941705:TGGT:T	donor_gain	1.0000
12:103941707:G:GG	donor_gain	1.0000
12:103941708:T:A	donor_loss	1.0000
12:103941820:T:TA	acceptor_gain	1.0000
12:103941824:A:AG	acceptor_gain	1.0000
12:103941824:ATCT:A	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000180615 (12:103961528 C>G,T), RS1000377654 (12:103965028 G>A,T), RS1000385508 (12:103955962 G>A), RS1000733591 (12:103960353 C>A,G), RS1000935131 (12:103966489 C>T), RS1001678218 (12:103955521 C>G), RS1001876438 (12:103966113 G>C), RS1001991023 (12:103966198 C>G,T), RS1002150335 (12:103955171 G>A), RS1002179979 (12:103960196 G>A), RS1002212907 (12:103959965 G>A), RS1002319695 (12:103966114 C>G,T), RS1002415167 (12:103953816 C>G,T), RS1002471087 (12:103959751 T>C), RS1002527918 (12:103950378 A>G)

Disease associations

OMIM: gene MIM:618812 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
methylmercuric chloride	decreases expression	1
arsenite	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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