UQCC5

Summary

UQCC5 (ubiquinol-cytochrome c reductase complex assembly factor 5, HGNC:37257) is a protein-coding gene on chromosome 3p21.1, encoding Ubiquinol-cytochrome c reductase complex assembly factor 5 (Q8WVI0). 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….

Enables mitochondrial ribosome binding activity. Involved in mitochondrial cytochrome c oxidase assembly. Located in mitochondrion. Is active in mitochondrial inner membrane.

Source: NCBI Gene 440957 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_001124767

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37257
Approved symbol	UQCC5
Name	ubiquinol-cytochrome c reductase complex assembly factor 5
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000168273
Ensembl biotype	protein_coding
OMIM	620435
Entrez	440957

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000307106, ENST00000476842, ENST00000477703, ENST00000482728, ENST00000491607, ENST00000916170

RefSeq mRNA: 1 — MANE Select: NM_001124767 NM_001124767

CCDS: CCDS46844

Canonical transcript exons

ENST00000477703 — 2 exons

Exon	Start	End
ENSE00001285599	52536605	52536906
ENSE00001954171	52540424	52541890

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 97.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.6558 / max 814.9422, expressed in 1822 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36877	62.6193	1819
36882	6.7637	1710
36879	5.8160	1723
36881	2.4388	1433
36876	1.6946	930
36878	0.9808	623
36880	0.3425	149

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left adrenal gland cortex	UBERON:0035825	97.37	gold quality
left adrenal gland	UBERON:0001234	97.07	gold quality
right adrenal gland	UBERON:0001233	96.68	gold quality
right adrenal gland cortex	UBERON:0035827	96.42	gold quality
adenohypophysis	UBERON:0002196	95.94	gold quality
apex of heart	UBERON:0002098	95.89	gold quality
right atrium auricular region	UBERON:0006631	95.52	gold quality
adrenal cortex	UBERON:0001235	95.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.96	gold quality
adrenal gland	UBERON:0002369	94.82	gold quality
left lobe of thyroid gland	UBERON:0001120	94.75	gold quality
heart left ventricle	UBERON:0002084	94.11	gold quality
cardiac atrium	UBERON:0002081	93.80	gold quality
right lobe of thyroid gland	UBERON:0001119	93.54	gold quality
muscle of leg	UBERON:0001383	93.54	gold quality
cardiac ventricle	UBERON:0002082	93.47	gold quality
gastrocnemius	UBERON:0001388	93.43	gold quality
pituitary gland	UBERON:0000007	93.14	gold quality
thyroid gland	UBERON:0002046	93.01	gold quality
heart	UBERON:0000948	92.53	gold quality
left ovary	UBERON:0002119	92.49	gold quality
metanephros cortex	UBERON:0010533	91.47	gold quality
right ovary	UBERON:0002118	90.75	gold quality
left coronary artery	UBERON:0001626	90.23	gold quality
mucosa of stomach	UBERON:0001199	90.19	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.45	gold quality
lower esophagus	UBERON:0013473	89.41	gold quality
right coronary artery	UBERON:0001625	89.26	gold quality
endocervix	UBERON:0000458	88.68	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-11	yes	93.72
E-ANND-3	yes	15.74

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Defining the interactome of the human mitochondrial ribosome identifies SMIM4 and TMEM223 as respiratory chain assembly factors. (PMID:34969438)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	uqcc5	ENSDARG00000089921
mus_musculus	Uqcc5	ENSMUSG00000058351
rattus_norvegicus	Uqcc5	ENSRNOG00000068020
drosophila_melanogaster	sloth1	FBGN0052736

Protein

Protein identifiers

Ubiquinol-cytochrome c reductase complex assembly factor 5 — Q8WVI0 (reviewed: Q8WVI0)

Alternative names: Small integral membrane protein 4

All UniProt accessions (3): C9JAX8, Q8WVI0, F8W7Q2

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 involved in the first steps of cytochrome c oxidase complex (complex IV) assembly.

Subunit / interactions. Associates with the mitochondrial ribosome. Interacts with UQCC6. Interacts with MT-CYB; interacts with newly synthesizes MT-CYB. Forms a complex, named COMB/coordinator of mitochondrial CYTB biogenesis, composed of UQCC1, UQCC2, UQCC4, UQCC5 and UQCC6; regulates MT-CYB synthesis and promotes its membrane insertion.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the UQCC5 family.

RefSeq proteins (1): NP_001118239* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028183	UQCC5	Family

Pfam: PF15114

UniProt features (4 total): topological domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WVI0-F1	68.34	0.07

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9865881	Complex III assembly

MSigDB gene sets: 0 (showing top):

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

GO Molecular Function (1): mitochondrial ribosome binding (GO:0097177)

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
ribosome 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

390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UQCC5	TMEM223	A0PJW6	577
UQCC5	NT5DC2	Q9H857	511
UQCC5	OXA1L	Q15070	494
UQCC5	MAGED2	Q9UNF1	477
UQCC5	P4HTM	Q9NXG6	475
UQCC5	AGR2	O95994	444
UQCC5	INPP4B	O15327	444
UQCC5	GTPBP10	A4D1E9	443
UQCC5	MALSU1	Q96EH3	437
UQCC5	UQCC1	Q9NVA1	431
UQCC5	UQCC6	Q69YU5	420
UQCC5	MRM3	Q9HC36	414
UQCC5	DDX28	Q9NUL7	413
UQCC5	MCMDC2	Q4G0Z9	406
UQCC5	TIMMDC1	Q9NPL8	399

IntAct

17 interactions, top by confidence:

A	B	Type	Score
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATF2	PLOD2	psi-mi:“MI:0914”(association)	0.350
MYC	AP3B1	psi-mi:“MI:0914”(association)	0.350
STAT3	IDH3B	psi-mi:“MI:0914”(association)	0.350
CASP3	TMEM223	psi-mi:“MI:0914”(association)	0.350
FOS	TMEM223	psi-mi:“MI:0914”(association)	0.350
GATA2	C11orf98	psi-mi:“MI:0914”(association)	0.350
ATF3	C11orf98	psi-mi:“MI:0914”(association)	0.350
CASP3	NACA	psi-mi:“MI:0914”(association)	0.350
CTNNA1	KIF2A	psi-mi:“MI:0914”(association)	0.350
ERBB2	AP3B1	psi-mi:“MI:0914”(association)	0.350
FOS	C11orf98	psi-mi:“MI:0914”(association)	0.350
ERBB2	AGPS	psi-mi:“MI:0914”(association)	0.350
STAT3	NACA	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): SMIM4 (Affinity Capture-MS), SMIM4 (Affinity Capture-MS), SMIM4 (Affinity Capture-MS), SMIM4 (Affinity Capture-MS), SMIM4 (Affinity Capture-MS), SMIM4 (Cross-Linking-MS (XL-MS)), SMIM4 (Affinity Capture-RNA)

ESM2 similar proteins: A1L2P2, A2VDV9, A5PJ82, D2H617, D3Z9R8, D4ACP2, E2R5I0, E7EXZ6, F6USH3, G1QDE8, G1S9B8, O00483, O95298, P11951, P14790, P56378, P56379, Q0MQ97, Q0MQ98, Q0MQ99, Q0MQF7, Q0MQF8, Q0MQF9, Q0Q4Z0, Q28EM2, Q28GF4, Q2NKS2, Q4FZG9, Q502E5, Q5BKW8, Q5RCY6, Q5RDZ8, Q5REX0, Q62425, Q68EV8, Q69YU5, Q78IK2, Q78RX3, Q7YRJ8, Q7YRK7

Diamond homologs: Q8C1Q6, Q8WVI0, Q9W3T5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of gene expression	5	9.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1970 predictions. Top by Δscore:

Variant	Effect	Δscore
3:52536907:G:GG	donor_gain	1.0000
3:52548231:TCGAG:T	acceptor_gain	1.0000
3:52548232:CGAG:C	acceptor_gain	1.0000
3:52548232:CGAGC:C	acceptor_gain	1.0000
3:52548233:GAG:G	acceptor_gain	1.0000
3:52548234:AG:A	acceptor_gain	1.0000
3:52548236:C:CC	acceptor_gain	1.0000
3:52548236:CTGA:C	acceptor_loss	1.0000
3:52548242:A:AC	acceptor_gain	1.0000
3:52548242:A:C	acceptor_gain	1.0000
3:52548243:T:C	acceptor_gain	1.0000
3:52548243:T:TC	acceptor_gain	1.0000
3:52548248:G:C	acceptor_gain	1.0000
3:52548248:G:GC	acceptor_gain	1.0000
3:52550415:TCTTA:T	donor_loss	1.0000
3:52550416:CTTA:C	donor_loss	1.0000
3:52550417:TTACC:T	donor_loss	1.0000
3:52550418:TACC:T	donor_loss	1.0000
3:52550419:A:AC	donor_gain	1.0000
3:52550419:ACCT:A	donor_loss	1.0000
3:52550419:ACCTG:A	donor_gain	1.0000
3:52550420:C:CC	donor_gain	1.0000
3:52550420:C:CT	donor_loss	1.0000
3:52550420:CCTG:C	donor_gain	1.0000
3:52550420:CCTGC:C	donor_gain	1.0000
3:52550635:CACCT:C	acceptor_loss	1.0000
3:52550637:CCTGA:C	acceptor_loss	1.0000
3:52550639:T:G	acceptor_loss	1.0000
3:52550814:ACACC:A	acceptor_loss	1.0000
3:52550815:CAC:C	acceptor_gain	1.0000

AlphaMissense

446 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:52536875:G:A	M40I	0.992
3:52536875:G:C	M40I	0.992
3:52536875:G:T	M40I	0.992
3:52536903:T:C	F50L	0.992
3:52536905:C:A	F50L	0.992
3:52536905:C:G	F50L	0.992
3:52540436:G:C	R55P	0.987
3:52540440:A:C	R56S	0.982
3:52540440:A:T	R56S	0.982
3:52536866:G:C	E37D	0.979
3:52536866:G:T	E37D	0.979
3:52536853:G:A	G33E	0.978
3:52536904:T:G	F50C	0.976
3:52536852:G:A	G33R	0.974
3:52536852:G:C	G33R	0.974
3:52536847:T:A	V31D	0.972
3:52536856:G:A	G34E	0.972
3:52536904:T:C	F50S	0.971
3:52540439:G:C	R56T	0.971
3:52536832:T:G	L26R	0.970
3:52536865:A:T	E37V	0.967
3:52536901:C:T	T49I	0.967
3:52540435:C:A	R55S	0.967
3:52536864:G:A	E37K	0.964
3:52536867:T:A	W38R	0.962
3:52536867:T:C	W38R	0.962
3:52536835:C:G	P27R	0.961
3:52536855:G:A	G34R	0.961
3:52536855:G:C	G34R	0.961
3:52536877:T:C	I41T	0.961

dbSNP variants (sampled 300 via entrez): RS1000039280 (3:52536808 A>G), RS1000051190 (3:52537691 G>A), RS1000151301 (3:52537912 C>G), RS1001108182 (3:52539324 C>T), RS1001322787 (3:52537550 A>G), RS1002174375 (3:52537324 G>A), RS1002267647 (3:52537631 G>A), RS1002394953 (3:52538670 A>G), RS1002599940 (3:52539333 C>T), RS1002734126 (3:52538965 C>G,T), RS1003880542 (3:52540193 A>C,G), RS1004162234 (3:52539879 C>T), RS1004175265 (3:52535277 A>T), RS1004227702 (3:52535569 A>G), RS1004283767 (3:52541983 T>C,G)

Disease associations

OMIM: gene MIM:620435 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST002149_14	Schizophrenia	1.000000e-08
GCST002539_48	Schizophrenia	4.000000e-11
GCST004521_123	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST004521_201	Autism spectrum disorder or schizophrenia	4.000000e-08
GCST004521_259	Autism spectrum disorder or schizophrenia	6.000000e-09
GCST005316_399	Intelligence (MTAG)	1.000000e-08
GCST006803_55	Schizophrenia	1.000000e-11
GCST008103_3	Bipolar disorder	7.000000e-11
GCST010698_14	Subcortical volume (min-P)	8.000000e-09
GCST010699_73	Brain morphology (min-P)	1.000000e-18
GCST010701_137	Cortical surface area (MOSTest)	8.000000e-10
GCST010702_70	Subcortical volume (MOSTest)	2.000000e-11
GCST010703_327	Brain morphology (MOSTest)	1.000000e-10
GCST012228_63	Waist-hip index	5.000000e-11
GCST012230_260	Waist-to-hip ratio adjusted for BMI	6.000000e-10
GCST90020025_1342	Waist-to-hip ratio adjusted for BMI	5.000000e-13
GCST90020027_124	Waist-hip index	1.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004346	neuroimaging measurement
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	2
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
ICG 001	decreases expression	1
jinfukang	increases expression	1
Acetaminophen	increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2GP	Abcam HeLa SMIM4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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