UQCC4

Summary

UQCC4 (ubiquinol-cytochrome c reductase complex assembly factor 4, HGNC:27558) is a protein-coding gene on chromosome 16p13.3, encoding Ubiquinol-cytochrome c reductase complex assembly factor 4 (Q4G0I0). 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….

Predicted to be involved in mitochondrial respiratory chain complex III assembly. Located in mitochondrion.

Source: NCBI Gene 283951 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001272051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27558
Approved symbol	UQCC4
Name	ubiquinol-cytochrome c reductase complex assembly factor 4
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	gs103, CCSMST1, URLC5
Ensembl gene	ENSG00000174109
Ensembl biotype	protein_coding
OMIM	620578
Entrez	283951

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000442039, ENST00000563974

RefSeq mRNA: 1 — MANE Select: NM_001272051 NM_001272051

CCDS: CCDS61789

Canonical transcript exons

ENST00000442039 — 2 exons

Exon	Start	End
ENSE00001769495	1419752	1420612
ENSE00001801629	1420692	1420747

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 89.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9750 / max 83.3943, expressed in 1804 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155844	12.9750	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	89.35	silver quality
tibialis anterior	UBERON:0001385	88.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.69	gold quality
mucosa of transverse colon	UBERON:0004991	87.44	gold quality
right adrenal gland	UBERON:0001233	86.76	gold quality
right adrenal gland cortex	UBERON:0035827	86.76	gold quality
left adrenal gland	UBERON:0001234	86.60	gold quality
left adrenal gland cortex	UBERON:0035825	86.47	gold quality
deltoid	UBERON:0001476	86.28	silver quality
gastrocnemius	UBERON:0001388	86.23	gold quality
adrenal cortex	UBERON:0001235	86.21	gold quality
prefrontal cortex	UBERON:0000451	86.06	gold quality
kidney epithelium	UBERON:0004819	86.03	gold quality
ileal mucosa	UBERON:0000331	85.87	gold quality
muscle of leg	UBERON:0001383	85.63	gold quality
tendon of biceps brachii	UBERON:0008188	85.43	silver quality
apex of heart	UBERON:0002098	85.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.19	gold quality
adrenal gland	UBERON:0002369	84.88	gold quality
heart left ventricle	UBERON:0002084	84.82	gold quality
cortical plate	UBERON:0005343	84.78	gold quality
cardiac ventricle	UBERON:0002082	84.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.63	gold quality
anterior cingulate cortex	UBERON:0009835	84.28	gold quality
right frontal lobe	UBERON:0002810	84.12	gold quality
frontal cortex	UBERON:0001870	83.94	gold quality
cerebellar vermis	UBERON:0004720	83.92	gold quality
skin of leg	UBERON:0001511	83.87	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	83.82	gold quality
quadriceps femoris	UBERON:0001377	83.81	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.65
E-MTAB-7052	no	89.71

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	uqcc4	ENSDARG00000100025
mus_musculus	Uqcc4	ENSMUSG00000067722
rattus_norvegicus	Uqcc4	ENSRNOG00000029415

Protein

Protein identifiers

Ubiquinol-cytochrome c reductase complex assembly factor 4 — Q4G0I0 (reviewed: Q4G0I0)

Alternative names: Protein CCSMST1

All UniProt accessions (2): Q4G0I0, A0A0A8K8N9

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.

Subunit / interactions. 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. Complexes COMA and COMB are bound to the mitochondrion inner membrane by UQCC4.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the UQCC4 family.

RefSeq proteins (1): NP_001258980* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023248	UQCC4_vert	Family
IPR029160	UQCC4	Family

Pfam: PF15013

UniProt features (7 total): topological domain 2, region of interest 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0I0-F1	63.40	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, GOCC_MITOCHONDRIAL_ENVELOPE, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_LIVER_CANCER_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOCC_ORGANELLE_INNER_MEMBRANE, NIKOLSKY_BREAST_CANCER_16P13_AMPLICON, GOCC_ORGANELLE_ENVELOPE, EIF4E_UP, BCL6B_TARGET_GENES

GO Biological Process (1): mitochondrial respiratory chain complex III assembly (GO:0034551)

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UQCC4	C15orf61	A6NNL5	511
UQCC4	GKN2	Q86XP6	509
UQCC4	GKN1	Q9NS71	485
UQCC4	MAGEF1	Q9HAY2	395
UQCC4	NDUFAF8	A1L188	392
UQCC4	DMAC1	Q96GE9	367
UQCC4	RCN2	Q14257	366
UQCC4	CEBPZOS	A8MTT3	352
UQCC4	QTRT1	Q9BXR0	348
UQCC4	NTMT1	Q9BV86	324
UQCC4	HMBS	P08396	319
UQCC4	FRYL	O94915	301
UQCC4	ACTBL2	Q562R1	298
UQCC4	BOLA3	Q53S33	296
UQCC4	FLAD1	Q8NFF5	294

IntAct

8 interactions, top by confidence:

A	B	Type	Score
COX20	ECM1	psi-mi:“MI:0914”(association)	0.350
	PLOD3	psi-mi:“MI:0914”(association)	0.350
CHODL	RAD51C	psi-mi:“MI:0914”(association)	0.350
UQCC2	UQCC4	psi-mi:“MI:0914”(association)	0.350
COX20	UQCC4	psi-mi:“MI:0914”(association)	0.350
CLMN	UQCC4	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): C16orf91 (Affinity Capture-MS), C16orf91 (Affinity Capture-MS), C16orf91 (Affinity Capture-MS), C16orf91 (Affinity Capture-MS), C16orf91 (Affinity Capture-MS), C16orf91 (Affinity Capture-MS), C16orf91 (Affinity Capture-RNA)

ESM2 similar proteins: A1A4P4, A1CH36, A2ALW5, A5AAL8, B0BN56, O42911, O70279, P0C2B7, P58468, P83565, Q0CLE8, Q1ECT8, Q290P4, Q2GVC2, Q3SZ86, Q4G0I0, Q4V7Q1, Q5B4U6, Q5BJW9, Q5RFR4, Q5XJW2, Q61733, Q6RUT7, Q753F1, Q7SDU5, Q7SHR9, Q80ZS3, Q86TS9, Q8BGX2, Q8BK72, Q8CHP5, Q8SPE7, Q8TAE8, Q8VD26, Q8WUQ7, Q96AN5, Q96DF8, Q9BRP8, Q9BSF4, Q9BYN8

Diamond homologs: A8WGU8, Q1ECT8, Q4G0I0, Q5RFR4, Q6RUT7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 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

186 predictions. Top by Δscore:

Variant	Effect	Δscore
16:1420728:G:GA	donor_gain	0.9900
16:1420685:AGCT:A	donor_loss	0.9800
16:1420686:GCTC:G	donor_loss	0.9800
16:1420687:CT:C	donor_loss	0.9800
16:1420688:TCAC:T	donor_loss	0.9800
16:1420689:CACC:C	donor_loss	0.9800
16:1420690:A:AG	donor_loss	0.9800
16:1420690:AC:A	donor_gain	0.9800
16:1420691:CC:C	donor_gain	0.9800
16:1420691:CCCGG:C	donor_gain	0.9800
16:1420746:ACG:A	donor_gain	0.9800
16:1420747:CGC:C	donor_gain	0.9800
16:1420690:A:AC	donor_gain	0.9700
16:1420691:C:CC	donor_gain	0.9700
16:1420737:C:CA	donor_gain	0.9600
16:1420608:CGGCC:C	acceptor_gain	0.9500
16:1420745:G:T	donor_gain	0.9500
16:1420613:C:CC	acceptor_gain	0.9400
16:1420736:T:TA	donor_gain	0.9200
16:1420610:GCCC:G	acceptor_loss	0.9100
16:1420612:CCT:C	acceptor_loss	0.9100
16:1420614:T:A	acceptor_loss	0.9100
16:1420611:CC:C	acceptor_gain	0.8800
16:1420612:CC:C	acceptor_gain	0.8800
16:1420671:CCGAG:C	donor_gain	0.8800
16:1420610:GCC:G	acceptor_gain	0.8700
16:1420611:CCC:C	acceptor_gain	0.8700
16:1420609:GGCC:G	acceptor_gain	0.8500
16:1420726:C:CT	donor_gain	0.8500
16:1420727:T:TT	donor_gain	0.8500

AlphaMissense

849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:1420489:A:C	F52L	0.986
16:1420489:A:T	F52L	0.986
16:1420491:A:G	F52L	0.986
16:1420396:G:C	S83R	0.978
16:1420396:G:T	S83R	0.978
16:1420398:T:G	S83R	0.978
16:1420490:A:C	F52C	0.930
16:1420395:A:G	C84R	0.927
16:1420480:G:C	S55R	0.927
16:1420480:G:T	S55R	0.927
16:1420482:T:G	S55R	0.927
16:1420459:C:A	W62C	0.925
16:1420459:C:G	W62C	0.925
16:1420490:A:G	F52S	0.922
16:1420461:A:G	W62R	0.911
16:1420461:A:T	W62R	0.911
16:1420371:A:G	W92R	0.899
16:1420371:A:T	W92R	0.899
16:1420357:C:A	R96S	0.898
16:1420357:C:G	R96S	0.898
16:1420368:A:G	C93R	0.895
16:1420358:C:A	R96M	0.880
16:1420481:C:A	S55I	0.872
16:1420481:C:T	S55N	0.872
16:1420358:C:G	R96T	0.841
16:1420382:G:T	A88E	0.822
16:1420340:T:A	D102V	0.807
16:1420414:C:A	W77C	0.803
16:1420414:C:G	W77C	0.803
16:1420339:G:C	D102E	0.796

dbSNP variants (sampled 300 via entrez): RS1000318633 (16:1422451 C>T), RS1001819866 (16:1422636 C>T), RS1002578574 (16:1422109 G>A), RS1003213206 (16:1420339 G>A,C,T), RS1003267625 (16:1420131 C>G), RS1004745771 (16:1422664 G>A,T), RS1005447294 (16:1420387 G>A), RS1007116505 (16:1420015 G>A,C), RS1007157155 (16:1421714 G>A), RS1008167844 (16:1420781 G>A,T), RS1009099218 (16:1421626 A>G), RS1010619480 (16:1419699 T>C), RS1010857728 (16:1420077 G>A), RS1010966089 (16:1421091 C>G,T), RS1011443500 (16:1420935 G>A,C,T)

Disease associations

OMIM: gene MIM:620578 | 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

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases mutagenesis, affects methylation	2
aristolochic acid I	increases expression	1
arsenite	increases reaction, affects binding	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects methylation	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Doxorubicin	increases expression	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Zinc	affects cotreatment, increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1SR	HAP1 C16orf91 (-) 1	Cancer cell line	Male
CVCL_E1SS	HAP1 C16orf91 (-) 2	Cancer cell line	Male
CVCL_E1ST	HAP1 C16orf91 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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