COX7C

Summary

COX7C (cytochrome c oxidase subunit 7C, HGNC:2292) is a protein-coding gene on chromosome 5q14.3, encoding Cytochrome c oxidase subunit 7C, mitochondrial (P15954). Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. It is a selective cancer dependency (DepMap: 81.8% of cell lines).

Cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain, catalyzes the electron transfer from reduced cytochrome c to oxygen. This component is a heteromeric complex consisting of 3 catalytic subunits encoded by mitochondrial genes and multiple structural subunits encoded by nuclear genes. The mitochondrially-encoded subunits function in electron transfer, and the nuclear-encoded subunits may function in the regulation and assembly of the complex. This nuclear gene encodes subunit VIIc, which shares 87% and 85% amino acid sequence identity with mouse and bovine COX VIIc, respectively, and is found in all tissues. A pseudogene COX7CP1 has been found on chromosome 13.

Source: NCBI Gene 1350 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 17 total
• Cancer dependency (DepMap): dependent in 81.8% of screened cell lines
• MANE Select transcript: NM_001867

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2292
Approved symbol	COX7C
Name	cytochrome c oxidase subunit 7C
Location	5q14.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000127184
Ensembl biotype	protein_coding
OMIM	603774
Entrez	1350

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000247655, ENST00000505430, ENST00000509578, ENST00000510447, ENST00000511472, ENST00000513124, ENST00000515763, ENST00000900830, ENST00000900831, ENST00000927184, ENST00000927185, ENST00000927186, ENST00000927187, ENST00000927188

RefSeq mRNA: 1 — MANE Select: NM_001867 NM_001867

CCDS: CCDS4063

Canonical transcript exons

ENST00000247655 — 3 exons

Exon	Start	End
ENSE00000998734	86617941	86618130
ENSE00000998735	86620668	86620962
ENSE00003492291	86619353	86619496

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 351.2982 / max 4860.3445, expressed in 1827 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57439	318.1383	1827
57440	11.8908	1753
57441	10.6691	1675
57442	8.2334	1596
203616	2.3666	1210

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.82	gold quality
right atrium auricular region	UBERON:0006631	99.82	gold quality
cardiac atrium	UBERON:0002081	99.80	gold quality
cardiac ventricle	UBERON:0002082	99.80	gold quality
heart left ventricle	UBERON:0002084	99.80	gold quality
apex of heart	UBERON:0002098	99.79	gold quality
heart	UBERON:0000948	99.77	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.77	gold quality
adult mammalian kidney	UBERON:0000082	99.73	gold quality
prefrontal cortex	UBERON:0000451	99.73	gold quality
ganglionic eminence	UBERON:0004023	99.72	gold quality
biceps brachii	UBERON:0001507	99.71	gold quality
mucosa of transverse colon	UBERON:0004991	99.70	gold quality
cortical plate	UBERON:0005343	99.70	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.70	gold quality
anterior cingulate cortex	UBERON:0009835	99.70	gold quality
caudate nucleus	UBERON:0001873	99.69	gold quality
cingulate cortex	UBERON:0003027	99.69	gold quality
muscle of leg	UBERON:0001383	99.68	gold quality
nucleus accumbens	UBERON:0001882	99.68	gold quality
right frontal lobe	UBERON:0002810	99.68	gold quality
metanephros cortex	UBERON:0010533	99.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.68	gold quality
gastrocnemius	UBERON:0001388	99.67	gold quality
adenohypophysis	UBERON:0002196	99.67	gold quality
myocardium	UBERON:0002349	99.67	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.67	gold quality
pituitary gland	UBERON:0000007	99.66	gold quality
muscle organ	UBERON:0001630	99.66	gold quality
skeletal muscle organ	UBERON:0014892	99.66	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	3731.78
E-CURD-98	yes	2464.62
E-MTAB-9221	yes	48.35
E-MTAB-7316	yes	24.40
E-MTAB-10042	yes	15.31
E-HCAD-9	yes	8.10
E-HCAD-10	no	2429.77
E-MTAB-10596	no	2335.45
E-MTAB-10662	no	2310.36
E-GEOD-86618	no	395.11
E-HCAD-4	no	83.52
E-MTAB-8410	no	45.85
E-MTAB-8271	no	9.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BAP1, HCFC1, RNF2, YY1

miRNA regulators (miRDB)

6 targeting COX7C, 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-766-5P	99.47	67.91	2225
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-640	98.44	66.93	644
HSA-MIR-11401	90.58	63.72	128
HSA-MIR-598-3P	89.25	67.61	112

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 81.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• The expression level of COX7C associates with venous thromboembolism in colon cancer patients. (PMID:32653968)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cox7c	ENSDARG00000104537
mus_musculus	Cox7c	ENSMUSG00000017778
rattus_norvegicus		ENSRNOG00000063840
rattus_norvegicus	Cox7cl1	ENSRNOG00000065320
rattus_norvegicus		ENSRNOG00000066702
drosophila_melanogaster	COX7C	FBGN0040773
caenorhabditis_elegans	cox-7C	WBGENE00009161

Protein

Protein identifiers

Cytochrome c oxidase subunit 7C, mitochondrial — P15954 (reviewed: P15954)

Alternative names: Cytochrome c oxidase polypeptide VIIc

All UniProt accessions (2): P15954, D6R9Z7

UniProt curated annotations — full annotation on UniProt →

Function. Component of the cytochrome c oxidase, the last enzyme in 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. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.

Subunit / interactions. Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C, COX7A2 (or COX7A1), COX7B, COX7C, COX8A and COXFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)). Interacts with RAB5IF.

Subcellular location. Mitochondrion inner membrane.

Pathway. Energy metabolism; oxidative phosphorylation.

Similarity. Belongs to the cytochrome c oxidase VIIc family.

RefSeq proteins (1): NP_001858* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004202	COX7C/Cox8	Family
IPR036636	COX7C/Cox8_sf	Homologous_superfamily

Pfam: PF02935

UniProt features (7 total): topological domain 2, modified residue 2, transit peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9I6F	ELECTRON MICROSCOPY	2.95
9I7U	ELECTRON MICROSCOPY	3.15
5Z62	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15954-F1	91.28	0.63

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 (2): 25, 25

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-611105	Respiratory electron transport
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 193 (showing top): MODULE_93, HONMA_DOCETAXEL_RESISTANCE, MODULE_151, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, MORF_UBE2I, MORF_HDAC1, HSIAO_HOUSEKEEPING_GENES, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MORF_SKP1A, GOBP_OXIDATIVE_PHOSPHORYLATION, MORF_CTBP1, GOBP_ELECTRON_TRANSPORT_CHAIN, GNF2_FBL, KEGG_HUNTINGTONS_DISEASE

GO Biological Process (4): generation of precursor metabolites and energy (GO:0006091), mitochondrial electron transport, cytochrome c to oxygen (GO:0006123), cellular respiration (GO:0045333), oxidative phosphorylation (GO:0006119)

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

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial membrane (GO:0031966), respiratory chain complex IV (GO:0045277), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transcriptional Regulation by TP53	1
Aerobic respiration and respiratory electron transport	1
Cellular response to chemical stress	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

1738 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COX7C	COX6C	P09669	987
COX7C	COX5B	P10606	983
COX7C	COX7B	P24311	948
COX7C	COX6B1	P14854	908
COX7C	COX6A1	P12074	846
COX7C	COX8A	P10176	846
COX7C	COX5A	P20674	839
COX7C	COX6A2	Q02221	810
COX7C	COXFA4	O00483	798
COX7C	COX7A1	P24310	764
COX7C	NDUFA1	O15239	737
COX7C	MT-ND5	P03915	736
COX7C	NDUFB9	Q9Y6M9	725
COX7C	MT-CO2	P00403	713
COX7C	COA6	Q5JTJ3	704

IntAct

23 interactions, top by confidence:

A	B	Type	Score
COX7C	MAGEA2	psi-mi:“MI:0915”(physical association)	0.560
COX7C	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
MT-CO2	COX6C	psi-mi:“MI:0915”(physical association)	0.560
COX5B	COX7A2L	psi-mi:“MI:0914”(association)	0.530
COX7C	E6	psi-mi:“MI:0915”(physical association)	0.370
K8.1	EXOC5	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NUDT19	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NDUFS8	psi-mi:“MI:0914”(association)	0.350
NDUFA4	COX7A2L	psi-mi:“MI:0914”(association)	0.350
rep	STXBP3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
COX7C	COX7A2L	psi-mi:“MI:0914”(association)	0.350
CLPP	NDUFA4	psi-mi:“MI:2364”(proximity)	0.270
COX7C	MAGEA2	psi-mi:“MI:0915”(physical association)	0.000
COX7C	CIDEB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (108): COX7C (Affinity Capture-MS), COX7C (Affinity Capture-MS), COX7C (Affinity Capture-MS), EIF3C (Positive Genetic), PGK1 (Negative Genetic), SKA3 (Positive Genetic), COX7C (Proximity Label-MS), BCAP31 (Co-fractionation), COX7C (Co-fractionation), COX7C (Co-fractionation), COX7C (Co-fractionation), COX7C (Co-fractionation), COX5A (Co-fractionation), PHB (Co-fractionation), ATP5F1 (Co-fractionation)

ESM2 similar proteins: C0HLM6, D3Z7Q2, D3ZAF6, E7EXZ6, F1MDB2, O95563, P00130, P00430, P12633, P13182, P13184, P14406, P15954, P17665, P29419, P35171, P56135, P56385, P60025, P61638, P61639, P80432, Q00361, Q01321, Q06185, Q1W0Y2, Q28851, Q2KHV4, Q3B8P0, Q53CF9, Q53CG2, Q5R4Z3, Q5R5H4, Q5RBW2, Q5XIA8, Q5XJY4, Q62425, Q7YRK5, Q8L7H8, Q8N5G0

Diamond homologs: P00430, P15954, P17665, P60025, P61638, P61639, P80334, P80432, Q1W0Y2, Q53CF9, Q53CG2, Q7YRK5, Q8SPI1, Q8SQ80, Q8SQ81

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
YY1	“up-regulates quantity by expression”	COX7C	“transcriptional regulation”
COX7C	“form complex”	“Cytochrome c oxidase-Mitochondrial respiratory chain complex IV”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Respiratory electron transport	5	43.3×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

584 predictions. Top by Δscore:

Variant	Effect	Δscore
5:86619393:C:G	donor_gain	1.0000
5:86619443:G:GG	donor_gain	1.0000
5:86619471:G:GT	donor_gain	1.0000
5:86618051:GCG:G	donor_gain	0.9900
5:86619349:ACAG:A	acceptor_loss	0.9900
5:86619350:CA:C	acceptor_loss	0.9900
5:86619351:A:AG	acceptor_gain	0.9900
5:86619351:AG:A	acceptor_loss	0.9900
5:86619352:G:GG	acceptor_gain	0.9900
5:86619352:G:T	acceptor_loss	0.9900
5:86619352:GA:G	acceptor_gain	0.9900
5:86619352:GAA:G	acceptor_gain	0.9900
5:86619397:GATGT:G	donor_gain	0.9900
5:86619440:GTA:G	donor_gain	0.9900
5:86619441:T:TA	donor_gain	0.9900
5:86619442:A:AA	donor_gain	0.9900
5:86619466:A:G	donor_gain	0.9900
5:86620662:TTGCA:T	acceptor_loss	0.9900
5:86620663:TGCA:T	acceptor_loss	0.9900
5:86620664:GCA:G	acceptor_loss	0.9900
5:86620665:CAGA:C	acceptor_loss	0.9900
5:86620666:A:AG	acceptor_gain	0.9900
5:86620666:A:C	acceptor_loss	0.9900
5:86620667:G:GG	acceptor_gain	0.9900
5:86620667:GAT:G	acceptor_gain	0.9900
5:86620667:GATAT:G	acceptor_gain	0.9900
5:86618116:G:GT	donor_gain	0.9800
5:86619352:GAATT:G	acceptor_gain	0.9800
5:86619466:A:AG	donor_gain	0.9800
5:86618128:AAG:A	donor_loss	0.9700

AlphaMissense

403 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:86619414:G:A	G46E	0.991
5:86619426:C:A	A50D	0.991
5:86619413:G:A	G46R	0.989
5:86619413:G:C	G46R	0.989
5:86619401:T:C	C42R	0.981
5:86619420:C:A	A48E	0.981
5:86619362:T:C	F29L	0.980
5:86619363:T:C	F29S	0.980
5:86619364:T:A	F29L	0.980
5:86619364:T:G	F29L	0.980
5:86619407:T:G	Y44D	0.980
5:86619393:C:A	A39D	0.972
5:86618087:C:T	T11I	0.970
5:86619360:C:A	P28Q	0.962
5:86618096:T:A	V14D	0.960
5:86619355:T:A	N26K	0.959
5:86619355:T:G	N26K	0.959
5:86619399:T:G	M41R	0.958
5:86619425:G:C	A50P	0.958
5:86618126:G:A	G24E	0.953
5:86619434:T:C	F53L	0.953
5:86619436:C:A	F53L	0.953
5:86619436:C:G	F53L	0.953
5:86618080:T:C	F9L	0.948
5:86618082:C:A	F9L	0.948
5:86618082:C:G	F9L	0.948
5:86618126:G:T	G24V	0.948
5:86619399:T:A	M41K	0.948
5:86619429:C:A	T51K	0.947
5:86618125:G:T	G24W	0.946

dbSNP variants (sampled 300 via entrez): RS1000433990 (5:86618363 C>A,T), RS1000465045 (5:86618621 C>T), RS1000630921 (5:86617281 T>C), RS1000795389 (5:86617435 C>T), RS1001435985 (5:86619810 C>T), RS1002624077 (5:86619709 C>G,T), RS1002870116 (5:86616417 A>G), RS1002901137 (5:86616788 T>C), RS1003772964 (5:86621234 A>G), RS1003868323 (5:86617905 G>C,T), RS1004564099 (5:86620541 C>A), RS1005196971 (5:86618174 T>G), RS10059868 (5:86616740 T>C), RS1006209316 (5:86619012 T>C), RS1006241997 (5:86619268 G>A,C)

Disease associations

OMIM: gene MIM:603774 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002041_5	Blood trace element (Cu levels)	2.000000e-06
GCST006618_3	Uterine fibroid size (maximum dimension)	8.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005267	serum copper measurement
EFO:0009410	uterine fibroid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
Acetaminophen	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Doxorubicin	affects expression, increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	increases expression	1
arsenite	affects binding, increases reaction	1
methylparaben	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	increases expression	1
isobutyl alcohol	increases abundance, affects cotreatment, decreases expression	1
pinosylvin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases expression	1
chloropicrin	decreases expression	1
K 7174	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Estradiol	decreases expression	1
Fluorouracil	affects expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Hydralazine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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