COX7A1

Summary

COX7A1 (cytochrome c oxidase subunit 7A1, HGNC:2287) is a protein-coding gene on chromosome 19q13.12, encoding Cytochrome c oxidase subunit 7A1, mitochondrial (P24310). Component of the mitochondrial respiratory complex IV (CIV, also named cytochrome c oxidase complex), the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.

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 polypeptide 1 (muscle isoform) of subunit VIIa and the polypeptide 1 is present only in muscle tissues. Other polypeptides of subunit VIIa are present in both muscle and nonmuscle tissues, and are encoded by different genes.

Source: NCBI Gene 1346 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_001864

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2287
Approved symbol	COX7A1
Name	cytochrome c oxidase subunit 7A1
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	COX7AH
Ensembl gene	ENSG00000161281
Ensembl biotype	protein_coding
OMIM	123995
Entrez	1346

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000292907, ENST00000437291, ENST00000481297, ENST00000589154

RefSeq mRNA: 1 — MANE Select: NM_001864 NM_001864

CCDS: CCDS12490

Canonical transcript exons

ENST00000292907 — 4 exons

Exon	Start	End
ENSE00001057391	36152393	36152447
ENSE00003514987	36151669	36151755
ENSE00003684500	36151462	36151546
ENSE00003700794	36150922	36151034

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.96.

FANTOM5 (CAGE): breadth broad, TPM avg 14.4040 / max 932.8178, expressed in 851 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180658	13.7906	826
208792	0.4785	25
180660	0.1349	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.96	gold quality
apex of heart	UBERON:0002098	99.92	gold quality
left ventricle myocardium	UBERON:0006566	99.91	gold quality
diaphragm	UBERON:0001103	99.90	gold quality
cardiac ventricle	UBERON:0002082	99.89	gold quality
heart left ventricle	UBERON:0002084	99.89	gold quality
cardiac atrium	UBERON:0002081	99.88	gold quality
right atrium auricular region	UBERON:0006631	99.88	gold quality
biceps brachii	UBERON:0001507	99.86	gold quality
myocardium	UBERON:0002349	99.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.86	gold quality
vastus lateralis	UBERON:0001379	99.85	gold quality
gastrocnemius	UBERON:0001388	99.85	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.85	gold quality
quadriceps femoris	UBERON:0001377	99.83	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.82	gold quality
triceps brachii	UBERON:0001509	99.81	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.81	gold quality
gluteal muscle	UBERON:0002000	99.79	gold quality
skeletal muscle tissue	UBERON:0001134	99.77	gold quality
body of tongue	UBERON:0011876	99.75	gold quality
heart	UBERON:0000948	99.69	gold quality
vena cava	UBERON:0004087	99.60	gold quality
muscle organ	UBERON:0001630	99.53	gold quality
muscle tissue	UBERON:0002385	99.52	gold quality
muscle of leg	UBERON:0001383	99.42	gold quality
tibialis anterior	UBERON:0001385	99.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.35	gold quality
deltoid	UBERON:0001476	99.33	gold quality
popliteal artery	UBERON:0002250	99.33	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-79	yes	609.09
E-MTAB-6701	yes	114.87
E-HCAD-1	yes	77.12
E-MTAB-10287	yes	47.89
E-MTAB-8410	yes	25.85
E-CURD-46	yes	10.15
E-GEOD-84465	yes	8.69
E-MTAB-7037	no	142.21
E-MTAB-8060	no	110.51
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MEF2A, TRPV4

Literature-anchored findings (GeneRIF, showing 7)

• promoter contains and is regulated by sequence elements typical of contractile muscle as well as the element for the common transcription factor Sp1 (PMID:11997101)
• While DNA methylation of the COX7A1 promoter was increased in muscle from elderly compared with young twins, the opposite was found for COX7A1 mRNA expression (PMID:18488190)
• Data found that subunits Cox6a, Cox6b and Cox7a assembled into pre-existing complex IV, while Cox4-1 and Cox6c subunits assembled into subcomplexes that may represent rate-limiting intermediates. (PMID:19843159)
• We demonstrate a developmental isoform switch of COX6A and COX7A subunits in human and mouse skeletal muscle (PMID:25666558)
• COX7A1 is a novel gene that might play a crucial role in the etiology of lung adenocarcinoma and can serve as a biomarker for lung cancer disease progression (PMID:27866983)
• COX7A1 enhances the sensitivity of human NSCLC cells to cystine deprivation-induced ferroptosis via regulating mitochondrial metabolism. (PMID:36418320)
• Overexpression of COX7A1 Promotes the Resistance of Gastric Cancer to Oxaliplatin and Weakens the Efficacy of Immunotherapy. (PMID:38830579)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cox7a1	ENSMUSG00000074218
rattus_norvegicus	Cox7a1	ENSRNOG00000076290
drosophila_melanogaster	COX7AL	FBGN0037579
drosophila_melanogaster	COX7AL2	FBGN0085201

Paralogs (2): COX7A2 (ENSG00000112695), COX7A2L (ENSG00000115944)

Protein

Protein identifiers

Cytochrome c oxidase subunit 7A1, mitochondrial — P24310 (reviewed: P24310)

Alternative names: Cytochrome c oxidase subunit VIIa-heart, Cytochrome c oxidase subunit VIIa-muscle

All UniProt accessions (4): P24310, K7ER11, Q6FGI7, U3KQH8

UniProt curated annotations — full annotation on UniProt →

Function. Component of the mitochondrial respiratory complex IV (CIV, also named cytochrome c oxidase complex), the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The CIV complex is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Acts as an assembly factor that specifically drives the homodimerization of CIV complexes, mediating the formation of mitochondrial respiratory supercomplexes (respirasomes) containing two CIV: supercomplxes with two molecules of CIV show improved activity. Despite being highly expressed in brown adipose tissue, not required for thermogenesis.

Subunit / interactions. Component of the complex IV (CIV, cytochrome c oxidase), 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, COX6A2 (or COX6A1), COX6B1 (or COX6B2), COX6C, COX7A1 (or COX7A2), COX7B, COX7C, COX8B 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)).

Subcellular location. Mitochondrion inner membrane.

Pathway. Energy metabolism; oxidative phosphorylation.

Similarity. Belongs to the cytochrome c oxidase VIIa family.

RefSeq proteins (1): NP_001855* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003177	Cytc_oxidase_su7a_met	Family
IPR036539	Cyt_c_oxidase_su7a_sf	Homologous_superfamily
IPR039297	COX7a	Family

Pfam: PF02238

UniProt features (5 total): topological domain 2, transit peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24310-F1	88.43	0.68

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5628897	TP53 Regulates Metabolic Genes
R-HSA-611105	Respiratory electron transport
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 205 (showing top): MODULE_93, YAGI_AML_WITH_INV_16_TRANSLOCATION, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GNF2_MYL3, TANG_SENESCENCE_TP53_TARGETS_UP, GOBP_MONOATOMIC_CATION_TRANSPORT, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, MODULE_66, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, GOBP_OXIDATIVE_PHOSPHORYLATION, WONG_ENDMETRIUM_CANCER_DN, GOBP_ELECTRON_TRANSPORT_CHAIN

GO Biological Process (5): generation of precursor metabolites and energy (GO:0006091), oxidative phosphorylation (GO:0006119), mitochondrial electron transport, cytochrome c to oxygen (GO:0006123), mitochondrial respirasome assembly (GO:0097250), proton transmembrane transport (GO:1902600)

GO Molecular Function (3): cytochrome-c oxidase activity (GO:0004129), oxidoreductase activity (GO:0016491), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial membrane (GO:0031966), respiratory chain complex IV (GO:0045277), respiratory chain complex (GO:0098803), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Transcriptional Regulation by TP53	1
Aerobic respiration and respiratory electron transport	1
Cellular response to chemical stress	1
Transcriptional regulation of brown and beige adipocyte differentiation	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	1
aerobic respiration	1
proton motive force-driven ATP synthesis	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
mitochondrion organization	1
mitochondrial respiratory chain complex assembly	1
monoatomic cation transmembrane transport	1
electron transfer activity	1
proton transmembrane transporter activity	1
oxidoreduction-driven active transmembrane transporter activity	1
oxidoreductase activity, acting on a heme group of donors	1
active monoatomic ion transmembrane transporter activity	1
catalytic activity	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
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COX7A1	COX6B1	P14854	952
COX7A1	UQCRC1	P31930	945
COX7A1	UQCR11	O14957	932
COX7A1	COX6A2	Q02221	886
COX7A1	COX5B	P10606	883
COX7A1	COX6A1	P12074	870
COX7A1	UQCRB	P14927	799
COX7A1	CIDEA	O60543	788
COX7A1	COX7C	P15954	764
COX7A1	COXFA4	O00483	763
COX7A1	COX4I2	Q96KJ9	731
COX7A1	COX5A	P20674	728
COX7A1	COX4I1	P13073	725
COX7A1	FXYD5	Q96DB9	722
COX7A1	UCP1	P25874	721

IntAct

14 interactions, top by confidence:

A	B	Type	Score
NDUFS1	COX7A1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	COX7A1	psi-mi:“MI:0915”(physical association)	0.560
NUP58	COX7A1	psi-mi:“MI:0915”(physical association)	0.560
DNAJB6	COX7A1	psi-mi:“MI:0915”(physical association)	0.560
COX7A1	GLS	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): PLGRKT (Affinity Capture-MS), GLS (Affinity Capture-MS), UBR1 (Affinity Capture-MS), COX6C (Affinity Capture-MS), COX4I1 (Affinity Capture-MS), POLG (Affinity Capture-MS), COX6B1 (Affinity Capture-MS), COX2 (Affinity Capture-MS), COX3 (Affinity Capture-MS), COX1 (Affinity Capture-MS), COX5B (Affinity Capture-MS), PFDN1 (Cross-Linking-MS (XL-MS)), TCERG1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1XQS2, A4IJ20, F6QZ15, O14548, O60397, P0CU26, P13183, P14406, P24310, P34660, P46269, P56392, Q0V9J0, Q17ED3, Q290M9, Q2KI08, Q2M2S2, Q3T061, Q4QQV3, Q4R6H1, Q4VC39, Q5R504, Q5RE99, Q5REP2, Q5XIJ4, Q5XKA2, Q5ZML6, Q61387, Q64445, Q7JX57, Q7QHP6, Q7SXI1, Q7Z4L0, Q8BGY7, Q8BTC1, Q91W29, Q91Y94, Q99KD6, Q9BUB7, Q9BVV7

Diamond homologs: O14548, O60397, P07470, P13184, P14406, P24310, P35171, P48771, P56392, Q08CE7, Q3T061, Q53CF6, Q61387, Q7SXI1, Q8SPJ9, Q99KD6, Q9N234, Q9TR29, Q9VHS2, Q9TR28, Q9TR30, Q9TRZ8, P80333

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

500 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36151680:T:TA	donor_gain	1.0000
19:36151460:ACCG:A	donor_gain	0.9900
19:36151460:ACCGC:A	donor_gain	0.9900
19:36151461:CCG:C	donor_gain	0.9900
19:36151461:CCGC:C	donor_gain	0.9900
19:36151461:CCGCC:C	donor_gain	0.9900
19:36151487:TCGG:T	donor_gain	0.9900
19:36151694:A:AC	donor_gain	0.9900
19:36151695:C:CC	donor_gain	0.9900
19:36151455:CGCT:C	donor_loss	0.9800
19:36151456:GCTC:G	donor_loss	0.9800
19:36151458:T:TC	donor_loss	0.9800
19:36151459:C:CC	donor_loss	0.9800
19:36151460:A:AC	donor_gain	0.9800
19:36151461:C:CC	donor_gain	0.9800
19:36151488:CGGT:C	donor_gain	0.9800
19:36151756:CTGCG:C	acceptor_loss	0.9800
19:36151544:CTC:C	acceptor_gain	0.9700
19:36151547:C:CC	acceptor_gain	0.9700
19:36151753:CAC:C	acceptor_gain	0.9700
19:36152386:GCCTC:G	donor_loss	0.9600
19:36152387:CCTCA:C	donor_loss	0.9600
19:36152388:CTCA:C	donor_loss	0.9600
19:36152389:TCA:T	donor_loss	0.9600
19:36152390:CACCC:C	donor_loss	0.9600
19:36152391:AC:A	donor_gain	0.9600
19:36152392:CC:C	donor_gain	0.9600
19:36152439:C:A	donor_gain	0.9600
19:36151474:G:C	donor_gain	0.9500
19:36152411:G:A	donor_gain	0.9400

AlphaMissense

505 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:36151021:G:C	S67R	0.983
19:36151021:G:T	S67R	0.983
19:36151023:T:G	S67R	0.983
19:36151517:C:A	K44N	0.973
19:36151517:C:G	K44N	0.973
19:36151672:G:C	F33L	0.973
19:36151672:G:T	F33L	0.973
19:36151674:A:G	F33L	0.973
19:36151681:C:A	Q30H	0.961
19:36151681:C:G	Q30H	0.961
19:36151673:A:C	F33C	0.957
19:36151465:C:G	G62R	0.947
19:36151464:C:T	G62D	0.945
19:36151471:A:G	C60R	0.930
19:36151673:A:G	F33S	0.929
19:36151503:T:A	D49V	0.928
19:36151502:G:C	D49E	0.927
19:36151502:G:T	D49E	0.927
19:36151462:C:G	G63R	0.923
19:36151034:C:T	G63D	0.920
19:36151521:A:G	L43P	0.920
19:36151669:C:A	Q34H	0.919
19:36151669:C:G	Q34H	0.919
19:36151518:T:A	K44M	0.918
19:36151518:T:G	K44T	0.918
19:36151504:C:G	D49H	0.911
19:36151729:G:C	F14L	0.910
19:36151729:G:T	F14L	0.910
19:36151731:A:G	F14L	0.910
19:36151503:T:G	D49A	0.909

dbSNP variants (sampled 300 via entrez): RS1000585096 (19:36152850 C>G,T), RS1000617632 (19:36152663 G>T), RS1002351480 (19:36152059 G>T), RS1003165174 (19:36153589 G>A), RS1003994734 (19:36151031 G>A), RS1004487313 (19:36154446 C>T), RS1004851907 (19:36153006 T>C), RS1004874128 (19:36153872 A>T), RS1005886213 (19:36152336 G>A), RS1008534287 (19:36154204 T>C), RS1008717833 (19:36154254 A>G), RS1010930947 (19:36151345 C>G,T), RS1010962214 (19:36151071 A>G), RS1011754945 (19:36153255 C>A,G,T), RS1012184648 (19:36150640 A>G)

Disease associations

OMIM: gene MIM:123995 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002592_32	Neuritic plaque	6.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006798	neuritic plaque measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
JP8 aviation fuel	decreases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Acetaminophen	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Nickel	decreases expression	1
Progesterone	decreases expression	1
Selenium	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Zidovudine	decreases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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