COX8C

Summary

COX8C (cytochrome c oxidase subunit 8C, HGNC:24382) is a protein-coding gene on chromosome 14q32.12, encoding Cytochrome c oxidase subunit 8C, mitochondrial (Q7Z4L0). Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.

Predicted to be involved in mitochondrial electron transport, cytochrome c to oxygen. Located in mitochondrion.

Source: NCBI Gene 341947 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_182971

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24382
Approved symbol	COX8C
Name	cytochrome c oxidase subunit 8C
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Aliases	COX8-3
Ensembl gene	ENSG00000187581
Ensembl biotype	protein_coding
OMIM	616855
Entrez	341947

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000342144

RefSeq mRNA: 1 — MANE Select: NM_182971 NM_182971

CCDS: CCDS9910

Canonical transcript exons

ENST00000342144 — 2 exons

Exon	Start	End
ENSE00001370680	93347182	93347394
ENSE00001375230	93348028	93348356

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 96.42.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1866 / max 193.9665, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141175	0.1866	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	96.42	gold quality
left testis	UBERON:0004533	96.16	gold quality
testis	UBERON:0000473	95.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.83	gold quality
apex of heart	UBERON:0002098	60.21	gold quality
placenta	UBERON:0001987	59.85	gold quality
right uterine tube	UBERON:0001302	58.54	gold quality
lower esophagus mucosa	UBERON:0035834	55.13	gold quality
right hemisphere of cerebellum	UBERON:0014890	54.67	gold quality
heart left ventricle	UBERON:0002084	53.86	gold quality
cerebellar hemisphere	UBERON:0002245	53.22	gold quality
cerebellar cortex	UBERON:0002129	52.95	gold quality
cerebellum	UBERON:0002037	52.89	gold quality
fallopian tube	UBERON:0003889	52.30	gold quality
mucosa of transverse colon	UBERON:0004991	51.63	gold quality
gastrocnemius	UBERON:0001388	51.13	gold quality
heart	UBERON:0000948	50.75	gold quality
right coronary artery	UBERON:0001625	50.23	gold quality
mucosa of stomach	UBERON:0001199	49.22	gold quality
muscle of leg	UBERON:0001383	49.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	48.95	gold quality
smooth muscle tissue	UBERON:0001135	48.72	gold quality
right atrium auricular region	UBERON:0006631	48.69	gold quality
right ovary	UBERON:0002118	48.31	gold quality
descending thoracic aorta	UBERON:0002345	48.17	gold quality
Ammon’s horn	UBERON:0001954	48.13	gold quality
right lobe of liver	UBERON:0001114	47.77	gold quality
substantia nigra	UBERON:0002038	47.19	gold quality
metanephros cortex	UBERON:0010533	46.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting COX8C, 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-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cox8a	ENSDARG00000095273
mus_musculus	Cox8b	ENSMUSG00000025488
rattus_norvegicus	Cox8b	ENSRNOG00000073367

Paralogs (1): COX8A (ENSG00000176340)

Protein

Protein identifiers

Cytochrome c oxidase subunit 8C, mitochondrial — Q7Z4L0 (reviewed: Q7Z4L0)

Alternative names: Cytochrome c oxidase polypeptide 8 isoform 3, Cytochrome c oxidase polypeptide VIII isoform 3, Cytochrome c oxidase subunit 8-3, Cytochrome c oxidase subunit VIIIC

All UniProt accessions (1): Q7Z4L0

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)).

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. It is not yet known where COX8C is expressed.

Pathway. Energy metabolism; oxidative phosphorylation.

Similarity. Belongs to the cytochrome c oxidase VIII family.

RefSeq proteins (1): NP_892016* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003205	Cyt_c_oxidase_su8	Family
IPR036548	Cyt_c_oxidase_su8_sf	Homologous_superfamily

Pfam: PF02285

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-Q7Z4L0-F1	78.94	0.41

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: 48 (showing top): GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_OXIDATIVE_PHOSPHORYLATION, GATA6_01, GOBP_ELECTRON_TRANSPORT_CHAIN, KEGG_HUNTINGTONS_DISEASE, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_CELLULAR_RESPIRATION, KEGG_ALZHEIMERS_DISEASE, chr14q32, GOCC_CYTOCHROME_COMPLEX, CP2_01, GOCC_ORGANELLE_INNER_MEMBRANE, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, KEGG_CARDIAC_MUSCLE_CONTRACTION

GO Biological Process (2): mitochondrial electron transport, cytochrome c to oxygen (GO:0006123), oxidative phosphorylation (GO:0006119)

GO Molecular Function (0):

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), 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
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
aerobic respiration	1
proton motive force-driven ATP synthesis	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial 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

398 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COX8C	COX7A2	P14406	652
COX8C	COX4I2	Q96KJ9	626
COX8C	COX8A	P10176	609
COX8C	COX15	Q7KZN9	581
COX8C	COX4I1	P13073	559
COX8C	COX6B2	Q6YFQ2	523
COX8C	COX7B2	Q8TF08	488
COX8C	COX6A2	Q02221	483
COX8C	COX6A1	P12074	447
COX8C	COX7C	P15954	437
COX8C	COX6B1	P14854	431
COX8C	MT-CO2	P00403	425
COX8C	COX7A1	P24310	419
COX8C	COX6C	P09669	415
COX8C	MT-CO3	P00414	406

IntAct

0 interactions, top by confidence:

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: A6H666, Q7TNN2, Q7YRF4, Q7Z4L0, Q863F8, P10175, P10176, P14622, P16221, P48772, P60181, P60182, P60183, P80433, Q64445, Q862Z8, Q862Z9, Q863F9, Q863G0, Q863G1, Q863G2, Q863G3, Q863G4, Q863G5, Q863G6, Q863G7, Q863G8, Q863G9, Q8SPI5, Q8SQ78, Q8SQ79

SIGNOR signaling

0 interactions.

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	14
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

330 predictions. Top by Δscore:

Variant	Effect	Δscore
14:93347392:GCG:G	donor_gain	0.9900
14:93347395:G:GG	donor_gain	0.9900
14:93347395:G:T	donor_loss	0.9900
14:93347397:GAG:G	donor_loss	0.9900
14:93348027:GGAA:G	acceptor_gain	0.9900
14:93347400:T:G	donor_gain	0.9800
14:93348023:TCCAG:T	acceptor_loss	0.9800
14:93348024:CCA:C	acceptor_loss	0.9800
14:93348025:CAGGA:C	acceptor_loss	0.9800
14:93348026:A:AG	acceptor_gain	0.9800
14:93348026:AGGA:A	acceptor_loss	0.9800
14:93348027:G:GA	acceptor_loss	0.9800
14:93348027:G:GG	acceptor_gain	0.9800
14:93347390:CCGCG:C	donor_gain	0.9700
14:93347391:CGCG:C	donor_gain	0.9700
14:93347392:GCGG:G	donor_gain	0.9700
14:93347393:CG:C	donor_gain	0.9700
14:93347394:GG:G	donor_gain	0.9700
14:93348124:G:GT	donor_gain	0.9700
14:93348026:AG:A	acceptor_gain	0.9600
14:93348027:GG:G	acceptor_gain	0.9600
14:93348027:GGA:G	acceptor_gain	0.9600
14:93348114:G:GT	donor_gain	0.9600
14:93348027:GGAAA:G	acceptor_gain	0.9500
14:93348205:T:G	donor_gain	0.9500
14:93347398:A:AC	donor_loss	0.9200
14:93347673:C:A	acceptor_gain	0.9200
14:93348173:C:G	donor_gain	0.9100
14:93347927:GTC:G	donor_gain	0.8600
14:93347928:TCT:T	donor_gain	0.8600

AlphaMissense

444 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:93348106:T:C	F69L	0.923
14:93348108:C:A	F69L	0.923
14:93348108:C:G	F69L	0.923
14:93348077:C:A	A59D	0.922
14:93348038:T:A	V46D	0.909
14:93348059:C:A	T53K	0.909
14:93348074:C:A	P58Q	0.904
14:93348040:G:A	G47R	0.900
14:93348040:G:C	G47R	0.900
14:93348055:T:C	F52L	0.880
14:93348057:T:A	F52L	0.880
14:93348057:T:G	F52L	0.880
14:93348050:T:A	V50E	0.867
14:93348074:C:G	P58R	0.861
14:93348041:G:A	G47E	0.852
14:93348059:C:G	T53R	0.848
14:93348044:T:A	L48H	0.846
14:93348035:C:A	A45D	0.841
14:93348064:T:C	F55L	0.838
14:93348066:C:A	F55L	0.838
14:93348066:C:G	F55L	0.838
14:93348047:T:A	V49E	0.830
14:93348071:C:A	T57K	0.810
14:93348082:T:G	Y61D	0.806
14:93348074:C:T	P58L	0.795
14:93348029:A:T	E43V	0.787
14:93348071:C:G	T57R	0.787
14:93348082:T:A	Y61N	0.782
14:93348086:T:A	V62E	0.776
14:93348095:A:T	N65I	0.762

dbSNP variants (sampled 300 via entrez): RS1003634299 (14:93348162 T>C), RS1003963761 (14:93346168 G>T), RS1005405431 (14:93345182 T>C,G), RS1005694353 (14:93348551 G>A), RS1007716748 (14:93346071 A>C), RS1008311054 (14:93347599 C>A,T), RS1009005062 (14:93348637 G>T), RS1009054005 (14:93346749 A>G), RS1009813032 (14:93347370 G>A,T), RS1009825745 (14:93346120 T>A,C), RS1009846502 (14:93347226 C>A,G), RS1010185324 (14:93346472 A>G), RS1012175556 (14:93345795 G>A,C,T), RS1012244195 (14:93347822 C>A,T), RS1012295268 (14:93347638 G>A,T)

Disease associations

OMIM: gene MIM:616855 | 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
GCST005951_7	Body mass index	4.000000e-08
GCST90000514_23	Gastroesophageal reflux disease	8.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
potassium perchlorate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
licochalcone B	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	decreases expression	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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