COX6B2

Summary

COX6B2 (cytochrome c oxidase subunit 6B2, HGNC:24380) is a protein-coding gene on chromosome 19q13.42, encoding Cytochrome c oxidase subunit 6B2 (Q6YFQ2). Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.

Predicted to be involved in oxidative phosphorylation. Located in mitochondrial crista.

Source: NCBI Gene 125965 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_144613

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24380
Approved symbol	COX6B2
Name	cytochrome c oxidase subunit 6B2
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	COXVIB2, FLJ32865, CT59
Ensembl gene	ENSG00000160471
Ensembl biotype	protein_coding
OMIM	618127
Entrez	125965

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000326529, ENST00000586191, ENST00000587357, ENST00000587854, ENST00000588572, ENST00000588586, ENST00000589467, ENST00000589879, ENST00000590900, ENST00000593184

RefSeq mRNA: 5 — MANE Select: NM_144613 NM_001369798, NM_001369799, NM_001369800, NM_001436135, NM_144613

CCDS: CCDS42630

Canonical transcript exons

ENST00000326529 — 5 exons

Exon	Start	End
ENSE00002897826	55354650	55354719
ENSE00003561018	55353607	55353774
ENSE00003605343	55349704	55350800
ENSE00003702939	55353866	55353966
ENSE00003710277	55354410	55354539

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 98.13.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1689 / max 155.6243, expressed in 343 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182791	0.5563	248
182793	0.4653	127
182792	0.0915	34
182794	0.0558	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.13	gold quality
left testis	UBERON:0004533	97.91	gold quality
testis	UBERON:0000473	93.32	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.35	gold quality
left ventricle myocardium	UBERON:0006566	86.69	gold quality
kidney epithelium	UBERON:0004819	81.48	gold quality
nasal cavity epithelium	UBERON:0005384	81.42	gold quality
myocardium	UBERON:0002349	80.09	gold quality
epithelial cell of pancreas	CL:0000083	78.28	gold quality
buccal mucosa cell	CL:0002336	77.42	gold quality
transverse colon	UBERON:0001157	77.21	gold quality
upper arm skin	UBERON:0004263	76.40	gold quality
mucosa of transverse colon	UBERON:0004991	75.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.31	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.28	gold quality
heart right ventricle	UBERON:0002080	73.97	gold quality
rectum	UBERON:0001052	73.66	gold quality
vastus lateralis	UBERON:0001379	72.85	gold quality
quadriceps femoris	UBERON:0001377	71.61	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.32	gold quality
lower esophagus mucosa	UBERON:0035834	70.29	gold quality
biceps brachii	UBERON:0001507	69.95	gold quality
oocyte	CL:0000023	69.10	gold quality
skin of abdomen	UBERON:0001416	68.39	gold quality
secondary oocyte	CL:0000655	67.05	gold quality
lateral nuclear group of thalamus	UBERON:0002736	66.97	gold quality
esophagus mucosa	UBERON:0002469	65.41	gold quality
zone of skin	UBERON:0000014	65.11	gold quality
skin of leg	UBERON:0001511	65.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	3.13
E-ANND-3	no	2.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

42 targeting COX6B2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-409-3P	99.50	66.33	1192
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-7160-5P	99.11	67.17	2207

Literature-anchored findings (GeneRIF, showing 2)

• Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in human lung adenocarcinoma. (PMID:32990599)
• [High expression of COX6B2 in gastric cancer is associated with poor long-term prognosis and promotes cell proliferation and cell cycle progression by inhibiting p53 signaling]. (PMID:38501414)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cox6b2	ENSDARG00000037860
danio_rerio	cox6b1	ENSDARG00000045230
mus_musculus	Cox6b2	ENSMUSG00000051811
rattus_norvegicus	Cox6b2	ENSRNOG00000077802
drosophila_melanogaster	COX6B	FBGN0031066
caenorhabditis_elegans		WBGENE00022170

Paralogs (1): COX6B1 (ENSG00000126267)

Protein

Protein identifiers

Cytochrome c oxidase subunit 6B2 — Q6YFQ2 (reviewed: Q6YFQ2)

Alternative names: Cancer/testis antigen 59, Cytochrome c oxidase subunit VIb isoform 2, Cytochrome c oxidase subunit VIb, testis-specific isoform

All UniProt accessions (1): Q6YFQ2

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. Testis specific. Weak expression in thymus and heart. Expressed in cancer cell lines.

Pathway. Energy metabolism; oxidative phosphorylation.

Similarity. Belongs to the cytochrome c oxidase subunit 6B family.

RefSeq proteins (5): NP_001356727, NP_001356728, NP_001356729, NP_001423064, NP_653214* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003213	Cyt_c_oxidase_su6B	Family
IPR036549	CX6/COA6-like_sf	Homologous_superfamily
IPR048280	COX6B-like	Family

Pfam: PF02297

UniProt features (7 total): short sequence motif 2, disulfide bond 2, chain 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6YFQ2-F1	89.53	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 32–67, 42–56

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: 87 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, RICKMAN_METASTASIS_DN, GOBP_OXIDATIVE_PHOSPHORYLATION, KEGG_HUNTINGTONS_DISEASE, GOCC_MITOCHONDRIAL_ENVELOPE, ONGUSAHA_TP53_TARGETS, GOBP_CELLULAR_RESPIRATION, MARKEY_RB1_ACUTE_LOF_UP, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, KEGG_ALZHEIMERS_DISEASE, GOCC_CYTOCHROME_COMPLEX, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (1): 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 crista (GO:0030061), 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
cellular anatomical structure	2
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
mitochondrial inner membrane	1
cytochrome complex	1
respiratory chain complex	1
transmembrane transporter complex	1
oxidoreductase complex	1

Protein interactions and networks

STRING

1178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COX6B2	MT-CO1	P00395	617
COX6B2	COX6A2	Q02221	608
COX6B2	COX6A1	P12074	561
COX6B2	COX8C	Q7Z4L0	523
COX6B2	COX4I2	Q96KJ9	517
COX6B2	COX5A	P20674	499
COX6B2	COX5B	P10606	485
COX6B2	COX7C	P15954	473
COX6B2	COX7A2	P14406	447
COX6B2	ATP5MC2	Q06055	439
COX6B2	COX11	Q9Y6N1	433
COX6B2	COX7B2	Q8TF08	432
COX6B2	MT-CO2	P00403	421
COX6B2	SPATA19	Q7Z5L4	419
COX6B2	COX4I1	P13073	417

IntAct

8 interactions, top by confidence:

A	B	Type	Score
COX6B2	FRMD6	psi-mi:“MI:0915”(physical association)	0.560
FRMD6	COX6B2	psi-mi:“MI:0915”(physical association)	0.560
PROP1	COX6B2	psi-mi:“MI:0915”(physical association)	0.560
COX6B2	TNS2	psi-mi:“MI:0915”(physical association)	0.370
PROP1	COX6B2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): COX6B2 (Two-hybrid), COX6B2 (Two-hybrid), PROP1 (Two-hybrid), COX6B2 (Negative Genetic)

ESM2 similar proteins: A1L3N6, A6ZMQ6, A9ULB4, B3LM82, B5FXK1, C8ZF59, O42921, O43715, O43920, O60200, O94581, P00429, P0CB87, P0CB88, P0CT19, P14854, P48504, P56277, P56391, Q01519, Q02379, Q0MQH3, Q0MQH4, Q0P451, Q208S3, Q28BU7, Q28CA1, Q2NKR3, Q3E7A9, Q3ZCK8, Q4R374, Q4R3M6, Q53CG4, Q5RCT0, Q5RFJ0, Q6DD38, Q6DHJ6, Q6INR6, Q6YFQ2, Q7S4H6

Diamond homologs: O94581, P00429, P14854, P56391, Q01519, Q1K8U2, Q4R374, Q53CG4, Q54P95, Q5RCT0, Q6YFP9, Q6YFQ1, Q6YFQ2, Q7YRK6, Q80ZN9, Q945L0, Q9LPJ2, Q9S7L9, Q9SUD3

SIGNOR signaling

0 interactions.

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	11
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1296 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55353783:C:CT	acceptor_gain	1.0000
19:55353784:A:T	acceptor_gain	1.0000
19:55353865:CCCAG:C	donor_gain	1.0000
19:55354537:CTC:C	acceptor_gain	1.0000
19:55350798:TGG:T	acceptor_gain	0.9900
19:55350798:TGGCT:T	acceptor_loss	0.9900
19:55350799:GG:G	acceptor_gain	0.9900
19:55350800:GCTG:G	acceptor_loss	0.9900
19:55350801:C:CC	acceptor_gain	0.9900
19:55350801:C:T	acceptor_loss	0.9900
19:55353601:GCATA:G	donor_loss	0.9900
19:55353602:CATAC:C	donor_loss	0.9900
19:55353603:ATACC:A	donor_loss	0.9900
19:55353604:TACCA:T	donor_loss	0.9900
19:55353605:A:AC	donor_gain	0.9900
19:55353605:A:T	donor_loss	0.9900
19:55353606:C:CC	donor_gain	0.9900
19:55353770:TCCAC:T	acceptor_gain	0.9900
19:55353771:CCAC:C	acceptor_gain	0.9900
19:55353771:CCACC:C	acceptor_gain	0.9900
19:55353772:CAC:C	acceptor_gain	0.9900
19:55353772:CACC:C	acceptor_gain	0.9900
19:55353773:ACCTG:A	acceptor_loss	0.9900
19:55353774:CCTGG:C	acceptor_loss	0.9900
19:55353775:C:CC	acceptor_gain	0.9900
19:55353775:CTGGG:C	acceptor_loss	0.9900
19:55353862:T:TA	donor_loss	0.9900
19:55353862:TCAC:T	donor_loss	0.9900
19:55353863:C:CC	donor_loss	0.9900
19:55353863:C:CG	donor_loss	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000147287 (19:55353753 T>G), RS1000483841 (19:55352568 C>A), RS1001809020 (19:55353347 G>A), RS1001923007 (19:55353521 C>T), RS1002312740 (19:55352655 C>T), RS1002366510 (19:55352887 C>T), RS1002493370 (19:55350225 T>C,G), RS1002999048 (19:55355376 T>C), RS1003205913 (19:55354918 G>A,T), RS1003261752 (19:55349259 G>A), RS1003898362 (19:55354688 G>A), RS1003977457 (19:55351658 T>C), RS1004234345 (19:55356143 G>A,T), RS1004726306 (19:55349834 A>G), RS1004934070 (19:55350243 C>G)

Disease associations

OMIM: gene MIM:618127 | 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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	increases expression	1
Dexamethasone	affects cotreatment, decreases expression, increases expression	1
Indomethacin	affects cotreatment, decreases expression, increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methotrexate	increases expression	1
Triclosan	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression, increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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