COX19

Summary

COX19 (cytochrome c oxidase assembly factor COX19, HGNC:28074) is a protein-coding gene on chromosome 7p22.3, encoding Cytochrome c oxidase assembly protein COX19 (Q49B96). Assembly factor for cytochrome c oxidase (respiratory chain complex IV, CIV). It is a selective cancer dependency (DepMap: 26.7% of cell lines).

COX19 encodes a cytochrome c oxidase (COX)-assembly protein. The S. cerevisiae Cox19 protein may play a role in metal transport to the mitochondrial intermembrane space and assembly of complex IV of the mitochondrial respiratory chain (Sacconi et al., 2005 [PubMed 16212937]).

Source: NCBI Gene 90639 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 20 total
• Cancer dependency (DepMap): dependent in 26.7% of screened cell lines
• MANE Select transcript: NM_001031617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28074
Approved symbol	COX19
Name	cytochrome c oxidase assembly factor COX19
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC104475
Ensembl gene	ENSG00000240230
Ensembl biotype	protein_coding
OMIM	610429
Entrez	90639

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 retained_intron, 1 protein_coding, 1 nonsense_mediated_decay

ENST00000344111, ENST00000457254, ENST00000466146, ENST00000466853

RefSeq mRNA: 1 — MANE Select: NM_001031617 NM_001031617

CCDS: CCDS34582

Canonical transcript exons

ENST00000344111 — 3 exons

Exon	Start	End
ENSE00001379053	964852	969456
ENSE00001384461	973181	973292
ENSE00003485938	975428	975549

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 90.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.8096 / max 178.9283, expressed in 1813 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82397	23.8096	1813
82398	1.3006	886
82396	0.3698	106

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	90.87	gold quality
vena cava	UBERON:0004087	89.13	gold quality
buccal mucosa cell	CL:0002336	88.87	silver quality
cerebellar vermis	UBERON:0004720	88.35	silver quality
upper arm skin	UBERON:0004263	87.85	gold quality
prefrontal cortex	UBERON:0000451	87.67	gold quality
corpus callosum	UBERON:0002336	87.63	gold quality
pylorus	UBERON:0001166	87.43	gold quality
cardia of stomach	UBERON:0001162	87.37	gold quality
body of tongue	UBERON:0011876	87.05	silver quality
right uterine tube	UBERON:0001302	86.68	gold quality
superficial temporal artery	UBERON:0001614	86.68	gold quality
globus pallidus	UBERON:0001875	85.94	gold quality
inferior vagus X ganglion	UBERON:0005363	85.79	gold quality
medial globus pallidus	UBERON:0002477	85.73	gold quality
subthalamic nucleus	UBERON:0001906	85.70	silver quality
lateral globus pallidus	UBERON:0002476	85.66	silver quality
nipple	UBERON:0002030	85.64	silver quality
dorsal plus ventral thalamus	UBERON:0001897	85.29	silver quality
pons	UBERON:0000988	84.93	silver quality
pericardium	UBERON:0002407	84.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	84.85	silver quality
trachea	UBERON:0003126	84.72	silver quality
substantia nigra pars compacta	UBERON:0001965	84.45	silver quality
medulla oblongata	UBERON:0001896	84.28	silver quality
superior vestibular nucleus	UBERON:0007227	83.97	silver quality
left adrenal gland cortex	UBERON:0035825	83.72	gold quality
adrenal cortex	UBERON:0001235	83.62	gold quality
left adrenal gland	UBERON:0001234	83.34	gold quality
monocyte	CL:0000576	83.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting COX19, 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-4425	100.00	67.59	1049
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4652-3P	99.33	70.02	2742
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Both hCox18p and hCox19p present significant amino acid identity with the corresponding yeast polypeptides and reveal highly conserved functional domains. (PMID:16212937)
• COX19 is necessary for the transduction of a SCO1-dependent mitochondrial redox signal that regulates ATP7A-mediated cellular copper efflux. (PMID:23345593)
• COX19 Is a New Target of MACC1 and Promotes Colorectal Cancer Progression by Regulating Copper Transport in Mitochondria. (PMID:38141772)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cox19	ENSDARG00000063882
mus_musculus	Cox19	ENSMUSG00000045438
drosophila_melanogaster	CG42496	FBGN0260222
caenorhabditis_elegans	cox-19	WBGENE00009745

Paralogs (1): CHCHD5 (ENSG00000125611)

Protein

Protein identifiers

Cytochrome c oxidase assembly protein COX19 — Q49B96 (reviewed: Q49B96)

All UniProt accessions (2): F8WEL9, Q49B96

UniProt curated annotations — full annotation on UniProt →

Function. Assembly factor for cytochrome c oxidase (respiratory chain complex IV, CIV). Acts as a COX11 chaperone that supports COX11 copper coordination. Also stimulates SCO2-mediated metalation of COX2. Required for the transduction of an SCO1-dependent redox signal from the mitochondrion to ATP7A to regulate cellular copper homeostasis. In the absence of COX11, capable of stimulating copper delivery to the copper B site of COX1.

Subunit / interactions. Interacts with CHCHD4/MIA40 forming transient intermolecular disulfide bridges. Interacts with COX11; to support COX11 dimerization and copper coordination.

Subcellular location. Cytoplasm. Cytosol. Mitochondrion intermembrane space. Mitochondrion.

Tissue specificity. Ubiquitously expressed. Highly expressed in skeletal muscle.

Similarity. Belongs to the COX19 family.

RefSeq proteins (1): NP_001026788* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009069	Cys_alpha_HP_mot_SF	Homologous_superfamily
IPR010625	CHCH	Domain
IPR051383	COX19	Family

Pfam: PF06747

UniProt features (10 total): short sequence motif 2, disulfide bond 2, initiator methionine 1, chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q49B96-F1	81.23	0.47

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 (1): 2

Disulfide bonds (2): 30–61, 40–51

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 113 (showing top): GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, chr7p22, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, GOBP_PROTEIN_MATURATION, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_PROTEIN_FOLDING, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_COPPER_ION_HOMEOSTASIS, NIKOLSKY_BREAST_CANCER_7P22_AMPLICON, CHANDRAN_METASTASIS_UP

GO Biological Process (2): intracellular copper ion homeostasis (GO:0006878), mitochondrial respiratory chain complex IV assembly (GO:0033617)

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

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein localization	1
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
intracellular monoatomic cation homeostasis	1
copper ion homeostasis	1
mitochondrion	1
respiratory chain complex IV assembly	1
mitochondrial respiratory chain complex assembly	1
binding	1
intracellular membrane-bounded organelle	1
mitochondrial envelope	1
organelle envelope lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COX19	COX17	Q14061	975
COX19	COX11	Q9Y6N1	848
COX19	COA5	Q86WW8	743
COX19	COA6	Q5JTJ3	729
COX19	CHCHD4	Q8N4Q1	728
COX19	CHCHD7	Q9BUK0	666
COX19	SCO1	O75880	651
COX19	SCO2	O43819	605
COX19	COA4	Q9NYJ1	599
COX19	GFER	P55789	592
COX19	COX15	Q7KZN9	579
COX19	CMC2	Q9NRP2	564
COX19	COX14	Q96I36	560
COX19	COX20	Q5RI15	528
COX19	ATOX1	O00244	520

IntAct

9 interactions, top by confidence:

A	B	Type	Score
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
COQ9	ACOT7	psi-mi:“MI:0914”(association)	0.350
COX11	COX19	psi-mi:“MI:0914”(association)	0.350
AIFM1	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
SCO1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
SFXN1	HAX1	psi-mi:“MI:2364”(proximity)	0.270
PARL	HAX1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (10): COX19 (Affinity Capture-MS), COX19 (Proximity Label-MS), COX19 (Proximity Label-MS), COX19 (Proximity Label-MS), COX19 (Synthetic Lethality), COX19 (Proximity Label-MS), COX19 (Proximity Label-MS), COX19 (Affinity Capture-MS), COX19 (Affinity Capture-MS), COX19 (Affinity Capture-RNA)

ESM2 similar proteins: A8E4L1, D2K759, F1QH17, O46404, O70133, P0DI19, P35614, P35615, P62495, P62496, P62497, P62498, P83870, P83871, Q0VCX5, Q0WMV8, Q0WWE3, Q15691, Q3ZBD9, Q49B96, Q5R4C7, Q5R7Z5, Q5U2Q7, Q5XIT1, Q5ZKU1, Q5ZLC7, Q61166, Q61187, Q64143, Q66HR2, Q66T82, Q68FK8, Q6IRE4, Q6PER3, Q6V291, Q76EZ2, Q7RTV0, Q7Z7K0, Q7ZYA7, Q8BWY3

Diamond homologs: A8E4L1, O14056, P0CM86, P0CM87, P0CT19, Q3E731, Q462Q7, Q49B96, Q4P821, Q54IA0, Q5AL10, Q6CS47, Q6FVQ3, Q75AF9, Q8K0C8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3237 predictions. Top by Δscore:

Variant	Effect	Δscore
7:898945:CTCCA:C	acceptor_gain	1.0000
7:898947:CCA:C	acceptor_gain	1.0000
7:898948:CA:C	acceptor_gain	1.0000
7:898948:CAC:C	acceptor_gain	1.0000
7:898950:C:CC	acceptor_gain	1.0000
7:899039:ACT:A	donor_gain	1.0000
7:899040:CTC:C	donor_gain	1.0000
7:899093:C:CA	donor_gain	1.0000
7:899413:CCTTA:C	donor_loss	1.0000
7:899414:CTTA:C	donor_loss	1.0000
7:899415:TTACC:T	donor_loss	1.0000
7:899416:TA:T	donor_loss	1.0000
7:899417:A:AC	donor_gain	1.0000
7:899417:A:AT	donor_loss	1.0000
7:899418:C:CC	donor_gain	1.0000
7:899418:C:CT	donor_loss	1.0000
7:899489:TG:T	acceptor_gain	1.0000
7:899489:TGC:T	acceptor_loss	1.0000
7:899490:GCTG:G	acceptor_loss	1.0000
7:899491:C:CC	acceptor_gain	1.0000
7:900097:CCCA:C	donor_loss	1.0000
7:900099:CACCT:C	donor_loss	1.0000
7:900101:C:A	donor_loss	1.0000
7:900162:CAG:C	acceptor_gain	1.0000
7:900165:C:CC	acceptor_gain	1.0000
7:900528:CTCA:C	donor_loss	1.0000
7:900529:TCA:T	donor_loss	1.0000
7:900530:CACAT:C	donor_loss	1.0000
7:900531:A:AC	donor_gain	1.0000
7:900531:A:C	donor_loss	1.0000

AlphaMissense

604 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:975444:G:C	F22L	0.994
7:975444:G:T	F22L	0.994
7:975446:A:G	F22L	0.994
7:973189:C:A	R62S	0.989
7:973189:C:G	R62S	0.989
7:973286:C:G	C30S	0.987
7:973287:A:T	C30S	0.987
7:973190:C:G	R62T	0.986
7:975445:A:C	F22C	0.986
7:973190:C:A	R62M	0.982
7:973223:C:G	C51S	0.982
7:973224:A:T	C51S	0.982
7:973193:C:G	C61S	0.981
7:973194:A:T	C61S	0.981
7:973203:A:G	Y58H	0.975
7:975445:A:G	F22S	0.973
7:969451:A:G	L67S	0.972
7:973202:T:C	Y58C	0.972
7:973285:A:C	C30W	0.972
7:973287:A:G	C30R	0.969
7:973199:A:G	L59S	0.968
7:973264:G:C	F37L	0.968
7:973264:G:T	F37L	0.968
7:973266:A:G	F37L	0.968
7:973286:C:A	C30F	0.967
7:975436:T:A	D25V	0.967
7:973191:T:C	R62G	0.966
7:975452:C:G	G20R	0.966
7:975435:A:C	D25E	0.965
7:975435:A:T	D25E	0.965

dbSNP variants (sampled 300 via entrez): RS1000154253 (7:975123 C>T), RS1000377491 (7:970147 T>C), RS1000553979 (7:965040 G>C), RS1000766496 (7:967043 T>G), RS1000979995 (7:974184 G>A), RS1000983091 (7:971247 A>T), RS1001154716 (7:975968 G>A), RS1001246795 (7:971042 A>C), RS1001313388 (7:966352 C>G,T), RS1001585873 (7:967630 T>C), RS1001610164 (7:975320 T>A,C), RS1001688571 (7:969916 A>C), RS1001895095 (7:970459 T>G), RS1002288075 (7:967423 G>A), RS1002319322 (7:967250 G>A,C)

Disease associations

OMIM: gene MIM:610429 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002104_3	Bronchopulmonary dysplasia	3.000000e-06
GCST010244_205	Triglyceride levels	1.000000e-08
GCST90002388_14	Lymphocyte count	1.000000e-12
GCST90002389_141	Lymphocyte percentage of white cells	2.000000e-12
GCST90002395_495	Mean platelet volume	1.000000e-09
GCST90002401_446	Platelet distribution width	7.000000e-10
GCST90002402_9	Platelet count	4.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
sodium arsenite	increases expression	2
Particulate Matter	increases expression, affects cotreatment, decreases expression, increases abundance	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
nivalenol	increases expression	1
beta-methylcholine	affects expression	1
avobenzone	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Copper	affects binding, increases expression	1
Ethyl Methanesulfonate	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Quercetin	increases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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