COA5

Summary

COA5 (cytochrome c oxidase assembly factor 5, HGNC:33848) is a protein-coding gene on chromosome 2q11.2, encoding Cytochrome c oxidase assembly factor 5 (Q86WW8). Assembly factor for cytochrome c oxidase (respiratory chain complex IV). It is a selective cancer dependency (DepMap: 41.7% of cell lines).

This gene encodes an ortholog of yeast Pet191, which in yeast is a subunit of a large oligomeric complex associated with the mitochondrial inner membrane, and required for the assembly of the cytochrome c oxidase complex. Mutations in this gene are associated with mitochondrial complex IV deficiency, a disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations, ranging from isolated myopathy to a severe disease affecting several tissues and organs.

Source: NCBI Gene 493753 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial disease (Limited, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 36 total — 1 pathogenic
• Phenotypes (HPO): 5
• Cancer dependency (DepMap): dependent in 41.7% of screened cell lines
• MANE Select transcript: NM_001008215

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33848
Approved symbol	COA5
Name	cytochrome c oxidase assembly factor 5
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC52110, FLJ27524, Pet191
Ensembl gene	ENSG00000183513
Ensembl biotype	protein_coding
OMIM	613920
Entrez	493753

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000328709, ENST00000409997, ENST00000466848, ENST00000480666, ENST00000483527, ENST00000917722, ENST00000917723, ENST00000917724

RefSeq mRNA: 1 — MANE Select: NM_001008215 NM_001008215

CCDS: CCDS33257

Canonical transcript exons

ENST00000328709 — 3 exons

Exon	Start	End
ENSE00001289705	98599314	98600793
ENSE00001296686	98608307	98608512
ENSE00003550119	98604108	98604191

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 96.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.8118 / max 182.1816, expressed in 1816 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29841	28.8118	1816

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	96.07	gold quality
left ovary	UBERON:0002119	95.61	gold quality
right uterine tube	UBERON:0001302	95.59	gold quality
right ovary	UBERON:0002118	95.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.48	gold quality
mucosa of stomach	UBERON:0001199	95.44	gold quality
cerebellar hemisphere	UBERON:0002245	95.44	gold quality
tibial nerve	UBERON:0001323	95.38	gold quality
cerebellar cortex	UBERON:0002129	95.32	gold quality
adenohypophysis	UBERON:0002196	95.29	gold quality
left lobe of thyroid gland	UBERON:0001120	95.20	gold quality
metanephros cortex	UBERON:0010533	95.19	gold quality
gastrocnemius	UBERON:0001388	95.16	gold quality
spinal cord	UBERON:0002240	95.12	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.12	gold quality
endothelial cell	CL:0000115	95.10	gold quality
endocervix	UBERON:0000458	95.06	gold quality
right frontal lobe	UBERON:0002810	95.03	gold quality
body of uterus	UBERON:0009853	95.02	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.02	gold quality
muscle of leg	UBERON:0001383	94.99	gold quality
lower esophagus	UBERON:0013473	94.97	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.97	gold quality
anterior cingulate cortex	UBERON:0009835	94.96	gold quality
oviduct epithelium	UBERON:0004804	94.87	gold quality
monocyte	CL:0000576	94.83	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.82	gold quality
thyroid gland	UBERON:0002046	94.78	gold quality
right lobe of thyroid gland	UBERON:0001119	94.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	918.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

86 targeting COA5, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1250-3P	99.96	70.04	4038
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-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-345-3P	99.89	70.23	1421
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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 41.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• C2orf64 is essential for complex IV assembly, and C2orf64 mutational analysis should be considered for complex IV deficient patients, in particular those with hypertrophic cardiomyopathy (PMID:21457908)
• Ortholog of fungal COX assembly protein PET191 (PMID:22356826)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	coa5	ENSDARG00000094833
mus_musculus	Coa5	ENSMUSG00000026112
rattus_norvegicus	Coa5	ENSRNOG00000078514
drosophila_melanogaster	CG13018	FBGN0040751
caenorhabditis_elegans	coa-5	WBGENE00012483

Protein

Protein identifiers

Cytochrome c oxidase assembly factor 5 — Q86WW8 (reviewed: Q86WW8)

All UniProt accessions (2): B9A057, Q86WW8

UniProt curated annotations — full annotation on UniProt →

Function. Assembly factor for cytochrome c oxidase (respiratory chain complex IV). Stabilizes an early formation of cytochrome c oxidase assembly factors, until it is displaced by the metallochaperone copper-delivery protein COX17.

Subcellular location. Mitochondrion intermembrane space.

Disease relevance. Mitochondrial complex IV deficiency, nuclear type 9 (MC4DN9) [MIM:616500] An autosomal recessive, infantile disorder with a fatal course in the first weeks of life, and characterized by hypertrophic cardiomyopathy and mitochondrial complex IV deficiency. Postmortem microscopic investigations show accumulation of lipid droplets in cardiomyocytes and mitochondrial proliferation. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the PET191 family.

RefSeq proteins (1): NP_001008216* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018793	Cyt_c_oxidase_assmbl_Pet191	Family

Pfam: PF10203

UniProt features (8 total): short sequence motif 2, disulfide bond 2, chain 1, domain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WW8-F1	82.42	0.54

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): 37

Disulfide bonds (2): 30–57, 41–47

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 141 (showing top): GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_THYMUS_DEVELOPMENT, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, MARTINEZ_RB1_TARGETS_UP, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_HEMATOPOIETIC_OR_LYMPHOID_ORGAN_DEVELOPMENT, GOBP_MULTICELLULAR_ORGANISM_GROWTH, GOCC_MITOCHONDRIAL_ENVELOPE, MILI_PSEUDOPODIA_CHEMOTAXIS_UP, MARTINEZ_RB1_AND_TP53_TARGETS_UP, GOBP_SPLEEN_DEVELOPMENT

GO Biological Process (5): leukocyte differentiation (GO:0002521), mitochondrial respiratory chain complex IV assembly (GO:0033617), multicellular organism growth (GO:0035264), spleen development (GO:0048536), thymus development (GO:0048538)

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

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hematopoietic or lymphoid organ development	2
hemopoiesis	1
cell differentiation	1
mitochondrion	1
respiratory chain complex IV assembly	1
mitochondrial respiratory chain complex assembly	1
multicellular organismal process	1
developmental growth	1
gland development	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1

Protein interactions and networks

STRING

1000 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COA5	CHCHD7	Q9BUK0	755
COA5	COA6	Q5JTJ3	751
COA5	SCO1	O75880	750
COA5	COX17	Q14061	743
COA5	COX19	Q49B96	743
COA5	CHCHD4	Q8N4Q1	688
COA5	COX11	Q9Y6N1	688
COA5	COX14	Q96I36	680
COA5	SCO2	O43819	680
COA5	TIMM9	Q9Y5J7	647
COA5	PET117	Q6UWS5	640
COA5	ACAD9	Q9H845	614
COA5	COA3	Q9Y2R0	612
COA5	PET100	P0DJ07	611
COA5	COX10	Q12887	607

IntAct

17 interactions, top by confidence:

A	B	Type	Score
CHCHD4	SSNA1	psi-mi:“MI:0914”(association)	0.640
COA5	KRT31	psi-mi:“MI:0915”(physical association)	0.560
COA5	CYSRT1	psi-mi:“MI:0915”(physical association)	0.560
TCF4	COA5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	COA5	psi-mi:“MI:0915”(physical association)	0.560
COA5	A2ML1	psi-mi:“MI:0914”(association)	0.350
	LAMA5	psi-mi:“MI:0914”(association)	0.350
PTBP3		psi-mi:“MI:0914”(association)	0.350
COA5	KRTAP1-3	psi-mi:“MI:0915”(physical association)	0.000
COA5	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
COA5	TCF4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): COA5 (Two-hybrid), COA5 (Positive Genetic), TCF4 (Two-hybrid), CYSRT1 (Two-hybrid), KRTAP1-3 (Two-hybrid), S100A7A (Affinity Capture-MS), RNASE7 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), TYMP (Affinity Capture-MS), COA5 (Affinity Capture-MS), GAPDHS (Affinity Capture-MS), CRABP2 (Affinity Capture-MS), S100A7 (Affinity Capture-MS), SERPINB8 (Affinity Capture-MS)

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: A1L3N6, O42921, Q02772, Q0P451, Q28CA1, Q3ZCK8, Q5RFJ0, Q86WW8, Q99M07

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	12
Likely benign	16
Benign	5

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
31087	NM_001008215.3(COA5):c.157G>C (p.Ala53Pro)	Pathogenic

SpliceAI

489 predictions. Top by Δscore:

Variant	Effect	Δscore
2:98600789:TCCAA:T	acceptor_gain	1.0000
2:98600790:CCAA:C	acceptor_gain	1.0000
2:98600790:CCAAC:C	acceptor_gain	1.0000
2:98600791:CAA:C	acceptor_gain	1.0000
2:98600791:CAAC:C	acceptor_gain	1.0000
2:98600794:C:CC	acceptor_gain	1.0000
2:98604107:CCA:C	donor_gain	1.0000
2:98608308:TGG:T	donor_gain	1.0000
2:98608400:A:AC	donor_gain	1.0000
2:98608400:AGG:A	donor_gain	1.0000
2:98600793:AC:A	acceptor_loss	0.9900
2:98600794:C:CG	acceptor_loss	0.9900
2:98600795:T:G	acceptor_loss	0.9900
2:98608281:C:CT	donor_gain	0.9900
2:98608350:T:TA	donor_gain	0.9900
2:98608401:G:C	donor_gain	0.9900
2:98600792:AA:A	acceptor_gain	0.9800
2:98604137:A:AC	donor_gain	0.9800
2:98604138:C:CC	donor_gain	0.9800
2:98608195:ACGC:A	donor_gain	0.9800
2:98608196:CGCC:C	donor_gain	0.9800
2:98608261:G:A	donor_gain	0.9800
2:98608282:C:CT	donor_gain	0.9800
2:98608312:C:CT	donor_gain	0.9800
2:98608416:C:A	donor_gain	0.9800
2:98608195:ACG:A	donor_gain	0.9700
2:98608196:CGC:C	donor_gain	0.9700
2:98608415:T:TA	donor_gain	0.9700
2:98604100:CCACT:C	donor_loss	0.9600
2:98604101:CACTT:C	donor_loss	0.9600

AlphaMissense

466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:98604121:C:G	C57S	0.992
2:98604122:A:T	C57S	0.992
2:98604169:C:G	C41S	0.991
2:98604170:A:T	C41S	0.991
2:98604151:C:T	C47Y	0.985
2:98600773:G:C	F68L	0.984
2:98600773:G:T	F68L	0.984
2:98600775:A:G	F68L	0.984
2:98604117:T:A	K58N	0.984
2:98604117:T:G	K58N	0.984
2:98604151:C:G	C47S	0.984
2:98604152:A:T	C47S	0.984
2:98604122:A:G	C57R	0.983
2:98604170:A:G	C41R	0.981
2:98608335:C:G	C24S	0.981
2:98608336:A:T	C24S	0.981
2:98604113:A:G	S60P	0.980
2:98608365:C:G	C14S	0.980
2:98608366:A:T	C14S	0.980
2:98604121:C:A	C57F	0.977
2:98600782:C:A	R65S	0.976
2:98600782:C:G	R65S	0.976
2:98604121:C:T	C57Y	0.976
2:98604150:G:C	C47W	0.976
2:98604168:A:C	C41W	0.976
2:98608336:A:G	C24R	0.976
2:98608365:C:T	C14Y	0.974
2:98608366:A:G	C14R	0.974
2:98600783:C:A	R65M	0.973
2:98604120:A:C	C57W	0.973

dbSNP variants (sampled 300 via entrez): RS1000001827 (2:98602610 C>G,T), RS1000044007 (2:98601000 C>T), RS1000173271 (2:98601954 A>G), RS1000565631 (2:98598873 A>AG), RS1000953295 (2:98599850 A>G), RS1001273814 (2:98603524 T>C), RS1001333967 (2:98609550 G>A,C,T), RS1001626534 (2:98603324 T>A), RS1001890636 (2:98605526 G>A), RS1001921705 (2:98605241 A>G,T), RS1002356064 (2:98608993 G>T), RS1002661477 (2:98602544 G>A), RS1002889090 (2:98604662 C>T), RS1003225751 (2:98606529 C>T), RS1003276796 (2:98606788 C>G)

Disease associations

OMIM: gene MIM:613920 | disease phenotypes: MIM:616500

GenCC curated gene-disease

Disease	Classification	Inheritance
cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
mitochondrial disease	Limited	AR

Mondo (1): cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 3 (MONDO:0014667)

Orphanet (1): Fatal infantile cytochrome C oxidase deficiency (Orphanet:1561)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001639	Hypertrophic cardiomyopathy
HP:0003577	Congenital onset
HP:0008347	Decreased activity of mitochondrial complex IV
HP:0031320	Cardiomyocyte mitochondrial proliferation

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

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, decreases methylation	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
jinfukang	increases expression, affects cotreatment	1
Leflunomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Thiram	decreases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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