COA1

Summary

COA1 (cytochrome c oxidase assembly factor 1, HGNC:21868) is a protein-coding gene on chromosome 7p13, encoding Cytochrome c oxidase assembly factor 1 homolog (Q9GZY4). Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.

Involved in mitochondrial cytochrome c oxidase assembly and mitochondrial respiratory chain complex I assembly. Located in cytosol and mitochondrial inner membrane.

Source: NCBI Gene 55744 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_018224

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21868
Approved symbol	COA1
Name	cytochrome c oxidase assembly factor 1
Location	7p13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10803, MITRAC15
Ensembl gene	ENSG00000106603
Ensembl biotype	protein_coding
OMIM	614769
Entrez	55744

Gene structure

Transcript identifiers

Ensembl transcripts: 75 — 64 protein_coding, 5 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 2 retained_intron

ENST00000223336, ENST00000310564, ENST00000395879, ENST00000415076, ENST00000415798, ENST00000418140, ENST00000420441, ENST00000431651, ENST00000438444, ENST00000446330, ENST00000446564, ENST00000448704, ENST00000451651, ENST00000457939, ENST00000459713, ENST00000470156, ENST00000478504, ENST00000488813, ENST00000490251, ENST00000896974, ENST00000896975, ENST00000896976, ENST00000896977, ENST00000896978, ENST00000896979, ENST00000896980, ENST00000896981, ENST00000896982, ENST00000896983, ENST00000896984, ENST00000896985, ENST00000896986, ENST00000896987, ENST00000896988, ENST00000896989, ENST00000896990, ENST00000896991, ENST00000896992, ENST00000896993, ENST00000896994, ENST00000896995, ENST00000896996, ENST00000896997, ENST00000896998, ENST00000896999, ENST00000897000, ENST00000897001, ENST00000897002, ENST00000934870, ENST00000934871, ENST00000934872, ENST00000934873, ENST00000934874, ENST00000934875, ENST00000934876, ENST00000934877, ENST00000934878, ENST00000934879, ENST00000934880, ENST00000934881, ENST00000934882, ENST00000934883, ENST00000934884, ENST00000934885, ENST00000934886, ENST00000934887, ENST00000934888, ENST00000934889, ENST00000949438, ENST00000949439, ENST00000949440, ENST00000949441, ENST00000949442, ENST00000949443, ENST00000949444

RefSeq mRNA: 27 — MANE Select: NM_018224 NM_001321197, NM_001321198, NM_001321199, NM_001321200, NM_001321201, NM_001321202, NM_001321203, NM_001321204, NM_001321205, NM_001350924, NM_001350925, NM_001350926, NM_001350927, NM_001350928, NM_001371307, NM_001371308, NM_001371309, NM_001371310, NM_001371311, NM_001371312, NM_001371313, NM_001371314, NM_001371315, NM_001371316, NM_001371317, NM_001371318, NM_018224

CCDS: CCDS5471, CCDS83177

Canonical transcript exons

ENST00000223336 — 6 exons

Exon	Start	End
ENSE00001176880	43647535	43647634
ENSE00001713359	43729429	43729523
ENSE00003479589	43639257	43639681
ENSE00003627047	43648600	43648652
ENSE00003787087	43640573	43640649
ENSE00003789929	43645251	43645399

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.9367 / max 1015.0117, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83811	50.5321	1816
83810	0.8064	531
83809	0.3808	54
83805	0.2174	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.70	gold quality
oocyte	CL:0000023	97.68	gold quality
apex of heart	UBERON:0002098	94.51	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.46	gold quality
heart left ventricle	UBERON:0002084	94.20	gold quality
endometrium epithelium	UBERON:0004811	94.07	gold quality
body of pancreas	UBERON:0001150	94.04	gold quality
cardiac ventricle	UBERON:0002082	93.96	gold quality
muscle of leg	UBERON:0001383	93.84	gold quality
gastrocnemius	UBERON:0001388	93.74	gold quality
right atrium auricular region	UBERON:0006631	93.38	gold quality
islet of Langerhans	UBERON:0000006	93.31	gold quality
ganglionic eminence	UBERON:0004023	92.85	gold quality
heart	UBERON:0000948	92.76	gold quality
right uterine tube	UBERON:0001302	92.53	gold quality
pancreas	UBERON:0001264	92.45	gold quality
ventricular zone	UBERON:0003053	92.42	gold quality
prefrontal cortex	UBERON:0000451	92.39	gold quality
muscle organ	UBERON:0001630	92.35	gold quality
skeletal muscle organ	UBERON:0014892	92.35	gold quality
cingulate cortex	UBERON:0003027	92.30	gold quality
anterior cingulate cortex	UBERON:0009835	92.27	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.21	gold quality
right frontal lobe	UBERON:0002810	92.19	gold quality
cardiac atrium	UBERON:0002081	92.17	gold quality
colonic epithelium	UBERON:0000397	92.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.03	gold quality
left ovary	UBERON:0002119	91.75	gold quality
lymph node	UBERON:0000029	91.70	gold quality
monocyte	CL:0000576	91.66	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7381	no	513.51
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting COA1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-145-3P	99.33	67.66	764
HSA-MIR-4451	98.82	68.17	1455
HSA-MIR-6773-3P	98.17	65.51	1213
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-550B-2-5P	96.56	64.61	646
HSA-MIR-5579-5P	96.32	68.54	730
HSA-MIR-193A-5P	95.70	65.33	613
HSA-MIR-6503-3P	93.87	66.39	348

Literature-anchored findings (GeneRIF, showing 5)

• Encodes a mitochondrial protein (PMID:22356826)
• Human ortholog of fungal COA1 (Cytochrome Oxidase Assembly 1) (PMID:22356826)
• Restoration of miR-127-3p and miR-376a-3p counteracts the neoplastic phenotype of giant cell tumor of bone derived stromal cells by targeting COA1, GLE1 and PDIA6. (PMID:26655997)
• MITRAC15/COA1 promotes mitochondrial translation in a ND2 ribosome-nascent chain complex. (PMID:31721420)
• Association of COA1 with Patellar Tendonitis: A Genome-wide Association Analysis. (PMID:34081057)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	coa1	ENSDARG00000076360
drosophila_melanogaster	CG15653	FBGN0034578
drosophila_melanogaster	CG31913	FBGN0051913

Protein

Protein identifiers

Cytochrome c oxidase assembly factor 1 homolog — Q9GZY4 (reviewed: Q9GZY4)

Alternative names: Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 15 kDa

All UniProt accessions (5): C9J6J1, C9JA07, Q9GZY4, F2Z2J3, F8WBS2

UniProt curated annotations — full annotation on UniProt →

Function. Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. MITRAC complexes regulate both translation of mitochondrial encoded components and assembly of nuclear-encoded components imported in mitochondrion. Required for assembly of mitochondrial respiratory chain complex I and complex IV. As part of the MCIA complex, required for efficient assembly of the mitochondrial complex I.

Subunit / interactions. Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14. Interacts with COX17 and COA6. Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the COA1 family.

RefSeq proteins (27): NP_001308126, NP_001308127, NP_001308128, NP_001308129, NP_001308130, NP_001308131, NP_001308132, NP_001308133, NP_001308134, NP_001337853, NP_001337854, NP_001337855, NP_001337856, NP_001337857, NP_001358236, NP_001358237, NP_001358238, NP_001358239, NP_001358240, NP_001358241, NP_001358242, NP_001358243, NP_001358244, NP_001358245, NP_001358246, NP_001358247, NP_060694* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014807	Coa1	Family

Pfam: PF08695

UniProt features (7 total): sequence conflict 3, topological domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZY4-F1	88.13	0.72

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-6799198	Complex I biogenesis
R-HSA-9864848	Complex IV assembly

MSigDB gene sets: 109 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GOZGIT_ESR1_TARGETS_DN, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, MORF_RAD21, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, MORF_SKP1A, BACOLOD_RESISTANCE_TO_ALKYLATING_AGENTS_DN, MORF_ATOX1, GOCC_MITOCHONDRIAL_ENVELOPE, DODD_NASOPHARYNGEAL_CARCINOMA_UP, chr7p13, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (2): mitochondrial respiratory chain complex I assembly (GO:0032981), mitochondrial respiratory chain complex IV assembly (GO:0033617)

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

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Respiratory electron transport	2
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrial respiratory chain complex assembly	2
cytoplasm	2
cellular anatomical structure	2
NADH dehydrogenase complex assembly	1
mitochondrion	1
respiratory chain complex IV assembly	1
binding	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1

Protein interactions and networks

STRING

502 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COA1	COX14	Q96I36	791
COA1	COA3	Q9Y2R0	774
COA1	MSS51	Q4VC12	754
COA1	SURF1	Q15526	664
COA1	COX5A	P20674	658
COA1	TMEM186	Q96B77	597
COA1	ACAD9	Q9H845	589
COA1	COX15	Q7KZN9	582
COA1	COX16	Q9P0S2	568
COA1	NDUFAF5	Q5TEU4	566
COA1	TIMM21	Q9BVV7	542
COA1	PET117	Q6UWS5	540
COA1	COA5	Q86WW8	535
COA1	SMIM20	Q8N5G0	527
COA1	PET100	P0DJ07	479

IntAct

48 interactions, top by confidence:

A	B	Type	Score
RNF185	TMBIM6	psi-mi:“MI:0914”(association)	0.740
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
COA3	MT-CO1	psi-mi:“MI:0914”(association)	0.610
SLC9A6	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ECSIT	NDUFS8	psi-mi:“MI:0914”(association)	0.530
ZACN	GPAA1	psi-mi:“MI:0914”(association)	0.530
NDUFC2	NDUFS4	psi-mi:“MI:0914”(association)	0.530
ACAD9	PPL	psi-mi:“MI:0914”(association)	0.530
TIMM21	TIMM23	psi-mi:“MI:0914”(association)	0.500
STK4	IGHA1	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
ACAD9	A2ML1	psi-mi:“MI:0914”(association)	0.350
POLR2M	BIN1	psi-mi:“MI:0914”(association)	0.350
HTR3A	GPAA1	psi-mi:“MI:0914”(association)	0.350
ATAD3A	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
ATP2A1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
PIPSL	C1orf226	psi-mi:“MI:0914”(association)	0.350
ZACN	FAM234B	psi-mi:“MI:0914”(association)	0.350
MAGEA8	METTL15	psi-mi:“MI:0914”(association)	0.350
CRLF2	METTL15	psi-mi:“MI:0914”(association)	0.350
SLC22A4	RTL8C	psi-mi:“MI:0914”(association)	0.350
KDSR	ACOT7	psi-mi:“MI:0914”(association)	0.350
MYZAP	BIN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS), COA1 (Affinity Capture-MS)

ESM2 similar proteins: A3KP48, A4IJ20, A8WGU8, B5DF07, D3ZS74, D6WIX5, O14320, P40452, P53220, Q02380, Q08CK1, Q08DT6, Q0MQ83, Q1L987, Q1LY46, Q2NKR7, Q3SZN3, Q3SZV6, Q3ZBC2, Q4HZ95, Q4QQV3, Q4X1I8, Q59VW7, Q5R504, Q5REP2, Q5U2X7, Q5XKA2, Q66JD1, Q6BVK1, Q6CAQ9, Q6CW96, Q6DC58, Q6FMZ2, Q75CX4, Q7S8S5, Q80VP5, Q811I0, Q8CCM6, Q8IQ70, Q8K2Y7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
COA1	“form complex”	“MITRAC complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Complex I biogenesis	7	25.8×	2e-06
Respiratory electron transport	6	12.7×	9e-04
Aerobic respiration and respiratory electron transport	5	9.8×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial respiratory chain complex I assembly	7	47.2×	6e-08
intracellular zinc ion homeostasis	5	39.5×	4e-05
mitochondrial electron transport, NADH to ubiquinone	5	29.4×	1e-04
aerobic respiration	5	20.3×	4e-04
monoatomic ion transmembrane transport	5	17.1×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2920 predictions. Top by Δscore:

Variant	Effect	Δscore
7:43619595:A:AG	acceptor_gain	1.0000
7:43619596:G:GG	acceptor_gain	1.0000
7:43619720:GTGG:G	donor_gain	1.0000
7:43619721:TGGG:T	donor_loss	1.0000
7:43619722:GG:G	donor_gain	1.0000
7:43619723:GG:G	donor_gain	1.0000
7:43619723:GGTAA:G	donor_loss	1.0000
7:43619724:G:GG	donor_gain	1.0000
7:43619724:GTA:G	donor_loss	1.0000
7:43619725:TA:T	donor_loss	1.0000
7:43619726:AAGTA:A	donor_loss	1.0000
7:43623876:T:G	donor_gain	1.0000
7:43623884:CCTGA:C	donor_gain	1.0000
7:43623885:CTGA:C	donor_gain	1.0000
7:43623886:TGA:T	donor_gain	1.0000
7:43623887:GA:G	donor_gain	1.0000
7:43623887:GAG:G	donor_gain	1.0000
7:43623889:G:GG	donor_gain	1.0000
7:43623889:GT:G	donor_loss	1.0000
7:43623890:T:G	donor_loss	1.0000
7:43624515:CA:C	acceptor_loss	1.0000
7:43624516:A:AC	acceptor_loss	1.0000
7:43624516:A:AG	acceptor_gain	1.0000
7:43624517:G:GA	acceptor_gain	1.0000
7:43624517:GA:G	acceptor_gain	1.0000
7:43624517:GAGA:G	acceptor_gain	1.0000
7:43624517:GAGAT:G	acceptor_gain	1.0000
7:43645398:CT:C	acceptor_gain	1.0000
7:43647635:C:CC	acceptor_gain	1.0000
7:43647636:T:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008037 (7:43615780 A>G), RS1000027965 (7:43713844 G>C), RS1000029352 (7:43650832 CAGA>C), RS1000079443 (7:43704547 G>A), RS1000086702 (7:43720054 G>A), RS1000129748 (7:43632436 A>G), RS1000171123 (7:43691744 A>T), RS1000175143 (7:43648323 ATTT>A), RS1000238960 (7:43683590 C>T), RS1000257740 (7:43725881 T>C), RS1000263211 (7:43662289 G>A), RS1000269967 (7:43683354 C>T), RS1000288485 (7:43685511 G>A), RS1000339680 (7:43638514 G>A), RS1000354497 (7:43727396 T>C)

Disease associations

OMIM: gene MIM:614769 | 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
GCST011743_76	HDL cholesterol levels in HIV infection	5.000000e-06
GCST90002397_501	Mean spheric corpuscular volume	9.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	4
bisphenol A	decreases expression, decreases methylation, increases expression	3
Formaldehyde	decreases expression, increases expression	2
Nickel	increases expression	2
TAK-243	increases sumoylation	1
uranyl acetate	affects expression	1
primycin	decreases expression	1
arsenite	affects binding, increases reaction	1
1,6-hexamethylene diisocyanate	increases methylation	1
afimoxifene	decreases expression, decreases reaction	1
cobaltous chloride	increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
bicalutamide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
PCI 5002	affects cotreatment, decreases expression	1
Irinotecan	decreases expression	1
Decitabine	affects expression	1
Vorinostat	decreases expression	1
Panobinostat	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects expression	1
Coumestrol	increases expression	1
Estrogens	decreases expression, decreases reaction	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Phenylmercuric Acetate	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2UQ	Abcam HEK293T COA1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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