COA4

Summary

COA4 (cytochrome c oxidase assembly factor 4 homolog, HGNC:24604) is a protein-coding gene on chromosome 11q13.4, encoding Cytochrome c oxidase assembly factor 4 homolog, mitochondrial (Q9NYJ1). Putative COX assembly factor.

Predicted to be involved in mitochondrial cytochrome c oxidase assembly. Located in mitochondrion.

Source: NCBI Gene 51287 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_016565

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24604
Approved symbol	COA4
Name	cytochrome c oxidase assembly factor 4 homolog
Location	11q13.4
Locus type	gene with protein product
Status	Approved
Aliases	E2IG2, CMC3
Ensembl gene	ENSG00000181924
Ensembl biotype	protein_coding
OMIM	608016
Entrez	51287

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000355693, ENST00000537289, ENST00000537581, ENST00000541455, ENST00000544575, ENST00000545127, ENST00000876824, ENST00000876826, ENST00000876828, ENST00000876829, ENST00000876831, ENST00000940620, ENST00000940621, ENST00000940622

RefSeq mRNA: 1 — MANE Select: NM_016565 NM_016565

CCDS: CCDS8225

Canonical transcript exons

ENST00000355693 — 2 exons

Exon	Start	End
ENSE00002230170	73872667	73873394
ENSE00002321826	73876757	73876846

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 97.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.4780 / max 266.5556, expressed in 1817 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121274	53.3678	1817
121273	0.1103	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	97.75	gold quality
right adrenal gland cortex	UBERON:0035827	97.46	gold quality
left adrenal gland	UBERON:0001234	97.39	gold quality
left adrenal gland cortex	UBERON:0035825	97.22	gold quality
adrenal cortex	UBERON:0001235	97.06	gold quality
adrenal gland	UBERON:0002369	96.92	gold quality
tendon of biceps brachii	UBERON:0008188	96.81	gold quality
mucosa of transverse colon	UBERON:0004991	96.22	gold quality
parotid gland	UBERON:0001831	96.21	gold quality
adrenal tissue	UBERON:0018303	96.11	gold quality
right lobe of liver	UBERON:0001114	95.88	gold quality
right atrium auricular region	UBERON:0006631	95.40	gold quality
cardiac atrium	UBERON:0002081	94.97	gold quality
gall bladder	UBERON:0002110	94.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.93	gold quality
adult mammalian kidney	UBERON:0000082	94.68	gold quality
gastrocnemius	UBERON:0001388	94.63	gold quality
heart left ventricle	UBERON:0002084	94.56	gold quality
cardiac ventricle	UBERON:0002082	94.50	gold quality
rectum	UBERON:0001052	94.49	gold quality
transverse colon	UBERON:0001157	94.49	gold quality
heart	UBERON:0000948	94.48	gold quality
body of stomach	UBERON:0001161	94.48	gold quality
left coronary artery	UBERON:0001626	94.47	gold quality
right lobe of thyroid gland	UBERON:0001119	94.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.41	gold quality
body of pancreas	UBERON:0001150	94.34	gold quality
left lobe of thyroid gland	UBERON:0001120	94.30	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.30	gold quality
muscle of leg	UBERON:0001383	94.25	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.66
E-MTAB-8271	yes	6.70
E-MTAB-4850	no	93.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting COA4, 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-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-6512-5P	98.76	69.29	1195
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-3167	96.81	67.09	1236
HSA-MIR-591	96.29	68.16	611
HSA-MIR-4256	96.22	67.70	669
HSA-MIR-11181-5P	96.12	67.46	665

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	coa4	ENSDARG00000078974
mus_musculus	Coa4	ENSMUSG00000044881
rattus_norvegicus	Coa4	ENSRNOG00000077991

Protein

Protein identifiers

Cytochrome c oxidase assembly factor 4 homolog, mitochondrial — Q9NYJ1 (reviewed: Q9NYJ1)

Alternative names: Coiled-coil-helix-coiled-coil-helix domain-containing protein 8, E2-induced gene 2 protein

All UniProt accessions (1): Q9NYJ1

UniProt curated annotations — full annotation on UniProt →

Function. Putative COX assembly factor.

Subcellular location. Mitochondrion.

Induction. Up-regulated by estrogen.

Similarity. Belongs to the COA4 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NYJ1-1	1	yes
Q9NYJ1-2	2

RefSeq proteins (1): NP_057649* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010625	CHCH	Domain
IPR039870	Coa4-like	Family

Pfam: PF06747

UniProt features (11 total): region of interest 2, short sequence motif 2, compositionally biased region 2, disulfide bond 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NYJ1-F1	87.37	0.70

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): 34–64, 44–54

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import

MSigDB gene sets: 65 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, chr11q13, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, GOCC_MITOCHONDRIAL_ENVELOPE, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOCC_ORGANELLE_ENVELOPE_LUMEN, BOCHKIS_FOXA2_TARGETS, GOCC_ORGANELLE_ENVELOPE, REACTOME_PROTEIN_LOCALIZATION, ARID5B_TARGET_GENES, CEBPZ_TARGET_GENES, H1_6_TARGET_GENES

GO Biological Process (1): mitochondrial respiratory chain complex IV assembly (GO:0033617)

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

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial intermembrane space (GO:0005758)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein localization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	1
respiratory chain complex IV assembly	1
mitochondrial respiratory chain complex assembly	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial envelope	1
organelle envelope lumen	1

Protein interactions and networks

STRING

796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COA4	COA6	Q5JTJ3	714
COA4	CMC4	P56277	664
COA4	COX17	Q14061	627
COA4	CHCHD4	Q8N4Q1	627
COA4	CMC2	Q9NRP2	615
COA4	COX19	Q49B96	599
COA4	COA7	Q96BR5	598
COA4	COA3	Q9Y2R0	570
COA4	COA5	Q86WW8	539
COA4	LYRM7	Q5U5X0	518
COA4	SDHAF4	Q5VUM1	507
COA4	COQ3	Q9NZJ6	492
COA4	CHCHD7	Q9BUK0	475
COA4	COX6B1	P14854	450
COA4	COX11	Q9Y6N1	433

IntAct

6 interactions, top by confidence:

A	B	Type	Score
COA4	COX11	psi-mi:“MI:0915”(physical association)	0.500
	SUPT5H	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
ATG4B	RPS3A	psi-mi:“MI:0914”(association)	0.350
COX11	COX19	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): COA4 (Co-fractionation), MSRB2 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), AK3 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation), COA4 (Co-fractionation)

ESM2 similar proteins: A1CH57, A5DUN2, A6ZMQ6, A9ULB4, B3LM82, B5RTE0, C8ZF59, G2TRP6, P00429, P0CM70, P0CM71, P0CM86, P0CM87, P0CT19, P21976, P56277, P90789, Q02373, Q05809, Q0P451, Q0UWF1, Q17Q91, Q1DJH5, Q208S3, Q2M2S5, Q2TAP8, Q3E7A9, Q3E846, Q462Q7, Q4IAJ1, Q4R374, Q53CG4, Q5B4S6, Q6C4R1, Q6CIT9, Q6DD38, Q6FQX5, Q6INR6, Q75D94, Q7S4H6

Diamond homologs: Q8BT51, Q9NYJ1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

466 predictions. Top by Δscore:

Variant	Effect	Δscore
11:73873390:GGAGT:G	acceptor_gain	0.9900
11:73873391:GAGT:G	acceptor_gain	0.9900
11:73873392:AGT:A	acceptor_gain	0.9900
11:73873393:GT:G	acceptor_gain	0.9900
11:73873395:C:CC	acceptor_gain	0.9900
11:73873393:GTCTA:G	acceptor_loss	0.9800
11:73876467:T:A	donor_gain	0.9800
11:73876663:TTGA:T	donor_gain	0.9800
11:73876728:T:TA	donor_gain	0.9800
11:73873397:A:C	acceptor_gain	0.9600
11:73876755:A:AC	donor_gain	0.9600
11:73876756:C:CC	donor_gain	0.9600
11:73876756:CCGAA:C	donor_gain	0.9600
11:73876448:A:AC	donor_gain	0.9500
11:73876749:ATGCT:A	donor_loss	0.9500
11:73876751:GC:G	donor_loss	0.9500
11:73876752:CTCAC:C	donor_loss	0.9500
11:73876754:CA:C	donor_loss	0.9500
11:73876755:ACC:A	donor_loss	0.9500
11:73876002:ACG:A	donor_gain	0.9400
11:73876003:CGC:C	donor_gain	0.9400
11:73876748:GATGC:G	donor_loss	0.9400
11:73875544:T:TA	donor_gain	0.9300
11:73876750:TGCT:T	donor_loss	0.9300
11:73876788:CG:C	donor_gain	0.9300
11:73876791:T:A	donor_gain	0.9300
11:73876903:G:C	donor_gain	0.9300
11:73873404:A:C	acceptor_gain	0.9200
11:73875914:G:C	donor_gain	0.9100
11:73875906:TGG:T	donor_gain	0.9000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000254941 (11:73877580 T>A), RS1000568787 (11:73878330 A>C,G), RS1000914254 (11:73872493 G>A,T), RS1001525926 (11:73876543 T>C), RS1002020737 (11:73877198 C>G,T), RS1002165064 (11:73876141 A>G), RS1002261528 (11:73875132 A>G,T), RS1002539334 (11:73875524 A>C), RS1003078310 (11:73875933 T>C), RS1003991219 (11:73877930 CTATT>C), RS1005052300 (11:73875974 A>C,G), RS1005659600 (11:73876796 C>A,G), RS1006175682 (11:73875772 G>T), RS1006454042 (11:73875452 C>G,T), RS1007816520 (11:73877614 A>C,G)

Disease associations

OMIM: gene MIM:608016 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005760_4	Dimensional psychopathology (Cognitive)	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009098	cognitive domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, decreases expression, affects expression	2
GSK-J4	decreases expression	1
beta-lapachone	increases expression	1
arsenite	increases reaction, affects binding	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
Temozolomide	increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression, increases abundance	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Gold Compounds	decreases expression	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Vitamin K 3	affects 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_B2US	Abcam HEK293T COA4 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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