COA8 (cytochrome c oxidase assembly factor 8)

Gene

• Entrez ID: 84334
• Gene name: Cytochrome c oxidase assembly factor 8
• Gene symbol: COA8
• Synonyms (NCBI Gene): APOP, APOP1, APOPT1, C14orf153, MC4DN17
• Chromosome: 14
• Chromosome location: 14q32.33
• Summary: This gene encodes a protein that localizes to the mitochondria, where it stimulates the release of cytochrome c, thereby promoting programmed cell death. Mutations in this gene have been found in individuals with mitochondrial complex IV deficiency. Alter

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587777784	C>G,T	Pathogenic	Coding sequence variant, missense variant, stop gained, non coding transcript variant
rs587777785	G>A	Pathogenic	Splice acceptor variant
rs587777786	T>C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, non coding transcript variant
rs587777787	GAA>-	Pathogenic	Coding sequence variant, intron variant, inframe deletion, non coding transcript variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000302	Process	Response to reactive oxygen species	IDA	30552096
GO:0005515	Function	Protein binding	IPI	28514442, 33961781
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	25175347
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0006915	Process	Apoptotic process	IEA
GO:0016020	Component	Membrane	IEA
GO:0033617	Process	Mitochondrial cytochrome c oxidase assembly	IDA	30552096
GO:0033617	Process	Mitochondrial cytochrome c oxidase assembly	IMP	25175347
GO:0050821	Process	Protein stabilization	IDA	30552096
GO:0097193	Process	Intrinsic apoptotic signaling pathway	IEA
GO:0099617	Component	Matrix side of mitochondrial inner membrane	IDA	30552096

Other IDs

• MIM: 616003
• HGNC: 20492
• e!Ensembl: ENSG00000256053

Protein

• UniProt ID: Q96IL0
• Protein name: Cytochrome c oxidase assembly factor 8 (COA8) (Apoptogenic protein 1, mitochondrial) (APOP-1)
• Protein function: Required for cytochrome c complex (COX) IV assembly and function Protects COX assembly from oxidation-induced degradation, COX being the terminal component of the mitochondrial respiratory chain. {ECO:0000269|PubMed:25175347, ECO:0000269|PubMed:
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10231	DUF2315	66 → 194	Apoptogenic protein 1	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in fibroblasts. {ECO:0000269|PubMed:25175347}.
• Sequence:

  MLPCAAGARGRGAMVVLRAGKKTFLPPLCRAFACRGCQLAPERGAERRDTAPSGVSRFCP
  PRKSCHDWIGPPDKYSNLRPVHFYIPENESPLEQKLRKLRQETQEWNQQFWANQNLTFSK
  EKEEFIHSRLKTKGLGLRTESGQKATLNAEEMADFYKEFLSKNFQKHMYYNRDWYKRNFA
  ITFFMGKVALERIWNKLKQKQKKRSN

• Sequence length: 206

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Mitochondrial complex IV deficiency, nuclear type 1	Likely pathogenic	rs759966247	RCV000791189	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial complex IV deficiency, nuclear type 17	Likely pathogenic; Pathogenic	rs753824369, rs587777784, rs587777785, rs587777787, rs2507478587, rs778874587, rs2507477807, rs769966495	RCV001808927 RCV000144485 RCV000144486 RCV000144488 RCV003111524 RCV003228733 RCV003332426 RCV003493227	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COA8-related disorder	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBESITY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OBSESSIVE-COMPULSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult Fanconi syndrome	Fanconi syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blepharoptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Child Development Disorders, Pervasive	Development Disorder	GWASCAT_DG	28540026		★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cytochrome c Oxidase Deficiency	Cytochrome c oxidase deficiency	Pubtator	25175347	Associate	★☆☆☆☆ Found in Text Mining only
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	BEFREE	25175347, 31555154		★☆☆☆☆ Found in Text Mining only
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	GENOMICS_ENGLAND_DG	25175347		★☆☆☆☆ Found in Text Mining only
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	UNIPROT_DG	25175347, 29577824, 30552096		★☆☆☆☆ Found in Text Mining only
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Cytochrome-c Oxidase Deficiency	Cytochrome-C Oxidase Deficiency	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Erectile dysfunction	Erectile Dysfunction	BEFREE	29935293		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	BEFREE	31220173		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Leukodystrophy	Leukodystrophy	BEFREE	29577824		★☆☆☆☆ Found in Text Mining only
Leukodystrophy Metachromatic	Metachromatic leukodystrophy	Pubtator	25175347	Associate	★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	BEFREE	25175347		★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	25175347		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mitochondrial Diseases	Mitochondrial disease	Pubtator	25175347	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Non-progressive predominantly posterior cavitating leukoencephalopathy with peripheral neuropathy	Leukoencephalopathy With Peripheral Neuropathy	Orphanet			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Phosphate Diabetes	Phosphate Diabetes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ptosis	Ptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal tubular disorder	Renal Tubular Disorder	HPO_DG			★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	HPO_DG			★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	25056061, 26198764, 28540026, 30285260, 31268507, 31374203		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural hearing loss, bilateral	Sensorineural hearing loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Skeletal muscle steatosis	Skeletal muscle steatosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spastic tetraparesis	Spastic tetraparesis	HPO_DG			★☆☆☆☆ Found in Text Mining only