COX18

protein-coding

cytochrome c oxidase assembly factor COX18, the group of Mitochondrial respiratory chain complex assembly factors

Gene summary

This gene encodes a cytochrome c oxidase assembly protein. The encoded protein is essential for integral membrane protein insertion into the mitochondrial inner membrane. It is also required for cytochrome c oxidase assembly and activity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

MANE transcript

NM_001297732.2

Inheritance

—

ClinVar variants

P:2U:62B:6

Top phenotype

Charcot-marie-tooth disease, axonal, type 2MM

gnomAD constraint

pLI —, LoF o/e 1.18

Max pathogenic AF

—

Genomic locus

chr4:73,052,362-73,069,755

External References & Databases

Ensembl (ENSG00000163626)

Transcript & Mutation Effects

hg38 • Region Span ~17.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COX18 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 60

Charcot-marie-tooth disease, axonal, type 2MMTotal: 4

Mitochondrial complex 4 deficiency, nuclear type 25Total: 2

not providedTotal: 1

Mitochondrial complex IV deficiency, nuclear type 1Total: 1

Sensorineural hearing loss disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001297732.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	1 clinvar		2
missense	2 clinvar		60 clinvar	5 clinvar		67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	2	0	62	6	0	70

Highest pathogenic variant AF is 0.0000177878

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001297732.2	RefSeq	NP_001284661.1	6	MANE Select
ENST00000507544.3	Ensembl	ENSP00000425261.3	6	MANE Select
NM_001297733.2	RefSeq	NP_001284662.1	4	Standard
NM_001300729.1	RefSeq	NP_001287658.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thermogenesis - Homo sapiens (human)
Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription
Respiratory electron transport

Biological Process

respiratory chain complex IV assembly
protein transport
protein insertion into mitochondrial inner membrane from matrix
mitochondrial respiratory chain complex IV assembly
protein insertion into mitochondrial membrane

Molecular Function

protein binding
protein transporter activity
membrane insertase activity

Cellular Component

integral component of mitochondrial inner membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295890
Coding exons: 6
Length: 13676
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125747
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.132	184	189	0.973	0.0000101	2077
Missense (PolyPhen)		30	35.141	0.85371		413
Synonymous	0.241	73	75.7	0.965	0.00000393	714
Loss of Function	-0.697	20	16.9	1.18	8.92e-7	174

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mitochondrial membrane insertase required for the translocation of the C-terminus of cytochrome c oxidase subunit II (MT-CO2/COX2) across the mitochondrial inner membrane. Plays a role in MT-CO2/COX2 maturation following the COX20-mediated stabilization of newly synthesized MT-CO2/COX2 protein and before the action of the metallochaperones SCO1/2. Essential for the assembly and stability of the mitochondrial respiratory chain complex IV (also known as cytochrome c oxidase). {ECO:0000269|PubMed:16911509, ECO:0000269|PubMed:28330871}.;

Recessive Scores

pRec: 0.0977

Intolerance Scores

LoFtool: 0.301
RVIS EVS: -0.23
RVIS percentile EVS: 37.11

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.508

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium