COMMD8

protein-coding

COMM domain containing 8, the group of COMM domain containing|CCC complex

Gene summary

The protein encoded by this gene binds coiled-coil domain-containing protein 22 (CCDC22), and this complex can regulate the turnover of I-kappa-B and the activation of NF-kappa-B. [provided by RefSeq, Jul 2016]

MANE transcript

NM_017845.5

Inheritance

—

ClinVar variants

U:31B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.16

Max pathogenic AF

—

Genomic locus

chr4:47,450,787-47,463,702

External References & Databases

Ensembl (ENSG00000169019)

Transcript & Mutation Effects

hg38 • Region Span ~12.9 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 COMMD8 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017845.5. 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						0
missense			29 clinvar	5 clinvar		34
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	31	5	0	36

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017845.5	RefSeq	NP_060315.1	5	MANE Select
ENST00000381571.6	Ensembl	ENSP00000370984.4	5	MANE Select
NM_001329668.2	RefSeq	NP_001316597.1	5	Standard
ENST00000860334.1	Ensembl	ENSP00000530393.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
Neddylation

Molecular Function

protein binding

Cellular Component

nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381571
Coding exons: 5
Length: 12852
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125731
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0422	90	91.1	0.988	0.00000428	1185
Missense (PolyPhen)		25	25.689	0.97318		373
Synonymous	-1.23	43	33.9	1.27	0.00000172	327
Loss of Function	-0.496	13	11.2	1.16	6.41e-7	121

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000056	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.00033	0.00033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). May down-regulate activation of NF-kappa-B (PubMed:15799966). {ECO:0000269|PubMed:15799966, ECO:0000305|PubMed:21778237}.;

Recessive Scores

pRec: 0.0935

Intolerance Scores

RVIS EVS: 0.81
RVIS percentile EVS: 87.82

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.531

Gene Damage Prediction

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