COMMD4

protein-coding

COMM domain containing 4, the group of CCC complex|COMM domain containing

Gene summary

Predicted to be involved in signal transduction. Located in cytosol. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_017828.5

Inheritance

—

ClinVar variants

U:40

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr15:75,336,020-75,343,224

External References & Databases

Ensembl (ENSG00000140365)

Transcript & Mutation Effects

hg38 • Region Span ~7.2 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 COMMD4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 33

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017828.5. 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			35 clinvar			35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	40	0	0	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 93 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017828.5	RefSeq	NP_060298.2	8	MANE Select
ENST00000267935.13	Ensembl	ENSP00000267935.8	8	MANE Select
NM_001284377.2	RefSeq	NP_001271306.1	7	Standard
NM_001284378.2	RefSeq	NP_001271307.1	6	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

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000267935
Coding exons: 8
Length: 6037
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 125746
p: 0.000107

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0709	118	116	1.02	0.00000679	1264
Missense (PolyPhen)		32	39.16	0.81715		464
Synonymous	0.220	51	53.0	0.962	0.00000325	408
Loss of Function	1.21	7	11.4	0.613	4.82e-7	140

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00018	0.00016	rare
Finnish	0.00031	0.00028	rare
European (Non-Finnish)	0.000082	0.000079	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.546
RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.341

Gene Damage Prediction

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