COMMD4

Chr 15

COMM domain containing 4

NCBI Gene: 54939 ENSG00000140365 UniProt: Q9H0A8 OMIM: 616701

Scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos; the commander complex is composed of the CCC subcomplex and the retriever subcomplex (PubMed:37172566, PubMed:38459129). May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). Down-regulates activation of NF-kappa-B (PubMed:23637203)

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 1.21

OE 0.61 (0.35–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.07Z-score

OE missense 1.02 (0.88–1.19)

118 obs / 115.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.61 (0.35–1.15)

0≤0.351.4

Missense OE?1.02 (0.88–1.19)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 7 / 11.4Missense obs/exp: 118 / 115.9Syn Z: 0.22

Background carrier burden — how many people carry a rare variant somewhere in COMMD4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

308 rare PASS variants

Rare truncating (LoF)

1 in 1,300

55 rare PASS variants

Rare synonymous (reference)

1 in 290

133 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COMMD4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 280	1 in 1,300
South Asian	~43k	1 in 75	1 in 3,300
Remaining (unassigned)	~30k	1 in 110	1 in 1,300
European (Finnish)	~27k	1 in 1,100	1 in 1,100
Admixed American	~22k	1 in 130	1 in 2,600
African / African American	~21k	1 in 240	1 in 1,300
East Asian	~20k	1 in 230	1 in 690
Ashkenazi Jewish	~13k	1 in 340	none seen
Middle Eastern	~2,884	1 in 150	≈ 1 in 1,100

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓