COMMD2

Chr 3

COMM domain containing 2

ENSG00000114744 UniProt: Q86X83 OMIM: 616699

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). May down-regulate activation of NF-kappa-B (PubMed:15799966)

OMIM Research

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

1.82

LOEUF

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Mechanism

Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.82LOEUF

pLI 0.000

Z-score -0.61

OE 1.21 (0.77–1.82)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.69Z-score

OE missense 0.81 (0.68–0.97)

83 obs / 102.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.21 (0.77–1.82)

0≤0.351.4

Missense OE?0.81 (0.68–0.97)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 12 / 9.9Missense obs/exp: 83 / 102.6Syn Z: -1.13

Background carrier burden — how many people carry a rare variant somewhere in COMMD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

243 rare PASS variants

Rare truncating (LoF)

1 in 3,000

46 rare PASS variants

Rare synonymous (reference)

1 in 1,700

104 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COMMD2. 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 220	1 in 3,100
South Asian	~43k	1 in 230	1 in 2,100
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 9,700
European (Finnish)	~27k	1 in 760	1 in 5,200
Admixed American	~22k	1 in 280	≈ 1 in 11,000
African / African American	~21k	1 in 210	1 in 1,700
East Asian	~20k	1 in 280	1 in 2,800
Ashkenazi Jewish	~13k	1 in 1,500	1 in 1,700
Middle Eastern	~2,884	1 in 220	none seen

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): 4 of 5 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 5.? see exons ↓