COMMD3

Chr 10

COMM domain containing 3

Also known as: BUP, C10orf8

NCBI Gene: 23412 ENSG00000148444 UniProt: Q9UBI1 OMIM: 616700

COMMD3 encodes a scaffold protein in the commander complex that is essential for endosomal recycling of transmembrane cargos and modulates sodium transport in epithelial cells by regulating amiloride-sensitive sodium channel expression. The gene shows low constraint to loss-of-function variation (pLI 0.00003, LOEUF 1.14), and no established human disease associations have been reported to date. Additional research is needed to determine if COMMD3 variants cause neurological or other clinical phenotypes.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in endocytic recycling. Predicted to act upstream of or within intracellular copper ion homeostasis. Part of protein-containing complex. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.14

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.14LOEUF

pLI 0.000

Z-score 1.20

OE 0.65 (0.39–1.14)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.35Z-score

OE missense 1.10 (0.94–1.28)

113 obs / 103.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.39–1.14)

0≤0.351.4

Missense OE?1.10 (0.94–1.28)

0≤0.61.4

Synonymous OE?1.36

0≤1.21.6

LoF obs/exp: 9 / 13.8Missense obs/exp: 113 / 103.1Syn Z: -1.73

Background carrier burden — how many people carry a rare variant somewhere in COMMD3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

387 rare PASS variants

Rare truncating (LoF)

1 in 810

90 rare PASS variants

Rare synonymous (reference)

1 in 1,100

74 rare PASS variants

Rare missense and truncating variants are carried at similar rates in COMMD3; this gene does not show strong loss-of-function constraint by this measure. 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 390	1 in 930
South Asian	~43k	1 in 130	1 in 1,800
Remaining (unassigned)	~30k	1 in 150	1 in 720
European (Finnish)	~27k	1 in 460	1 in 1,600
Admixed American	~22k	1 in 130	1 in 1,800
African / African American	~21k	1 in 100	1 in 1,300
East Asian	~20k	1 in 220	1 in 460
Ashkenazi Jewish	~13k	1 in 650	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 150	≈ 1 in 2,800

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 ↓