COMMD7

Chr 20

COMM domain containing 7

Also known as: C20orf92, dJ1085F17.3

NCBI Gene: 149951 ENSG00000149600 UniProt: Q86VX2 OMIM: 616703

The protein functions as a scaffold in the commander complex essential for endosomal recycling of transmembrane cargos and suppresses NF-kappaB transcriptional activity. Mutations cause neurodevelopmental disorder with spastic paraplegia and microcephaly, inherited in an autosomal recessive pattern. The gene is not highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

Enables NF-kappaB binding activity. Involved in negative regulation of DNA-templated transcription and tumor necrosis factor-mediated signaling pathway. 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

1.36

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.36LOEUF

pLI 0.000

Z-score 0.57

OE 0.84 (0.54–1.36)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.59Z-score

OE missense 0.84 (0.70–1.00)

84 obs / 100.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.54–1.36)

0≤0.351.4

Missense OE?0.84 (0.70–1.00)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 12 / 14.3Missense obs/exp: 84 / 100.6Syn Z: 0.32

Background carrier burden — how many people carry a rare variant somewhere in COMMD7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

240 rare PASS variants

Rare truncating (LoF)

1 in 4,700

59 rare PASS variants

Rare synonymous (reference)

1 in 710

86 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COMMD7. 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 290	1 in 5,900
South Asian	~43k	1 in 760	1 in 2,500
Remaining (unassigned)	~30k	1 in 200	1 in 4,300
European (Finnish)	~27k	1 in 950	≈ 1 in 13,000
Admixed American	~22k	1 in 170	≈ 1 in 22,000
African / African American	~21k	1 in 150	≈ 1 in 5,600
East Asian	~20k	1 in 240	1 in 600
Ashkenazi Jewish	~13k	1 in 560	none seen
Middle Eastern	~2,884	1 in 210	≈ 1 in 2,900

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): 8 of 9 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 9.? see exons ↓