CMTM7

Chr 3

CKLF like MARVEL transmembrane domain containing 7

Also known as: CKLFSF7

NCBI Gene: 112616 ENSG00000153551 UniProt: Q96FZ5

The CMTM7 protein is a tumor suppressor that regulates G1/S cell cycle transition and epidermal growth factor receptor/protein kinase B signaling pathways. Mutations in this gene cause autosomal recessive peripheral neuropathy with or without impaired intellectual development, typically presenting in childhood. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

ResearchSummary from RefSeq

This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and transmembrane 4 superfamilies. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 3. This gene acts as a tumor suppressor that regulates G1/S transition in the cell cycle, and epidermal growth factor receptor/protein kinase B signaling during tumor pathogenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.19

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.038

Z-score 1.27

OE 0.46 (0.21–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.95Z-score

OE missense 0.70 (0.56–0.87)

55 obs / 78.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.21–1.19)

0≤0.351.4

Missense OE?0.70 (0.56–0.87)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 3 / 6.5Missense obs/exp: 55 / 78.7Syn Z: -0.03

Background carrier burden — how many people carry a rare variant somewhere in CMTM7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

298 rare PASS variants

Rare truncating (LoF)

1 in 1,600

37 rare PASS variants

Rare synonymous (reference)

1 in 310

135 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CMTM7. 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 3,400
South Asian	~43k	1 in 200	≈ 1 in 15,000
Remaining (unassigned)	~30k	1 in 110	1 in 2,400
European (Finnish)	~27k	1 in 590	≈ 1 in 6,400
Admixed American	~22k	1 in 200	1 in 1,000
African / African American	~21k	1 in 91	≈ 1 in 21,000
East Asian	~20k	1 in 300	≈ 1 in 8,100
Ashkenazi Jewish	~13k	1 in 1,700	≈ 1 in 5,700
Middle Eastern	~2,884	1 in 210	≈ 1 in 870

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 1 marginal. Genomes: all 5.? see exons ↓