CMTM8

Chr 3

CKLF like MARVEL transmembrane domain containing 8

Also known as: CKLFSF8, CKLFSF8-V2

NCBI Gene: 152189 ENSG00000170293 UniProt: Q8IZV2

The protein functions as a tumor suppressor and negative regulator of epidermal growth factor-induced signaling, controlling cell migration. Mutations in this gene have not been established as a cause of recognized human genetic disease. The gene shows no evidence of constraint against loss-of-function variants in the general population.

ResearchSummary from RefSeq

This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the 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, and plays a role in regulating the migration of tumor cells. The encoded protein is thought to function as a a negative regulator of epidermal growth factor-induced signaling. 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

1.02

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?

1.02LOEUF

pLI 0.060

Z-score 1.55

OE 0.39 (0.18–1.02)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.98 (0.83–1.16)

98 obs / 100.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.39 (0.18–1.02)

0≤0.351.4

Missense OE?0.98 (0.83–1.16)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 3 / 7.6Missense obs/exp: 98 / 100.0Syn Z: 0.63

Background carrier burden — how many people carry a rare variant somewhere in CMTM8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

235 rare PASS variants

Rare truncating (LoF)

1 in 6,500

24 rare PASS variants

Rare synonymous (reference)

1 in 320

98 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CMTM8. 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 340	1 in 6,100
South Asian	~43k	1 in 130	≈ 1 in 20,000
Remaining (unassigned)	~30k	1 in 170	≈ 1 in 15,000
European (Finnish)	~27k	1 in 990	≈ 1 in 8,600
Admixed American	~22k	1 in 230	1 in 3,600
African / African American	~21k	1 in 260	≈ 1 in 4,200
East Asian	~20k	1 in 290	≈ 1 in 18,000
Ashkenazi Jewish	~13k	1 in 2,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 170	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): 3 of 4 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 4.? see exons ↓