KLF6

Chr 10

KLF transcription factor 6

Also known as: BCD1, CBA1, COPEB, CPBP, GBF, PAC1, ST12, ZF9

NCBI Gene: 1316 ENSG00000067082 UniProt: Q99612 OMIM: 602053

KLF6 encodes a zinc finger transcription factor that activates gene transcription by binding GC box motifs and may function in B-cell growth and development. Mutations cause gastric cancer and prostate cancer as somatic (acquired) alterations rather than inherited germline conditions. This gene is highly constrained against loss-of-function variants (pLI 0.98, LOEUF 0.25), indicating it is essential for normal cellular function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the Kruppel-like family of transcription factors. The zinc finger protein is a transcriptional activator, and functions as a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene, some of which are implicated in carcinogenesis. [provided by RefSeq, May 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Gastric cancer, somaticMIM #613659

Prostate cancer, somaticMIM #176807

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Gastric cancer, somatic; Prostate cancer, somatic; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

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Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.25LOEUF

pLI 0.979

Z-score 3.19

OE 0.00 (0.00–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.85Z-score

OE missense 0.59 (0.50–0.70)

95 obs / 161.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.25)

0≤0.351.4

Missense OE?0.59 (0.50–0.70)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 0 / 11.9Missense obs/exp: 95 / 161.2Syn Z: -0.54

Background carrier burden — how many people carry a rare variant somewhere in KLF6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

334 rare PASS variants

Rare truncating (LoF)

1 in 12,000

19 rare PASS variants

Rare synonymous (reference)

1 in 190

191 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KLF6. 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 270	1 in 13,000
South Asian	~43k	1 in 110	none seen
Remaining (unassigned)	~30k	1 in 200	≈ 1 in 9,900
European (Finnish)	~27k	1 in 860	≈ 1 in 24,000
Admixed American	~22k	1 in 160	≈ 1 in 18,000
African / African American	~21k	1 in 220	≈ 1 in 9,200
East Asian	~20k	1 in 220	≈ 1 in 6,100
Ashkenazi Jewish	~13k	1 in 1,400	none seen
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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓