KLF5

Chr 13

KLF transcription factor 5

Also known as: BTEB2, CKLF, IKLF

NCBI Gene: 688 ENSG00000102554 UniProt: Q13887

KLF5 encodes a zinc finger transcription factor that binds to GC box promoter elements and activates transcription of target genes. Mutations cause autosomal dominant intellectual disability with hypotonia and speech delay, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (pLI 0.82, LOEUF 0.44), indicating that complete loss of function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the Kruppel-like factor subfamily of zinc finger proteins. The encoded protein is a transcriptional activator that binds directly to a specific recognition motif in the promoters of target genes. This protein acts downstream of multiple different signaling pathways and is regulated by post-translational modification. It may participate in both promoting and suppressing cell proliferation. Expression of this gene may be changed in a variety of different cancers and in cardiovascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ResearchGenerating clinical summary…

Clinical highlights

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

194

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.44

LOEUF

LOF

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

Moderate LoF intolerance

LoF Constraint?

0.44LOEUF

pLI 0.818

Z-score 3.03

OE 0.14 (0.06–0.44)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.58Z-score

OE missense 0.70 (0.61–0.80)

151 obs / 216.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.14 (0.06–0.44)

0≤0.351.4

Missense OE?0.70 (0.61–0.80)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 2 / 14.4Missense obs/exp: 151 / 216.4Syn Z: 0.19

Background carrier burden — how many people carry a rare variant somewhere in KLF5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 100

559 rare PASS variants

Rare truncating (LoF)

1 in 12,000

24 rare PASS variants

Rare synonymous (reference)

1 in 290

268 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KLF5. 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 130	1 in 11,000
South Asian	~43k	1 in 140	1 in 2,100
Remaining (unassigned)	~30k	1 in 120	≈ 1 in 23,000
European (Finnish)	~27k	1 in 450	none seen
Admixed American	~22k	1 in 110	none seen
African / African American	~21k	1 in 110	≈ 1 in 12,000
East Asian	~20k	1 in 150	none seen
Ashkenazi Jewish	~13k	1 in 820	none seen
Middle Eastern	~2,884	1 in 220	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): 2 of 4 coding exons well covered in gnomAD exomes; exons 1, 3 marginal. Genomes: all 4.? see exons ↓