KLF15

Chr 3

KLF transcription factor 15

Also known as: KKLF

NCBI Gene: 28999 ENSG00000163884 UniProt: Q9UIH9 OMIM: 606465

KLF15 encodes a transcriptional regulator that binds to specific DNA sequences and controls gene expression, particularly in cardiac and renal tissues where it regulates ion channel expression, cardiac fibrosis, and podocyte differentiation. Mutations cause hypokalemic periodic paralysis type 4, an autosomal dominant disorder characterized by episodic muscle weakness triggered by low potassium levels. The gene shows moderate constraint against loss-of-function variants, suggesting some intolerance to complete gene disruption.

OMIM ResearchSummary from RefSeq, UniProt

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of peptidyl-lysine acetylation and positive regulation of transcription by RNA polymerase II. Located in nuclear speck. [provided by Alliance of Genome Resources, Jul 2025]

OMIM 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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.61

LOEUF

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.61LOEUF

pLI 0.488

Z-score 2.39

OE 0.19 (0.08–0.61)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.98Z-score

OE missense 0.82 (0.73–0.93)

202 obs / 245.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.19 (0.08–0.61)

0≤0.351.4

Missense OE?0.82 (0.73–0.93)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 2 / 10.3Missense obs/exp: 202 / 245.4Syn Z: 0.15

Background carrier burden — how many people carry a rare variant somewhere in KLF15?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

524 rare PASS variants

Rare truncating (LoF)

1 in 12,000

21 rare PASS variants

Rare synonymous (reference)

1 in 170

260 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KLF15. 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 160	1 in 12,000
South Asian	~43k	1 in 130	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 110	≈ 1 in 15,000
European (Finnish)	~27k	1 in 240	none seen
Admixed American	~22k	1 in 100	1 in 3,800
African / African American	~21k	1 in 120	none seen
East Asian	~20k	1 in 150	none seen
Ashkenazi Jewish	~13k	1 in 250	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 89	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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓