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…

LOFmechanismLOEUF 0.61

Clinical Summary— KLF15

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.19) despite low pLI — interpret in context.

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ClinVar Variants

67 VUS of 76 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.5870th %ile

GOF

0.3293th %ile

LOF

0.69top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

76 submitted variants in ClinVar

ClinVar

Classification Summary

VUS67

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	67	67
Likely Benign	5	5
Benign	0	0
Total	72	72

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

13 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap KLF15 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →