KLF15
protein-codingKLF transcription factor 15, the group of Kruppel like factors|Zinc fingers C2H2-type
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KLF15 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014079.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 67 | 5 | 72 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 68 | 5 | 0 | 73 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_054798.1 | 2 | MANE Select | |
| Ensembl | ENSP00000296233.3 | 2 | MANE Select | |
| Ensembl | ENSP00000562132.1 | 2 | Standard | |
| Ensembl | ENSP00000562133.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- White fat cell differentiation
- Adipogenesis
- BMAL1-CLOCK,NPAS2 activates circadian gene expression
- White fat cell differentiation
- Transcriptional cascade regulating adipogenesis
Biological Process
- cellular glucose homeostasis
- regulation of transcription by RNA polymerase II
- glial cell differentiation
- cardiac muscle hypertrophy in response to stress
- response to insulin
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- protein binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000296233
- Coding exons
- 2
- Length
- 14808
- Individuals with no LoFs
- 125536
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125541
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.985 | 202 | 245 | 0.823 | 0.0000157 | 2666 |
| Missense (PolyPhen) | 51 | 86.406 | 0.59024 | 973 | ||
| Synonymous | 0.151 | 104 | 106 | 0.981 | 0.00000735 | 884 |
| Loss of Function | 2.39 | 2 | 10.3 | 0.195 | 5.14e-7 | 130 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000038 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional regulator that binds to the GA element of the CLCNKA promoter. Binds to the KCNIP2 promoter and regulates KCNIP2 circadian expression in the heart (By similarity). Is a repressor of CTGF expression, involved in the control of cardiac fibrosis. It is also involved in the control of cardiac hypertrophy acting through the inhibition of MEF2A and GATA4 (By similarity). Involved in podocyte differentiation (By similarity). Inhibits MYOCD activity. Is a negative regulator of TP53 acetylation. Inhibits NF-kappa-B activation through repression of EP300-dependent RELA acetylation. {ECO:0000250, ECO:0000269|PubMed:18586263, ECO:0000269|PubMed:20375365, ECO:0000269|PubMed:20566642, ECO:0000269|PubMed:23999430}.;
- Disease
- DISEASE: Note=KLF15 deficiency results in loss of rhythmic QT variation and abnormal heart repolarization (PubMed:22367544). It may play a role in susceptibility to ventricular arrhythmias (PubMed:22367544), and development of pathological cardiac hypertrophy leading to heart failure (PubMed:20375365). {ECO:0000269|PubMed:20375365, ECO:0000269|PubMed:22367544}.;
Recessive Scores
- pRec
- 0.142
Intolerance Scores
- LoFtool
- 0.200
- RVIS EVS
- -0.67
- RVIS percentile EVS
- 15.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.826
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |