KLF15

Summary

KLF15 (KLF transcription factor 15, HGNC:14536) is a protein-coding gene on chromosome 3q21.3, encoding Krueppel-like factor 15 (Q9UIH9). Transcriptional regulator that binds to the GA element of the CLCNKA promoter.

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.

Source: NCBI Gene 28999 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 76 total
• Transcription factor: yes — 28 downstream targets (CollecTRI)
• MANE Select transcript: NM_014079

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14536
Approved symbol	KLF15
Name	KLF transcription factor 15
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	KKLF
Ensembl gene	ENSG00000163884
Ensembl biotype	protein_coding
OMIM	606465
Entrez	28999

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000296233, ENST00000509675, ENST00000892073, ENST00000892074, ENST00000892075, ENST00000892076, ENST00000892077

RefSeq mRNA: 1 — MANE Select: NM_014079 NM_014079

CCDS: CCDS3036

Canonical transcript exons

ENST00000296233 — 3 exons

Exon	Start	End
ENSE00001079374	126351841	126352947
ENSE00001241575	126357237	126357408
ENSE00001241585	126342635	126343895

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 98.94.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3848 / max 152.5360, expressed in 733 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44335	3.2331	538
44336	2.0147	580
44334	0.0790	9
44333	0.0366	10
44332	0.0215	11

Top tissues by expression

282 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.94	gold quality
cardia of stomach	UBERON:0001162	96.82	gold quality
lower lobe of lung	UBERON:0008949	96.53	silver quality
sural nerve	UBERON:0015488	96.45	gold quality
renal medulla	UBERON:0000362	95.78	gold quality
mucosa of stomach	UBERON:0001199	95.69	gold quality
right lobe of liver	UBERON:0001114	95.67	gold quality
inferior vagus X ganglion	UBERON:0005363	94.98	gold quality
ventral tegmental area	UBERON:0002691	94.76	gold quality
lateral globus pallidus	UBERON:0002476	94.36	gold quality
body of tongue	UBERON:0011876	94.22	gold quality
subthalamic nucleus	UBERON:0001906	93.77	gold quality
pericardium	UBERON:0002407	93.73	gold quality
superior vestibular nucleus	UBERON:0007227	93.63	gold quality
right lung	UBERON:0002167	93.49	gold quality
body of pancreas	UBERON:0001150	93.42	gold quality
gastrocnemius	UBERON:0001388	93.30	gold quality
cerebellar vermis	UBERON:0004720	93.03	gold quality
trigeminal ganglion	UBERON:0001675	92.98	gold quality
left ovary	UBERON:0002119	92.78	gold quality
popliteal artery	UBERON:0002250	92.76	gold quality
tibial artery	UBERON:0007610	92.74	gold quality
right ovary	UBERON:0002118	92.68	gold quality
tongue	UBERON:0001723	92.57	gold quality
liver	UBERON:0002107	92.53	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.45	gold quality
aorta	UBERON:0000947	92.27	gold quality
muscle of leg	UBERON:0001383	92.27	gold quality
vena cava	UBERON:0004087	92.23	gold quality
trachea	UBERON:0003126	92.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9801	yes	78.56
E-ANND-3	yes	6.14
E-MTAB-9067	yes	4.54

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

28 targets.

Target	Regulation
ACSS1
ADM
AKR1C3	Unknown
BMPER	Activation
C1QTNF12	Unknown
CCN2	Repression
CEBPA
CLCNKA	Unknown
CMKLR1	Activation
CMKLR2	Activation
DEPP1
E2F1	Activation
GRB10
KLF15
LRP5	Activation
MT2A	Activation
MYOCD
NFATC1
NR3C1
PCK2	Activation
PPARG	Activation
PPARGC1A	Unknown
RARRES2	Activation
RBP3	Repression
RHO	Repression
SLC2A4	Activation
TYRP1
UCP1

JASPAR motifs

Motif	Name	Family
MA1513.1	KLF15	Three-zinc finger Kruppel-related
MA1513.2	KLF15	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:28473536

Upstream regulators (CollecTRI, top): IL17A, KLF15, NR3C1

miRNA regulators (miRDB)

106 targeting KLF15, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Literature-anchored findings (GeneRIF, showing 40)

• KLF15 binds to multiple 9 bp consensus sites in the Rhodospin and IRBP promoters including the CRS-1 and G-rich repressor elements. An in vivo role for KLF15 in repressing photoreceptor-specific gene expression in the inner retina is hypothesized. (PMID:15963234)
• These studies identify KLF15 as part of a heretofore unrecognized pathway regulating the cardiac response to hemodynamic stress (PMID:17438289)
• KLF15 is a negative regulator of connective tissue growth factor expression and cardiac fibrosis. (PMID:18586263)
• KLF15 is potentially a novel link between the regulation of testosterone production and fat stores by insulin in humans. (PMID:19366843)
• Both Kruppel-like factor 15 and specificity protein 1 binding motifs are essential for human LRP5 promoter activity. (PMID:20141633)
• Deficiency of the transcriptional regulator Kruppel-like factor 15 (Klf15) in mice leads to both heart failure and aortic aneurysm and Klf15 concentrations are markedly reduced in failing human hearts and in human aortic aneurysm tissues. (PMID:20375365)
• KLF11, but not KLF15, was essential for UCP1 expression during brown adipocyte differentiation of muBM3.1. (PMID:20709022)
• Glucocorticoid receptors promote adipogenesis via KLF15 gene expression as a transcriptional direct target. (PMID:20956975)
• the GR target, Klf15, has a role in modulating airway function (PMID:21257922)
• Kruppel-like factor 15 activates hepatitis B virus gene expression and replication. (PMID:21503941)
• serves as a molecular link between myogenic factors and the activity of the D4Z4 enhancer, and it thus contributes to the overexpression of the DUX4c and FRG2 genes during normal myogenic differentiation and in FSHD. (PMID:21937448)
• Nitrogen homeostasis exhibits circadian rhythmicity, and is orchestrated by Kruppel-like factor 15. (PMID:22405069)
• Elucidation of this heretofore unrecognized role for KLF15 now implicates this factor as a central component of the transcriptional circuitry that coordinates physiologic flux of all three basic cellular nutrients: glucose, amino acids, and lipids (PMID:22493257)
• a critical role of KLF15 in mediating podocyte differentiation and in protecting podocytes against injury. (PMID:22493483)
• A previously unrecognized KLF15-dependent pathway regulates vascular smooth muscle cell proinflammatory activation. (PMID:23999430)
• Host Kruppel-like factor 15, Slug, and SPDEF, stimulated the herpes simplex virus type 1 ICP0 promoter more than 150-fold. (PMID:24027338)
• KLF15 as a key regulator of myocardial lipid utilization and is the first to implicate the KLF transcription factor family in cardiac metabolism. (PMID:24407292)
• Our results indicate that nuclear KLF15 expression suppresses breast cancer cell proliferation at least partially through p21 up-regulation and subsequent cell cycle arrest (PMID:25869021)
• GR and KLF15 physically interact via low affinity GR binding sites within glucocorticoid response elements (GREs) for PRODH and AASS that contribute to combinatorial regulation with KLF15. (PMID:26088140)
• Case Reports: 2 girls with primary renal myoepithelial carcinomas with a novel EWSR1-KLF15 fusion. (PMID:26523541)
• Findings suggest that, in obese status, the lower expression level of A2bAR, KLF4, and KLF15 of visceral adipose tissue may correlate with obese-dyslipidemia induced inflammation in Uygur population. (PMID:27199507)
• In breast cancer cells, KLF6 and KLF15 are suppressed via miR-4262. (PMID:27629257)
• the expression of KLF15 increased in the RA-treated cells regardless of fluidic condition (PMID:28320523)
• KLF15 is directly induced by glucocorticoids in primary human airway smooth muscle and it represses ASM hypertrophy. (PMID:28375666)
• The KLF15 SNP rs9838915 A allele was associated in a dominant manner with Left ventricular mass before and after adjustment for age, gender, body mass index and hypertension, and with adjusted septal and posterior wall thickness. (PMID:28400202)
• In general, our study revealed that KLF15 is dramatically down-regulated in GC tissues and cell lines and that KLF15 is negatively associated with aggressive clinical characteristics, such as tumor stage, lymph node metastasis, and DFS. Importantly, up-regulation of KLF15 inhibits cell proliferation by regulating CDKN1A/p21 and CDKN1C/p57. (PMID:28421457)
• analysis of the role of KLF15 in type 2 diabetes patients with left ventricle hypertrophy (LVH) has really advanced the importance of KLF15 in the physiology and pathophysiology of cardiac conditions, and also promoted us to understand the mechanism of type 2 diabetes-induced LVH. All these will lay a theoretical foundation for the potentially clinical prevention and treatment of LVH. (PMID:28499925)
• study identifies novel genes associated with insulin sensitivity in adipocytes in women independently of obesity. KFL15 and SLC25A10 are inhibitors of insulin-stimulated lipogenesis under conditions when glucose transport is the rate limiting step (PMID:28570579)
• KLF15 activates SOX9 expression directly. SOX9 is involved in KLF15 function during chondrogenic differentiation. (PMID:28923246)
• KLF15 is a critical regulator of pulmonary endothelial homeostasis via repression of endothelial Arg2 expression. KLF15 abundance and nuclear compartmentalization are regulated by SUMOylation/deSUMOylation-a hypoxia-sensitive process that is controlled by SENP1. (PMID:29472234)
• This review provides a summary of the experimental and human studies that have investigated the role of KLF15 in the development of cardiac hypertrophy. [review] (PMID:29702551)
• low expression of KLF15 was associated with chronic podocyte injury. (PMID:29901095)
• the results of the present study suggested that overexpression of KLF15 in Eahy926 cells exhibited a protective effect against TNFalpha induced dysfunction via activation of Nrf2 signaling and inhibition of nuclear factor kappaB signaling. (PMID:29956764)
• KLF15 over expression suppressed lung adenocarcinma cell growth, which was partly mediated by up-regulation of CDKN1A/p21 and CDKN2A/p15 expression. (PMID:29990857)
• KLF15 regulates the expression of MMP-3 in human chondrocytes; results suggest that KLF15 might be a novel therapeutic target of osteoarthritis (PMID:30036111)
• a novel mechanism by which miR-223-3p protects against cardiomyocyte apoptosis and oxidative stress by targeting KLF15 (PMID:30336138)
• miR-190a-5p participates in the regulation of hypoxia-induced pulmonary hypertension by targeting KLF15 expression in endothelial cells. (PMID:30538440)
• Regulation of differential proton-coupled folate transporter gene expression in human tumors: transactivation by KLF15 with NRF-1 and the role of Sp1. (PMID:30914440)
• TTN-AS1 promoted colorectal cancer proliferation and invasion through miR-376a-3p/KLF15 axis. Our findings suggested that TTN-AS1 might be a potential therapeutic target in CRC treatment. (PMID:31610194)
• KLF15 expression was decreased patients with hypertensive nephropathy. KLF15 levels decreased after the application of 4mmHg pressure in podocytes. (PMID:31697927)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	klf15	ENSDARG00000091127
mus_musculus	Klf15	ENSMUSG00000030087
rattus_norvegicus	Klf15	ENSRNOG00000017808

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), KLF10 (ENSG00000155090), SP8 (ENSG00000164651), KLF13 (ENSG00000169926), SP7 (ENSG00000170374), KLF17 (ENSG00000171872), KLF11 (ENSG00000172059), SP6 (ENSG00000189120), SP5 (ENSG00000204335), SP9 (ENSG00000217236), KLF14 (ENSG00000266265), KLF18 (ENSG00000283039)

Protein

Protein identifiers

Krueppel-like factor 15 — Q9UIH9 (reviewed: Q9UIH9)

Alternative names: Kidney-enriched krueppel-like factor

All UniProt accessions (1): Q9UIH9

UniProt curated annotations — full annotation on UniProt →

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. Is a repressor of CCN2 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. Involved in podocyte differentiation. Inhibits MYOCD activity. Is a negative regulator of TP53 acetylation. Inhibits NF-kappa-B activation through repression of EP300-dependent RELA acetylation.

Subunit / interactions. Interacts with MYOCD and EP300.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in liver, skeletal muscle, and kidney. Expressed in cardiomyocytes. Expression is highly reduced in cardiac tissue of patients with non-ischemic cardiomyopathy and aortic aneurysm, and in glomerular disease. Not expressed in bone marrow or lymphoid tissues.

Disease relevance. KLF15 deficiency results in loss of rhythmic QT variation and abnormal heart repolarization. It may play a role in susceptibility to ventricular arrhythmias, and development of pathological cardiac hypertrophy leading to heart failure.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

Induction. In podocytes, up-regulated by retinoic acid.

Similarity. Belongs to the Sp1 C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_054798* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (11 total): zinc finger region 3, compositionally biased region 2, strand 2, chain 1, helix 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2ENT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIH9-F1	51.51	0.00

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1368108	BMAL1:CLOCK,NPAS2 activates circadian expression
R-HSA-400253

MSigDB gene sets: 204 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, AHRARNT_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, NKX61_01, GOBP_PEPTIDYL_LYSINE_MODIFICATION, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_KIDNEY_DEVELOPMENT

GO Biological Process (15): intracellular glucose homeostasis (GO:0001678), regulation of transcription by RNA polymerase II (GO:0006357), glial cell differentiation (GO:0010001), cardiac muscle hypertrophy in response to stress (GO:0014898), regulation of Wnt signaling pathway (GO:0030111), response to insulin (GO:0032868), negative regulation of collagen biosynthetic process (GO:0032966), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of D-glucose import across plasma membrane (GO:0046326), negative regulation of transforming growth factor beta production (GO:0071635), podocyte differentiation (GO:0072112), cellular response to endothelin (GO:1990859), negative regulation of peptidyl-lysine acetylation (GO:2000757), regulation of gene expression (GO:0010468), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (11): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Circadian clock	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
glucose homeostasis	1
intracellular chemical homeostasis	1
cell differentiation	1
gliogenesis	1
muscle hypertrophy in response to stress	1
cardiac muscle hypertrophy	1
cardiac muscle adaptation	1
regulation of signal transduction	1
Wnt signaling pathway	1
response to peptide hormone	1
negative regulation of biosynthetic process	1
negative regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
positive regulation of DNA-templated transcription	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
negative regulation of cytokine production	1
transforming growth factor beta production	1
regulation of transforming growth factor beta production	1
renal filtration cell differentiation	1
glomerular epithelial cell differentiation	1
cellular response to peptide hormone stimulus	1
response to endothelin	1
peptidyl-lysine acetylation	1
negative regulation of protein acetylation	1
regulation of peptidyl-lysine acetylation	1
gene expression	1
regulation of macromolecule biosynthetic process	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1

Protein interactions and networks

STRING

1272 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF15	CFAP100	Q494V2	861
KLF15	TMCC1	O94876	847
KLF15	PODXL2	Q9NZ53	843
KLF15	CLCNKA	P51800	793
KLF15	PLXND1	Q9Y4D7	767
KLF15	CLCNKB	P51801	762
KLF15	MEF2A	Q02078	738
KLF15	PPARA	Q07869	655
KLF15	PLXNA1	Q9UIW2	649
KLF15	GATA2	P23769	613
KLF15	BMAL1	O00327	609
KLF15	GATA4	P43694	608
KLF15	BCAT2	O15382	597
KLF15	SIRT1	Q96EB6	525
KLF15	CTNNB1	P35222	514

IntAct

168 interactions, top by confidence:

A	B	Type	Score
PRKAB2	KLF15	psi-mi:“MI:0915”(physical association)	0.870
KLF15	PRKAB2	psi-mi:“MI:0915”(physical association)	0.870
KLF15	ZBTB24	psi-mi:“MI:0915”(physical association)	0.830
ZBTB24	KLF15	psi-mi:“MI:0915”(physical association)	0.830
ZNF76	KLF15	psi-mi:“MI:0915”(physical association)	0.560
NFYC	KLF15	psi-mi:“MI:0915”(physical association)	0.560
DVL3	KLF15	psi-mi:“MI:0915”(physical association)	0.560
KBTBD7	KLF15	psi-mi:“MI:0915”(physical association)	0.560
NRF1	KLF15	psi-mi:“MI:0915”(physical association)	0.560
BANP	KLF15	psi-mi:“MI:0915”(physical association)	0.560
KLF15	ZNF330	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	KLF15	psi-mi:“MI:0915”(physical association)	0.560
C11orf68	KLF15	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	KLF15	psi-mi:“MI:0915”(physical association)	0.560
POLR1C	KLF15	psi-mi:“MI:0915”(physical association)	0.560
SHFL	KLF15	psi-mi:“MI:0915”(physical association)	0.560
AIRIM	KLF15	psi-mi:“MI:0915”(physical association)	0.560
SCNM1	KLF15	psi-mi:“MI:0915”(physical association)	0.560
DR1	KLF15	psi-mi:“MI:0915”(physical association)	0.560
	KLF15	psi-mi:“MI:0915”(physical association)	0.560
FOS	KLF15	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (309): KLF15 (Two-hybrid), KLF15 (Two-hybrid), EP300 (Affinity Capture-Western), KLF15 (Two-hybrid), KLF15 (Two-hybrid), KLF15 (Two-hybrid), KLF15 (Two-hybrid), KLF15 (Two-hybrid), VWA2 (Affinity Capture-MS), PPP2R5E (Affinity Capture-MS), ADD3 (Affinity Capture-MS), PRKAB2 (Two-hybrid), ZBTB24 (Two-hybrid), KLF15 (Two-hybrid), KLF15 (Two-hybrid)

ESM2 similar proteins: A2A5K6, F1QQA8, G3V893, O08696, O14901, O57415, P36197, P37275, P97691, Q04891, Q07243, Q08050, Q14872, Q16254, Q2QGD7, Q3UH06, Q5EAC5, Q5F293, Q60542, Q62255, Q62947, Q64318, Q66K89, Q6DBW0, Q6YND2, Q7TS63, Q80X44, Q86V15, Q86VK4, Q8BG87, Q8BKX7, Q8BX22, Q8C8V1, Q8CCE9, Q8IVH2, Q91X45, Q92766, Q96CK0, Q99607, Q9BYN7

Diamond homologs: O08584, O08876, O14901, O35738, O35819, O43474, O62259, O70494, O75840, O89090, O89091, O95600, P08047, P0CG40, P46099, P57682, P58334, Q01714, Q02446, Q02447, Q0VA40, Q13118, Q13351, Q13887, Q14V87, Q19A40, Q19A41, Q22678, Q24266, Q3SY56, Q5XGT8, Q60793, Q60843, Q60980, Q62445, Q64HY3, Q64HY5, Q65ZG6, Q6BEB4, Q6NW96

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
IL17A	“down-regulates quantity by repression”	KLF15	“transcriptional regulation”
KLF15	“down-regulates quantity by repression”	RBP3	“transcriptional regulation”
KLF15	“down-regulates quantity by repression”	RHO	“transcriptional regulation”
KLF15	“up-regulates quantity by expression”	PPARG	“transcriptional regulation”
NR3C1	“up-regulates quantity by expression”	KLF15	“transcriptional regulation”
KLF15	up-regulates	Adipogenesis	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

836 predictions. Top by Δscore:

Variant	Effect	Δscore
3:126352943:GGCGG:G	acceptor_gain	1.0000
3:126352945:CGG:C	acceptor_gain	1.0000
3:126352948:C:CC	acceptor_gain	1.0000
3:126343893:AACC:A	acceptor_loss	0.9900
3:126343896:C:CC	acceptor_gain	0.9900
3:126352944:GCGG:G	acceptor_gain	0.9900
3:126352945:CGGC:C	acceptor_gain	0.9900
3:126352946:GG:G	acceptor_gain	0.9900
3:126352947:GCTG:G	acceptor_loss	0.9900
3:126352949:T:G	acceptor_loss	0.9900
3:126352951:C:CT	acceptor_gain	0.9900
3:126352952:A:T	acceptor_gain	0.9900
3:126356713:G:C	acceptor_gain	0.9800
3:126357107:T:A	donor_gain	0.9800
3:126343892:GAAC:G	acceptor_gain	0.9700
3:126343894:AC:A	acceptor_gain	0.9700
3:126343895:CC:C	acceptor_gain	0.9700
3:126356177:T:TA	donor_gain	0.9600
3:126352867:A:C	donor_gain	0.9500
3:126356541:G:C	donor_gain	0.9500
3:126356592:T:TA	donor_gain	0.9400
3:126356442:C:CT	donor_gain	0.9300
3:126356717:G:C	acceptor_gain	0.9300
3:126343893:AAC:A	acceptor_gain	0.9200
3:126357184:A:AC	donor_gain	0.9200
3:126356152:A:C	donor_gain	0.9100
3:126356716:C:CT	acceptor_gain	0.9100
3:126356487:C:A	donor_gain	0.9000
3:126357231:TCCCA:T	donor_loss	0.9000
3:126357232:CCCA:C	donor_loss	0.9000

AlphaMissense

2708 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:126343781:G:C	H399Q	1.000
3:126343781:G:T	H399Q	1.000
3:126343791:A:G	L396P	1.000
3:126343808:G:C	F390L	1.000
3:126343808:G:T	F390L	1.000
3:126343809:A:C	F390C	1.000
3:126343809:A:G	F390S	1.000
3:126343810:A:G	F390L	1.000
3:126343820:G:C	C386W	1.000
3:126343821:C:G	C386S	1.000
3:126343821:C:T	C386Y	1.000
3:126343822:A:G	C386R	1.000
3:126343822:A:T	C386S	1.000
3:126343829:A:C	C383W	1.000
3:126343830:C:G	C383S	1.000
3:126343831:A:G	C383R	1.000
3:126343831:A:T	C383S	1.000
3:126343853:G:C	H375Q	1.000
3:126343853:G:T	H375Q	1.000
3:126343855:G:C	H375D	1.000
3:126343865:G:C	H371Q	1.000
3:126343865:G:T	H371Q	1.000
3:126343867:G:C	H371D	1.000
3:126343875:A:G	L368P	1.000
3:126343892:G:C	F362L	1.000
3:126343892:G:T	F362L	1.000
3:126343893:A:G	F362S	1.000
3:126343894:A:G	F362L	1.000
3:126351864:G:C	C353W	1.000
3:126351865:C:T	C353Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000023938 (3:126304874 A>C), RS1000056811 (3:126301228 A>T), RS1000058238 (3:126353913 T>A,C), RS1000064476 (3:126296029 T>C), RS1000117159 (3:126338813 T>C), RS1000143872 (3:126349805 C>T), RS1000252343 (3:126316599 G>A,T), RS1000264617 (3:126290777 G>T), RS1000302949 (3:126305063 C>T), RS1000421528 (3:126332055 G>C), RS1000454370 (3:126301921 T>C), RS1000485356 (3:126298742 T>C), RS1000540368 (3:126306662 A>G), RS1000545223 (3:126327487 T>A), RS1000563684 (3:126342596 C>T)

Disease associations

OMIM: gene MIM:606465 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001852_4	Metabolite levels	2.000000e-06
GCST002932_33	Manganese levels	3.000000e-06
GCST004171_4	Macular telangiectasia type 2	2.000000e-07
GCST006661_116	Male-pattern baldness	1.000000e-16
GCST006661_117	Male-pattern baldness	4.000000e-16
GCST008971_152	Urate levels	7.000000e-09
GCST008972_224	Urate levels	8.000000e-09
GCST010002_438	Refractive error	9.000000e-21

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004471	insulin sensitivity measurement
EFO:1002009	macular telangiectasia type 2
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	5
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases methylation, increases methylation, decreases expression	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
tributyltin	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression	1
arsenic disulfide	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
prothioconazole	increases expression	1
(+)-JQ1 compound	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Amiodarone	increases expression	1
Carbamazepine	affects expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3P6	SEES3-1V human KLF15, clone1	Embryonic stem cell	Male
CVCL_A3P7	SEES3-1V human KLF15, clone2	Embryonic stem cell	Male
CVCL_A3P8	SEES3-1V human KLF15, clone3	Embryonic stem cell	Male
CVCL_QX78	ESIBIe002-A-1	Embryonic stem cell	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.