KLF5

Summary

KLF5 (KLF transcription factor 5, HGNC:6349) is a protein-coding gene on chromosome 13q22.1, encoding Krueppel-like factor 5 (Q13887). Transcription factor that binds to GC box promoter elements. It is a selective cancer dependency (DepMap: 26.7% of cell lines).

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.

Source: NCBI Gene 688 — RefSeq curated summary.

At a glance

• GWAS associations: 34
• Clinical variants (ClinVar): 85 total — 2 pathogenic
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 3 cancer types
• Cancer dependency (DepMap): dependent in 26.7% of screened cell lines
• Transcription factor: yes — 77 downstream targets (CollecTRI)
• MANE Select transcript: NM_001730

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6349
Approved symbol	KLF5
Name	KLF transcription factor 5
Location	13q22.1
Locus type	gene with protein product
Status	Approved
Aliases	IKLF, CKLF
Ensembl gene	ENSG00000102554
Ensembl biotype	protein_coding
OMIM	602903
Entrez	688

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000377687, ENST00000464404, ENST00000476859, ENST00000477333, ENST00000539231, ENST00000851191

RefSeq mRNA: 2 — MANE Select: NM_001730 NM_001286818, NM_001730

CCDS: CCDS66562, CCDS9448

Canonical transcript exons

ENST00000377687 — 4 exons

Exon	Start	End
ENSE00001474860	73075708	73077538
ENSE00001474889	73059005	73059588
ENSE00003625079	73063824	73063883
ENSE00003679404	73061861	73062734

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.9067 / max 3153.4597, expressed in 1582 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135350	31.7625	1582
135347	0.0732	3
135349	0.0611	32
135348	0.0074	3
135346	0.0025	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.51	gold quality
epithelium of nasopharynx	UBERON:0001951	99.49	gold quality
gingival epithelium	UBERON:0001949	99.40	gold quality
penis	UBERON:0000989	99.33	gold quality
pharyngeal mucosa	UBERON:0000355	99.32	gold quality
esophagus squamous epithelium	UBERON:0006920	99.31	gold quality
gingiva	UBERON:0001828	99.29	gold quality
amniotic fluid	UBERON:0000173	99.27	gold quality
squamous epithelium	UBERON:0006914	99.18	gold quality
nasal cavity mucosa	UBERON:0001826	99.08	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.02	gold quality
nipple	UBERON:0002030	99.01	gold quality
colonic mucosa	UBERON:0000317	98.98	gold quality
skin of abdomen	UBERON:0001416	98.98	gold quality
oral cavity	UBERON:0000167	98.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.95	gold quality
esophagus mucosa	UBERON:0002469	98.90	gold quality
rectum	UBERON:0001052	98.89	gold quality
nasal cavity epithelium	UBERON:0005384	98.87	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.84	gold quality
skin of leg	UBERON:0001511	98.82	gold quality
palpebral conjunctiva	UBERON:0001812	98.78	gold quality
cervix squamous epithelium	UBERON:0006922	98.77	gold quality
mucosa of transverse colon	UBERON:0004991	98.76	gold quality
zone of skin	UBERON:0000014	98.58	gold quality
urethra	UBERON:0000057	98.43	gold quality
jejunal mucosa	UBERON:0000399	98.40	gold quality
upper arm skin	UBERON:0004263	98.33	gold quality
upper leg skin	UBERON:0004262	98.32	gold quality
epithelium of esophagus	UBERON:0001976	98.20	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	279.84
E-HCAD-1	yes	233.43
E-MTAB-10018	yes	173.52
E-CURD-114	yes	58.53
E-MTAB-8410	yes	48.89
E-MTAB-10287	yes	38.71
E-HCAD-10	yes	13.68
E-MTAB-7249	yes	10.99
E-ENAD-27	yes	6.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

77 targets.

Target	Regulation
ABCG2	Unknown
ANP32B
APLN
B3GNT9
BIRC5	Activation
CCNA2	Repression
CCNB1	Activation
CCND1	Activation
CCNE1	Unknown
CD55	Activation
CD74
CDK1	Repression
CDKN1A	Unknown
CDKN2B	Unknown
CDT1	Repression
CEBPA	Activation
CTSD
CXCR4	Activation
DCN
DHCR24
DYM
E2F3
EGF
EGFR
EGR1
F3	Activation
FASN	Activation
FGFBP1	Activation
FOXA1	Unknown
FOXO1	Unknown

JASPAR motifs

Motif	Name	Family
MA0599.1	KLF5	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:15740636

Upstream regulators (CollecTRI, top): AR, CEBPB, CEBPD, CTNNB1, EGR1, HMGA2, KLF5, NR3C1, PGR, PRDM4, RUNX2, SMURF2, SP1, TP53

miRNA regulators (miRDB)

155 targeting KLF5, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 26.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Overexpression of KLF5 in transfected cells led to increased cell proliferation including foci formation and anchorage-independent growth in a manner consistent with a transformed phenotype. (PMID:11152667)
• This study describes the opposite effect of KLF4 and KLF5 on transcription of the KLF4 gene. (PMID:12087155)
• KLF5 suppresses tumor cell growth in breast cancer. (PMID:12242654)
• KLF5 bound and efficiently transactivated the TCR Dbeta1 promoter (PMID:12576331)
• Gene deletion and loss of expression and cell growth suppression indicate that KLF5 may be tumor suppressor gene at 13q21 in prostate cancer. Mutation and promoter methylation do not commonly inactivate KLF5 in prostate cancer. (PMID:12661032)
• KLF4, but not KLF5, was frequently downregulated in bladder cancer cell lines and cancer tissues. (PMID:12901861)
• KLF5 and p50 are important for induction of PDGF-A chain. (PMID:14573617)
• BTEB2, a zinc finger transcription factor, may contribute to the establishment of the choroidal neovascularization observed in the pathogenesis of age-related macular degeneration and idiopathic choroidal neovascularization (PMID:14587307)
• Positive and negative regulation of the cardiovascular transcription factor KLF5 by p300 and the oncogenic regulator SET through interaction and acetylation on the DNA-binding domain. (PMID:14612398)
• intestinal tumor progression is associated with a change in the growth-related functions of KLF5 (PMID:14726538)
• KLF5 mediates the transforming effect of oncogenic H-Ras in NIH3T3 fibroblast cells and does so by transactivating the cyclin D1 promoter (PMID:15077182)
• Results indicate that Kruppel-like factor 5 is a potential mediator for the inhibitory effect of all-trans retinoid acid on intestinal epithelial cell proliferation. (PMID:15581624)
• This study describes that the inhibitory effect of all-trans retinoic acid (ATRA) on proliferation of intestinal epithelial cells is a result of ATRA-mediated expression of KLF5. (PMID:15581624)
• HDAC1 negatively regulates the cardiovascular transcription factor KLF5 through direct interaction (PMID:15668237)
• KLF5 protein is degraded at least in part through ubiquitination-proteasome pathway, which may have become hyperactive for KLF5 in cancer cells (PMID:15735697)
• This is an review article that summarizes the function of KLF4 and KLF5 in regulating cell proliferation. (PMID:15740636)
• In co-transfection assays in K562 cells, it was demonstrated that KLF2, 5 and 13 positively regulate, and KLF8 negatively regulates, the gamma-globin gene through the CACCC promoter element. (PMID:16023392)
• KLF5 is a key component of the transcription factor network controlling adipocyte differentiation (PMID:16054042)
• KLF5 is an essential transcription factor in cardiovascular remodeling (review) (PMID:16102021)
• This study reports that KLF5 is activated by oncogenic HRAS and that activated KLF5 promotes mitosis by inducing transcription of the cyclin B1 and Cdc2 genes. (PMID:16102754)
• KLF5 is a target of the E3 ubiquitin ligase WWP1 for proteolysis in epithelial cells (PMID:16223724)
• KLF2 is a transcription factor important in the integration of multiple endothelial functions associated with regions of the arterial vasculature that are relatively resistant to atherogenesis. (PMID:16341264)
• This study describes that KLF5 is an important downstream mediator for the pro-inflammatory activity of NF-kB in intestinal epithelial cells. (PMID:16500892)
• analysis of a novel regulatory pathway for the expression of survivin under the control of KLF5 and p53 (PMID:16595680)
• Patients with higher KLF5 expression have shorter disease-free survival and overall survival than patients with lower KLF5 expression. (PMID:16638850)
• This study examines the physical interaction between KLF5 and protein inhibitor of activated STAT 1 (PIAS1) which enhances KLF5’s pro-proliferative activity. (PMID:17178721)
• KLF5 protein degradation is blocked by an N-terminal FLAG tag or a small N-terminal deletion without reducing ubiquitination and degradation mediated by WWP1. (PMID:17320083)
• KLF5 as a target of lysophosphatidic acid mediated signaling and suggest a role of KLF5 in promoting proliferation of intestinal epithelia in response to lysophosphatidic acid . (PMID:17430902)
• A review article that describes the biological and pathobiological functions in the intestinal epithelium. (PMID:17508399)
• Plays an important role in modulating apoptosis secondary to DNA damage through a p53-independent pathway (PMID:17603560)
• analysis of SNPs, located in the KLF2, KLF4 and KLF5 gene did not show an association with Type 2 diabetes in this French population (PMID:17688680)
• recruitment of ANP32B onto the promoter region requires KLF5 and results in promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B (PMID:18039846)
• This study reports that KLF5 is an important downstream mediator for the transforming effect of activated KRAS in intestinal epithelial cells and colorectal cancer. (PMID:18054006)
• These findings suggest that the KLF5 gene is a novel schizophrenia-susceptibility gene, and that the expression of the gene is involved in the pathophysiology of schizophrenia via glutamatergic neurotransmission. (PMID:18226501)
• KLF5 causes cartilage matrix degradation through transcriptional induction of MMP9, providing the first evidence that transcriptional regulation of a proteinase contributes to endochondral ossification and skeletal development. (PMID:18617520)
• Results suggest that the FASN gene is activated by the synergistic action of KLF5 and SREBP-1, which was induced by androgen in androgen-dependent prostate cancer cells. (PMID:18774944)
• nuclear export signal in KLF5 directs a fused green fluorescence protein to the cytoplasm (PMID:18782761)
• TGFbeta recruited acetylase p300 to acetylate KLF5, and acetylation in turn altered the binding of KLF5 to p15 promoter, resulting in the reversal of KLF5 function. (PMID:19056724)
• Activation of TGFbeta recruits p300 to the KLF5-Smad complex to acetylate KLF5, and the complex with acetylated KLF5 binds to the Smad binding element and alters the binding of other factors to p15 promoter to induce its transcription (PMID:19419955)
• KLF5 mediates the signaling functions in cell proliferation, cell cycle, apoptosis, migration, differentiation, and stemness by regulating gene expression in response to environment stimuli. [review] (PMID:19448973)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	klf5a	ENSDARG00000015506
danio_rerio	klf5b	ENSDARG00000062106
mus_musculus	Klf5	ENSMUSG00000005148
rattus_norvegicus	Klf5	ENSRNOG00000008785
drosophila_melanogaster	CG3065	FBGN0034946
drosophila_melanogaster	luna	FBGN0040765

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), KLF10 (ENSG00000155090), KLF15 (ENSG00000163884), 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 5 — Q13887 (reviewed: Q13887)

Alternative names: Basic transcription element-binding protein 2, Colon krueppel-like factor, GC-box-binding protein 2, Intestinal-enriched krueppel-like factor, Transcription factor BTEB2

All UniProt accessions (2): Q13887, Q5T6X2

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds to GC box promoter elements. Activates the transcription of these genes.

Subunit / interactions. Interacts with WWP1. Interacts with ANP32B; this interaction induces promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B.

Subcellular location. Nucleus.

Tissue specificity. Expressed only in testis and placenta.

Post-translational modifications. Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein. Deubiquitinated by ATXN3L.

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

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q13887-1	1	yes
Q13887-2	2
Q13887-3	3
Q13887-4	4

RefSeq proteins (2): NP_001273747, NP_001721* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (27 total): strand 5, cross-link 4, splice variant 4, zinc finger region 3, helix 3, region of interest 3, chain 1, sequence variant 1, mutagenesis site 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EBT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13887-F1	47.38	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 52, 94, 110, 31

Mutagenesis-validated functional residues (1):

Position	Phenotype
324–328	impairs ubiquitination and degradation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-9616222	Transcriptional regulation of granulopoiesis
R-HSA-1266738	Developmental Biology
R-HSA-9843745	Adipogenesis

MSigDB gene sets: 615 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, RNGTGGGC_UNKNOWN, E2F_Q4_01, RRAGTTGT_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, TGCGCANK_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of cell population proliferation (GO:0008284), skeletal muscle satellite cell differentiation (GO:0014816), satellite cell activation involved in skeletal muscle regeneration (GO:0014901), myotube differentiation involved in skeletal muscle regeneration (GO:0014908), microvillus assembly (GO:0030033), regulation of microvillus assembly (GO:0032534), positive regulation of fat cell differentiation (GO:0045600), positive regulation of transcription by RNA polymerase II (GO:0045944), intestinal epithelial cell development (GO:0060576), positive regulation of transcription by transcription factor localization (GO:0061586), cellular response to leukemia inhibitory factor (GO:1990830), cellular response to endothelin (GO:1990859), regulation of gene expression (GO:0010468), skeletal muscle cell differentiation (GO:0035914), skeletal muscle tissue regeneration (GO:0043403), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (11): 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), MRF binding (GO:0043426), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (5): chromatin (GO:0000785), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), Golgi apparatus (GO:0005794), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Developmental Biology	2
Adipogenesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
skeletal muscle tissue regeneration	2
positive regulation of DNA-templated transcription	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
skeletal muscle cell differentiation	1
skeletal muscle satellite cell activation	1
myotube differentiation	1
microvillus organization	1
plasma membrane bounded cell projection assembly	1
microvillus assembly	1
regulation of microvillus organization	1
regulation of plasma membrane bounded cell projection assembly	1
fat cell differentiation	1
positive regulation of cell differentiation	1
regulation of fat cell differentiation	1
columnar/cuboidal epithelial cell development	1
intestinal epithelial cell differentiation	1
intracellular protein localization	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
cellular response to peptide hormone stimulus	1
response to endothelin	1
gene expression	1
regulation of macromolecule biosynthetic process	1
skeletal muscle tissue development	1
cell differentiation	1
tissue regeneration	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

2392 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF5	ESRRB	O95718	841
KLF5	ESR2	Q92731	835
KLF5	CEBPB	P17676	816
KLF5	CEBPD	P49716	797
KLF5	JUN	P05412	785
KLF5	RARA	P10276	773
KLF5	EP300	Q09472	738
KLF5	PPARD	Q03181	716
KLF5	CPT1B	Q92523	713
KLF5	CPT1C	Q8TCG5	698
KLF5	MYH10	P35580	696
KLF5	CEBPA	P49715	681
KLF5	CTNNB1	P35222	679
KLF5	FBXW7	Q969H0	672
KLF5	TP53	P04637	671

IntAct

45 interactions, top by confidence:

A	B	Type	Score
ATXN1	KLF5	psi-mi:“MI:0915”(physical association)	0.660
NDUFS1	KLF5	psi-mi:“MI:0915”(physical association)	0.560
ICAM5	KLF5	psi-mi:“MI:0915”(physical association)	0.560
DNALI1	KLF5	psi-mi:“MI:0915”(physical association)	0.560
BAG6	KLF5	psi-mi:“MI:0915”(physical association)	0.560
KLF11	KLF5	psi-mi:“MI:0915”(physical association)	0.560
NUP58	KLF5	psi-mi:“MI:0915”(physical association)	0.560
DNAJB6	KLF5	psi-mi:“MI:0915”(physical association)	0.560
COL26A1	KLF5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (286): KLF5 (Biochemical Activity), CTNNB1 (Affinity Capture-Western), KLF5 (Affinity Capture-Western), SREBF1 (Affinity Capture-Western), KLF5 (Affinity Capture-Western), KLF5 (Biochemical Activity), KLF5 (Affinity Capture-Western), KLF5 (Affinity Capture-Western), NCOR1 (Two-hybrid), NCOR2 (Two-hybrid), KLF5 (Affinity Capture-Western), PPARG (Co-localization), PPARG (Two-hybrid), CREBBP (Two-hybrid), KLF5 (Affinity Capture-Western)

ESM2 similar proteins: A5D8R3, A6ZJ71, G5EEG1, O16867, O36398, O36399, O42366, O42601, O70477, O89038, O94900, P03206, P09775, P34663, P35693, P50534, P52369, P55347, P97368, Q09370, Q11103, Q13887, Q17308, Q18909, Q196U8, Q1HVG1, Q1KKR6, Q27403, Q2HJ84, Q3KQ35, Q3KSS8, Q5NDM2, Q66652, Q66JW3, Q6F2F0, Q6GLH8, Q6P2Z3, Q8AWH2, Q8AWH3, Q8AWZ0

Diamond homologs: B5DE03, B7ZSG3, O08876, O14901, O62651, O89091, P19544, P22561, P49952, P49953, P50902, P57682, P79958, Q13118, Q13887, Q19A41, Q5JT82, Q60980, Q8K1S5, O08584, O35738, O35819, O43474, O62259, O70494, O75840, O89090, O95600, P08047, P0CG40, P46099, P58334, Q01714, Q02446, Q02447, Q0VA40, Q13351, Q14V87, Q19A40, Q22678

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
GSK3B	down-regulates	KLF5	phosphorylation
PRKCD	“up-regulates activity”	KLF5	phosphorylation
WWP1	“up-regulates activity”	KLF5	ubiquitination
SMURF2	“down-regulates quantity by destabilization”	KLF5	ubiquitination
CEBPB	“up-regulates quantity by expression”	KLF5	“transcriptional regulation”
CEBPD	“up-regulates quantity by expression”	KLF5	“transcriptional regulation”
KLF5	up-regulates	PPARG	“transcriptional regulation”
NR3C1	“up-regulates quantity by expression”	KLF5	“transcriptional regulation”
TRIM25	“down-regulates quantity by destabilization”	KLF5	polyubiquitination

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 3 cancer types — BLCA, CESC, LUSC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	72
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
694066	NM_001730.5(KLF5):c.1100T>A (p.Leu367Ter)	Pathogenic
815600	GRCh37/hg19 13q21.33-31.1(chr13:71502357-86571730)x1	Pathogenic

SpliceAI

516 predictions. Top by Δscore:

Variant	Effect	Δscore
13:73075703:CACA:C	acceptor_loss	1.0000
13:73075705:CAGGT:C	acceptor_loss	1.0000
13:73059584:TCC:T	donor_gain	0.9900
13:73059584:TCCAG:T	donor_loss	0.9900
13:73059585:CCAGG:C	donor_loss	0.9900
13:73059586:CAGG:C	donor_loss	0.9900
13:73059587:AGGTA:A	donor_loss	0.9900
13:73059588:GG:G	donor_loss	0.9900
13:73059590:T:G	donor_loss	0.9900
13:73063818:TTTTA:T	acceptor_loss	0.9900
13:73063819:TTTAG:T	acceptor_loss	0.9900
13:73063820:TTAGG:T	acceptor_loss	0.9900
13:73063821:TAGGT:T	acceptor_loss	0.9900
13:73063822:A:AC	acceptor_loss	0.9900
13:73063823:G:GT	acceptor_loss	0.9900
13:73063884:G:GG	donor_gain	0.9900
13:73075706:A:AG	acceptor_gain	0.9900
13:73075707:G:GG	acceptor_gain	0.9900
13:73075707:GGT:G	acceptor_gain	0.9900
13:73060453:GGT:G	donor_gain	0.9800
13:73061860:GACA:G	acceptor_gain	0.9800
13:73061860:GACAA:G	acceptor_gain	0.9800
13:73062731:CCTGG:C	donor_loss	0.9800
13:73062733:TGGT:T	donor_loss	0.9800
13:73062734:GGT:G	donor_loss	0.9800
13:73062735:G:GA	donor_loss	0.9800
13:73062735:G:GG	donor_gain	0.9800
13:73062736:TATG:T	donor_loss	0.9800
13:73063881:CTGGT:C	donor_loss	0.9800
13:73063883:GGTA:G	donor_loss	0.9800

AlphaMissense

2992 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:73062722:T:C	C375R	1.000
13:73062724:C:G	C375W	1.000
13:73063826:T:A	C380S	1.000
13:73063826:T:C	C380R	1.000
13:73063827:G:C	C380S	1.000
13:73063869:T:C	L394P	1.000
13:73075725:T:A	C405S	1.000
13:73075725:T:C	C405R	1.000
13:73075726:G:C	C405S	1.000
13:73075727:T:G	C405W	1.000
13:73075752:T:C	F414L	1.000
13:73075753:T:C	F414S	1.000
13:73075754:C:A	F414L	1.000
13:73075754:C:G	F414L	1.000
13:73075771:T:C	L420P	1.000
13:73075815:T:C	C435R	1.000
13:73075824:T:C	C438R	1.000
13:73075836:T:C	F442L	1.000
13:73075837:T:C	F442S	1.000
13:73075838:C:A	F442L	1.000
13:73075838:C:G	F442L	1.000
13:73062722:T:A	C375S	0.999
13:73062723:G:A	C375Y	0.999
13:73062723:G:C	C375S	0.999
13:73063826:T:G	C380G	0.999
13:73063827:G:A	C380Y	0.999
13:73063828:C:G	C380W	0.999
13:73063838:T:G	Y384D	0.999
13:73063857:T:C	L390S	0.999
13:73063865:C:G	H393D	0.999

dbSNP variants (sampled 300 via entrez): RS1000064104 (13:73060708 A>G), RS1000091633 (13:73053760 C>T), RS1000119501 (13:73053949 G>C), RS1000125694 (13:73064392 TGTTAAAATCAG>T), RS1000193472 (13:73054411 A>C,G), RS1000453235 (13:73055394 T>C), RS1000700603 (13:73057602 A>G), RS1000731362 (13:73057279 T>G), RS1000892376 (13:73068843 C>T), RS1001023940 (13:73073114 A>C,G), RS1001197615 (13:73062811 G>A,C,T), RS1001314182 (13:73066822 A>G), RS1001345011 (13:73066993 T>A), RS1001347956 (13:73053966 A>G), RS1001382194 (13:73053671 A>G)

Disease associations

OMIM: gene MIM:602903 | disease phenotypes: MIM:613286

GenCC curated gene-disease

Mondo (1): dilated cardiomyopathy 1FF (MONDO:0013211)

Orphanet (1): Familial isolated dilated cardiomyopathy (Orphanet:154)

HPO phenotypes

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

GWAS associations

34 associations (top):

Study	Trait	p-value
GCST000574_1	Pancreatic cancer	3.000000e-11
GCST002553_5	Pancreatic cancer	4.000000e-14
GCST002806_13	Type 2 diabetes	2.000000e-07
GCST002991_8	Pancreatic cancer	2.000000e-10
GCST003148_13	Prostate cancer	1.000000e-06
GCST003436_2	Endometrial cancer	4.000000e-12
GCST003842_22	Breast cancer (estrogen-receptor negative)	3.000000e-07
GCST003845_23	Breast cancer	5.000000e-10
GCST003845_24	Breast cancer	4.000000e-08
GCST005038_83	Allergic disease (asthma, hay fever or eczema)	3.000000e-08
GCST005075_4	Breast Cancer in BRCA1 mutation carriers	4.000000e-07
GCST005076_23	Breast cancer (estrogen-receptor negative)	9.000000e-10
GCST005434_12	Pancreatic cancer	1.000000e-22
GCST006014_36	Creatine kinase levels	2.000000e-09
GCST006412_82	Intraocular pressure	2.000000e-08
GCST006464_20	Endometrial cancer	3.000000e-17
GCST006465_30	Endometrial cancer (endometrioid histology)	5.000000e-15
GCST006624_26	Systolic blood pressure	8.000000e-16
GCST007552_40	Colorectal cancer	6.000000e-12
GCST007576_113	Chronotype	2.000000e-08
GCST007732_25	Allergic disease (asthma, hay fever or eczema)	3.000000e-08
GCST007856_66	Colorectal cancer or advanced adenoma	6.000000e-07
GCST007856_73	Colorectal cancer or advanced adenoma	3.000000e-09
GCST008062_16	Blood urea nitrogen levels	7.000000e-11
GCST008860_29	Prostate cancer	7.000000e-08
GCST009725_95	Intraocular pressure	8.000000e-06
GCST011878_10	Mitochondrial heteroplasmy measurement	7.000000e-12
GCST90002389_479	Lymphocyte percentage of white cells	3.000000e-09
GCST90002393_297	Monocyte count	2.000000e-09
GCST90002398_212	Neutrophil count	1.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004534	creatine kinase measurement
EFO:0004695	intraocular pressure measurement
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0600008	mitochondrial heteroplasmy measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567654	Cardiomyopathy, Dilated, 1FF (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293249 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 2 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
cid_5951923	IC50	2250 nM

ChEMBL bioactivities

119 potent at pChembl≥5 of 122 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.16	IC50	6.98	nM	CHEMBL1495977
7.37	IC50	43.06	nM	CHEMBL3199673
7.27	IC50	54	nM	CHEMBL4462423
7.14	IC50	72	nM	CHEMBL4544912
7.00	IC50	98.83	nM	CHEMBL1352969
6.98	IC50	104.3	nM	CHEMBL1313520
6.97	IC50	107.3	nM	CHEMBL1338085
6.96	IC50	109	nM	CHEMBL1325413
6.88	IC50	133.4	nM	CHEMBL1576870
6.78	IC50	164.6	nM	OUABAIN
6.78	IC50	165.9	nM	CHEMBL1453996
6.68	IC50	206.7	nM	CHEMBL1381392
6.57	IC50	270	nM	CHEMBL1330145
6.57	IC50	266.6	nM	CHEMBL1370087
6.57	IC50	270.2	nM	CHEMBL1468181
6.48	IC50	331.8	nM	CHEMBL1607086
6.44	IC50	359.6	nM	CHEMBL405317
6.42	IC50	382.9	nM	CHEMBL1468011
6.40	IC50	394.7	nM	CHEMBL513150
6.40	IC50	401.4	nM	CHEMBL3196263
6.38	IC50	415.5	nM	CHEMBL1342896
6.38	IC50	421.2	nM	CHEMBL1378232
6.37	IC50	423.5	nM	CHEMBL1384292
6.31	IC50	485.6	nM	CHEMBL1582965
6.30	IC50	501.8	nM	CHEMBL1581759
6.29	IC50	517.6	nM	CHEMBL1330145
6.28	IC50	519.8	nM	CHEMBL1569975
6.25	IC50	563.1	nM	CHEMBL1392142
6.25	IC50	561.9	nM	CHEMBL1998606
6.21	IC50	617.2	nM	CHEMBL1972959
6.18	IC50	659.8	nM	CHEMBL1525789
6.16	IC50	695.3	nM	CHEMBL1468323
6.15	IC50	702.6	nM	CHEMBL1339678
6.13	IC50	734.9	nM	CHEMBL1427279
6.10	IC50	797.5	nM	CHEMBL265686
6.09	IC50	819.8	nM	CHEMBL3192873
6.08	IC50	838.1	nM	CHEMBL1559529
6.02	IC50	950.5	nM	CHEMBL373784
6.02	IC50	949.6	nM	CHEMBL1379970
6.02	IC50	959.6	nM	CHEMBL1461730
6.00	IC50	997.6	nM	CHEMBL2007601
5.99	IC50	1030	nM	CHEMBL3197990
5.98	IC50	1048	nM	CHEMBL1334514
5.97	IC50	1061	nM	CHEMBL1492399
5.94	IC50	1157	nM	CHEMBL1390450
5.91	IC50	1238	nM	CHEMBL3198794
5.91	IC50	1245	nM	CHEMBL1371507
5.91	IC50	1240	nM	CHEMBL1480522
5.90	IC50	1260	nM	CHEMBL1397452
5.89	IC50	1287	nM	CHEMBL1491705

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, affects cotreatment, affects reaction, increases abundance (+1 more)	7
Valproic Acid	affects cotreatment, increases expression	7
sodium arsenite	affects cotreatment, affects reaction, increases abundance, increases expression, increases reaction (+1 more)	5
trichostatin A	affects cotreatment, increases expression	4
Doxorubicin	decreases expression, increases cleavage, increases reaction, decreases phosphorylation, increases expression (+4 more)	4
perfluorooctanoic acid	decreases reaction, increases activity, increases expression, affects expression	3
Arsenic Trioxide	increases expression, decreases response to substance	3
Acetaminophen	affects expression, increases expression	3
Progesterone	affects expression, decreases reaction, increases expression	3
Tetrachlorodibenzodioxin	affects expression, increases expression	3
Tobacco Smoke Pollution	affects localization, decreases reaction, increases expression, decreases expression	3
Cyclosporine	decreases expression, increases expression	3
methylmercuric chloride	decreases expression, increases expression	2
bisphenol A	decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
belinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Lipopolysaccharides	affects cotreatment, decreases expression, increases expression, affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Testosterone	decreases expression, affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	increases expression, increases cleavage	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
geraniol	increases expression	1

ChEMBL screening assays

3 unique, capped per target: 2 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613906	Functional	PUBCHEM_BIOASSAY: Luminescence-based dose response cell-based high throughput screening assay for inhibitors of kruppel-like factor 5 (KLF5). (Class of assay: confirmatory) [Related pubchem assays: 1700 (Primary screen.), 1834 (Confirmation	PubChem BioAssay data set
CHEMBL4418633	Binding	Inhibition of KLF5 promoter activity in human DLD1 cells by luciferase reporter gene assay	Klf5 modulators

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3R1	SEES3-1V human KLF5, clone1	Embryonic stem cell	Male
CVCL_A3R2	SEES3-1V human KLF5, clone2	Embryonic stem cell	Male
CVCL_A3R3	SEES3-1V human KLF5, clone3	Embryonic stem cell	Male
CVCL_D1X8	Abcam A-549 KLF5 KO	Cancer cell line	Male
CVCL_D2BH	Abcam HCT 116 KLF5 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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