KLF6

Summary

KLF6 (KLF transcription factor 6, HGNC:2235) is a protein-coding gene on chromosome 10p15.2, encoding Krueppel-like factor 6 (Q99612). Transcriptional activator.

This gene encodes a member of the Kruppel-like family of transcription factors. The zinc finger protein is a transcriptional activator, and functions as a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene, some of which are implicated in carcinogenesis.

Source: NCBI Gene 1316 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 41 total — 6 pathogenic
• Phenotypes (HPO): 5
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Transcription factor: yes — 62 downstream targets (CollecTRI)
• MANE Select transcript: NM_001300

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2235
Approved symbol	KLF6
Name	KLF transcription factor 6
Location	10p15.2
Locus type	gene with protein product
Status	Approved
Aliases	CPBP, GBF, Zf9, PAC1
Ensembl gene	ENSG00000067082
Ensembl biotype	protein_coding
OMIM	602053
Entrez	1316

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000173785, ENST00000380946, ENST00000461124, ENST00000469435, ENST00000492125, ENST00000497571, ENST00000542957, ENST00000875519, ENST00000875520

RefSeq mRNA: 3 — MANE Select: NM_001300 NM_001160124, NM_001160125, NM_001300

CCDS: CCDS53490, CCDS7060

Canonical transcript exons

ENST00000497571 — 4 exons

Exon	Start	End
ENSE00001094752	3781641	3782214
ENSE00001843492	3784913	3785209
ENSE00001880146	3775996	3779590
ENSE00003607563	3780106	3780229

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 127.0623 / max 4097.7352, expressed in 1827 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107972	96.7507	1825
107971	13.1657	1702
107973	8.4917	1745
107967	2.1402	785
107956	1.3005	450
107966	1.0936	463
107965	0.7754	277
107945	0.5972	289
107943	0.4101	186
107954	0.3632	157

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	99.54	gold quality
lower lobe of lung	UBERON:0008949	99.52	gold quality
upper leg skin	UBERON:0004262	99.48	gold quality
saphenous vein	UBERON:0007318	99.45	gold quality
vena cava	UBERON:0004087	99.35	gold quality
pericardium	UBERON:0002407	99.17	gold quality
mucosa of stomach	UBERON:0001199	99.14	gold quality
skin of hip	UBERON:0001554	98.97	gold quality
monocyte	CL:0000576	98.90	gold quality
synovial joint	UBERON:0002217	98.89	gold quality
penis	UBERON:0000989	98.80	gold quality
gall bladder	UBERON:0002110	98.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.72	gold quality
mononuclear cell	CL:0000842	98.68	gold quality
bone marrow cell	CL:0002092	98.67	gold quality
mammary duct	UBERON:0001765	98.61	gold quality
leukocyte	CL:0000738	98.59	gold quality
nerve	UBERON:0001021	98.59	gold quality
tibial nerve	UBERON:0001323	98.59	gold quality
skin of abdomen	UBERON:0001416	98.59	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.58	gold quality
trigeminal ganglion	UBERON:0001675	98.50	gold quality
skin of leg	UBERON:0001511	98.37	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.29	gold quality
omental fat pad	UBERON:0010414	98.28	gold quality
olfactory bulb	UBERON:0002264	98.27	gold quality
peritoneum	UBERON:0002358	98.27	gold quality
urethra	UBERON:0000057	98.24	gold quality
superficial temporal artery	UBERON:0001614	98.17	gold quality
pharyngeal mucosa	UBERON:0000355	98.15	gold quality

Single-cell (SCXA)

Detected in 30 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	7432.83
E-CURD-122	yes	3798.30
E-MTAB-8410	yes	1705.52
E-MTAB-6701	yes	70.33
E-CURD-88	yes	69.04
E-CURD-46	yes	60.36
E-MTAB-10287	yes	56.13
E-HCAD-4	yes	43.71
E-HCAD-1	yes	43.31
E-GEOD-134144	yes	25.26
E-CURD-119	yes	19.79
E-MTAB-10553	yes	19.21
E-GEOD-125970	yes	16.77
E-MTAB-9388	yes	12.57
E-MTAB-10042	yes	12.16

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

62 targets.

Target	Regulation
A2M
ACVRL1
ADAM2
ADCYAP1
ADRA1D
ALB	Activation
ASAH1	Unknown
ATF3	Activation
BCL2L1	Repression
CCL2	Activation
CCL20	Unknown
CCND1	Repression
CDH1	Unknown
CDKN1A	Activation
CERS2	Activation
CGB3	Activation
CTSB
CTSG
CXCL2	Activation
CXCL8	Activation
DAPK2	Activation
DLK1	Unknown
ENG	Unknown
FHIT
FSHB
GCK
GSK3B
GSTP1
IGF1
IGF1R	Unknown

JASPAR motifs

Motif	Name	Family
MA1517.1	KLF6	Three-zinc finger Kruppel-related
MA1517.2	KLF6	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:11443140

Upstream regulators (CollecTRI, top): E2F1, F2R, F2RL1, FOXO3, JUN, NR1I2, PPARG, SP1, TP53

miRNA regulators (miRDB)

203 targeting KLF6, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-656-3P	100.00	72.15	2788
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
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-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585

Literature-anchored findings (GeneRIF, showing 40)

• data suggest that KLF6 is a tumor suppressor gene involved in human prostate cancer (PMID:11752579)
• KLF6 gene may be involved in carcinogenesis of sporadic nasopharyngeal carcinomas. (PMID:12508640)
• Studies of binding of KLF6 to the human iNOS promoter reveal CACCC binding sites and transactivation of iNOS promoter in diverse pathophysiological conditions: NaCN-induced hypoxia, heat shock, serum starvation, and PMA/ionophore stimulation (PMID:12590140)
• may act as a suppressor of prostatic cancer. (review) (PMID:12651597)
• role in prostate cancers; significant genetic alterations of KLF6 occur in a minority of high-grade prostate cancers (PMID:12651626)
• Mutations of the KLF6 gene play a role in the pathogenesis of astrocytic gliomas. (PMID:12740910)
• Zf9 transcription factor represents an additional candidate susceptibility gene for investigating hereditary predisposition to Dupuytren disease. (PMID:12794452)
• Deregulation of KLF6 by a combination of allelic imbalance and mutation may play a role in the development of colorectal cancer (PMID:15057748)
• Our results provide the first evidence of functional tumor suppression by KFL6, and its loss may contribute to glial tumor progression. (PMID:15064720)
• Altered mRNA expression is associated with prostate cancer recurrence. (PMID:15067324)
• Diminished expression of KLF6 correlates with poor prognosis and high probability of therapy failure in prostate cancer patients. (PMID:15067324)
• Transcriptional activation of the insulin-like growth factor I receptor gene by the Kruppel-like factor 6 (KLF6) tumor suppressor protein. (PMID:15131018)
• KLF6 germ-like mutations are of marginal importance in prostate cancer predisposition in Finland. (PMID:15247715)
• examination of role as potential tumor suppressor gene product (PMID:15378003)
• KLF6 is deregulated by loss and/or mutation in hepatocellular carcinoma, and its inactivation may contribute to pathogenesis in a significant number of these tumors. (PMID:15486921)
• genetic alterations of KLF6 gene might play an important role in the development or progression of sporadic gastric cancers (PMID:15824733)
• Repression of Dlk1 requires HDAC3 deacetylase activity, which is recruited to the endogenous Dlk1 promoter where it interacts with KLF6. The interaction between HDAC3 and KLF6 is identified as a potential mechanism underlying adipogenesis. (PMID:15917248)
• Absence of mutation in the putative tumor-suppressor gene KLF6 is demonstrated in colorectal neoplasms. (PMID:16044160)
• KLF6 gene transcription is under control of a TATA-box independent initiation mechanism together with an evolutionary conserved array of positive cis-acting elements. (PMID:16054710)
• Transcription factor KLF6 downregulates the alpha1-PI gene in corneal epithelial cells and may thereby be involved in keratoconus. (PMID:16431954)
• These results provide the first characterization of the Acid Ceremidase promoter from any species and demonstrate that Kruppel-like factor 6 (KLF6) is one transcription factor involved in the regulation of AC gene expression. (PMID:16500425)
• The negative association between KLF6 IVS1-27A and prostate cancer risk supports a population-specific effect of susceptibility alleles in prostate tumorigenesis. (PMID:16598737)
• KLF6-mediated changes in E-cadherin levels are accompanied by downstream changes in both the subcellular localization of beta-catenin and c-myc expression levels. (PMID:16702959)
• KLF6 and KLF6-SV1 are associated with key clinical features of ovarian cancer and suggest that their therapeutic targeting may alter ovarian cancer growth, progression, and dissemination. (PMID:16778100)
• KLF6 gene may be one of the candidate tumor suppressor genes in colorectal cancers and that genetic alteration of the KLF6 gene might play a role in the development of colorectal carcinomas. (PMID:16856969)
• The results suggest that genetic and epigenetic alteration of KLF6 may play a minor role in the development of hepatocellular carcinoma (HCC) (PMID:16872311)
• KLF6 may be involved in pathogenesis of hepatocellular carcinoma (PMID:16972326)
• Human transcription factors KLF2 and KLF6 are targets of the P. aeruginosa type III exoenzymes S and Y, with potential importance in host cell death. (PMID:16988269)
• an SP2/KLF6 repression complex by SHP is required for farnesoid X receptor-induced endothelial cell migration (PMID:17071613)
• Deregulation of KLF6 stability may alter its tumor suppressor function and/or the response of tumors to chemotherapeutics (PMID:17113081)
• Association of KLF6 germline polymorphism with prostate cancer risk, but not benign prostatic hyperplasia risk in Finland. (PMID:17125911)
• KLF6 coding sequences are altered in 10% brain tumors, 8% NSLC, and 4% of cancer cell lines. (PMID:17143513)
• our results suggest a potential involvement of KLF6 polymorphisms in lung cancer risk (PMID:17223258)
• Loss of heterozygosity of the KLF6 at chromosome 10p15 contributes to the invasion step from an intramucosal carcinoma to an invasive carcinoma specifically in sporadic colorectal carcinogenesis (PMID:17347589)
• Data demonstrated that KLF6 is essential for hepatocellular carcinoma -derived cells to evade apoptosis. (PMID:17347668)
• KLF6 allelic imbalance and decreased KLF6 and increased KLF6-SV1 expression are common findings in primary GBM tumors (PMID:17514651)
• KLF6 loss of heterozygosity represents a clinically-relevant biomarker predicting patient survival and tumor recurrence (PMID:17621627)
• KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not (PMID:17663506)
• Expression of Sp1 and KLF6 is developmentally regulated, providing basis for further investigations on regulation of Sp1 and KLF6 gene during course of corneal development and in corneal diseases such as keratoconus. (PMID:17893646)
• The CpG islands in TFPI-2 promoter was hypermethylated in highly invasive breast cancer cell line, and DNA methylation in the entire promoter region caused TFPI-2 repression by inducing inactive chromatin structure and decreasing KLF6 binding. (PMID:18053161)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	klf6a	ENSDARG00000029072
mus_musculus	Klf6	ENSMUSG00000000078
rattus_norvegicus	Klf6	ENSRNOG00000016885
drosophila_melanogaster	luna	FBGN0040765

Paralogs (22): KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), 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 6 — Q99612 (reviewed: Q99612)

Alternative names: B-cell-derived protein 1, Core promoter element-binding protein, GC-rich sites-binding factor GBF, Proto-oncogene BCD1, Suppressor of tumorigenicity 12 protein, Transcription factor Zf9

All UniProt accessions (2): Q99612, D3GC14

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator. Binds a GC box motif. Could play a role in B-cell growth and development.

Subunit / interactions. Interacts with ZZEF1.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in placenta followed by spleen, thymus, prostate, testis, small intestine and colon. Weakly expressed in pancreas, lung, liver, heart and skeletal muscle. Also expressed in fetal brain, spleen and thymus.

Disease relevance. Gastric cancer (GASC) [MIM:613659] A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. The disease is caused by variants affecting the gene represented in this entry. Prostate cancer (PC) [MIM:176807] A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The acidic N-terminal part may favor interaction with the basic domain of transcription factors. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF6, the motif is inactive.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q99612-1	1	yes
Q99612-2	2
Q99612-3	3

RefSeq proteins (3): NP_001153596, NP_001153597, NP_001291* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (19 total): sequence variant 8, zinc finger region 3, compositionally biased region 2, splice variant 2, chain 1, sequence conflict 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99612-F1	59.24	0.03

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 540 (showing top): RNGTGGGC_UNKNOWN, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, AMIT_DELAYED_EARLY_GENES, GOBP_B_CELL_ACTIVATION, NKX25_02, AMIT_EGF_RESPONSE_60_HELA, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, SOUCEK_MYC_TARGETS, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, AMIT_SERUM_RESPONSE_40_MCF10A, NAGASHIMA_NRG1_SIGNALING_UP

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), B cell differentiation (GO:0030183), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (8): 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), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): chromatin (GO:0000785), fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
nuclear lumen	2
lymphocyte differentiation	1
B cell activation	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
chromosome	1
nucleolus	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cytoplasm	1

Protein interactions and networks

STRING

2018 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF6	TP53	P04637	854
KLF6	CCND1	P24385	728
KLF6	JUN	P05412	691
KLF6	SERPINH1	P29043	624
KLF6	ATF3	P18847	606
KLF6	DUSP1	P28562	605
KLF6	CEBPB	P17676	598
KLF6	PSCA	O43653	572
KLF6	SMAD3	P84022	563
KLF6	DUSP12	Q9UNI6	554
KLF6	BTG2	P78543	543
KLF6	MMP14	P50281	541
KLF6	IL6	P05231	538
KLF6	LCOR	Q96JN0	537
KLF6	MDM2	Q00987	523

IntAct

34 interactions, top by confidence:

A	B	Type	Score
RELA	NFKBIA	psi-mi:“MI:0914”(association)	0.980
RELA	NFKB1	psi-mi:“MI:0914”(association)	0.790
KLF6	RELA	psi-mi:“MI:0915”(physical association)	0.580
RELA	KLF6	psi-mi:“MI:0915”(physical association)	0.580
KLF6	GARS1	psi-mi:“MI:0915”(physical association)	0.560
LMNA	KLF6	psi-mi:“MI:0915”(physical association)	0.560
KLF6	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
KLF6	EHMT2	psi-mi:“MI:0915”(physical association)	0.370
KLF6	CCL2	psi-mi:“MI:0914”(association)	0.350
CXCL2	KLF6	psi-mi:“MI:0914”(association)	0.350
	KLF6	psi-mi:“MI:0914”(association)	0.350
NFKBIA	KLF6	psi-mi:“MI:0914”(association)	0.350
KLF6		psi-mi:“MI:0914”(association)	0.350
KLF6	IMPDH2	psi-mi:“MI:0914”(association)	0.350
KLF6	ACTA2	psi-mi:“MI:2364”(proximity)	0.270
KLF6	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
KLF6	ssuA	psi-mi:“MI:0915”(physical association)	0.000
	KLF6	psi-mi:“MI:0915”(physical association)	0.000
KLF6	APOM	psi-mi:“MI:0915”(physical association)	0.000
KLF6	GTF3C1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (106): EHMT2 (Two-hybrid), RUNX1 (Affinity Capture-Western), SP1 (Affinity Capture-Western), KLF6 (Affinity Capture-RNA), KLF6 (Co-localization), KLF6 (Co-localization), KLF6 (Co-localization), CHI3L1 (Co-localization), APOM (Two-hybrid), GTF3C1 (Two-hybrid), PNO1 (Two-hybrid), POLA2 (Two-hybrid), KLF4 (Affinity Capture-Western), SP1 (Affinity Capture-Western), SP1 (Reconstituted Complex)

ESM2 similar proteins: A9ZPC9, O08584, O08876, O08954, O14901, O35739, O35819, O43623, O70343, O75840, O89091, P10244, P22227, P36197, P37275, P41182, P43300, P43301, P48972, P55878, P79288, P97469, Q01713, Q06889, Q4V7E1, Q5EXX3, Q5ZM39, Q60542, Q62947, Q64318, Q6DCW1, Q6NRM0, Q6XDT6, Q753Y2, Q804R0, Q865B7, Q8AWY2, Q8NAP3, Q8NCP5, Q8R0A2

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

7 interactions.

A	Effect	B	Mechanism
KLF6	up-regulates	Adipogenesis
KLF6	“down-regulates quantity by repression”	DLK1	“transcriptional regulation”
KLF6	down-regulates	DLK1	“transcriptional regulation”
F2RL1	“up-regulates quantity by expression”	KLF6	“transcriptional regulation”
F2R	“up-regulates quantity by expression”	KLF6	“transcriptional regulation”
GSK3B	“up-regulates activity”	KLF6	phosphorylation
KLF6	“up-regulates quantity by expression”	ATF3	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — MEL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
7569	NM_001300.6(KLF6):c.346T>C (p.Ser116Pro)	Pathogenic
7570	NM_001300.6(KLF6):c.410C>A (p.Ser137Ter)	Pathogenic
7571	NM_001300.6(KLF6):c.368C>A (p.Ala123Asp)	Pathogenic
7572	NM_001300.6(KLF6):c.190T>C (p.Trp64Arg)	Pathogenic
7573	NM_001300.6(KLF6):c.506T>C (p.Leu169Pro)	Pathogenic
7574	NM_001300.6(KLF6):c.465C>A (p.Ser155Arg)	Pathogenic

SpliceAI

654 predictions. Top by Δscore:

Variant	Effect	Δscore
10:3782217:G:GC	acceptor_gain	1.0000
10:3784908:TTTA:T	donor_loss	1.0000
10:3784909:TTA:T	donor_loss	1.0000
10:3784910:TACC:T	donor_loss	1.0000
10:3784911:A:T	donor_loss	1.0000
10:3776400:CAGG:C	acceptor_gain	0.9900
10:3781636:CTGA:C	donor_loss	0.9900
10:3781637:TGA:T	donor_loss	0.9900
10:3781638:GAC:G	donor_loss	0.9900
10:3781639:A:C	donor_loss	0.9900
10:3781692:T:A	donor_gain	0.9900
10:3782210:CAGGT:C	acceptor_gain	0.9900
10:3782212:GGT:G	acceptor_gain	0.9900
10:3782213:GT:G	acceptor_gain	0.9900
10:3782215:C:CC	acceptor_gain	0.9900
10:3782216:T:C	acceptor_loss	0.9900
10:3782217:G:C	acceptor_gain	0.9900
10:3782220:C:CT	acceptor_gain	0.9900
10:3782221:A:T	acceptor_gain	0.9900
10:3784907:GTTTA:G	donor_loss	0.9900
10:3776404:C:CC	acceptor_gain	0.9800
10:3780100:ACGT:A	donor_loss	0.9800
10:3780101:CGTA:C	donor_loss	0.9800
10:3780102:GT:G	donor_loss	0.9800
10:3780103:T:TG	donor_loss	0.9800
10:3780104:AC:A	donor_loss	0.9800
10:3780105:C:CG	donor_loss	0.9800
10:3780227:CTC:C	acceptor_gain	0.9800
10:3780228:TCCTG:T	acceptor_loss	0.9800
10:3780230:CT:C	acceptor_loss	0.9800

AlphaMissense

1861 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:3779584:A:C	F269L	1.000
10:3779584:A:T	F269L	1.000
10:3779586:A:G	F269L	1.000
10:3780183:A:C	F241L	1.000
10:3780183:A:T	F241L	1.000
10:3780184:A:G	F241S	1.000
10:3780185:A:G	F241L	1.000
10:3781645:G:C	H224Q	1.000
10:3781645:G:T	H224Q	1.000
10:3781652:C:G	R222P	1.000
10:3779557:G:C	H278Q	0.999
10:3779557:G:T	H278Q	0.999
10:3779559:G:C	H278D	0.999
10:3779567:A:G	L275P	0.999
10:3779579:C:A	R271M	0.999
10:3779585:A:G	F269S	0.999
10:3780122:A:G	C262R	0.999
10:3780126:A:C	F260L	0.999
10:3780126:A:T	F260L	0.999
10:3780128:A:G	F260L	0.999
10:3780144:G:C	H254Q	0.999
10:3780144:G:T	H254Q	0.999
10:3780146:G:C	H254D	0.999
10:3780151:C:G	R252P	0.999
10:3780156:G:C	H250Q	0.999
10:3780156:G:T	H250Q	0.999
10:3780158:G:C	H250D	0.999
10:3780166:A:G	L247S	0.999
10:3780184:A:C	F241C	0.999
10:3780185:A:T	F241I	0.999

dbSNP variants (sampled 300 via entrez): RS1000028978 (10:3785564 C>G,T), RS1000139557 (10:3785549 C>G,T), RS1000161882 (10:3786428 T>C), RS1000630000 (10:3784589 A>C), RS1000701468 (10:3783422 G>A), RS1001107150 (10:3779009 G>A,T), RS1001136930 (10:3779129 C>T), RS1001359517 (10:3786440 A>G), RS1001793902 (10:3776311 G>A,C), RS1002130914 (10:3777588 C>G,T), RS1002267505 (10:3785193 A>G), RS1002496131 (10:3779917 C>T), RS1002616428 (10:3779626 G>A), RS1003005770 (10:3783672 T>C), RS1003237825 (10:3778368 T>C,G)

Disease associations

OMIM: gene MIM:602053 | disease phenotypes: MIM:613659

GenCC curated gene-disease

Mondo (2): hypotensive disorder (MONDO:0005468), gastric cancer (MONDO:0001056)

Orphanet (0):

HPO phenotypes

5 total (6 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001442	Typified by somatic mosaicism
HP:0012125	Prostate cancer
HP:0012126	Stomach cancer
HP:0410067	Increased level of L-fucose in urine
HP:0002615	Hypotension

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001911_1	Asthma (bronchodilator response)	2.000000e-07
GCST002097_20	Coronary artery calcification	3.000000e-07
GCST006288_458	Heel bone mineral density	1.000000e-09
GCST006288_625	Heel bone mineral density	2.000000e-10
GCST006979_559	Heel bone mineral density	4.000000e-19
GCST007094_176	Diastolic blood pressure	5.000000e-08
GCST008369_10	Plasma anti-thyroglobulin levels	2.000000e-06
GCST009144_1	Disease progression in age-related macular degeneration (adjusted for baseline)	9.000000e-06
GCST009597_236	Multiple sclerosis	1.000000e-07
GCST010396_150	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06
GCST90002393_321	Monocyte count	2.000000e-14
GCST90002394_337	Monocyte percentage of white cells	7.000000e-12
GCST90002403_251	Red blood cell count	4.000000e-12
GCST90013468_27	Height	4.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0009270	heel bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0008336	disease progression measurement
EFO:0007874	gut microbiome measurement
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007022	Hypotension	C14.907.514

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects cotreatment, increases expression, affects expression	7
Cisplatin	increases expression, affects expression, affects cotreatment, decreases expression	5
Estradiol	decreases expression, decreases reaction, affects binding, affects cotreatment, increases expression	5
Benzo(a)pyrene	affects cotreatment, affects expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, decreases reaction, increases expression	3
Doxorubicin	decreases expression	3
Progesterone	increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
cupric chloride	increases expression, affects expression	2
nickel sulfate	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Acetaminophen	increases expression	2
Cadmium	increases expression	2
Dinitrochlorobenzene	increases expression	2
Formaldehyde	increases expression	2
Hydrogen Peroxide	affects cotreatment, increases expression, affects expression	2
Oxazolone	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
Silver	increases expression	2
Zinc	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
Asbestos, Crocidolite	increases expression	2
beta-Naphthoflavone	increases expression, affects cotreatment	2
Vitamin K 3	affects cotreatment, increases expression, increases reaction, decreases reaction, affects expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
TAK-243	increases sumoylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3R4	SEES3-1V human KLF6, clone1	Embryonic stem cell	Male
CVCL_A3R5	SEES3-1V human KLF6, clone2	Embryonic stem cell	Male
CVCL_A3R6	SEES3-1V human KLF6, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00115726	PHASE4	COMPLETED	Trial Assessing the Effect of Preoperative Furosemide on Intraoperative Blood Pressure
NCT00173706	PHASE4	UNKNOWN	Evaluation of the Effects of L-Carnitine Injection in Patients Undergoing Hemodialysis
NCT00694343	PHASE4	COMPLETED	Efficacy of Voluven® for the Prevention of Hypotension During Spinal Anesthesia for Cesarean Section
NCT00777166	PHASE4	COMPLETED	Cardiac Effects of Oxytocin Administrated During Cesarean Section, Signs of Myocardial Ischemia
NCT00781157	PHASE4	COMPLETED	Phenylephrine for Spinal Induced Hypotension
NCT00846651	PHASE4	COMPLETED	Spinal Anesthesia Induced Hypotension During Cesarean Section
NCT00922844	PHASE4	TERMINATED	The Effect of Sevoflurane Versus Isoflurane on Vasopressor Need
NCT00991627	PHASE4	COMPLETED	Different Approaches to Maternal Hypotension During Cesarean Section
NCT00996190	PHASE4	COMPLETED	Best Regimen for Phenylephrine Administration During Cesarean Section
NCT01067391	PHASE4	COMPLETED	Effect of Tadalafil (Cialis) on the Cardiovascular System of Spinal Cord Injury (SCI) Males
NCT01414842	PHASE4	COMPLETED	HFR A-equilibrium on Cardiovascular Stability
NCT01415284	PHASE4	UNKNOWN	ED50 Determination of Hydroxyethylstarch for Treatment of Hypotension During Cesarean Section Under Spinal Anesthesia
NCT01418118	PHASE4	COMPLETED	Assessment of the Effects of Pressors on Graft Blood Flow After Free Tissue Transfer Surgery
NCT01481740	PHASE4	COMPLETED	Preventing Hypotension in Parturients With an Elevated Body Mass Index (BMI)
NCT01549223	PHASE4	COMPLETED	Oxytocin And Uterotonic Agent Use For Cesarean Delivery
NCT02004834	PHASE4	ACTIVE_NOT_RECRUITING	Levobupivacaine and Lidocaine for Paravertebral Block Causes Greater Hemodynamic Oscillations Than Levobupivacaine
NCT02135146	PHASE4	COMPLETED	Evaluating Fluid Strategies in Thoracic Surgery Patients Utilizing a Goal Directed Approach
NCT02323399	PHASE4	RECRUITING	Study to Determine the Pharmacokinetics and Pharmacodynamic Effects of Phenylephrine on BP Via IV
NCT02393196	PHASE4	UNKNOWN	Colloid Preload Versus Colloid Coload During Cesarean Deliveries
NCT02477501	PHASE4	COMPLETED	Ephedrine vs. Nor Epinephrine Infusion in Preventing Hypotension After Spinal Anesthesia for Cesarean Section
NCT02737813	PHASE4	COMPLETED	Cardiac Output Changes During Hyperbaric and Isobaric Bupivacaine in Patients Undergoing Cesarean Section
NCT02771158	PHASE4	WITHDRAWN	Midodrine During Recovery From Septic Shock
NCT02802683	PHASE4	COMPLETED	Hemodynamic Impact of Hyperbaric Versus Isobaric for Spinal Anesthesia During Cesarean Delivery
NCT02854787	PHASE4	COMPLETED	Intravenous Bolus of Phenylephrine vs. Norepinephrine in Preventing Hypotension After Spinal Anesthesia
NCT02913768	PHASE4	COMPLETED	Reduction in Spinal-induced Hypotension With Ondansetron in Parturients Undergoing Caesarean Section
NCT02969239	PHASE4	UNKNOWN	Norepinephrine and Phenylephrine for Maternal Cardiac Output During Spinal Anesthesia for Elective Cesarean Delivery
NCT03595319	PHASE4	UNKNOWN	Median Sevoflurane Concentration for Hypotension Between Young and Elderlypatients: Adaptive Clinical Trial
NCT03602014	PHASE4	COMPLETED	Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury
NCT03664037	PHASE4	COMPLETED	Dexamethasone Blunts the Hypotensive Effect of Spinal Anesthesia in Geriatric Patients Undergoing Lower Limb Orthopedic Surgeries
NCT03704909	PHASE4	COMPLETED	Manging Post Spinal Hypotension During Elective Cesarean Section
NCT03706755	PHASE4	COMPLETED	Comparison of Two Doses of Norepinephrine in Preventing Hypotension After Spinal Anesthesia
NCT03973411	PHASE4	UNKNOWN	Ondansetron in the Prevention of Hypotension in Patients Undergoing Spinal Anesthesia
NCT04529005	PHASE4	COMPLETED	Angiotensin II in the Perioperative Management of Hypotension in Kidney Transplant Recipients
NCT04575675	PHASE4	COMPLETED	Dapagliflozin on Hypotensive Heart Failure Patients After Sacubitril/Valsartan Therapy
NCT04701190	PHASE4	COMPLETED	Different Noradrenaline Protocols in Post Spinal Hypotension in CS
NCT04705896	PHASE4	RECRUITING	Albumin To Enhance Recovery After Acute Kidney Injury
NCT04789330	PHASE4	COMPLETED	Norepinephrine vs Phenylephrine During General Anesthesia
NCT04908592	PHASE4	COMPLETED	Efficacy of Dexamethasone in Attenuation of Postinduction Hypotension in Geriatric Patients Undergoing General Anesthesia
NCT05166330	PHASE4	UNKNOWN	Two Ratios of Propofol-ketamine Admixture for Rapid-sequence Induction Anesthesia for Emergency Laparotomy
NCT05248932	PHASE4	COMPLETED	Norepinephrine to Prevent Hypotension in Ceasrean Delivery