KLF10

Summary

KLF10 (KLF transcription factor 10, HGNC:11810) is a protein-coding gene on chromosome 8q22.3, encoding Krueppel-like factor 10 (Q13118). Transcriptional repressor which binds to the consensus sequence 5’-GGTGTG-3'.

This gene encodes a member of a family of proteins that feature C2H2-type zinc finger domains. The encoded protein is a transcriptional repressor that acts as an effector of transforming growth factor beta signaling. Activity of this protein may inhibit the growth of cancers, particularly pancreatic cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7071 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypertrophic cardiomyopathy (Limited, ClinGen)
• GWAS associations: 8
• Clinical variants (ClinVar): 311 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• Transcription factor: yes — 32 downstream targets (CollecTRI)
• MANE Select transcript: NM_005655

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11810
Approved symbol	KLF10
Name	KLF transcription factor 10
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	EGRA, TIEG1
Ensembl gene	ENSG00000155090
Ensembl biotype	protein_coding
OMIM	601878
Entrez	7071

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000285407, ENST00000395884, ENST00000907828, ENST00000911510

RefSeq mRNA: 2 — MANE Select: NM_005655 NM_001032282, NM_005655

CCDS: CCDS47905, CCDS6294

Canonical transcript exons

ENST00000285407 — 4 exons

Exon	Start	End
ENSE00001019116	102651149	102652061
ENSE00001162038	102648784	102650391
ENSE00001192585	102655566	102655725
ENSE00001617611	102652164	102652397

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 51.3461 / max 1019.8626, expressed in 1811 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94291	49.6294	1809
94288	1.0781	464
94289	0.4399	250
94290	0.1986	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of paranasal sinus	UBERON:0005030	98.75	gold quality
skin of hip	UBERON:0001554	98.67	gold quality
upper leg skin	UBERON:0004262	98.57	gold quality
germinal epithelium of ovary	UBERON:0001304	98.50	gold quality
mucosa of stomach	UBERON:0001199	98.44	gold quality
synovial joint	UBERON:0002217	98.39	gold quality
parietal pleura	UBERON:0002400	98.20	gold quality
saphenous vein	UBERON:0007318	98.17	gold quality
mammary duct	UBERON:0001765	97.89	gold quality
pleura	UBERON:0000977	97.87	gold quality
penis	UBERON:0000989	97.85	gold quality
monocyte	CL:0000576	97.80	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.76	gold quality
mononuclear cell	CL:0000842	97.75	gold quality
tibialis anterior	UBERON:0001385	97.66	gold quality
cauda epididymis	UBERON:0004360	97.60	gold quality
visceral pleura	UBERON:0002401	97.57	gold quality
nipple	UBERON:0002030	97.51	gold quality
epithelium of mammary gland	UBERON:0003244	97.45	gold quality
gastrocnemius	UBERON:0001388	97.34	gold quality
vena cava	UBERON:0004087	97.29	gold quality
leukocyte	CL:0000738	97.17	gold quality
deltoid	UBERON:0001476	97.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.12	gold quality
lower lobe of lung	UBERON:0008949	97.10	gold quality
pericardium	UBERON:0002407	96.92	gold quality
jejunum	UBERON:0002115	96.75	gold quality
muscle of leg	UBERON:0001383	96.71	gold quality
body of tongue	UBERON:0011876	96.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.53	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-76312	yes	1062.76
E-MTAB-6678	yes	7.96
E-MTAB-10137	no	740.02
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

32 targets.

Target	Regulation
ADAM2
BMAL1	Unknown
CBLIF
CCN2
CDKN1A	Activation
CEL
EGFR	Repression
FGFR1	Repression
FOXP3	Unknown
GDNF
GPS2	Activation
GSTP1
HAMP	Unknown
IL12B
ITGAD	Activation
KDR	Activation
MAOB	Repression
MYCN
POMC	Repression
PTGS1	Activation
PTTG1	Unknown
RUNX2	Unknown
SERPINE1	Activation
SMAD2	Activation
SMAD3	Repression
SMAD4	Repression
SMAD7	Unknown
STMN1	Repression
TGFB1	Activation
TGFBI	Activation

JASPAR motifs

Motif	Name	Family
MA1511.1	KLF10	Three-zinc finger Kruppel-related
MA1511.2	KLF10	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:11443140

Upstream regulators (CollecTRI, top): APP, BMAL1, CLOCK, CLU, DKK1, E2F1, E2F4, MLXIPL, NCOA1, VHL

miRNA regulators (miRDB)

164 targeting KLF10, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
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-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 40)

• no sequence alterations or alterations in expression were found in TIEG1 in pancreatic cancer; an essential role of TIEG1 in pancreatic cancer can be excluded (PMID:12065093)
• TIEG amplies Smad signaling. (PMID:12173049)
• Up-regulation of CD11d expression following differentiation of myeloid cells is mediated through increased binding of TIEG1 binding to the CD11d promoter. (PMID:15087465)
• Differential gene expression of TIEG, a tumor suppressor gene, plays a significant role in the proliferation of breast cancer (PMID:15218362)
• Expression of TIEG is known to inhibit Smad7 expression in bronchial epithelial cells. (PMID:17377371)
• TIEG1 induces apoptosis through mitochondrial apoptotic pathway and promotes apoptosis induced by homoharringtonine and velcade. (PMID:17659279)
• Gene variants may weakly contribute to a particular genetic background that increases the susceptibility to development of type 2 diabetes. (PMID:17931948)
• TGFBI is up-regulated in clear cell carcinoma by VHL through a Kruppel-like transcriptional factor 10. (PMID:18359287)
• TIEG is rapidly induced in response to estrogen in osteoblasts by ERbeta, but not ERalpha (PMID:18483178)
• Data suggest that TGFbeta and BMP-6 in the bone marrow microenvironment allow leukemia cells to escape therapy. Further, the data indicate that TIEG1 might be involved in mediating this effect from the microenvironment onto the leukemia cells. (PMID:18798273)
• KLF10 has been shown to play a major role in the TGFbeta inhibition of cell proliferation and inflammation and induction of apoptosis, and its overexpression in human osteoblasts and pancreatic carcinoma cells mimics the actions of TGFbeta[review] (PMID:20087894)
• Results indicate that HPV-16 oncoprotein E7 binds to the C-terminus of TIEG1 and induces its degradation via the ubiquitin pathway. E7 not only increased the ubiquitination of TIEG1 but also influenced the ability of TIEG1 to affect apoptosis. (PMID:20691807)
• JARID1B is the first TIEG1 corepressor identified, explaining how TIEG1 represses transcription through inducing histone H3 lysine 4 demethylation, which may be important for TIEG1 function in both normal and cancer cells. (PMID:20863814)
• KLF10 is upregulated in human PDLCs subjected to tensile stress related to mechano-induced cell cycle arrest. (PMID:20934684)
• the pathway by which estrogen induces apoptosis is possibly through an up-regulation of Klf10 that decreases BI-1 and finally increases the concentration of cytoplasmic calcium (PMID:21262377)
• TIEG1 has a role in regulating the expression and activity of Runx2 in osteoblasts (PMID:21559363)
• TIEG1 inhibits breast cancer cell invasion by inhibition of the EGFR signaling pathway. (PMID:22025675)
• study identified 6 novel, hypertrophic cardiomyopathy associated TIEG1 missense variants and have demonstrated that a number of these variants have abnormal function with regard to mutant TIEG1’s ability to regulate either the PTTG1 or SMAD7 promoters (PMID:22234868)
• KLF10 is a potential clinical predictor for progression of pancreatic cancer. (PMID:22688058)
• KLF10 may constitute a pharmacogenomic marker to discriminate between response and nonresponse to hydroxyurea treatment in beta-hemoglobinopathy patients. (PMID:23057549)
• KLF10 is an effective repressor of myoblast proliferation and represses FGFR1 promoter activity in these cells via an Sp1 binding site. (PMID:23569208)
• RAF-1 phosphorylation and PIN1 isomerization together regulate KLF10 stability and further affect the role of KLF10 in tumor progression. (PMID:23994618)
• The tumor suppressor function of LSAMP is most likely exerted by reducing the proliferation rate of the tumor cells, possibly by indirectly upregulating one or more of the genes HES1, CTAG2 or KLF10. (PMID:24885297)
• KLF10, functions as a toggle to integrate antagonistic signals regulating FOXP3 via Sin3-HDAC/PCAF pathway and, thus, immune activation. (PMID:24944246)
• KLF10 directly binds to TGF-BRII promoter in T cells, leading to enhanced gene expression. (PMID:25472963)
• CDK2 up-regulates the protein level of KLF10 through reducing its association with SIAH1, a KLF10 E3-ubiqutin ligase involved in proteasomal degradation. (PMID:25728284)
• photoexposure decreases expression in fibroblasts and keratinocytes (PMID:26119394)
• Results from a study on gene expression variability markers in early-stage human embryos shows that KLF10 is a putative marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• TIEG-1 overexpression in normal human skin fibroblasts results in improved resistance to oxidative stress (PMID:26922828)
• Zinc is capable of ameliorating the allogeneic immune reaction by enhancement of antigen-specific iTreg cells due to modulation of essential molecular targets by upregulation of Foxp3 and KLF-10 and downregulation of IRF-1. (PMID:27260002)
• the findings show that TIEG1 is highly expressed in human keloids and that it directly binds and represses Smad7 promoter-mediated activation of TGF-beta/Smad2 signaling (PMID:28108300)
• In clinical specimens of lung adenocarcinoma, low KLF10 expression associated with decreased patient survival, consistent with a pivotal role for KLF10 in distinguishing the antiproliferative versus prometastatic functions of TGFbeta. Our results establish that KLF10 functions to suppress TGFb-induced EMT, establishing a molecular basis for the dichotomy of TGFb function during tumor progression. (PMID:28249899)
• Thus, our study uncovers a novel regulatory mechanism underlying which KLF10 stability and its biological function are mediated by FBW7. (PMID:29198712)
• Klf10 silencing could inhibit bone differentiation of human periodontal ligament cells under mechanical force, which may be through regulation of hedgehog signaling pathway. (PMID:29691553)
• study illustrated a novel signaling cascade of LINC00641/miR-197-3p/KLF10/PTEN/PI3K/AKT pathway regulating bladder cancer development (PMID:30060954)
• targeting the KDM6A-KLF10 feedback loop may be beneficial to attenuate diabetes-induced kidney injury. (PMID:30948420)
• Our findings show that a KLF4 genomic variant (rs2236599) is associated with hydroxyurea treatment efficacy in sickle cell disease/beta-thalassemia compound heterozygous patients and two KLF10 genomic variants (rs980112, rs3191333) are associated with persistent HbF levels in nontransfusion dependent beta-thalassemia (NTDT) patients (PMID:31393228)
• KLF10 inhibits cell growth by regulating PTTG1 in multiple myeloma under the regulation of microRNA-106b-5p. (PMID:32549754)
• High Expression of KLF10 Is Associated with Favorable Survival in Patients with Oral Squamous Cell Carcinoma. (PMID:33379261)
• Hypoxic tumour cell-derived exosomal miR-340-5p promotes radioresistance of oesophageal squamous cell carcinoma via KLF10. (PMID:33485367)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Klf10	ENSMUSG00000037465
rattus_norvegicus	Klf10	ENSRNOG00000006118

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), 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 10 — Q13118 (reviewed: Q13118)

Alternative names: EGR-alpha, Transforming growth factor-beta-inducible early growth response protein 1

All UniProt accessions (1): Q13118

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor which binds to the consensus sequence 5’-GGTGTG-3’. Plays a role in the regulation of the circadian clock; binds to the GC box sequence in the promoter of the core clock component ARTNL/BMAL1 and represses its transcriptional activity. Regulates the circadian expression of genes involved in lipogenesis, gluconeogenesis, and glycolysis in the liver. Represses the expression of PCK2, a rate-limiting step enzyme of gluconeogenesis. May play a role in the cell cycle regulation.

Subcellular location. Nucleus.

Post-translational modifications. Ubiquitinated; mediated by SIAH1 and leading to its subsequent proteasomal degradation.

Induction. By TGFB1 and BMP2.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q13118-1	1	yes
Q13118-2	2
Q13118-3	3
Q13118-4	4

RefSeq proteins (2): NP_001027453, NP_005646* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (20 total): splice variant 5, strand 4, zinc finger region 3, turn 2, helix 2, modified residue 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EPA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13118-F1	50.62	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 (2): 184, 249

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 437 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_CIRCADIAN_RHYTHM, AHRARNT_01, RNGTGGGC_UNKNOWN, MODULE_97, GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, PAX4_01, MODULE_169, AMIT_DELAYED_EARLY_GENES, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, AMIT_EGF_RESPONSE_60_HELA, MODULE_182

GO Biological Process (14): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), cell-cell signaling (GO:0007267), circadian rhythm (GO:0007623), negative regulation of cell population proliferation (GO:0008285), cellular response to starvation (GO:0009267), bone mineralization (GO:0030282), somatic stem cell population maintenance (GO:0035019), regulation of circadian rhythm (GO:0042752), positive regulation of osteoclast differentiation (GO:0045672), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355), rhythmic process (GO:0048511)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), core promoter sequence-specific DNA binding (GO:0001046), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), 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 (2): chromatin (GO:0000785), nucleus (GO:0005634)

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
DNA-templated transcription	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
cell communication	1
signaling	1
rhythmic process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
ossification	1
biomineral tissue development	1
stem cell population maintenance	1
circadian rhythm	1
regulation of biological process	1
positive regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
negative regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
biological_process	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
transcription regulator activity	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1

Protein interactions and networks

STRING

1414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF10	SIN3A	Q96ST3	876
KLF10	TGFB1	P01137	635
KLF10	SMAD7	O15105	633
KLF10	HDAC1	Q13547	567
KLF10	KDM5B	Q9UGL1	530
KLF10	NAB2	Q15742	515
KLF10	NFYA	P23511	451
KLF10	IER3	P46695	445
KLF10	TRIB1	Q96RU8	437
KLF10	NFKB2	Q00653	418
KLF10	RELB	Q01201	417
KLF10	ATM	Q13315	414
KLF10	CCL20	P78556	412
KLF10	PTPRH	Q9HD43	407
KLF10	ARMC7	Q9H6L4	405

IntAct

26 interactions, top by confidence:

A	B	Type	Score
KLF10		psi-mi:“MI:0914”(association)	0.530
	KLF10	psi-mi:“MI:0914”(association)	0.530
KLF10	SP1	psi-mi:“MI:0915”(physical association)	0.510
SP1	KLF10	psi-mi:“MI:0915”(physical association)	0.510
KLF10	CDK6	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
KLF10	SIN3A	psi-mi:“MI:0915”(physical association)	0.400
KLF10	KAT2B	psi-mi:“MI:0915”(physical association)	0.400
	KLF10	psi-mi:“MI:0915”(physical association)	0.370
BOP1	KLF10	psi-mi:“MI:0915”(physical association)	0.370
LRRC75A-AS1	KLF10	psi-mi:“MI:0915”(physical association)	0.370
KLF10	CRIP2	psi-mi:“MI:0915”(physical association)	0.370
KLF10	LENG1	psi-mi:“MI:0915”(physical association)	0.370
KLF10	PIGC	psi-mi:“MI:0915”(physical association)	0.370
RPL14	KLF10	psi-mi:“MI:0915”(physical association)	0.370
SF3B3	KLF10	psi-mi:“MI:0915”(physical association)	0.370
TNS1	KLF10	psi-mi:“MI:0915”(physical association)	0.370
KLF10	ZNF512B	psi-mi:“MI:0915”(physical association)	0.370
KLF10	TFAP2A	psi-mi:“MI:0915”(physical association)	0.370
	KLF10	psi-mi:“MI:0914”(association)	0.350
KLF10	TPM3	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
KLF10	HIVEP1	psi-mi:“MI:2364”(proximity)	0.270
KLF10	ogl	psi-mi:“MI:0915”(physical association)	0.000
KLF10	TULP3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (59): KAT2B (Reconstituted Complex), SIN3A (Affinity Capture-Western), CDK2 (Affinity Capture-Western), CDK2 (Reconstituted Complex), CCNE1 (Affinity Capture-Western), KLF10 (Affinity Capture-Western), KLF10 (Affinity Capture-Western), KLF10 (Biochemical Activity), SIAH1 (Reconstituted Complex), KLF10 (Affinity Capture-Western), KLF10 (Reconstituted Complex), FBXW7 (Co-localization), SIN3A (Reconstituted Complex), KLF10 (Two-hybrid), KLF10 (Reconstituted Complex)

ESM2 similar proteins: A0A1L8H0H2, A0JPB4, F8VPJ6, O08876, O14901, O35738, O57415, O75626, O89091, O94993, P36197, P37275, P43300, P43301, P59667, P59759, P70284, Q03172, Q04891, Q06889, Q08050, Q0VDQ9, Q13118, Q2KHR2, Q3UH06, Q499D0, Q5EXX3, Q60542, Q60636, Q62255, Q62947, Q64318, Q6NRM0, Q80WT2, Q86V15, Q8BX22, Q8CGW4, Q8K1S5, Q8VIG0, Q8WNV5

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

7 interactions.

A	Effect	B	Mechanism
KLF10	“up-regulates quantity by expression”	TGFBI	“transcriptional regulation”
VHL	“down-regulates quantity by repression”	KLF10	“transcriptional regulation”
RAF1	“down-regulates quantity by destabilization”	KLF10	phosphorylation
PIN1	“down-regulates quantity by destabilization”	KLF10	binding
CDK2	“up-regulates quantity”	KLF10	phosphorylation
TYK2	“down-regulates activity”	KLF10	phosphorylation
KLF10	“up-regulates activity”	SIN3A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	175
Likely benign	103
Benign	25

Top pathogenic / likely-pathogenic (0)

SpliceAI

562 predictions. Top by Δscore:

Variant	Effect	Δscore
8:102652060:CA:C	acceptor_gain	1.0000
8:102652062:C:CC	acceptor_gain	1.0000
8:102652158:A:AC	donor_gain	1.0000
8:102652159:C:CC	donor_gain	1.0000
8:102652159:CTT:C	donor_loss	1.0000
8:102652160:TTA:T	donor_loss	1.0000
8:102652161:TA:T	donor_loss	1.0000
8:102652162:A:AC	donor_gain	1.0000
8:102652162:A:T	donor_loss	1.0000
8:102652163:C:CA	donor_gain	1.0000
8:102652163:CA:C	donor_gain	1.0000
8:102652163:CAA:C	donor_gain	1.0000
8:102652163:CAAA:C	donor_gain	1.0000
8:102652163:CAAAT:C	donor_gain	1.0000
8:102652393:TCCTC:T	acceptor_gain	1.0000
8:102652394:CCTCC:C	acceptor_gain	1.0000
8:102652395:CTC:C	acceptor_gain	1.0000
8:102652396:TC:T	acceptor_gain	1.0000
8:102652397:CC:C	acceptor_gain	1.0000
8:102652398:C:CA	acceptor_loss	1.0000
8:102652398:C:CC	acceptor_gain	1.0000
8:102652398:C:T	acceptor_gain	1.0000
8:102652400:A:AC	acceptor_gain	1.0000
8:102652400:A:C	acceptor_gain	1.0000
8:102652407:C:CT	acceptor_gain	1.0000
8:102655562:TTAC:T	donor_loss	1.0000
8:102655563:TA:T	donor_loss	1.0000
8:102655564:A:AC	donor_gain	1.0000
8:102655564:AC:A	donor_gain	1.0000
8:102655565:C:CT	donor_gain	1.0000

AlphaMissense

3160 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:102650234:A:C	H447Q	1.000
8:102650234:A:T	H447Q	1.000
8:102650250:T:A	D442V	1.000
8:102650256:C:A	R440M	1.000
8:102650261:G:C	F438L	1.000
8:102650261:G:T	F438L	1.000
8:102650262:A:G	F438S	1.000
8:102650263:A:G	F438L	1.000
8:102650275:A:G	C434R	1.000
8:102650284:A:G	C431R	1.000
8:102650288:A:C	F429L	1.000
8:102650288:A:T	F429L	1.000
8:102650290:A:G	F429L	1.000
8:102650306:G:C	H423Q	1.000
8:102650306:G:T	H423Q	1.000
8:102650308:G:C	H423D	1.000
8:102650318:G:C	H419Q	1.000
8:102650318:G:T	H419Q	1.000
8:102650320:G:C	H419D	1.000
8:102650320:G:T	H419N	1.000
8:102650328:A:G	L416P	1.000
8:102650345:A:C	F410L	1.000
8:102650345:A:T	F410L	1.000
8:102650346:A:G	F410S	1.000
8:102650347:A:G	F410L	1.000
8:102650374:A:G	C401R	1.000
8:102650378:G:C	F399L	1.000
8:102650378:G:T	F399L	1.000
8:102650380:A:G	F399L	1.000
8:102651194:A:C	Y380D	1.000

dbSNP variants (sampled 300 via entrez): RS1000275005 (8:102655249 C>T), RS1000331445 (8:102655477 C>T), RS1000435798 (8:102649336 T>A), RS1000635523 (8:102654249 G>A,T), RS1000768482 (8:102648531 T>A), RS1001222074 (8:102648302 C>T), RS1001310712 (8:102650931 A>G), RS1001319308 (8:102652236 T>C,G), RS1001537436 (8:102656368 CG>C), RS1001593469 (8:102655921 T>C), RS1001752009 (8:102649916 C>G), RS1001968647 (8:102656195 C>A,T), RS1002116386 (8:102654811 A>C), RS1002462124 (8:102656589 C>G,T), RS1002991093 (8:102650721 A>G)

Disease associations

OMIM: gene MIM:601878 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Limited	AD

Mondo (1): hypertrophic cardiomyopathy (MONDO:0005045)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002073_10	Chronic lymphocytic leukemia	5.000000e-08
GCST002943_4	IgA nephropathy	1.000000e-09
GCST008821_13	Neurofibrillary tangles	7.000000e-06
GCST008971_151	Urate levels	5.000000e-06
GCST008972_223	Urate levels	3.000000e-10
GCST011352_29	Alanine aminotransferase levels	3.000000e-08
GCST90011898_106	Alanine aminotransferase levels	6.000000e-17
GCST90013405_100	Liver enzyme levels (alanine transaminase)	2.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006797	neurofibrillary tangles measurement
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3407312 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 26,917 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1324	TOLCAPONE	4	13,819
CHEMBL641	ATOMOXETINE	4	13,098

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 11 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.00	IC50	1e+04	nM	CHEMBL1333704

PubChem BioAssay actives

1 with measured affinity, of 77 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(2,4-dioxo-1H-pyrimidin-5-yl)-3-methyl-4-nitrobenzamide	1196812: Inhibition of human KLF10 expressed in human HeLa cells assessed as reduction in transcriptional activity after 24 hrs by CACCC-responsive promoter driven TK-luciferase reporter gene assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	decreases expression, decreases reaction, affects expression, affects cotreatment, increases expression (+1 more)	4
sodium arsenite	decreases expression, increases expression	3
Hydrogen Peroxide	affects expression, decreases expression	3
Tretinoin	decreases expression, increases expression	3
Valproic Acid	increases expression	3
Cisplatin	decreases expression, increases reaction, increases expression	2
Vitamin K 3	affects expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
cinobufagin	increases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	affects expression	1
3,3’-diindolylmethane	decreases expression, decreases reaction	1
afimoxifene	decreases reaction, increases expression	1
sulforaphane	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
nickel chloride	increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
15-acetyldeoxynivalenol	increases expression	1
avobenzone	decreases expression	1
polyhexamethyleneguanidine	increases expression	1
tamibarotene	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
2-palmitoylglycerol	increases expression	1

ChEMBL screening assays

10 unique, capped per target: 10 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3411252	Binding	Inhibition of human KLF10 expressed in human HeLa cells assessed as reduction in transcriptional activity at 100 uM after 24 hrs by CACCC-responsive promoter driven TK-luciferase reporter gene assay	Discovery of small molecule inhibitors to Krüppel-like factor 10 (KLF10): implications for modulation of T regulatory cell differentiation. — J Med Chem

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_A3N4	SEES3-1V human KLF10, clone1	Embryonic stem cell	Male
CVCL_A3N5	SEES3-1V human KLF10, clone2	Embryonic stem cell	Male
CVCL_A3N6	SEES3-1V human KLF10, clone3	Embryonic stem cell	Male
CVCL_SU93	HAP1 KLF10 (-) 1	Cancer cell line	Male
CVCL_SU94	HAP1 KLF10 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00001631	PHASE2	COMPLETED	Study of Blood Flow in Heart Muscle
NCT00001894	PHASE2	COMPLETED	A Comparison of Two Treatments: Pacemaker and Percutaneous Transluminal Septal Ablation for Hypertrophic Cardiomyopathy
NCT00001960	PHASE2	COMPLETED	Studying the Effectiveness of Pacemaker Therapy in Children Who Have Thickened Heart Muscle
NCT00011076	PHASE2	COMPLETED	Pirfenidone to Treat Hypertrophic Cardiomyopathy
NCT00035386	PHASE2	COMPLETED	Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: A Pilot Study
NCT00430833	PHASE2	UNKNOWN	CHANCE - Candesartan in Hypertrophic Cardiomyopathy
NCT00500552	PHASE2	COMPLETED	Perhexiline Therapy in Patients With Hypertrophic Cardiomyopathy
NCT01150461	PHASE2	COMPLETED	Effect of Losartan in Patients With Nonobstructive Hypertrophic Cardiomyopathy
NCT01230918	PHASE2	TERMINATED	Study to Develop a Non-invasive Marker for Monitoring Myocardial Fibrosis
NCT01447654	PHASE2	COMPLETED	Inhibition of the Renin Angiotensin System With Losartan in Patients With Hypertrophic Cardiomyopathy
NCT01696370	PHASE2	UNKNOWN	Trimetazidine Therapy in Hypertrophic Cardiomyopathy
NCT01912534	PHASE2	COMPLETED	Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM
NCT02590809	PHASE2	COMPLETED	Hypertrophic Cardiomyopathy Symptom Release by BX1514M
NCT03496168	PHASE2	COMPLETED	Extension Study of Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Previously Enrolled in PIONEER
NCT03532802	PHASE2	COMPLETED	The Effect of Metoprolol in Patients With Hypertrophic Obstructive Cardiomyopathy.
NCT03832660	PHASE2	COMPLETED	Sacubitril/Valsartan vs Lifestyle in Hypertrophic Cardiomyopathy
NCT04219826	PHASE2	COMPLETED	Dose-finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CK-3773274 in Adults With Hypertrophic Cardiomyopathy
NCT04426578	PHASE2	UNKNOWN	Role of Perhexiline in Hypertrophic Cardiomyopathy