KLF11

Summary

KLF11 (KLF transcription factor 11, HGNC:11811) is a protein-coding gene on chromosome 2p25.1, encoding Krueppel-like factor 11 (O14901). Transcription factor.

The protein encoded by this gene is a zinc finger transcription factor that binds to SP1-like sequences in epsilon- and gamma-globin gene promoters. This binding inhibits cell growth and causes apoptosis. Defects in this gene are a cause of maturity-onset diabetes of the young type 7 (MODY7). Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 8462 — RefSeq curated summary.

At a glance

• Gene–disease (curated): maturity-onset diabetes of the young type 7 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 352 total
• Phenotypes (HPO): 30
• Transcription factor: yes — 31 downstream targets (CollecTRI)
• MANE Select transcript: NM_003597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11811
Approved symbol	KLF11
Name	KLF transcription factor 11
Location	2p25.1
Locus type	gene with protein product
Status	Approved
Aliases	Tieg3, MODY7, FKLF
Ensembl gene	ENSG00000172059
Ensembl biotype	protein_coding
OMIM	603301
Entrez	8462

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000305883, ENST00000401510, ENST00000440320, ENST00000448523, ENST00000535335, ENST00000540845, ENST00000921466

RefSeq mRNA: 3 — MANE Select: NM_003597 NM_001177716, NM_001177718, NM_003597

CCDS: CCDS1668, CCDS54333

Canonical transcript exons

ENST00000305883 — 4 exons

Exon	Start	End
ENSE00001171571	10047650	10048595
ENSE00001265488	10043550	10043758
ENSE00001337294	10052227	10054836
ENSE00003663314	10046150	10046419

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 98.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4009 / max 88.2077, expressed in 1701 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18804	8.9042	1695
18803	0.2598	106
18805	0.2073	96
18807	0.0192	5
18806	0.0103	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.47	gold quality
oocyte	CL:0000023	98.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.06	gold quality
upper leg skin	UBERON:0004262	92.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.90	gold quality
monocyte	CL:0000576	91.84	gold quality
mononuclear cell	CL:0000842	91.61	gold quality
saphenous vein	UBERON:0007318	91.36	gold quality
skin of hip	UBERON:0001554	91.35	gold quality
mucosa of stomach	UBERON:0001199	91.22	gold quality
leukocyte	CL:0000738	91.05	gold quality
amniotic fluid	UBERON:0000173	90.65	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.35	gold quality
omental fat pad	UBERON:0010414	90.29	gold quality
peritoneum	UBERON:0002358	90.26	gold quality
adipose tissue	UBERON:0001013	89.71	gold quality
body of pancreas	UBERON:0001150	89.68	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.41	gold quality
skin of abdomen	UBERON:0001416	89.13	gold quality
connective tissue	UBERON:0002384	89.12	gold quality
parietal pleura	UBERON:0002400	88.80	gold quality
testis	UBERON:0000473	88.68	gold quality
right lung	UBERON:0002167	88.59	gold quality
tibial artery	UBERON:0007610	88.26	gold quality
popliteal artery	UBERON:0002250	88.25	gold quality
adult organism	UBERON:0007023	88.24	gold quality
right testis	UBERON:0004534	88.14	gold quality
zone of skin	UBERON:0000014	88.02	gold quality
left testis	UBERON:0004533	88.02	gold quality
pancreas	UBERON:0001264	87.94	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

31 targets.

Target	Regulation
ADAM2
BCL2L1
CAT
CAV1	Repression
COL1A2	Unknown
DRD2	Repression
FGFR1
GRIN1
HBB
HBE1	Activation
HBG1	Activation
HBG2	Activation
HP
INS	Activation
KLF11
KRT9
MAOA
MAOB
ME3
MYC	Repression
PAEP
PDX1	Unknown
PLA2G4A	Repression
SMAD3	Activation
SMAD7	Repression
SP1	Repression
SUPT7L
TIE1	Activation
TNF
TPM1

JASPAR motifs

Motif	Name	Family
MA1512.1	KLF11	Three-zinc finger Kruppel-related
MA1512.2	KLF11	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:11443140

Upstream regulators (CollecTRI, top): KLF11, NR1H4, STAT3

miRNA regulators (miRDB)

107 targeting KLF11, 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-4668-3P	100.00	68.74	2635
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-338-5P	99.92	72.34	2951

Literature-anchored findings (GeneRIF, showing 40)

• TIEG2 is an activator of Monoamine oxidase B gene expression. (PMID:15024015)
• novel mechanism in TGF-beta-regulated gene expression: KLF11 potentiates Smad-signaling activity in normal epithelial cells through termination of the negative feedback loop imposed by Smad7. (PMID:15300592)
• in the presence of cholesterol, KLF11 acts as a dominant repressor of the caveolin-1 gene (PMID:15531587)
• KLF11 plays a role in the regulation of pancreatic beta cell physiology, and its variants may contribute to the development of diabetes. (PMID:15774581)
• These results suggest a central role for KLF11 in TGFbeta-induced c-myc repression and antiproliferation. (PMID:17114344)
• KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations. (PMID:17130512)
• results may help to increase the understanding of Tieg3-mediated transcriptional control and to characterize this TGF-beta-induced Sp1/Klf-like transcription factor (PMID:17252542)
• TIEG2 decreases the levels of the anti-apoptotic protein Bcl-X(L) and inhibits transcription driven by the Bcl-X(L) promoter. (PMID:17308981)
• Kruppel-like factor 11 inhibits human proinsulin promoter activity in pancreatic beta cells (PMID:17479246)
• KLF11 may interfere with glucose homeostasis in a Danish general population and that STAT3-mediated up-regulation of KLF11 transcription was impaired by the -1659G>C variant. (PMID:18505768)
• KLF11 is unlikely to play a major role in the etiology of T2 diabetes among this Native American population. (PMID:18593768)
• 19 polymorphisms, 6 of which are novel, were identified, but none of them showed association with type 2 diabetes. Functional analyses of these variants showed reduced effects on transcriptional activities of insulin, catalase1, & the Smad7 gene. (PMID:19122346)
• MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. (PMID:19843526)
• epigenetic inactivation and subsequent transcriptional repression of the KLF11 gene is quite frequent in MDS. (PMID:20002157)
• KLF11 is an integrator of progesterone receptor signaling and proliferation in uterine leiomyoma cells. (PMID:20124487)
• Kruppel-like factor 11 has a role in the regulation of prostaglandin E2 biosynthesis (PMID:20154088)
• KLF11, but not KLF15, was essential for UCP1 expression during brown adipocyte differentiation of muBM3.1. (PMID:20709022)
• an important role for KLF11 in the regulation of INS transcription via the novel c.-331 KLF site. (PMID:21592955)
• A PXVXL HP1-interacting domain identified at position 487-491 of KLF11 mediates the binding of HP1alpha and KLF11 in vitro and in cultured cells. (PMID:22318730)
• Here we report the characterization of two antagonistic, chromatin-mediated mechanisms by which KLF11 regulated the transcription of the dopamine D2 receptor. (PMID:22375010)
• KLF11 is an MAO A regulator and is produced in response to neuronal stress, which transcriptionally activates MAO A. (PMID:22628545)
• KLF11 has a role in fine-tuning insulin transcription in certain cellular situations rather than representing a major transcriptional activator or repressor of the insulin gene. (PMID:22801105)
• Data indicate that median methylation levels of BCAN, HOXD1, KCTD8, KLF11, NXPH1, POU4F1, SIM1, and TCF7L1 were >/=30% higher than in normal samples, representing potential biomarkers for tumor diagnosis. (PMID:22930747)
• Kruppel-like factor-11, a transcription factor involved in diabetes mellitus, suppresses endothelial cell activation via the nuclear factor-kappaB signaling pathway. (PMID:23042817)
• Data identify a novel pathogenic role for KLF11 in preventing de novo disease-associated fibrosis in endometriosis. (PMID:23555910)
• The A347S mutation disrupted KLF11-mediated increases in basal insulin levels and promoter activity and blunted glucose-stimulated insulin secretion. (PMID:23589285)
• Levels of KLF11 are significantly increased in the postmortem prefrontal cortex of subjects with alcohol dependence compared to controls. (PMID:23915421)
• KLF111 represses glycodelin-A levels and influences its role in the ovarian endometrium. (PMID:24060634)
• KLF11 is a critical transcription factor in the function of mesenchymal cells and, specifically, as a negative regulator of collagen secretion. (PMID:24069400)
• KLF11 regulates distinct gene networks. (PMID:24885560)
• KLF11 repressed most endometrial CYP enzymes (PMID:25076120)
• Results suggest a role for KLF11 in upregulating MAO-A in depressive disorder and chronic social stress, suggesting that inhibition of the pathways regulated by this transcription factor may aid in the therapeutics of neuropsychiatric illnesses (PMID:25502632)
• identified an evolutionarily conserved metabolic regulator, Kruppel-like factor 11 (KLF11), as a novel browning transcription factor in human adipocytes that is required for rosiglitazone-induced browning. (PMID:25504365)
• The data suggest a relationship between promoter DNA methylation and KLF11 gene expression in ovarian cancer tumorigenesis. (PMID:25931269)
• In endometrial-stromal fibroblasts, KLF11 recruited SIN3A/HDAC (histone deacetylase), resulting in COL1A1-promoter deacetylation and repression (PMID:26935598)
• Profibrotic gene expression was activated in a primary human peritoneal cell line in response to KLF11 short hairpin RNA and medroxyprogesterone acetate but not estradiol. (PMID:28938437)
• microRNA-30d mediated breast cancer invasion, migration, and epithelial-mesenchymal transition by targeting KLF11 and activating STAT3 pathway. (PMID:29923255)
• KLF11 has a critical role in regulating gastric cancer migration and invasion by increasing Twist1 expression (PMID:30509092)
• In human aortic smooth muscle cells, small interfering RNA-mediated knockdown of KLF11 increased tissue factor expression. (PMID:30602303)
• Specific variants of KLF11 (MODY7) with a dominant-negative effect underlie early childhood-onset type 1B diabetes with incomplete penetrance. This study documents a novel monogenic mutation associated with diabetes in children. (PMID:31124255)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	klf11b	ENSDARG00000013794
danio_rerio	klf11a	ENSDARG00000030844
mus_musculus	Klf11	ENSMUSG00000020653
rattus_norvegicus	Klf11	ENSRNOG00000054259

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), KLF10 (ENSG00000155090), KLF15 (ENSG00000163884), SP8 (ENSG00000164651), KLF13 (ENSG00000169926), SP7 (ENSG00000170374), KLF17 (ENSG00000171872), SP6 (ENSG00000189120), SP5 (ENSG00000204335), SP9 (ENSG00000217236), KLF14 (ENSG00000266265), KLF18 (ENSG00000283039)

Protein

Protein identifiers

Krueppel-like factor 11 — O14901 (reviewed: O14901)

Alternative names: Transforming growth factor-beta-inducible early growth response protein 2

All UniProt accessions (5): B5MCC4, C9JM94, E7EX78, O14901, Q53QU8

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor. Activates the epsilon- and gamma-globin gene promoters and, to a much lower degree, the beta-globin gene and represses promoters containing SP1-like binding inhibiting cell growth. Represses transcription of SMAD7 which enhances TGF-beta signaling. Induces apoptosis.

Subunit / interactions. Interacts with SIN3A.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. Higher expression in erythroid cells.

Disease relevance. Maturity-onset diabetes of the young 7 (MODY7) [MIM:610508] A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. The disease is caused by variants affecting the gene represented in this entry.

Induction. By TGFB1.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O14901-1	1	yes
O14901-2	2

RefSeq proteins (3): NP_001171187, NP_001171189, NP_003588* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (16 total): sequence variant 4, sequence conflict 4, zinc finger region 3, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14901-F1	49.73	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 (1): 124

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 276 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, chr2p25, TGCACTT_MIR519C_MIR519B_MIR519A, TTTGTAG_MIR520D, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_CELL_CYCLE_PHASE_TRANSITION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, CACCAGC_MIR138, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, DAUER_STAT3_TARGETS_UP, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), negative regulation of cell population proliferation (GO:0008285), positive regulation of apoptotic process (GO:0043065), cellular response to endothelin (GO:1990859), regulation of G1/S transition of mitotic cell cycle (GO:2000045), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (9): transcription cis-regulatory region binding (GO:0000976), 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 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 (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), focal adhesion (GO:0005925), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
negative regulation of DNA-templated transcription	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cellular response to peptide hormone stimulus	1
response to endothelin	1
G1/S transition of mitotic cell cycle	1
regulation of mitotic cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	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
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1016 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF11	SIN3A	Q96ST3	889
KLF11	BLK	P51451	823
KLF11	PAX4	O43316	803
KLF11	NEUROD1	Q13562	768
KLF11	HNF1A	P20823	739
KLF11	GCK	P35557	642
KLF11	PDX1	P52945	614
KLF11	ABCC8	Q09428	603
KLF11	INS	P01308	588
KLF11	HNF1B	P35680	587
KLF11	KCNJ11	Q14654	583
KLF11	APPL1	Q9UKG1	571
KLF11	PPARG	P37231	510
KLF11	RFX6	Q8HWS3	508
KLF11	GAPDH	P00354	500

IntAct

758 interactions, top by confidence:

A	B	Type	Score
TXNDC9	KLF11	psi-mi:“MI:0915”(physical association)	0.560
APPBP2	KLF11	psi-mi:“MI:0915”(physical association)	0.560
KLF11	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
KLF11	NFYC	psi-mi:“MI:0915”(physical association)	0.560
KLF11	ANXA8	psi-mi:“MI:0915”(physical association)	0.560
KLF11	AMBN	psi-mi:“MI:0915”(physical association)	0.560
KLF11	ANXA4	psi-mi:“MI:0915”(physical association)	0.560
KLF11	AQP8	psi-mi:“MI:0915”(physical association)	0.560
KLF11	ATP6V1B1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	BCAT1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	BCHE	psi-mi:“MI:0915”(physical association)	0.560
KLF11	PMF1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	KLF5	psi-mi:“MI:0915”(physical association)	0.560
KLF11	TEN1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	COX4I1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	COX7A1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	CRYBA2	psi-mi:“MI:0915”(physical association)	0.560
KLF11	DXO	psi-mi:“MI:0915”(physical association)	0.560
KLF11	DPYS	psi-mi:“MI:0915”(physical association)	0.560
KLF11	E4F1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	PHC2	psi-mi:“MI:0915”(physical association)	0.560
KLF11	FANCG	psi-mi:“MI:0915”(physical association)	0.560
KLF11	FYN	psi-mi:“MI:0915”(physical association)	0.560
GABPB1	KLF11	psi-mi:“MI:0915”(physical association)	0.560
KLF11	GABPB1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	GATA1	psi-mi:“MI:0915”(physical association)	0.560
KLF11	GPM6A	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (28): TXNDC9 (Two-hybrid), APPBP2 (Two-hybrid), SIN3A (Reconstituted Complex), HDAC1 (Reconstituted Complex), KLF11 (Two-hybrid), P4HB (Affinity Capture-MS), BOLA2 (Affinity Capture-MS), KLF11 (Affinity Capture-MS), MAPK3 (Affinity Capture-MS), KLF11 (Biochemical Activity), SIN3A (Affinity Capture-Western), KLF11 (Affinity Capture-MS), KLF11 (Affinity Capture-RNA), KLF11 (Proximity Label-MS), KLF11 (Affinity Capture-RNA)

ESM2 similar proteins: A0A1D5NS60, A0JN76, A1YFX5, A2T7G6, A6NJL1, D2HQI1, F1MJR8, O14901, P0CG00, P10754, P22227, P98182, Q0IJ29, Q1L8W0, Q3SWU4, Q5DW34, Q5EAC5, Q5EXX3, Q5RHB5, Q5SXI5, Q5T619, Q66H04, Q6NRM8, Q6NV66, Q6ZSB9, Q7M6U3, Q7TS63, Q7TSH3, Q7ZWZ4, Q801P1, Q86VK4, Q8BKX7, Q8BXX2, Q8NAM6, Q8NAP3, Q8NCP5, Q8R0A2, Q91VW9, Q96IT1, Q96N77

Diamond homologs: A5ABV9, O08876, O14901, O70494, O89090, O89091, P08047, P0CG40, P41696, Q01714, Q02446, Q02447, Q0VA40, Q13351, Q22678, Q3SY56, Q5XGT8, Q62445, Q64HY3, Q64HY5, Q6BEB4, Q6NW96, Q6P0J3, Q8BMJ8, Q8IXZ3, Q8K1S5, Q8TDD2, Q8VI67, Q90WR8, Q9ESX2, Q9JHX2, Q9TZ64, B5DE03, B7ZSG3, O62651, P19544, P22561, P49952, P49953, P50902

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
KLF11	“up-regulates quantity by expression”	HBG2	“transcriptional regulation”
KLF11	“up-regulates quantity by expression”	HBG1	“transcriptional regulation”
KLF11	“up-regulates quantity by expression”	HBE1	“transcriptional regulation”
KLF11	“up-regulates activity”	SIN3A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	208
Likely benign	74
Benign	34

Top pathogenic / likely-pathogenic (0)

SpliceAI

927 predictions. Top by Δscore:

Variant	Effect	Δscore
2:10043759:G:GG	donor_gain	1.0000
2:10046146:TTA:T	acceptor_loss	1.0000
2:10046147:TAGGT:T	acceptor_loss	1.0000
2:10046148:A:AG	acceptor_gain	1.0000
2:10046148:A:G	acceptor_loss	1.0000
2:10046149:G:GG	acceptor_gain	1.0000
2:10046149:G:T	acceptor_loss	1.0000
2:10046149:GGTT:G	acceptor_gain	1.0000
2:10046417:CTGG:C	donor_loss	1.0000
2:10046420:G:GG	donor_gain	1.0000
2:10046420:GTA:G	donor_loss	1.0000
2:10048592:ACAGG:A	donor_loss	1.0000
2:10048593:CAGGT:C	donor_loss	1.0000
2:10048594:AGGTA:A	donor_loss	1.0000
2:10048595:GGTA:G	donor_loss	1.0000
2:10048596:G:GA	donor_loss	1.0000
2:10052218:A:AG	acceptor_gain	1.0000
2:10052219:C:G	acceptor_gain	1.0000
2:10052223:ACAG:A	acceptor_gain	1.0000
2:10052223:ACAGG:A	acceptor_gain	1.0000
2:10052225:A:AG	acceptor_gain	1.0000
2:10052225:AG:A	acceptor_gain	1.0000
2:10052225:AGG:A	acceptor_gain	1.0000
2:10052226:G:GT	acceptor_gain	1.0000
2:10052226:GG:G	acceptor_gain	1.0000
2:10052226:GGG:G	acceptor_gain	1.0000
2:10052226:GGGGA:G	acceptor_gain	1.0000
2:10043754:GCGCA:G	donor_gain	0.9900
2:10043756:GCA:G	donor_gain	0.9900
2:10043816:G:GT	donor_gain	0.9900

AlphaMissense

3342 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:10048523:T:C	C396R	1.000
2:10048525:C:G	C396W	1.000
2:10048550:T:G	Y405D	1.000
2:10048569:T:C	L411P	1.000
2:10048577:C:G	H414D	1.000
2:10048579:T:A	H414Q	1.000
2:10048579:T:G	H414Q	1.000
2:10048581:T:C	L415P	1.000
2:10048583:C:A	R416S	1.000
2:10048589:C:G	H418D	1.000
2:10048591:C:A	H418Q	1.000
2:10048591:C:G	H418Q	1.000
2:10052271:T:C	F435L	1.000
2:10052272:T:C	F435S	1.000
2:10052273:T:A	F435L	1.000
2:10052273:T:G	F435L	1.000
2:10052298:C:G	H444D	1.000
2:10052334:T:C	C456R	1.000
2:10052355:T:C	F463L	1.000
2:10052356:T:C	F463S	1.000
2:10052357:C:A	F463L	1.000
2:10052357:C:G	F463L	1.000
2:10048523:T:A	C396S	0.999
2:10048524:G:A	C396Y	0.999
2:10048524:G:C	C396S	0.999
2:10048538:T:A	C401S	0.999
2:10048538:T:C	C401R	0.999
2:10048539:G:A	C401Y	0.999
2:10048539:G:C	C401S	0.999
2:10048540:C:G	C401W	0.999

dbSNP variants (sampled 300 via entrez): RS1000015589 (2:10045983 G>A), RS1000552546 (2:10044664 G>C,T), RS1000772563 (2:10046062 G>A,T), RS1000833672 (2:10043560 C>A,T), RS1000871285 (2:10049614 C>T), RS1001028882 (2:10045156 G>C), RS1001350285 (2:10047238 C>T), RS1001594733 (2:10051670 A>G), RS1001758091 (2:10047121 C>G,T), RS1001960367 (2:10051556 C>T), RS1002200787 (2:10042205 G>A,C), RS1002534030 (2:10044881 C>T), RS1002777718 (2:10047553 C>G,T), RS1003430284 (2:10048254 C>G,T), RS1003664389 (2:10052452 T>C)

Disease associations

OMIM: gene MIM:603301 | disease phenotypes: MIM:125853, MIM:610508, MIM:125850, MIM:606391

GenCC curated gene-disease

Disease	Classification	Inheritance
maturity-onset diabetes of the young type 7	Strong	Autosomal dominant
maturity-onset diabetes of the young	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
monogenic diabetes	Refuted	AD

Mondo (6): monogenic diabetes (MONDO:0015967), type 2 diabetes mellitus (MONDO:0005148), maturity-onset diabetes of the young type 7 (MONDO:0012513), diabetes mellitus (MONDO:0005015), hyperglycemia (MONDO:0002909), maturity-onset diabetes of the young (MONDO:0018911)

Orphanet (2): Rare genetic diabetes mellitus (Orphanet:183625), MODY (Orphanet:552)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000077	Abnormality of the kidney
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000119	Abnormality of the genitourinary system
HP:0000488	Retinopathy
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000956	Acanthosis nigricans
HP:0001511	Intrauterine growth retardation
HP:0001513	Obesity
HP:0001520	Large for gestational age
HP:0001738	Exocrine pancreatic insufficiency
HP:0001952	Glucose intolerance
HP:0001953	Diabetic ketoacidosis
HP:0001998	Neonatal hypoglycemia
HP:0002594	Pancreatic hypoplasia
HP:0003074	Hyperglycemia
HP:0003076	Glycosuria
HP:0004904	Maturity-onset diabetes of the young
HP:0004924	Abnormal oral glucose tolerance
HP:0005978	Type II diabetes mellitus
HP:0008255	Transient neonatal diabetes mellitus
HP:0012028	Hepatocellular adenoma
HP:0025502	Overweight
HP:0030057	Autoimmune antibody positivity
HP:0030794	Abnormal circulating C-peptide concentration
HP:0040214	Abnormal circulating insulin concentration
HP:0040216	Hypoinsulinemia
HP:0040217	Elevated hemoglobin A1c

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001942_5	Prostate cancer	3.000000e-08
GCST006940_140	Neurociticism	4.000000e-09
GCST006950_48	Feeling worry	1.000000e-08
GCST006979_908	Heel bone mineral density	8.000000e-14
GCST008163_418	Height	2.000000e-06
GCST009267_18	Dental caries (decayed, missing and filled teeth)	4.000000e-06
GCST009268_1	Dental caries (decayed, missing and filled tooth surfaces)	5.000000e-06
GCST90002397_763	Mean spheric corpuscular volume	3.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0009589	worry measurement
EFO:0009270	heel bone mineral density

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D003920	Diabetes Mellitus	C18.452.394.750; C19.246
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
D006943	Hyperglycemia	C18.452.394.952
C562772	Mason-Type Diabetes (supp.)
C566466	Maturity-Onset Diabetes of the Young, Type 7 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression, increases expression	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
perfluorooctane sulfonic acid	increases expression	2
(+)-JQ1 compound	decreases expression	2
Zoledronic Acid	increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Cadmium Chloride	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
geraniol	increases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
arsenite	affects binding, decreases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
propionic acid	decreases expression	1
nickel sulfate	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3N7	SEES3-1V human KLF11, clone1	Embryonic stem cell	Male
CVCL_A3N8	SEES3-1V human KLF11, clone2	Embryonic stem cell	Male
CVCL_A3N9	SEES3-1V human KLF11, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes
NCT00240422	PHASE4	COMPLETED	Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus