KLF12

Summary

KLF12 (KLF transcription factor 12, HGNC:6346) is a protein-coding gene on chromosome 13q22.1, encoding Krueppel-like factor 12 (Q9Y4X4). Confers strong transcriptional repression to the AP-2-alpha gene.

Activator protein-2 alpha (AP-2 alpha) is a developmentally-regulated transcription factor and important regulator of gene expression during vertebrate development and carcinogenesis. The protein encoded by this gene is a member of the Kruppel-like zinc finger protein family and can repress expression of the AP-2 alpha gene by binding to a specific site in the AP-2 alpha gene promoter. Repression by the encoded protein requires binding with a corepressor, CtBP1. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 11278 — RefSeq curated summary.

At a glance

• GWAS associations: 133
• Clinical variants (ClinVar): 62 total — 1 pathogenic
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_001400136

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6346
Approved symbol	KLF12
Name	KLF transcription factor 12
Location	13q22.1
Locus type	gene with protein product
Status	Approved
Aliases	AP-2rep, HSPC122, AP2REP
Ensembl gene	ENSG00000118922
Ensembl biotype	protein_coding
OMIM	607531
Entrez	11278

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000377669, ENST00000472022, ENST00000703967, ENST00000885983, ENST00000885984, ENST00000885985, ENST00000885986, ENST00000885987

RefSeq mRNA: 12 — MANE Select: NM_001400136 NM_001400136, NM_001400139, NM_001400141, NM_001400146, NM_001400147, NM_001400148, NM_001400149, NM_001400150, NM_001400151, NM_001400152, NM_001400153, NM_007249

CCDS: CCDS9449

Canonical transcript exons

ENST00000703967 — 8 exons

Exon	Start	End
ENSE00000802369	73715368	73715525
ENSE00000802370	73764938	73765000
ENSE00001380693	73813152	73813287
ENSE00001474797	73686089	73695671
ENSE00001474798	73994990	73995053
ENSE00003476919	73845827	73846373
ENSE00003752135	73943981	73944070
ENSE00003990465	74133972	74134404

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 92.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1849 / max 203.8795, expressed in 1567 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137609	3.6754	1287
137602	3.5279	955
137607	1.9166	980
137608	1.6731	881
137606	1.4914	751
137601	0.8764	254
137605	0.6482	292
137604	0.4730	169
137610	0.4120	216
137600	0.3391	139

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	92.65	gold quality
superficial temporal artery	UBERON:0001614	91.62	gold quality
pigmented layer of retina	UBERON:0001782	90.70	gold quality
caput epididymis	UBERON:0004358	89.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.77	gold quality
biceps brachii	UBERON:0001507	89.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.45	gold quality
tendon of biceps brachii	UBERON:0008188	88.98	gold quality
epithelium of nasopharynx	UBERON:0001951	88.45	gold quality
synovial joint	UBERON:0002217	88.16	gold quality
lateral nuclear group of thalamus	UBERON:0002736	88.05	gold quality
medial globus pallidus	UBERON:0002477	87.95	gold quality
ganglionic eminence	UBERON:0004023	87.55	gold quality
saphenous vein	UBERON:0007318	87.26	gold quality
ventricular zone	UBERON:0003053	87.06	gold quality
tendon	UBERON:0000043	87.03	gold quality
globus pallidus	UBERON:0001875	86.57	gold quality
cauda epididymis	UBERON:0004360	86.54	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.18	gold quality
postcentral gyrus	UBERON:0002581	85.86	gold quality
parietal pleura	UBERON:0002400	85.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.60	gold quality
renal medulla	UBERON:0000362	85.35	gold quality
parietal lobe	UBERON:0001872	85.21	gold quality
middle temporal gyrus	UBERON:0002771	85.13	gold quality
calcaneal tendon	UBERON:0003701	84.99	gold quality
tibia	UBERON:0000979	84.88	gold quality
pleura	UBERON:0000977	84.76	gold quality
oocyte	CL:0000023	84.39	gold quality
urethra	UBERON:0000057	84.28	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	57.34
E-ANND-3	yes	6.35
E-MTAB-9067	yes	3.79
E-MTAB-7606	no	1130.90
E-CURD-11	no	33.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
ABCC3
ACHE
IGFBP1
PRL	Repression
SCNN1A
SLC14A2	Activation
SLC47A1	Unknown
TBXT	Repression
TFAP2A	Repression
TNFRSF11A
WNT11	Repression

JASPAR motifs

Motif	Name	Family
MA0742.2	KLF12	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:16266294

Upstream regulators (CollecTRI, top): TFAP2A, TP63

miRNA regulators (miRDB)

533 targeting KLF12, 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-6867-5P	100.00	82.21	3464
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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833

Literature-anchored findings (GeneRIF, showing 30)

• KLF12 as a new susceptibility gene for rheumatoid arthritis. (PMID:18668548)
• Overexpression of Kruppel-like factor 12 is associated with gastric cancer progression. (PMID:19588488)
• In a large UK cohort of patients with rheumatoid arthritis, results have failed to add to the evidence for association at the KLF12 locus reported to be associated with rheumatoid arthritis in independent Spanish cohorts. (PMID:19907058)
• no association of genetic polymorphism with rheumatoid arthritis in Spanish and Dutch cohorts (PMID:21658422)
• The KLF12 rs1324913 A allele homozygous genotype is a possible predictor of Rheumatoid Arthritis. (PMID:22150086)
• overexpression of KLF12 in endometrial stromal cells significantly repressed the expression and secretion of decidualization biomarker genes and their products decidual prolactin and insulin-like growth factor binding protein-1 (PMID:23458459)
• Elevated KLF12 expression was accompanied by decreased FOXO1 expression in the endometria of patients with repeated implantation failure. (PMID:26223982)
• Data indicate Kruppel-like factor 12 protein (KLF12) as a metastasis-suppressor gene whose loss of function is associated with anoikis resistance through control of the cell cycle. (PMID:26455320)
• SLC29A1 rs760370 and KLF12 rs9543524 SNPs are associated with treatment induced thrombocytopenia in chronic hepatitis C patients treated with PEGIFN2b/ribavirin/combination. (PMID:26750805)
• our results supported that miR-205 was a miR specific to basal-like breast carcinoma (BLBC). which functioned as tumor suppressor gene through directly targeting and negatively regulating proto-oncogene KLF12. miR-205 dysregulation was involved in invasion and apoptosis. miR-205 and KLF12 provided a potential diagnosis biomarker and therapeutic approach for BLBC. (PMID:27278159)
• KLF12 promotes tumor growth by directly activating early growth response protein 1 (EGR1). The levels of KLF12 and EGR1 correlate synergistically with a poor prognosis. These results indicate that KLF12 likely plays an important role in CRC and could serve as a potential prognostic marker and therapeutic target. (PMID:27442508)
• Overexpression of KLF12 is associated with gastric cancer. (PMID:27468717)
• the overexpression of miR-141 augments anoikis resistance in ovarian cancer cells by targeting and repressing the expression of KLF12, which, in turn, competes for binding sites in the survivin promoter with Sp1. The subsequent increase in survivin then protects ovarian cancer cells against anoikis by blocking the intrinsic apoptotic activity. (PMID:28095864)
• Data show Kruppel-like factor 12 (KLF12) impairs endometrial decidualization by transcriptionally repressing Nur77 protein, and Nur77 overexpression reverses the poor decidual response of endometrial stromal cells (hESCs) in recurrent implantation failure (RIF) patients. (PMID:28359310)
• Results confirmed that KLF12 was highly expressed in nasopharyngeal carcinoma (NPC) tissues, and over-expressed KLF12 promoted NPC cell proliferation, while silencing KLF12 suppressed it. Furthermore, KLF12 was found to be a direct target for miR-1207 at its 3’-UTR mRNA. (PMID:30243935)
• DANCR also strongly suppressed hepatocellular carcinoma tumor growth in vivo via targeting miR-216a-5p and KLF12. (PMID:30430564)
• Results suggest that miR-137 reduces stemness features of pancreatic cancer cells by Targeting KLF12-associated Wnt/beta-catenin pathways. (PMID:30866999)
• miR-200a-3p plays tumor suppressor roles in gastric cancer cells by targeting KLF12 (PMID:31500453)
• Exosomal miR-141 promotes tumor angiogenesis via KLF12 in small cell lung cancer. (PMID:32958011)
• Circ_0005273 induces the aggravation of pancreatic cancer by targeting KLF12. (PMID:33275224)
• Kruppel-like factor 12 suppresses bladder cancer growth through transcriptionally inhibition of enolase 2. (PMID:33279628)
• Knockdown of circ_0075503 suppresses cell migration and invasion by regulating miR-15a-5p and KLF12 in endometriosis. (PMID:34117589)
• Circ-RNF111 aggravates the malignancy of gastric cancer through miR-876-3p-dependent regulation of KLF12. (PMID:34461926)
• Potentiated lung adenocarcinoma (LUAD) cell growth, migration and invasion by lncRNA DARS-AS1 via miR-188-5p/ KLF12 axis. (PMID:34644678)
• MicroRNA-650 suppresses KLF12 expression to regulate growth and metastasis of human ovarian cancer cells. (PMID:36272152)
• KLF12 promotes the proliferation of breast cancer cells by reducing the transcription of p21 in a p53-dependent and p53-independent manner. (PMID:37156774)
• MiR-17-5p promoter methylation regulated by DNA methyltransferase 3 beta (DNMT3B) expedites endometriosis via the Kruppel-like factor 12 (KLF12)/Wnt/beta-catenin axis. (PMID:37290172)
• Kruppel-like factor 12 regulates aging ovarian granulosa cell apoptosis by repressing SPHK1 transcription and sphingosine-1-phosphate (S1P) production. (PMID:37543362)
• KLF12 transcriptionally regulates PD-L1 expression in non-small cell lung cancer. (PMID:37606530)
• Circ_0084188 promotes colorectal cancer progression by sponging miR-654-3p and regulating kruppel-like factor 12. (PMID:37698263)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	klf12a	ENSDARG00000015312
danio_rerio	klf12b	ENSDARG00000032197
mus_musculus	Klf12	ENSMUSG00000072294
rattus_norvegicus	Klf12	ENSRNOG00000009145
drosophila_melanogaster	luna	FBGN0040765

Paralogs (22): KLF6 (ENSG00000067082), KLF8 (ENSG00000102349), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), 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 12 — Q9Y4X4 (reviewed: Q9Y4X4)

Alternative names: Transcriptional repressor AP-2rep

All UniProt accessions (1): Q9Y4X4

UniProt curated annotations — full annotation on UniProt →

Function. Confers strong transcriptional repression to the AP-2-alpha gene. Binds to a regulatory element (A32) in the AP-2-alpha gene promoter.

Subcellular location. Nucleus.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF12, the motif is inactive.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y4X4-1	1	yes
Q9Y4X4-2	2
Q9Y4X4-3	3

RefSeq proteins (12): NP_001387065, NP_001387068, NP_001387070, NP_001387075, NP_001387076, NP_001387077, NP_001387078, NP_001387079, NP_001387080, NP_001387081, NP_001387082, NP_009180 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (18 total): compositionally biased region 4, zinc finger region 3, splice variant 3, region of interest 3, modified residue 2, chain 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4X4-F1	51.57	0.06

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): 202, 313

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 373 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, RNGTGGGC_UNKNOWN, AAGCAAT_MIR137, FREAC2_01, TAATAAT_MIR126, GGTGTGT_MIR329, HNF3ALPHA_Q6, NKX25_02, TGCACTT_MIR519C_MIR519B_MIR519A, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, TGACCTY_ERR1_Q2, ATGCAGT_MIR217, FOXO4_01

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

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), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytosol (GO:0005829), 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
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
nucleic acid binding	1
transcription regulator activity	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
binding	1
cation binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF12	TFAP2A	P05549	780
KLF12	CHP1	Q99653	668
KLF12	KIAA1143	Q96AT1	617
KLF12	ETS1	P14921	552
KLF12	DNASE1	P24855	547
KLF12	MAGEB10	Q96LZ2	474
KLF12	FOXA2	Q9Y261	455
KLF12	SAMSN1	Q9NSI8	450
KLF12	TFAP2C	Q92754	432
KLF12	DNMT3B	Q9UBC3	422
KLF12	HMBOX1	Q6NT76	417
KLF12	KLF8	O95600	406
KLF12	ZNF750	Q32MQ0	396
KLF12	DAPK1	P53355	392
KLF12	FANCF	Q9NPI8	390

IntAct

63 interactions, top by confidence:

A	B	Type	Score
KLF12	CTBP1	psi-mi:“MI:0915”(physical association)	0.760
CTBP1	KLF12	psi-mi:“MI:0915”(physical association)	0.760
EHMT2	KLF12	psi-mi:“MI:0915”(physical association)	0.740
FHL2	KLF12	psi-mi:“MI:0915”(physical association)	0.670
KLF12	THAP1	psi-mi:“MI:0915”(physical association)	0.560
THAP1	KLF12	psi-mi:“MI:0915”(physical association)	0.560
FHL3	KLF12	psi-mi:“MI:0915”(physical association)	0.560
KLF12		psi-mi:“MI:0915”(physical association)	0.560
KLF12	PMP22	psi-mi:“MI:0915”(physical association)	0.560
PPIB	KLF12	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	KLF12	psi-mi:“MI:0915”(physical association)	0.560
KLF12	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
KAT5	KLF12	psi-mi:“MI:0915”(physical association)	0.560
LMO3	KLF12	psi-mi:“MI:0915”(physical association)	0.560
HTT	KLF12	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (227): KLF12 (Two-hybrid), THAP1 (Two-hybrid), KLF12 (Two-hybrid), KLF12 (Reconstituted Complex), KLF12 (Proximity Label-MS), KLF12 (Reconstituted Complex), KLF12 (Affinity Capture-MS), KLF12 (Affinity Capture-RNA), CTBP1 (Two-hybrid), KLF12 (Affinity Capture-RNA), KLF12 (Two-hybrid), FHL3 (Two-hybrid), EHMT2 (Two-hybrid), KLF12 (Positive Genetic), KLF12 (Affinity Capture-MS)

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: A0A0U1RQI7, C7EMF5, O35738, O35819, Q19A41, Q5JT82, Q60843, Q8CFA7, Q9ET58, Q9TZ64, Q9VZN4, Q9Y4X4, O08584, O08876, O14901, O43474, O62259, O70494, O75840, O89090, O89091, O95600, P08047, P0CG40, P46099, P57682, P58334, Q01714, Q02446, Q02447, Q0VA40, Q13118, Q13351, Q13887, Q14V87, Q19A40, Q22678, Q24266, Q3SY56, Q5XGT8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	51
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
441169	t(9;13)(q31.2;q22.1)	Pathogenic

SpliceAI

3291 predictions. Top by Δscore:

Variant	Effect	Δscore
13:73715521:TTGAA:T	acceptor_gain	1.0000
13:73715526:C:CC	acceptor_gain	1.0000
13:73764576:A:C	donor_gain	1.0000
13:73764930:ATACT:A	donor_loss	1.0000
13:73764931:TACT:T	donor_loss	1.0000
13:73764932:ACT:A	donor_loss	1.0000
13:73764933:CT:C	donor_loss	1.0000
13:73764934:TCA:T	donor_loss	1.0000
13:73764935:CACCA:C	donor_loss	1.0000
13:73764937:C:G	donor_loss	1.0000
13:73764999:CC:C	acceptor_gain	1.0000
13:73764999:CCCTG:C	acceptor_loss	1.0000
13:73765000:CC:C	acceptor_gain	1.0000
13:73765000:CCTG:C	acceptor_loss	1.0000
13:73765001:C:CA	acceptor_loss	1.0000
13:73765001:C:CC	acceptor_gain	1.0000
13:73765002:T:G	acceptor_loss	1.0000
13:73813150:A:AC	donor_gain	1.0000
13:73813151:C:CC	donor_gain	1.0000
13:73813151:CT:C	donor_gain	1.0000
13:73813585:AGCT:A	donor_gain	1.0000
13:73846372:GA:G	acceptor_gain	1.0000
13:73846374:C:CC	acceptor_gain	1.0000
13:73846376:G:C	acceptor_gain	1.0000
13:73932282:T:TA	donor_gain	1.0000
13:73943979:ACC:A	donor_gain	1.0000
13:73943980:CCC:C	donor_gain	1.0000
13:73944069:TT:T	acceptor_gain	1.0000
13:73695465:CG:C	donor_gain	0.9900
13:73715522:TGAA:T	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004384 (13:74246994 A>G), RS1000013005 (13:74100142 G>C,T), RS1000019342 (13:74267535 T>C), RS1000020181 (13:73713012 A>G,T), RS1000032488 (13:74069764 G>C), RS1000040952 (13:74004005 G>A), RS1000044291 (13:74083631 C>A,G), RS1000049954 (13:74042816 A>G), RS1000051391 (13:73927640 G>A,C), RS1000051580 (13:73847177 A>C,G), RS1000053998 (13:73888136 G>A,C), RS1000055903 (13:74287858 T>C), RS1000056069 (13:73918850 T>C,G), RS1000057331 (13:74212685 A>G), RS1000063149 (13:74173721 G>C,T)

Disease associations

OMIM: gene MIM:607531 | disease phenotypes: MIM:109730

GenCC curated gene-disease

Mondo (1): aortic valve disease 1 (MONDO:0024523)

Orphanet (0):

HPO phenotypes

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

GWAS associations

133 associations (top):

Study	Trait	p-value
GCST000574_1	Pancreatic cancer	3.000000e-11
GCST000872_4	QRS duration	1.000000e-08
GCST001414_6	Phospholipid levels (plasma)	1.000000e-08
GCST002104_9	Bronchopulmonary dysplasia	3.000000e-06
GCST002500_72	QT interval	2.000000e-08
GCST002541_95	Menarche (age at onset)	3.000000e-10
GCST002553_5	Pancreatic cancer	4.000000e-14
GCST002579_28	Heschl’s gyrus morphology	3.000000e-06
GCST002594_32	Neurofibrillary tangles	8.000000e-06
GCST002726_18	Glucose homeostasis traits	5.000000e-07
GCST002806_13	Type 2 diabetes	2.000000e-07
GCST002991_8	Pancreatic cancer	2.000000e-10
GCST003084_5	Glucocorticoid-induced osteonecrosis	4.000000e-06
GCST003524_1	Endometrial cancer	5.000000e-11
GCST003525_7	Endometrial endometrioid carcinoma	6.000000e-10
GCST003564_1	Waist-to-hip ratio adjusted for body mass index	3.000000e-06
GCST003598_13	QRS duration	4.000000e-10
GCST003598_40	QRS duration	5.000000e-08
GCST003842_22	Breast cancer (estrogen-receptor negative)	3.000000e-07
GCST003844_2	QRS duration	6.000000e-11
GCST003845_23	Breast cancer	5.000000e-10
GCST003845_24	Breast cancer	4.000000e-08
GCST003992_22	Photic sneeze reflex	3.000000e-08
GCST004412_13	Craniofacial microsomia	1.000000e-11
GCST004600_13	Eosinophil percentage of white cells	6.000000e-09
GCST004627_148	Lymphocyte count	7.000000e-25
GCST004632_38	Lymphocyte percentage of white cells	4.000000e-16
GCST004867_22	Systemic lupus erythematosus	2.000000e-06
GCST005036_6	Lean body mass	7.000000e-06
GCST005434_12	Pancreatic cancer	1.000000e-22

EFO canonical traits (21, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004703	age at menarche
EFO:0006797	neurofibrillary tangles measurement
EFO:0004471	insulin sensitivity measurement
EFO:1001514	endometrial endometrioid carcinoma
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0005054	QRS complex
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004995	lean body mass
EFO:0009270	heel bone mineral density
EFO:0008398	T wave morphology measurement
EFO:0004530	triglyceride measurement
EFO:0004327	electrocardiography
EFO:0004531	urate measurement
EFO:0004842	eosinophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	8
Benzo(a)pyrene	decreases expression, decreases methylation	3
arsenite	affects binding, decreases reaction, increases methylation	2
sodium arsenite	decreases expression, increases abundance	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Estradiol	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
aminomethylphosphonic acid (AMPA)	increases expression	1
geldanamycin	increases expression	1
beauvericin	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
versicolorin A	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
enniatins	affects cotreatment, decreases expression	1
rofecoxib	affects expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
ON 01910	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Vorinostat	decreases 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_A3P0	SEES3-1V human KLF12, clone1	Embryonic stem cell	Male
CVCL_A3P1	SEES3-1V human KLF12, clone2	Embryonic stem cell	Male
CVCL_A3P2	SEES3-1V human KLF12, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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