KLF8

Summary

KLF8 (KLF transcription factor 8, HGNC:6351) is a protein-coding gene on chromosome Xp11.21, encoding Krueppel-like factor 8 (O95600). Transcriptional repressor and activator.

This gene encodes a protein which is a member of the Sp/KLF family of transcription factors. Members of this family contain a C-terminal DNA-binding domain with three Kruppel-like zinc fingers. The encoded protein is thought to play an important role in the regulation of epithelial to mesenchymal transition, a process which occurs normally during development but also during metastasis. A pseudogene has been identified on chromosome 16. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 11279 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 108 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Transcription factor: yes — 23 downstream targets (CollecTRI)
• MANE Select transcript: NM_007250

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6351
Approved symbol	KLF8
Name	KLF transcription factor 8
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	BKLF3, ZNF741, DXS741
Ensembl gene	ENSG00000102349
Ensembl biotype	protein_coding
OMIM	300286
Entrez	11279

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000358094, ENST00000374928, ENST00000462627, ENST00000468660, ENST00000476898, ENST00000640927, ENST00000960354

RefSeq mRNA: 7 — MANE Select: NM_007250 NM_001159296, NM_001324099, NM_001324100, NM_001324102, NM_001324104, NM_001324105, NM_007250

CCDS: CCDS14373, CCDS55428, CCDS87749

Canonical transcript exons

ENST00000468660 — 6 exons

Exon	Start	End
ENSE00000671836	56265180	56265744
ENSE00001862404	56232356	56233341
ENSE00001897460	56284313	56291531
ENSE00003535168	56250231	56250304
ENSE00003590021	56269378	56269489
ENSE00003627905	56270182	56270321

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 89.16.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4810 / max 68.9155, expressed in 867 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196483	1.4187	580
196482	0.9808	523
196481	0.5024	323
196485	0.3382	147
196484	0.1380	60
196486	0.1029	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	89.16	gold quality
esophagus mucosa	UBERON:0002469	88.64	gold quality
lower esophagus mucosa	UBERON:0035834	88.43	gold quality
skin of abdomen	UBERON:0001416	87.96	gold quality
oral cavity	UBERON:0000167	87.16	gold quality
skin of leg	UBERON:0001511	86.98	gold quality
vagina	UBERON:0000996	86.21	gold quality
zone of skin	UBERON:0000014	86.10	gold quality
upper leg skin	UBERON:0004262	85.57	gold quality
cortical plate	UBERON:0005343	84.78	gold quality
epithelium of esophagus	UBERON:0001976	84.69	gold quality
popliteal artery	UBERON:0002250	84.65	gold quality
tibial artery	UBERON:0007610	84.64	gold quality
esophagus	UBERON:0001043	84.50	gold quality
skin of hip	UBERON:0001554	84.49	gold quality
parietal pleura	UBERON:0002400	84.34	gold quality
gingival epithelium	UBERON:0001949	83.43	gold quality
subcutaneous adipose tissue	UBERON:0002190	83.33	gold quality
right coronary artery	UBERON:0001625	82.72	gold quality
left coronary artery	UBERON:0001626	82.66	gold quality
adipose tissue	UBERON:0001013	82.53	gold quality
squamous epithelium	UBERON:0006914	82.38	gold quality
omental fat pad	UBERON:0010414	82.30	gold quality
peritoneum	UBERON:0002358	82.26	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.26	gold quality
aorta	UBERON:0000947	82.12	gold quality
ectocervix	UBERON:0012249	81.93	gold quality
connective tissue	UBERON:0002384	81.67	gold quality
buccal mucosa cell	CL:0002336	81.66	silver quality
gingiva	UBERON:0001828	81.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.04

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

23 targets.

Target	Regulation
ABCB1
AXIN1
BCL2
CALCA
CCND1	Unknown
CD44
CDH1	Activation
CDH17
CDH2	Repression
EPSTI1	Activation
FN1	Repression
HBB	Repression
HBG1
MMP14	Activation
MMP9	Activation
NUMB
PIK3C3
PIK3R1
PTK2
SLC22A3	Unknown
TIAM1
TNFRSF11A
VIM	Repression

JASPAR motifs

Motif	Name	Family
MA2681.1	KLF8	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:10756197

Upstream regulators (CollecTRI, top): KLF1, KLF3, SP1

miRNA regulators (miRDB)

252 targeting KLF8, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-8068	99.98	73.85	2376

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The gene KLF8 is abnormally expressed in a female patient with X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation. (PMID:11836360)
• In co-transfection assays in K562 cells, it was demonstrated that KLF2, 5 and 13 positively regulate, and KLF8 negatively regulates, the gamma-globin gene through the CACCC promoter element. (PMID:16023392)
• Over expression of KLF8 is associated with cancer (PMID:16832343)
• Functional studies using RNA interference revealed that the silencing of Sp1 and KLF8 resulted in elevated level of gamma globin expression in K562 cells. (PMID:17224162)
• Overexpression of Kruppel-like factor 8 is associated with epithelial to mesenchymal transition and epithelial cell invasion leading to breast cancer (PMID:17671186)
• FAK induces KLF8 expression in human ovarian cancer cells by activating the PI3K-Akt signaling pathway, leading to the activation of KLF8 promoter by Sp1 (PMID:18353772)
• KLF8 is possibly involved in regulating cell growth, invasion, apoptosis, and proliferation of renal carcinoma cancer; blocking this protein may be a therapeutic strategy for this cancer. (PMID:20182889)
• KLF8 promotes hepatocellular carcinoma cell proliferation and invasion, inhibits apoptosis, and induces the epithelial-to-mesenchymal transition (PMID:20728449)
• Immunohistochemical staining strongly correlated the co-expression of KLF8 and MMP9 with the patient tumor invasion, metastasis and poor survival (PMID:21151179)
• PARP-1 as a novel KLF8-binding and -regulating protein and provided new insights into the mechanisms underlying the regulation of KLF8 nuclear localization, stability, and functions. (PMID:21518760)
• Kruppel-like factor 8 (KLF8) is expressed in gliomas of different WHO grades and is essential for tumor cell proliferation. (PMID:22276196)
• Knockdown of beta-catenin by shRNA rescues the enhanced HepG2 and Hep3B cells proliferation ability induced by overexpression of KLF8 (PMID:22761862)
• KLF8 is necessary for cell survival and invasion in gastric cancer cells. (PMID:22766838)
• With pull down assay and co-immunoprecipitation assay, the study demonstrated that KLF8 bound directly to AR, and KLF8 enhanced AR target gene transcription in human prostate cancer cells. (PMID:23023312)
• a novel role and mechanism for KLF8 in the regulation of DNA repair and therapeutic resistance in breast cancer cells. (PMID:23105099)
• KLF8 overexpression is an important factor in human ovarian carcinoma pathogenesis. (PMID:23222713)
• Data show that TGF-beta1 regulates E-cadherin and vimentin expression through KLF8 pathway. (PMID:23504025)
• Hypoxia-reoxygenation reduces the expression and nuclear localization of KLF8 to inhibit the trophoblast invasion by downregulating MMP-9 levels. (PMID:23703536)
• KLF8 and FAK cooperatively enrich the active MMP14 on the cell surface required for the metastatic progression of breast cancer. (PMID:23812425)
• KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis (PMID:23885141)
• High KLF8 methylation was associated with biochemical recurrence in prostate cancer. (PMID:23918943)
• A novel KLF8 to EPSTI1 to VCP to NF-kappaB signaling mechanism potentially critical for breast cancer invasion and metastasis. (PMID:24096480)
• Positive nuclear KLF8 might be correlated with lower survival in gastric adenocarcinoma patients and might be an oncogene property in gastric adenocarcinoma carcinogenesis. (PMID:24461703)
• KLF8 knockdown suppresses proliferation and invasion in human osteosarcoma cells. (PMID:24604387)
• KLF8 is involved in hypoxia-induced multidrug resistance through inhibiting apoptosis and increasing the drug release rate by directly regulating MDR1 transcription. (PMID:25040744)
• KLF8 is a novel epithelial to mesenchymal transition regulating transcription factor that involved in the progression of gastric cancer. (PMID:25333643)
• In this review, we focus on the functions, roles, and regulatory networks of these five KLFs in HCC, summarize key pathways, and propose areas for further investigation (PMID:25652467)
• KLF8 and miR141/EGFR have roles in signaling pathway potentially crucial for breast cancer malignancy (PMID:26025929)
• KLF8 suppression induced cell differentiation and inhibited tumorigenesis in colorectal cancer (PMID:26133391)
• MiR-135a inhibits migration and invasion and regulates epithelial-mesenchymal transition-related marker genes by targeting KLF8 in lung cancer cells. (PMID:26235874)
• KLF8-induced FHL2 activation is a novel and critical signaling mechanism underlying human colorectal cancer invasion and metastasis. (PMID:26320172)
• High KLF8 expression is associated with breast cancer cell invasion, transendothelial migration and metastasis. (PMID:26993780)
• Overexpression of KLF8 may contribute to the progression of pancreatic cancer, and downregulation of KLF8 expression by lentivirus-delivered shRNA is a novel therapeutic approach for PC. (PMID:26995652)
• expression of miR-1236-3p was lower in lung adenocarcinoma tissues than that in adjacent normal tissue; in A549 cell line, miR-1236-3p decreased ability of cell invasion and migration; furthermore, KLF8 is targeted by miR-1236-3p, and expression of miR-1236-3p is negatively correlated with KLF8; additionally, miR-1236-3p suppressed the expression of KLF8 and EMT (epithelial mesenchymal transition)-related genes (PMID:28842254)
• High KLF8 expression is associated with Non-Small Cell Lung Cancer. (PMID:28986741)
• KLF8-overexpressing hepatocellular carcinoma cells had a higher potential for inducing angiogenesis. The up-regulation of KLF8 increased VEGFA protein levels and induced VEGFA promoter activity by binding to the CACCC region of the VEGFA promoter. (PMID:30479372)
• This study has unraveled a novel mechanism of ELF3-AS1-mediated oncogenesis in bladder cancer by reinforcement of ELF3-AS1/KLF8 signaling with potential implications for therapeutic intervention. (PMID:30528231)
• KLF8 is associated with poor prognosis and regulates glycolysis by targeting GLUT4 in gastric cancer. (PMID:31124603)
• Upregulated miRNA-1236-3p in osteosarcoma inhibits cell proliferation and induces apoptosis via targeting KLF8. (PMID:31364106)
• KLF8 promotes cancer stem cell-like phenotypes in osteosarcoma through miR-429-SOX2 signaling. (PMID:32122144)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	klf8	ENSDARG00000060661
mus_musculus	Klf8	ENSMUSG00000041649
rattus_norvegicus		ENSRNOG00000075589
drosophila_melanogaster	luna	FBGN0040765

Paralogs (22): KLF6 (ENSG00000067082), KLF5 (ENSG00000102554), KLF1 (ENSG00000105610), KLF3 (ENSG00000109787), KLF7 (ENSG00000118263), KLF12 (ENSG00000118922), KLF9 (ENSG00000119138), KLF2 (ENSG00000127528), KLF16 (ENSG00000129911), KLF4 (ENSG00000136826), KLF10 (ENSG00000155090), KLF15 (ENSG00000163884), SP8 (ENSG00000164651), KLF13 (ENSG00000169926), SP7 (ENSG00000170374), KLF17 (ENSG00000171872), KLF11 (ENSG00000172059), SP6 (ENSG00000189120), SP5 (ENSG00000204335), SP9 (ENSG00000217236), KLF14 (ENSG00000266265), KLF18 (ENSG00000283039)

Protein

Protein identifiers

Krueppel-like factor 8 — O95600 (reviewed: O95600)

Alternative names: Basic krueppel-like factor 3, Zinc finger protein 741

All UniProt accessions (2): O95600, Q05BZ3

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor and activator. Binds to CACCC-boxes promoter elements. Also binds the GT-box of cyclin D1 promoter and mediates cell cycle progression at G(1) phase as a downstream target of focal adhesion kinase (FAK).

Subunit / interactions. Interacts with corepressor CtBP2. Interacts with PIAS1, PIAS2, and PIAS4; the interaction with each ligase sumoylates KLF8.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Sumoylation at Lys-67 represses transcriptional activity and reduces cell cycle progression into the G(1) phase. Has no effect on subcellular location.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF8, the motif is inactive.

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

Isoforms (4)

UniProt ID	Names	Canonical?
O95600-1	1	yes
O95600-3	2
O95600-4	3
O95600-5	4

RefSeq proteins (7): NP_001152768, NP_001311028, NP_001311029, NP_001311031, NP_001311033, NP_001311034, NP_009181* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily

Pfam: PF00096

UniProt features (14 total): zinc finger region 3, splice variant 3, mutagenesis site 2, sequence conflict 2, chain 1, region of interest 1, short sequence motif 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95600-F1	52.04	0.09

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): 67

Mutagenesis-validated functional residues (2):

Position	Phenotype
67	abolishes sumoylation. no change in nuclear location. increases transcriptional activity and cell cycle progression. abo
217	no change in sumoylation. abolishes sumoylation; when associated with r-67.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 162 (showing top): WANG_CLIM2_TARGETS_UP, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, WANG_LMO4_TARGETS_DN, AACTTT_UNKNOWN, TAL1BETAE47_01, MODULE_342, TGGAAA_NFAT_Q4_01, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CDC5_01, TAL1BETAITF2_01, LIU_PROSTATE_CANCER_DN, CHYLA_CBFA2T3_TARGETS_UP

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (7): 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), zinc ion binding (GO:0008270), DNA binding (GO:0003677), metal ion binding (GO:0046872), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (5): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytosol (GO:0005829), aggresome (GO:0016235), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	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
transition metal ion binding	1
nucleic acid binding	1
cation binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1
inclusion body	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KLF8	CTBP2	P56545	951
KLF8	CTBP1	Q13363	950
KLF8	FOXC2	Q99958	516
KLF8	EP300	Q09472	502
KLF8	ELF3	P78545	500
KLF8	CDH1	P12830	475
KLF8	PTGDR	Q13258	470
KLF8	SLCO6A1	Q86UG4	431
KLF8	SNAI1	O95863	430
KLF8	TWIST1	Q15672	428
KLF8	ZEB1	P37275	415
KLF8	KLF12	Q9Y4X4	406
KLF8	ELF2	Q15723	406
KLF8	ZNF750	Q32MQ0	402
KLF8	HDAC9	Q9UKV0	383

IntAct

8 interactions, top by confidence:

A	B	Type	Score
NFIA	KLF8	psi-mi:“MI:0915”(physical association)	0.470
KLF8	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
NFIB	KLF8	psi-mi:“MI:0915”(physical association)	0.400
NFIC	KLF8	psi-mi:“MI:0915”(physical association)	0.400
KLF8		psi-mi:“MI:0914”(association)	0.350
KLF8	USP27X	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (342): BIN1 (Affinity Capture-MS), SGSM3 (Affinity Capture-MS), DGCR8 (Affinity Capture-MS), ANTXR1 (Affinity Capture-MS), MICALL1 (Affinity Capture-MS), CTBP1 (Affinity Capture-Western), KLF8 (Affinity Capture-Western), KLF8 (Two-hybrid), KLF8 (Affinity Capture-RNA), KLF8 (Positive Genetic), NEDD4 (Affinity Capture-Western), KLF8 (Reconstituted Complex), CTBP2 (Proximity Label-MS), EP300 (Proximity Label-MS), CREBBP (Proximity Label-MS)

ESM2 similar proteins: B4F6U4, O88873, O93602, O95600, P15336, P16951, P49140, P58929, P70365, P78364, Q00969, Q0VCW3, Q13625, Q15788, Q17R98, Q1LY51, Q2HJ87, Q2VPU4, Q3UTQ7, Q4PJW2, Q502P7, Q505G8, Q5SFM8, Q5VT52, Q62415, Q64028, Q6A098, Q6NXI6, Q6NXK2, Q6P4Y1, Q6ZNC4, Q7Z3K3, Q8BLM0, Q8BZH4, Q8CG79, Q8CHY6, Q8IXK0, Q8N9N5, Q8VBU8, Q93073

Diamond homologs: O08584, O08876, O14901, O35738, O35819, O43474, O62259, O70494, O75840, O89090, O89091, O95600, P08047, P0CG40, P46099, P57682, P58334, Q01714, Q02446, Q02447, Q0VA40, Q13118, Q13351, Q13887, Q14V87, Q19A40, Q19A41, Q22678, Q24266, Q3SY56, Q5XGT8, Q60793, Q60843, Q60980, Q62445, Q64HY3, Q64HY5, Q65ZG6, Q6BEB4, Q6NW96

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
KLF8	“up-regulates activity”	CTBP2	binding
KLF3	“down-regulates quantity by repression”	KLF8	“transcriptional regulation”
KLF1	“up-regulates quantity by expression”	KLF8	“transcriptional regulation”
KLF8	“down-regulates quantity by repression”	HBB	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

897 predictions. Top by Δscore:

Variant	Effect	Δscore
X:56233338:GTCG:G	donor_gain	1.0000
X:56233340:CGG:C	donor_loss	1.0000
X:56233341:GGTA:G	donor_loss	1.0000
X:56233342:GTAA:G	donor_loss	1.0000
X:56265178:A:AC	acceptor_loss	1.0000
X:56269376:A:AG	acceptor_gain	1.0000
X:56269376:AGT:A	acceptor_gain	1.0000
X:56269377:G:GA	acceptor_gain	1.0000
X:56269377:GTG:G	acceptor_gain	1.0000
X:56269377:GTGA:G	acceptor_gain	1.0000
X:56269377:GTGAA:G	acceptor_gain	1.0000
X:56269485:CAAGA:C	donor_gain	1.0000
X:56269486:AAGA:A	donor_gain	1.0000
X:56269487:AGA:A	donor_gain	1.0000
X:56269487:AGAGT:A	donor_loss	1.0000
X:56269488:GA:G	donor_gain	1.0000
X:56269488:GAG:G	donor_gain	1.0000
X:56269490:G:GG	donor_gain	1.0000
X:56269491:T:A	donor_loss	1.0000
X:56269492:GAGT:G	donor_loss	1.0000
X:56269493:AGTA:A	donor_loss	1.0000
X:56269494:G:GG	donor_gain	1.0000
X:56284309:TTAG:T	acceptor_loss	1.0000
X:56284310:TAG:T	acceptor_loss	1.0000
X:56233342:G:GG	donor_gain	0.9900
X:56233343:T:A	donor_loss	0.9900
X:56263335:GGC:G	donor_gain	0.9900
X:56265169:A:AG	acceptor_gain	0.9900
X:56265170:T:G	acceptor_gain	0.9900
X:56265173:A:AG	acceptor_gain	0.9900

AlphaMissense

2357 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:56270264:T:C	C281R	1.000
X:56284330:T:A	C306S	1.000
X:56284330:T:C	C306R	1.000
X:56284331:G:C	C306S	1.000
X:56284357:T:C	F315L	1.000
X:56284359:T:A	F315L	1.000
X:56284359:T:G	F315L	1.000
X:56284414:T:C	F334L	1.000
X:56284416:T:A	F334L	1.000
X:56284416:T:G	F334L	1.000
X:56284420:T:C	C336R	1.000
X:56284441:T:C	F343L	1.000
X:56284442:T:C	F343S	1.000
X:56284443:T:A	F343L	1.000
X:56284443:T:G	F343L	1.000
X:56270249:T:A	C276S	0.999
X:56270249:T:C	C276R	0.999
X:56270250:G:C	C276S	0.999
X:56270251:T:G	C276W	0.999
X:56270264:T:A	C281S	0.999
X:56270265:G:A	C281Y	0.999
X:56270265:G:C	C281S	0.999
X:56270266:C:G	C281W	0.999
X:56270276:T:G	Y285D	0.999
X:56270295:T:C	L291P	0.999
X:56270303:C:G	H294D	0.999
X:56270305:C:A	H294Q	0.999
X:56270305:C:G	H294Q	0.999
X:56270307:G:C	R295P	0.999
X:56270311:A:C	R296S	0.999

dbSNP variants (sampled 300 via entrez): RS1000003088 (X:56196030 G>C), RS1000005651 (X:56004474 C>A), RS1000006091 (X:56002112 A>G), RS1000025406 (X:56147543 T>C), RS1000033176 (X:56106845 G>T), RS1000035168 (X:55934787 CATT>C), RS1000036065 (X:55954936 T>A,C,G), RS1000036631 (X:56004775 A>G), RS1000041656 (X:56090287 G>A), RS1000045714 (X:56208564 T>G), RS1000046940 (X:56060577 T>C), RS1000051549 (X:56004548 G>T), RS1000052265 (X:56062351 C>T), RS1000057360 (X:56116101 T>G), RS1000064241 (X:55947526 C>A,T)

Disease associations

OMIM: gene MIM:300286 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002040_3	Blood trace element (Zn levels)	1.000000e-12
GCST003983_11	Male-pattern baldness	6.000000e-18
GCST006661_127	Male-pattern baldness	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	increases methylation	1
butyraldehyde	decreases expression	1
chromium hexavalent ion	increases expression	1
CGP 52608	affects binding, increases reaction	1
quinocetone	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Gemcitabine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Nickel	decreases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Acrylamide	decreases expression	1
Magnetite Nanoparticles	increases methylation	1

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3S0	SEES3-1V human KLF8, clone1	Embryonic stem cell	Male
CVCL_A3S1	SEES3-1V human KLF8, clone2	Embryonic stem cell	Male
CVCL_A3S2	SEES3-1V human KLF8, clone3	Embryonic stem cell	Male
CVCL_HC82	HEK293 eGFP-KLF8	Transformed cell line	Female

Clinical trials (associated diseases)

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