SETDB1 (SET domain bifurcated histone lysine methyltransferase 1)

Gene

• Entrez ID: 9869
• Gene name: SET domain bifurcated histone lysine methyltransferase 1
• Gene symbol: SETDB1
• Synonyms (NCBI Gene): ESET, H3-K9-HMTase4, KG1T, KMT1E, TDRD21
• Chromosome: 1
• Chromosome location: 1q21.3
• Summary: This gene encodes a histone methyltransferase which regulates histone methylation, gene silencing, and transcriptional repression. This gene has been identified as a target for treatment in Huntington Disease, given that gene silencing and transcription d

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT048947	hsa-miR-92a-3p	CLASH	23622248
MIRT045818	hsa-miR-152-3p	CLASH	23622248
MIRT043011	hsa-miR-324-3p	CLASH	23622248
MIRT038516	hsa-miR-296-3p	CLASH	23622248
MIRT052718	hsa-miR-1260b	CLASH	23622248
MIRT439145	hsa-let-7c-5p	3'LIFE	25074381
MIRT439145	hsa-let-7c-5p	3'LIFE	25074381
MIRT059476	hsa-miR-29a-3p	ChIP-seq, Immunohistochemistry, Luciferase reporter assay, Next Generation Sequencing (NGS), qRT-PCR, Western blot	26481868
MIRT059476	hsa-miR-29a-3p	ChIP-seq, Immunohistochemistry, Luciferase reporter assay, Next Generation Sequencing (NGS), qRT-PCR, Western blot	26481868
MIRT1340761	hsa-miR-1972	CLIP-seq
MIRT1340762	hsa-miR-29a	CLIP-seq
MIRT1340763	hsa-miR-29b	CLIP-seq
MIRT1340764	hsa-miR-29c	CLIP-seq
MIRT1340765	hsa-miR-3689a-3p	CLIP-seq
MIRT1340766	hsa-miR-3689c	CLIP-seq
MIRT1340767	hsa-miR-4650-5p	CLIP-seq
MIRT1340768	hsa-miR-4722-3p	CLIP-seq
MIRT1340769	hsa-miR-4728-5p	CLIP-seq
MIRT1340770	hsa-miR-4763-5p	CLIP-seq
MIRT1340771	hsa-miR-621	CLIP-seq
MIRT1340772	hsa-miR-1296	CLIP-seq
MIRT1340761	hsa-miR-1972	CLIP-seq
MIRT1340773	hsa-miR-198	CLIP-seq
MIRT1340762	hsa-miR-29a	CLIP-seq
MIRT1340763	hsa-miR-29b	CLIP-seq
MIRT1340764	hsa-miR-29c	CLIP-seq
MIRT1340774	hsa-miR-3154	CLIP-seq
MIRT1340775	hsa-miR-3202	CLIP-seq
MIRT1340776	hsa-miR-3663-5p	CLIP-seq
MIRT1340777	hsa-miR-4533	CLIP-seq
MIRT1340767	hsa-miR-4650-5p	CLIP-seq
MIRT1340778	hsa-miR-4713-3p	CLIP-seq
MIRT1340768	hsa-miR-4722-3p	CLIP-seq
MIRT1340770	hsa-miR-4763-5p	CLIP-seq
MIRT1340771	hsa-miR-621	CLIP-seq
MIRT2100812	hsa-miR-1200	CLIP-seq
MIRT2100813	hsa-miR-3065-5p	CLIP-seq
MIRT2100814	hsa-miR-3130-5p	CLIP-seq
MIRT2100815	hsa-miR-3667-5p	CLIP-seq
MIRT2100816	hsa-miR-421	CLIP-seq
MIRT2100817	hsa-miR-4324	CLIP-seq
MIRT2100818	hsa-miR-4482	CLIP-seq
MIRT2100819	hsa-miR-544b	CLIP-seq
MIRT2100820	hsa-miR-7	CLIP-seq
MIRT2100821	hsa-miR-873	CLIP-seq
MIRT2325356	hsa-miR-4723-5p	CLIP-seq
MIRT2100821	hsa-miR-873	CLIP-seq
MIRT1340772	hsa-miR-1296	CLIP-seq
MIRT2459173	hsa-miR-4695-3p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
DNMT3A	Unknown	16682412
MBD1	Repression	17066076
MBD1	Unknown	15327775

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003677	Function	DNA binding	IEA
GO:0003682	Function	Chromatin binding	IDA	27029610
GO:0005515	Function	Protein binding	IPI	16682412, 17577629, 20871592, 21170338, 23034801, 24705354, 26022416, 27029610, 27732843, 29774127, 32051553, 32296183, 32814053, 33961781, 35512704, 37179361
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	27732843
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	IMP	27732843
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	IMP	27732843
GO:0006325	Process	Chromatin organization	IEA
GO:0006346	Process	DNA methylation-dependent constitutive heterochromatin formation	IEA
GO:0006346	Process	DNA methylation-dependent constitutive heterochromatin formation	IMP	24623306, 27732843
GO:0008168	Function	Methyltransferase activity	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0010629	Process	Negative regulation of gene expression	IBA
GO:0010629	Process	Negative regulation of gene expression	IDA	39096901
GO:0016740	Function	Transferase activity	IEA
GO:0032259	Process	Methylation	IEA
GO:0042054	Function	Histone methyltransferase activity	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0046974	Function	Histone H3K9 methyltransferase activity	IBA
GO:0046974	Function	Histone H3K9 methyltransferase activity	IDA	14536086
GO:0046974	Function	Histone H3K9 methyltransferase activity	IEA
GO:0070828	Process	Heterochromatin organization	IBA
GO:0140938	Function	Histone H3 methyltransferase activity	TAS
GO:0140947	Function	Histone H3K9me2 methyltransferase activity	IEA
GO:0140948	Function	Histone H3K9 monomethyltransferase activity	IEA
GO:0140949	Function	Histone H3K9 trimethyltransferase activity	IDA	14536086
GO:0141005	Process	Transposable element silencing by heterochromatin formation	IDA	37938770
GO:0141005	Process	Transposable element silencing by heterochromatin formation	ISS
GO:0141005	Process	Transposable element silencing by heterochromatin formation	TAS
GO:1990841	Function	Promoter-specific chromatin binding	IDA	24623306
GO:1990841	Function	Promoter-specific chromatin binding	IEA

Other IDs

• MIM: 604396
• HGNC: 10761
• e!Ensembl: ENSG00000143379

Protein

• UniProt ID: Q15047
• Protein name: Histone-lysine N-methyltransferase SETDB1 (EC 2.1.1.366) (ERG-associated protein with SET domain) (ESET) (Histone H3-K9 methyltransferase 4) (H3-K9-HMTase 4) (Lysine N-methyltransferase 1E) (SET domain bifurcated 1)
• Protein function: Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated hist
• PDB: 3DLM, 4X3S, 5KCH, 5KCO, 5KE2, 5KE3, 5KH6, 5QT1, 5QT2, 6AU2, 6AU3, 6BHD, 6BHE, 6BHG, 6BHH, 6BHI, 6BPI, 7C9N, 7CAJ, 7CD9, 7CJT, 8G5E, 8IYA, 8UWP, 9CUW, 9CUX
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF18300	DUF5604	193 → 250	Domain of unknown function (DUF5604)	Domain
  PF18359	TUDOR_5	258 → 309	Histone methyltransferase Tudor domain 1	Domain
  PF18358	Tudor_4	348 → 397	Histone methyltransferase Tudor domain	Domain
  PF01429	MBD	594 → 668	Methyl-CpG binding domain	Domain
  PF05033	Pre-SET	682 → 795	Pre-SET motif	Family
  PF00856	SET	814 → 1266	SET domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. High expression in testis.
• Sequence:

  MSSLPGCIGLDAATATVESEEIAELQQAVVEELGISMEELRHFIDEELEKMDCVQQRKKQ
  LAELETWVIQKESEVAHVDQLFDDASRAVTNCESLVKDFYSKLGLQYRDSSSEDESSRPT
  EIIEIPDEDDDVLSIDSGDAGSRTPKDQKLREAMAALRKSAQDVQKFMDAVNKKSSSQDL
  HKGTLSQMSGELSKDGDLIVSMRILGKKRTKTWHKGTLIAIQTVGPGKKYKVKFDNKGKS
  LLSGNHIAYDYHPPADKLYVGSRVVAKYKDGNQVWLYAGIVAETPNVKNKLRFLIFFDDG
  YASYVTQSELYPICRPLKKTWEDIEDISCRDFIEEYVTAYPNRPMVLLKSGQLIKTEWEG
  TWWKSRVEEVDGSLVRILFLDDKRCEWIYRGSTRLEPMFSMKTSSASALEKKQGQLRTRP
  NMGAVRSKGPVVQYTQDLTGTGTQFKPVEPPQPTAPPAPPFPPAPPLSPQAGDSDLESQL
  AQSRKQVAKKSTSFRPGSVGSGHSSPTSPALSENVSGGKPGINQTYRSPLGSTASAPAPS
  ALPAPPAPPVFHGMLERAPAEPSYRAPMEKLFYLPHVCSYTCLSRVRPMRNEQYRGKNPL
  LVPLLYDFRRMTARRRVNRKMGFHVIYKTPCGLCLRTMQEIERYLFETGCDFLFLEMFCL
  DPYVLVDRKFQPYKPFYYILDITYGKEDVPLSCVNEIDTTPPPQVAYSKERIPGKGVFIN
  TGPEFLVGCDCKDGCRDKSKCACHQLTIQATACTPGGQINPNSGYQYKRLEECLPTGVYE
  CNKRCKCDPNMCTNRLVQHGLQVRLQLFKTQNKGWGIRCLDDIAKGSFVCIYAGKILTDD
  FADKEGLEMGDEYFANLDHIESVENFKEGYESDAPCSSDSSGVDLKDQEDGNSGTEDPEE
  SNDDSSDDNFCKDEDFSTSSVWRSYATRRQTRGQKENGLSETTSKDSHPPDLGPPHIPVP
  PSIPVGGCNPPSSEETPKNKVASWLSCNSVSEGGFADSDSHSSFKTNEGGEGRAGGSRME
  AEKASTSGLGIKDEGDIKQAKKEDTDDRNKMSVVTESSRNYGYNPSPVKPEGLRRPPSKT
  SMHQSRRLMASAQSNPDDVLTLSSSTESEGESGTSRKPTAGQTSATAVDSDDIQTISSGS
  EGDDFEDKKNMTGPMKRQVAVKSTRGFALKSTHGIAIKSTNMASVDKGESAPVRKNTRQF
  YDGEESCYIIDAKLEGNLGRYLNHSCSPNLFVQNVFVDTHDLRFPWVAFFASKRIRAGTE
  LTWDYNYEVGSVEGKELLCCCGAIECRGRLL

• Sequence length: 1291

Pathways

KEGG:

Lysine degradation
Metabolic pathways
Signaling pathways regulating pluripotency of stem cells

Reactome:

PKMTs methylate histone lysines

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANHEDONIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISTIC DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOR VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MELANOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MESOTHELIOMA, MALIGNANT	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL INFARCTION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of colon	Adenocarcinoma Of Colon	BEFREE	28913972		★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	22863622		★☆☆☆☆ Found in Text Mining only
Anhedonia	Anhedonia	BEFREE	20505083		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anhedonia	Anhedonia	PSYGENET_DG	20505083		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Asthma	Asthma	Pubtator	37569643	Associate	★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	Pubtator	34296393	Associate	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	27119313	Associate	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	35682642	Stimulate	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	27119313		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	BEFREE	23055267		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	Pubtator	23055267	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Benign Prostatic Hyperplasia	Benign Prostatic Hyperplasia	BEFREE	24556744		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	26840455, 29926931, 30309377, 30483750, 30545440, 31405032		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	26840455, 30545440, 31735020, 35395812	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	32305991	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	27164857	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	24556744		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	27164857	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	31811111, 33355042, 34843122	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	23770855, 25477335		★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	31686850		★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	30983519	Associate	★☆☆☆☆ Found in Text Mining only
Cockayne Syndrome	Cockayne syndrome	Pubtator	31276581	Associate	★☆☆☆☆ Found in Text Mining only
Cockayne Syndrome, Type II	Cockayne Syndrome	BEFREE	31276581		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	29158805, 30105513, 31306481		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	31896605	Associate	★☆☆☆☆ Found in Text Mining only
Congenital contractural arachnodactyly	Congenital Contractural Arachnodactyly	BEFREE	30983519		★☆☆☆☆ Found in Text Mining only
Encephalitis	Encephalitis	Pubtator	35682642	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	23055267	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	36077559	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	25602259	Associate	★☆☆☆☆ Found in Text Mining only
Head and Neck Carcinoma	Head And Neck Carcinoma	BEFREE	31768101		★☆☆☆☆ Found in Text Mining only
Hematopoietic Neoplasms	Hematopoietic Neoplasms	BEFREE	31422102		★☆☆☆☆ Found in Text Mining only
Hereditary Breast and Ovarian Cancer Syndrome	Hereditary breast and ovarian cancer syndrome	Pubtator	26840455	Associate	★☆☆☆☆ Found in Text Mining only
Huntington Disease	Huntington Disease	BEFREE	17142323, 24234436, 28593442, 28879500, 30452683		★☆☆☆☆ Found in Text Mining only
Huntington Disease	Huntington Disease	LHGDN	17142323		★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	25961932, 37850636	Associate	★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	31558673		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	28887438, 29066607	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	28887438, 29774127, 31558673		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	24844570, 26481868, 29739365, 30503969		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	35474385	Associate	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	32305991	Associate	★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	36436682	Stimulate	★☆☆☆☆ Found in Text Mining only
Malignant Head and Neck Neoplasm	Head and neck cancer	BEFREE	31768101		★☆☆☆☆ Found in Text Mining only
Malignant mesothelioma	Malignant Mesothelioma	CTD_human_DG	26928227		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	26840455, 29926931, 30309377, 30483750, 30545440, 31405032		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	23770855, 25477335		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	31686850		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	24556744, 26846621		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	CTD_human_DG	29610475		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	23770855, 26481868, 28076698, 29901162, 31306481		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	26840455		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	21430779, 21983785, 24673285, 30850015, 31131878		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
melanoma	Melanoma	CTD_human_DG	21983785		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	21983785, 31630191, 34906316	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mesothelioma	Mesothelioma	BEFREE	26824986		★☆☆☆☆ Found in Text Mining only
Mesothelioma	Mesothelioma	Pubtator	37369845	Associate	★☆☆☆☆ Found in Text Mining only
Mesothelioma Malignant	Mesothelioma	Pubtator	26824986, 34648949, 38630790	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	31276581	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	35372573	Stimulate	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	36992419	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	29901162		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23770855, 25404354, 25477335, 28076698, 28913972, 29739365, 30309377, 30692626, 31131878		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	28879500		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	27119313		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	25404354, 30054425, 30692626, 31398867		★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	31686850		★☆☆☆☆ Found in Text Mining only
Prader-Willi Syndrome	Prader-Willi Syndrome	BEFREE	24760766, 29228278, 30904443		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	24556744, 26846621		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	24556744	Stimulate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostatic Neoplasms	Prostatic Neoplasms	CTD_human_DG	29610475		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	23815974		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	BEFREE	28671686		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Small cell carcinoma of lung	Lung carcinoma	BEFREE	31327677		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	34108525	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	37970920	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	36436682	Associate	★☆☆☆☆ Found in Text Mining only