SETDB2

Summary

SETDB2 (SET domain bifurcated histone lysine methyltransferase 2, HGNC:20263) is a protein-coding gene on chromosome 13q14.2, encoding Histone-lysine N-methyltransferase SETDB2 (Q96T68). Histone methyltransferase involved in left-right axis specification in early development and mitosis.

This gene encodes a member of a family of proteins that contain a methyl-CpG-binding domain (MBD) and a SET domain and function as histone methyltransferases. This protein is recruited to heterochromatin and plays a role in the regulation of chromosome segregation. This region is commonly deleted in chronic lymphocytic leukemia. Naturally-occuring readthrough transcription occurs from this gene to the downstream PHF11 (PHD finger protein 11) gene. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 83852 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001160308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20263
Approved symbol	SETDB2
Name	SET domain bifurcated histone lysine methyltransferase 2
Location	13q14.2
Locus type	gene with protein product
Status	Approved
Aliases	CLLD8, CLLL8, KMT1F
Ensembl gene	ENSG00000136169
Ensembl biotype	protein_coding
OMIM	607865
Entrez	83852

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000317257, ENST00000354234, ENST00000481439, ENST00000611815, ENST00000921339, ENST00000921340, ENST00000965793, ENST00000965794, ENST00000965795

RefSeq mRNA: 9 — MANE Select: NM_001160308 NM_001160308, NM_001320699, NM_001393975, NM_001393976, NM_001393977, NM_001393978, NM_001393979, NM_001393980, NM_031915

CCDS: CCDS53868, CCDS9417

Canonical transcript exons

ENST00000611815 — 14 exons

Exon	Start	End
ENSE00000923456	49461097	49461162
ENSE00000923457	49467864	49467960
ENSE00000923458	49476476	49477039
ENSE00000923459	49480219	49480335
ENSE00000923460	49480947	49481116
ENSE00000923461	49482737	49482962
ENSE00000923462	49483464	49483563
ENSE00000923463	49485630	49485723
ENSE00000923465	49490822	49490910
ENSE00001319298	49488290	49488630
ENSE00001388535	49460107	49460232
ENSE00001428781	49451553	49451909
ENSE00001532349	49444274	49444857
ENSE00001821506	49491732	49495003

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 97.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.2034 / max 668.0896, expressed in 1724 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135118	5.6682	1374
135120	2.2838	975
135117	1.9338	960
135119	1.6858	638
135121	0.6317	309

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.44	gold quality
epithelial cell of pancreas	CL:0000083	91.00	gold quality
adrenal tissue	UBERON:0018303	88.14	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.29	gold quality
calcaneal tendon	UBERON:0003701	86.90	gold quality
endothelial cell	CL:0000115	86.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.03	gold quality
decidua	UBERON:0002450	84.72	gold quality
epithelium of nasopharynx	UBERON:0001951	84.71	gold quality
lymph node	UBERON:0000029	84.17	gold quality
germinal epithelium of ovary	UBERON:0001304	83.81	gold quality
oocyte	CL:0000023	83.59	gold quality
monocyte	CL:0000576	83.57	gold quality
leukocyte	CL:0000738	83.41	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.38	gold quality
tonsil	UBERON:0002372	83.36	gold quality
oviduct epithelium	UBERON:0004804	82.95	gold quality
secondary oocyte	CL:0000655	82.94	gold quality
amniotic fluid	UBERON:0000173	82.70	gold quality
ovary	UBERON:0000992	82.24	gold quality
tendon	UBERON:0000043	82.14	gold quality
visceral pleura	UBERON:0002401	82.06	gold quality
vermiform appendix	UBERON:0001154	81.86	gold quality
rectum	UBERON:0001052	81.79	gold quality
granulocyte	CL:0000094	81.61	gold quality
pigmented layer of retina	UBERON:0001782	81.57	gold quality
middle temporal gyrus	UBERON:0002771	81.26	gold quality
right adrenal gland cortex	UBERON:0035827	81.22	gold quality
left ovary	UBERON:0002119	81.16	gold quality
body of pancreas	UBERON:0001150	81.14	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.39
E-MTAB-2983	no	101.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

133 targeting SETDB2, 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-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
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
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917

Literature-anchored findings (GeneRIF, showing 15)

• Results provide evidence that CLLD8/KMT1F is recruited to heterochromatin regions and contributes in vivo to the deposition of trimethyl marks in concert with SUV39H1/KMT1A.SUV39H1/KMT1A. (PMID:20404330)
• Results indicate that the IgE-associated AT/G polymorphism (rs386770867) regulates transcription of SETDB2. (PMID:26378653)
• the relation of genetic variation in SETDB2-and its paralogue SETDB1-with different handedness phenotypes in 950 healthy adult participants, was investigated. (PMID:26572639)
• these findings identify Setdb2 as a novel regulator of the immune system in acute respiratory viral infection. (PMID:26709698)
• our data indicated that SETDB2 is often over-expressed in gastric cancer tissues and cell lines and SETDB2 overexpression significantly accelerated cell proliferation, migration and invasion of gastric cancer cells (PMID:27572307)
• SETDB2 transcripts were overexpressed in renal cell tumor subtypes and associated with prognosis. (PMID:29099276)
• Findings implicate SET domain bifurcated 2 (SETDB2) locus in the longstanding links of handedness with asthma and other atopic diseases. (PMID:29234167)
• an oncogenic role for the protein lysine methyltransferase SETDB2 in leukemia pathogenesis. It is overexpressed in pre-BCR(+) ALL and required for their maintenance in vitro and in vivo. SETDB2 expression is maintained as a direct target gene of the chimeric transcription factor E2A-PBX1 in a subset of ALL and suppresses expression of the cell-cycle inhibitor CDKN2C through histone H3K9 tri-methylation (PMID:29694893)
• A number of converging phenotypes outline a stress-responsive mechanism for SETDB1 and SETDB2 activation and subsequent increased tumor survival, providing novel insights into epigenetic biology. [review] (PMID:30850015)
• Setdb2 regulates macrophage plasticity during normal and pathologic wound repair (PMID:31350176)
• Coronavirus induces diabetic macrophage-mediated inflammation via SETDB2. (PMID:34479991)
• Histone lysine methyltransferase SETDB2 suppresses NRF2 to restrict tumor progression and modulates chemotherapy sensitivity in lung adenocarcinoma. (PMID:36504353)
• THE CRITICAL ROLE OF THE HISTONE MODIFICATION ENZYME SETDB2 IN THE PATHOGENESIS OF ACUTE RESPIRATORY DISTRESS SYNDROME. (PMID:37195726)
• Structural evidence for protein-protein interaction between the non-canonical methyl-CpG-binding domain of SETDB proteins and C11orf46. (PMID:38159574)
• The STAT3/SETDB2 axis dictates NF-kappaB-mediated inflammation in macrophages during wound repair. (PMID:39435663)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000101462
mus_musculus	Setdb2	ENSMUSG00000071350
rattus_norvegicus	LOC134482125	ENSRNOG00000021680
drosophila_melanogaster	ash1	FBGN0005386
drosophila_melanogaster	trr	FBGN0023518
drosophila_melanogaster	Set2	FBGN0030486
drosophila_melanogaster	CG4565	FBGN0037841
drosophila_melanogaster	G9a	FBGN0040372
drosophila_melanogaster	egg	FBGN0086908
caenorhabditis_elegans	set-32	WBGENE00008062
caenorhabditis_elegans		WBGENE00008206
caenorhabditis_elegans		WBGENE00008527
caenorhabditis_elegans		WBGENE00011729
caenorhabditis_elegans	met-1	WBGENE00016603
caenorhabditis_elegans		WBGENE00018023
caenorhabditis_elegans		WBGENE00019584
caenorhabditis_elegans		WBGENE00019690
caenorhabditis_elegans		WBGENE00019883
caenorhabditis_elegans		WBGENE00020006
caenorhabditis_elegans		WBGENE00020919
caenorhabditis_elegans		WBGENE00021282

Paralogs (19): KMT2C (ENSG00000055609), SETD1A (ENSG00000099381), SUV39H1 (ENSG00000101945), EZH2 (ENSG00000106462), EZH1 (ENSG00000108799), NSD2 (ENSG00000109685), ASH1L (ENSG00000116539), KMT2A (ENSG00000118058), SETD1B (ENSG00000139718), SETDB1 (ENSG00000143379), NSD3 (ENSG00000147548), SETBP1 (ENSG00000152217), SUV39H2 (ENSG00000152455), NSD1 (ENSG00000165671), KMT2D (ENSG00000167548), EHMT1 (ENSG00000181090), SETD2 (ENSG00000181555), EHMT2 (ENSG00000204371), KMT2B (ENSG00000272333)

Protein

Protein identifiers

Histone-lysine N-methyltransferase SETDB2 — Q96T68 (reviewed: Q96T68)

Alternative names: Chronic lymphocytic leukemia deletion region gene 8 protein, Lysine N-methyltransferase 1F, SET domain bifurcated 2

All UniProt accessions (2): A0A087WYZ9, Q96T68

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase involved in left-right axis specification in early development and mitosis. Specifically trimethylates ‘Lys-9’ of histone H3 (H3K9me3). H3K9me3 is a specific tag for epigenetic transcriptional repression that recruits HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Contributes to H3K9me3 in both the interspersed repetitive elements and centromere-associated repeats. Plays a role in chromosome condensation and segregation during mitosis.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Ubiquitous. Highest expression in heart, testis and ovary.

Domain organisation. In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96T68-1	1	yes
Q96T68-2	2
Q96T68-3	3

RefSeq proteins (9): NP_001153780, NP_001307628, NP_001380904, NP_001380905, NP_001380906, NP_001380907, NP_001380908, NP_001380909, NP_114121 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR001739	Methyl_CpG_DNA-bd	Domain
IPR007728	Pre-SET_dom	Domain
IPR016177	DNA-bd_dom_sf	Homologous_superfamily
IPR046341	SET_dom_sf	Homologous_superfamily
IPR047232	SETDB1/2-like_MBD	Domain
IPR051516	SETDB_methyltransferase	Family

Pfam: PF00856, PF01429, PF05033

Catalyzed reactions (Rhea), 1 shown:

• N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60288)

UniProt features (46 total): binding site 20, helix 8, domain 3, strand 3, compositionally biased region 3, splice variant 2, sequence variant 2, turn 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8HFP	X-RAY DIFFRACTION	1.82
5TFP	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96T68-F1	62.74	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (20): 293; 295; 299; 299; 305; 307; 345; 345; 349; 351; 356; 377–379 …

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization

MSigDB gene sets: 191 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, MODULE_308, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_HEART_TUBE_DEVELOPMENT, FOSTER_TOLERANT_MACROPHAGE_UP, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOBP_LEFT_RIGHT_AXIS_SPECIFICATION, GOBP_HEART_MORPHOGENESIS, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, KEGG_LYSINE_DEGRADATION, GOBP_MITOTIC_CELL_CYCLE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (11): mitotic cell cycle (GO:0000278), heart looping (GO:0001947), chromosome segregation (GO:0007059), negative regulation of gene expression (GO:0010629), methylation (GO:0032259), negative regulation of DNA-templated transcription (GO:0045892), cell division (GO:0051301), heterochromatin organization (GO:0070828), left/right axis specification (GO:0070986), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (11): DNA binding (GO:0003677), zinc ion binding (GO:0008270), histone H3K9 methyltransferase activity (GO:0046974), histone H3 methyltransferase activity (GO:0140938), histone H3K9me2 methyltransferase activity (GO:0140947), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), histone methyltransferase activity (GO:0042054), metal ion binding (GO:0046872), histone H3K9 monomethyltransferase activity (GO:0140948)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Chromatin organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
chromatin organization	2
histone H3K9 methyltransferase activity	2
cell cycle	1
mitotic nuclear division	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
cell cycle process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cellular process	1
axis specification	1
left/right pattern formation	1
cellular component organization	1
nucleic acid binding	1
transition metal ion binding	1
protein-lysine N-methyltransferase activity	1
histone H3 methyltransferase activity	1
histone methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
protein methyltransferase activity	1
histone modifying activity	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2180 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SETDB2	PHF11	Q9UIL8	941
SETDB2	ARL14EP	Q8N8R7	659
SETDB2	CDADC1	Q9BWV3	628
SETDB2	SUV39H2	Q9H5I1	590
SETDB2	SUV39H1	O43463	577
SETDB2	H3-3A	P06351	570
SETDB2	H3C14	Q71DI3	570
SETDB2	H3-5	Q6NXT2	570
SETDB2	H3-4	Q16695	570
SETDB2	H3-7	Q5TEC6	570
SETDB2	RCBTB1	Q8NDN9	570
SETDB2	H3C1	P02295	569
SETDB2	ATF7IP	Q6VMQ6	553
SETDB2	MLNR	O43193	541
SETDB2	KMT5B	Q4FZB7	536

IntAct

11 interactions, top by confidence:

A	B	Type	Score
ARL14EP	SETDB2	psi-mi:“MI:0915”(physical association)	0.740
DAXX	TNRC18	psi-mi:“MI:0914”(association)	0.530
SETDB2	NDUFV3	psi-mi:“MI:0915”(physical association)	0.400
IGHG1	PDPK1	psi-mi:“MI:0914”(association)	0.350
DAXX	SETD1A	psi-mi:“MI:0914”(association)	0.350
SETDB2	DHX16	psi-mi:“MI:0914”(association)	0.350
DAXX		psi-mi:“MI:0914”(association)	0.350

BioGRID (30): ARL14EP (Two-hybrid), ARL14EP (Affinity Capture-MS), SENP7 (Affinity Capture-MS), ZNF445 (Affinity Capture-MS), DHX16 (Affinity Capture-MS), SELENBP1 (Affinity Capture-MS), DUSP14 (Affinity Capture-MS), DSG4 (Affinity Capture-MS), LYG2 (Affinity Capture-MS), HEPHL1 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), ARL14EP (Two-hybrid), SETDB2 (Proximity Label-MS), SETDB2 (Affinity Capture-MS), IL1F10 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2TTB3, A0JMR6, A4IIA7, F4JNY0, F6RRD7, I3XHK1, O60934, O88622, P14629, P28715, P79457, Q08DZ8, Q12789, Q17RS7, Q1LWH4, Q28I29, Q32PL8, Q3B7T1, Q4R7Q1, Q5FWP4, Q5M954, Q5QJC2, Q5RA37, Q5RCV3, Q5ZIN2, Q66J91, Q6GQV7, Q6NVF4, Q6P1E7, Q6P1H6, Q6P256, Q6P7W5, Q76CY8, Q7TP65, Q86W56, Q8BMI4, Q8C0W1, Q8C5W4, Q8GT06, Q8IXW5

Diamond homologs: A0A1L7TZE5, A4IGY9, A7E2Z2, A8XI75, J9VWH9, O43463, O54864, O60016, O65312, O82175, O88491, O88974, O96028, P20659, P42124, P45975, P46995, P55200, P70351, P93831, Q03164, Q06ZW3, Q08BR4, Q08BS4, Q0VD24, Q15047, Q15910, Q24742, Q28CQ7, Q28D84, Q294B9, Q2NL30, Q32PH7, Q4PB36, Q4R381, Q4R3E0, Q4V863, Q53H47, Q5DW34, Q5F3W5

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SETDB2	“up-regulates activity”	H3-3A	methylation
SETDB2	“up-regulates activity”	H3-4	methylation
SETDB2	“up-regulates activity”	H3C1	methylation
SETDB2	“up-regulates activity”	“Histone H3”	methylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2792 predictions. Top by Δscore:

Variant	Effect	Δscore
13:49460103:TTAGG:T	acceptor_loss	1.0000
13:49460104:TAG:T	acceptor_loss	1.0000
13:49460105:A:AG	acceptor_gain	1.0000
13:49460105:AG:A	acceptor_gain	1.0000
13:49460105:AGGC:A	acceptor_gain	1.0000
13:49460106:G:GT	acceptor_gain	1.0000
13:49460106:GG:G	acceptor_gain	1.0000
13:49460106:GGC:G	acceptor_gain	1.0000
13:49460106:GGCG:G	acceptor_gain	1.0000
13:49460106:GGCGA:G	acceptor_gain	1.0000
13:49460230:AAGGT:A	donor_loss	1.0000
13:49460232:GGTA:G	donor_loss	1.0000
13:49460233:G:GA	donor_loss	1.0000
13:49460233:G:GG	donor_gain	1.0000
13:49460234:T:A	donor_loss	1.0000
13:49461093:ACAG:A	acceptor_loss	1.0000
13:49461094:CA:C	acceptor_loss	1.0000
13:49461095:A:AG	acceptor_gain	1.0000
13:49461095:A:G	acceptor_loss	1.0000
13:49461096:G:GT	acceptor_gain	1.0000
13:49461096:GA:G	acceptor_gain	1.0000
13:49461096:GAA:G	acceptor_gain	1.0000
13:49461096:GAAT:G	acceptor_gain	1.0000
13:49461096:GAATA:G	acceptor_gain	1.0000
13:49461161:GG:G	donor_gain	1.0000
13:49461161:GGGTA:G	donor_loss	1.0000
13:49461162:GG:G	donor_gain	1.0000
13:49461163:G:GA	donor_loss	1.0000
13:49461163:G:GG	donor_gain	1.0000
13:49461164:T:G	donor_loss	1.0000

AlphaMissense

4776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:49481059:T:A	W379R	1.000
13:49481059:T:C	W379R	1.000
13:49481069:G:C	R382P	0.999
13:49476659:A:C	R175S	0.998
13:49476659:A:T	R175S	0.998
13:49476799:T:C	F222S	0.998
13:49481000:G:C	R359P	0.998
13:49481061:G:C	W379C	0.998
13:49481061:G:T	W379C	0.998
13:49491808:T:C	C707R	0.998
13:49476652:T:C	F173S	0.997
13:49476658:G:C	R175T	0.997
13:49476705:T:G	Y191D	0.997
13:49480957:T:A	C345S	0.997
13:49480957:T:C	C345R	0.997
13:49480958:G:C	C345S	0.997
13:49481033:A:C	Q370P	0.997
13:49481038:T:C	F372L	0.997
13:49481040:C:A	F372L	0.997
13:49481040:C:G	F372L	0.997
13:49488612:T:A	N645K	0.997
13:49488612:T:G	N645K	0.997
13:49488620:G:C	R648P	0.997
13:49488622:T:C	F649L	0.997
13:49488623:T:C	F649S	0.997
13:49488624:C:A	F649L	0.997
13:49488624:C:G	F649L	0.997
13:49491755:T:C	L689P	0.997
13:49491760:T:A	W691R	0.997
13:49491760:T:C	W691R	0.997

dbSNP variants (sampled 300 via entrez): RS1000008576 (13:49482315 T>C), RS1000119436 (13:49454763 A>G), RS1000365556 (13:49467766 T>A,C), RS1000383891 (13:49493224 G>A), RS1000418113 (13:49447897 T>A), RS1000479484 (13:49475015 C>T), RS1000537743 (13:49479781 C>G,T), RS1000561729 (13:49442864 G>A), RS1000569271 (13:49487613 A>T), RS1000617345 (13:49442933 G>A), RS1000659871 (13:49494553 T>G), RS1000764714 (13:49461334 A>G), RS1000778904 (13:49494023 A>C,G), RS1000780434 (13:49442744 T>C), RS1000809462 (13:49449615 A>G)

Disease associations

OMIM: gene MIM:607865 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010002_186	Refractive error	1.000000e-36
GCST90002397_59	Mean spheric corpuscular volume	2.000000e-10

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.1.1.43 Histone methyltransferases (HMTs)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
potassium chromate(VI)	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Vorinostat	increases expression, affects cotreatment	1
Air Pollutants	affects expression, increases abundance	1
Ethanol	decreases expression	1
Berberine	increases expression	1
Cisplatin	affects expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Niclosamide	increases expression	1
Nitric Oxide	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	increases expression, affects cotreatment	1
Quercetin	decreases expression	1
Tretinoin	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1N6	HyCyte THP-1 KO-hSETDB2	Cancer cell line	Male
CVCL_TK75	HAP1 SETDB2 (-) 1	Cancer cell line	Male
CVCL_TK76	HAP1 SETDB2 (-) 2	Cancer cell line	Male
CVCL_TK77	HAP1 SETDB2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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