SETMAR

Summary

SETMAR (SET and mariner transposase domain methyltransferase, HGNC:10762) is a protein-coding gene on chromosome 3p26.1, encoding Histone-lysine N-methyltransferase SETMAR (Q53H47). Protein derived from the fusion of a methylase with the transposase of an Hsmar1 transposon that plays a role in DNA double-strand break repair, stalled replication fork restart and DNA integration.

This gene encodes a fusion protein that contains an N-terminal histone-lysine N-methyltransferase domain and a C-terminal mariner transposase domain. The encoded protein binds DNA and functions in DNA repair activities including non-homologous end joining and double strand break repair. The SET domain portion of this protein specifically methylates histone H3 lysines 4 and 36. This gene exists as a fusion gene only in anthropoid primates, other organisms lack mariner transposase domain. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 6419 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 83 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006515

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10762
Approved symbol	SETMAR
Name	SET and mariner transposase domain methyltransferase
Location	3p26.1
Locus type	gene with protein product
Status	Approved
Aliases	metnase
Ensembl gene	ENSG00000170364
Ensembl biotype	protein_coding
OMIM	609834
Entrez	6419

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000358065, ENST00000358950, ENST00000413809, ENST00000425046, ENST00000425863, ENST00000430981, ENST00000462115, ENST00000490691, ENST00000864987, ENST00000931285

RefSeq mRNA: 6 — MANE Select: NM_006515 NM_001243723, NM_001276325, NM_001320676, NM_001320677, NM_001320678, NM_006515

CCDS: CCDS2563, CCDS58814, CCDS63528

Canonical transcript exons

ENST00000358065 — 3 exons

Exon	Start	End
ENSE00001498847	4303369	4303526
ENSE00001733551	4312898	4313761
ENSE00003629826	4316212	4317265

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 91.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1389 / max 66.4794, expressed in 1764 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
35030	3.6798	1538
35031	2.4915	1350
35032	1.4849	842
35029	1.4826	953

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	91.65	gold quality
popliteal artery	UBERON:0002250	91.53	gold quality
tibial artery	UBERON:0007610	91.52	gold quality
left uterine tube	UBERON:0001303	90.49	gold quality
aorta	UBERON:0000947	89.89	gold quality
left ovary	UBERON:0002119	89.79	gold quality
right coronary artery	UBERON:0001625	89.47	gold quality
descending thoracic aorta	UBERON:0002345	89.24	gold quality
cortical plate	UBERON:0005343	89.19	gold quality
mucosa of stomach	UBERON:0001199	89.16	gold quality
right ovary	UBERON:0002118	88.98	gold quality
left coronary artery	UBERON:0001626	88.77	gold quality
ganglionic eminence	UBERON:0004023	88.61	gold quality
coronary artery	UBERON:0001621	88.15	gold quality
thoracic aorta	UBERON:0001515	87.93	gold quality
ascending aorta	UBERON:0001496	87.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	87.47	gold quality
lower esophagus	UBERON:0013473	87.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	87.41	gold quality
ovary	UBERON:0000992	87.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.29	gold quality
endocervix	UBERON:0000458	87.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.03	gold quality
ectocervix	UBERON:0012249	86.99	gold quality
omental fat pad	UBERON:0010414	86.66	gold quality
peritoneum	UBERON:0002358	86.63	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.18	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.88	gold quality
right adrenal gland cortex	UBERON:0035827	85.28	gold quality
adipose tissue	UBERON:0001013	85.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SOX11

Literature-anchored findings (GeneRIF, showing 28)

• Metnase is a nonhomologous end-joining repair protein that regulates genomic integration of exogenous DNA and establishes a relationship among histone modification, DNA repair, and integration. (PMID:16332963)
• These data suggest that vectors based on the Himar1 transposable element, in conjunction with the hyperactive mutant transposase C9, may be suitable vectors for gene therapy applications. (PMID:16989604)
• SETMAR is unlikely to catalyze transposition in the human genome, although the nicking activity may have a role in the DNA repair phenotype. (PMID:17130240)
• The activities of the SETMAR protein on transposon ends are described. (PMID:17403897)
• Results suggest that Metnase’s DNA cleavage activity, unlike those of other eukaryotic transposases, is not coupled to its sequence-specific DNA binding. (PMID:17877369)
• hPso4 is necessary to bring Metnase to the DSB sites for its function(s) in DNA repair (PMID:18263876)
• Metnase physically interacts and co-localizes with Topoisomerase IIalpha, the key chromosome decatenating enzyme. (PMID:18790802)
• myeloid leukemia cells fail to arrest at the mitotic decatenation checkpoint, and their progression through this checkpoint is regulated by the DNA repair component Metnase (also termed SETMAR) (PMID:19458360)
• hPso4, once it forms a complex with Metnase, negatively regulates Metnase’s TIR binding activity (PMID:20416268)
• results establish Metnase as a key factor that promotes restart of stalled replication forks, and implicate Metnase in the repair of collapsed forks. (PMID:20457750)
• Data show that DBN1, SETMAR and HIG2 are direct transcriptional targets of the SOX11 protein. (PMID:21124928)
• DNA repair protein Metnase (also SETMAR), which has a SET histone methylase domain, localized to an induced DSB and directly mediated the formation of H3K36me2 near the induced DSB (PMID:21187428)
• a role for Metnase’s endonuclease activity in promoting the joining of noncompatible ends (PMID:21491884)
• phosphorylation of Metnase S495 differentiates between these two functions, enhancing DSB repair and repressing replication fork restart. (PMID:22231448)
• a single mutation DDN(610) –> DDD(610), which restores the ancestral catalytic site, results in loss of function in Metnase (PMID:24573677)
• found known and novel SETMAR splice variants to be significantly increased in acute myeloid leukemia (PMID:24607956)
• 293 T transfected with Metnase revealed a large number of rescued plasmids. (PMID:24655462)
• Metnase may possess an important role in DNA repair, topoisomerase II function, and the maintenance of stemness during colon cancer development. (PMID:25333365)
• methylation of snRNP70 by SETMAR regulates constitutive and/or alternative splicing (PMID:25795785)
• The SET domain is needed for the 5’ end of ss-overhang cleavage with fork and non-fork DNA without affecting the Metnase-DNA interaction. This domain has a positive role in restart of replication fork and the 5’ end of ss-overhang cleavage. (PMID:26437079)
• These results suggest that Metnase enhances Exo1-mediated exonuclease activity on the lagging strand DNA by facilitating Exo1 loading onto a single strand gap at the stalled replication fork. (PMID:27974460)
• Various SETMAR proteins can be synthesized in human glioblastoma that may each have specific biophysical and/or biochemical properties and characteristics. (PMID:28038463)
• ur data is consistent with a model in which SETMAR is part of an anthropoid primate-specific regulatory network centered on the subset of genes containing a transposon end. (PMID:30329085)
• The roles of the human SETMAR protein in illegitimate DNA recombination and non-homologous end joining repair were studied. Contrary to previous reports, it was found that wild type SETMAR had little to no effect on the rate of cell division, DNA integration into the genome or non-homologous end joining. (PMID:31238295)
• Mutation and expression alterations of histone methylation-related NSD2, KDM2B and SETMAR genes in colon cancers. (PMID:33621919)
• Two repeated motifs enriched within some enhancers and origins of replication are bound by SETMAR isoforms in human colon cells. (PMID:33812898)
• Structural and genome-wide analyses suggest that transposon-derived protein SETMAR alters transcription and splicing. (PMID:35378129)
• Investigating the Expression Pattern of the SETMAR Gene Transcript Variants in Childhood Acute Leukemia: Revisiting an Old Gene. (PMID:36706314)

Cross-species orthologs

0 orthologs

Paralogs (1): GVQW3 (ENSG00000179240)

Protein

Protein identifiers

Histone-lysine N-methyltransferase SETMAR — Q53H47 (reviewed: Q53H47)

Alternative names: SET domain and mariner transposase fusion protein

All UniProt accessions (4): Q53H47, B9ZVV8, F8WB33, F8WEU1

UniProt curated annotations — full annotation on UniProt →

Function. Protein derived from the fusion of a methylase with the transposase of an Hsmar1 transposon that plays a role in DNA double-strand break repair, stalled replication fork restart and DNA integration. DNA-binding protein, it is indirectly recruited to sites of DNA damage through protein-protein interactions. Also has kept a sequence-specific DNA-binding activity recognizing the 19-mer core of the 5’-terminal inverted repeats (TIRs) of the Hsmar1 element and displays a DNA nicking and end joining activity. In parallel, has a histone methyltransferase activity and methylates ‘Lys-4’ and ‘Lys-36’ of histone H3. Specifically mediates dimethylation of H3 ‘Lys-36’ at sites of DNA double-strand break and may recruit proteins required for efficient DSB repair through non-homologous end-joining. Also regulates replication fork processing, promoting replication fork restart and regulating DNA decatenation through stimulation of the topoisomerase activity of TOP2A.

Subunit / interactions. Homodimer. Interacts with PRPF19; required for SETMAR recruitment to damaged DNA sites. Interacts with PCNA. Interacts with TOP2A; stimulates TOP2A topoisomerase activity. May interact with RAD9A and/or RAD9B.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Widely expressed, with highest expression in placenta and ovary and lowest expression in skeletal muscle.

Post-translational modifications. Methylated. Methylation regulates activity in DNA decatenation. Phosphorylated at Ser-508 by CHEK1 and dephosphorylated by protein phosphatase 2A/PP2A. Phosphorylation at Ser-508 is enhanced by DNA damage and promotes recruitment to damaged DNA. It stimulates DNA repair and impairs replication fork restart.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Domain organisation. The mariner transposase Hsmar1 region mediates DNA-binding. It has retained some of the nucleases activity but has lost its transposase activity because the active site contains an Asn in position 610 instead of an Asp residue. 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.

Miscellaneous. The mariner transposase region in only present in primates and appeared 40-58 million years ago, after the insertion of a transposon downstream of a preexisting SET gene, followed by the de novo exonization of previously non-coding sequence and the creation of a new intron.

Similarity. In the N-terminal section; belongs to the class V-like SAM-binding methyltransferase superfamily. In the C-terminal section; belongs to the mariner transposase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q53H47-1	1	yes
Q53H47-2	2
Q53H47-3	3

RefSeq proteins (6): NP_001230652, NP_001263254, NP_001307605, NP_001307606, NP_001307607, NP_006506* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR001888	Transposase_1	Family
IPR003616	Post-SET_dom	Domain
IPR007728	Pre-SET_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR041426	Mos1_HTH	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR052709	Transposase-MT_Hybrid	Family

Pfam: PF00856, PF01359, PF05033, PF17906

Enzyme classification (BRENDA):

• EC 2.1.1.357 — [histone H3]-lysine36 N-dimethyltransferase (BRENDA: 4 organisms, 14 substrates, 5 inhibitors, 4 Km, 2 kcat entries)
• EC 2.7.7.B22 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S-ADENOSYL-L-METHIONINE	0.0028–0.0038	2
CHICKEN NUCLEOSOME	0.0003	1
RECOMBINANT NUCLEOSOME	—	1

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-homocysteine + 2 H(+) (RHEA:60308)

UniProt features (103 total): binding site 22, helix 22, sequence conflict 19, strand 16, mutagenesis site 8, domain 3, turn 3, splice variant 3, modified residue 2, DNA-binding region 2, region of interest 2, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
3BO5	X-RAY DIFFRACTION	1.59
3F2K	X-RAY DIFFRACTION	1.85
3K9J	X-RAY DIFFRACTION	1.9
7S03	X-RAY DIFFRACTION	2.37
3K9K	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53H47-F1	83.32	0.59

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 (22): 77; 82; 82; 87; 89; 118; 118; 122; 124; 128; 149–151; 192 …

Post-translational modifications (2): 498, 508

Mutagenesis-validated functional residues (8):

Position	Phenotype
223	reduces activity in double-strand break repair.
261	reduces activity in double-strand break repair.
445	abolishes tir-specific dna-binding.
473	abolishes homodimerization and dna-binding and reduces cleavage of single-stranded dna.
496	abolishes dna cleavage.
503	reduces activity in double-strand break repair.
508	prevents phosphorylation. impairs recruitment to damaged dna and double-strand break repair. impairs interaction with hi
623	loss of function in dna repair. altered dna-binding properties.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_CHROMOSOME_ORGANIZATION, GOMF_ENDONUCLEASE_ACTIVITY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOMF_NUCLEASE_ACTIVITY, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_DNA_INTEGRATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_DNA_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS

GO Biological Process (16): DNA double-strand break processing (GO:0000729), double-strand break repair via nonhomologous end joining (GO:0006303), DNA catabolic process (GO:0006308), cell population proliferation (GO:0008283), DNA integration (GO:0015074), replication fork processing (GO:0031297), methylation (GO:0032259), mitotic DNA integrity checkpoint signaling (GO:0044774), nucleic acid metabolic process (GO:0090304), positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity (GO:2000373), positive regulation of double-strand break repair via nonhomologous end joining (GO:2001034), negative regulation of chromosome organization (GO:2001251), DNA repair (GO:0006281), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), DNA damage response (GO:0006974)

GO Molecular Function (25): single-stranded DNA endonuclease activity (GO:0000014), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), endonuclease activity (GO:0004519), zinc ion binding (GO:0008270), histone H3K4 methyltransferase activity (GO:0042800), protein homodimerization activity (GO:0042803), DNA topoisomerase binding (GO:0044547), histone H3K36 methyltransferase activity (GO:0046975), histone H3K36 dimethyltransferase activity (GO:0140954), nucleic acid binding (GO:0003676), catalytic activity (GO:0003824), nuclease activity (GO:0004518), protein binding (GO:0005515), methyltransferase activity (GO:0008168), N-methyltransferase activity (GO:0008170), protein methyltransferase activity (GO:0008276), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), protein-lysine N-methyltransferase activity (GO:0016279), transferase activity (GO:0016740), hydrolase activity (GO:0016787), histone methyltransferase activity (GO:0042054), metal ion binding (GO:0046872), histone H3 methyltransferase activity (GO:0140938)

GO Cellular Component (5): nucleus (GO:0005634), nucleolus (GO:0005730), site of double-strand break (GO:0035861), condensed chromosome (GO:0000793), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	4
methyltransferase activity	3
double-strand break repair	2
DNA binding	2
protein-lysine N-methyltransferase activity	2
histone H3 methyltransferase activity	2
binding	2
intracellular membraneless organelle	2
5’-3’ DNA exonuclease activity	1
DNA nuclease activity	1
nucleic acid catabolic process	1
cellular process	1
DNA-templated DNA replication maintenance of fidelity	1
metabolic process	1
mitotic cell cycle	1
mitotic cell cycle checkpoint signaling	1
DNA integrity checkpoint signaling	1
nucleobase-containing compound metabolic process	1
macromolecule metabolic process	1
DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity	1
positive regulation of ATP-dependent activity	1
positive regulation of catalytic activity	1
double-strand break repair via nonhomologous end joining	1
positive regulation of double-strand break repair	1
regulation of double-strand break repair via nonhomologous end joining	1
negative regulation of organelle organization	1
regulation of chromosome organization	1
chromosome organization	1
DNA damage response	1
cellular component organization	1
chromatin organization	1
cellular response to stress	1
DNA endonuclease activity	1
hydrolase activity, acting on ester bonds	1
nucleic acid binding	1
nuclease activity	1
transition metal ion binding	1
identical protein binding	1
protein dimerization activity	1
enzyme binding	1

Protein interactions and networks

STRING

1879 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SETMAR	PRPF19	Q9UMS4	987
SETMAR	BANP	Q8N9N5	896
SETMAR	SETD3	Q86TU7	718
SETMAR	H3-3A	P06351	669
SETMAR	H3C1	P02295	666
SETMAR	H3-7	Q5TEC6	665
SETMAR	H3C14	Q71DI3	664
SETMAR	H3-5	Q6NXT2	664
SETMAR	H3-4	Q16695	664
SETMAR	SMYD2	Q9NRG4	604
SETMAR	SUMF1	Q8NBK3	602
SETMAR	PGBD5	Q8N414	573
SETMAR	XRCC4	Q13426	535
SETMAR	PRDM16	Q9HAZ2	523
SETMAR	CDK1	P06493	519

IntAct

17 interactions, top by confidence:

A	B	Type	Score
SETMAR	YJU2	psi-mi:“MI:0915”(physical association)	0.620
LEO1	SUPT5H	psi-mi:“MI:0914”(association)	0.530
SETMAR	HSPA8	psi-mi:“MI:0914”(association)	0.530
IKZF3	SETMAR	psi-mi:“MI:0914”(association)	0.530
H3-5	SETMAR	psi-mi:“MI:0915”(physical association)	0.370
Naa50	WDR46	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
YJU2	PLRG1	psi-mi:“MI:0914”(association)	0.350
SETMAR	ELOC	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
VPS26C	SETMAR	psi-mi:“MI:0915”(physical association)	0.000
SETMAR	SETMAR	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (46): SETMAR (Affinity Capture-MS), SETMAR (Affinity Capture-MS), SETMAR (Affinity Capture-MS), SETMAR (Affinity Capture-MS), SETMAR (Affinity Capture-MS), SETMAR (Affinity Capture-MS), DOC2A (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), SETX (Affinity Capture-MS), PCBP1 (Affinity Capture-MS), SETMAR (Two-hybrid), SETMAR (Affinity Capture-MS), TCEB2 (Affinity Capture-MS), TCEB1 (Affinity Capture-MS), APPBP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A385XJE6, A2YNT8, A3QK15, B4J6Q0, B4LMQ3, P03009, P03934, P0CE49, P0CE50, P0CE51, P0CE52, P0CE53, P0CE54, P0CE55, P0CE56, P0CE57, P0CE58, P0CE59, P0CE60, P0CE61, P0CE62, P0CE63, P0CE64, P0CE65, P33124, P34257, P35509, P55616, P61922, P76071, P76102, Q02066, Q04202, Q0D4J7, Q14410, Q148G4, Q28BL6, Q42521, Q4R4D5, Q53H47

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

2 interactions.

A	Effect	B	Mechanism
SETMAR	“up-regulates quantity by stabilization”	CHEK1
CHEK1	“down-regulates activity”	SETMAR	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	70
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1180543	GRCh37/hg19 3p26.3-26.1(chr3:60001-8472742)x1	Pathogenic

SpliceAI

857 predictions. Top by Δscore:

Variant	Effect	Δscore
3:4316207:TTTA:T	acceptor_loss	1.0000
3:4316208:TTAG:T	acceptor_loss	1.0000
3:4316209:TAG:T	acceptor_loss	1.0000
3:4316210:A:AG	acceptor_gain	1.0000
3:4316211:G:A	acceptor_loss	1.0000
3:4316211:G:GA	acceptor_gain	1.0000
3:4316211:GA:G	acceptor_gain	1.0000
3:4316211:GACT:G	acceptor_gain	1.0000
3:4303473:G:GT	donor_gain	0.9900
3:4303474:A:T	donor_gain	0.9900
3:4312896:A:AG	acceptor_gain	0.9900
3:4312897:G:GG	acceptor_gain	0.9900
3:4314068:T:A	acceptor_gain	0.9900
3:4316199:AT:A	acceptor_gain	0.9900
3:4316200:T:G	acceptor_gain	0.9900
3:4316200:T:TA	acceptor_gain	0.9900
3:4316205:A:AG	acceptor_gain	0.9900
3:4316211:GAC:G	acceptor_gain	0.9900
3:4316211:GACTA:G	acceptor_gain	0.9900
3:4303523:CCAG:C	donor_loss	0.9800
3:4303524:CAGGT:C	donor_loss	0.9800
3:4303525:AG:A	donor_loss	0.9800
3:4303526:GGT:G	donor_loss	0.9800
3:4303527:GT:G	donor_loss	0.9800
3:4312897:GT:G	acceptor_gain	0.9800
3:4312897:GTACA:G	acceptor_gain	0.9800
3:4313226:G:GT	donor_gain	0.9800
3:4313532:G:GT	donor_gain	0.9800
3:4316206:T:G	acceptor_gain	0.9800
3:4316208:TTAGA:T	acceptor_gain	0.9800

AlphaMissense

4523 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:4313445:T:A	V235D	0.993
3:4313199:T:C	L153P	0.992
3:4313402:T:C	F221L	0.990
3:4313404:C:A	F221L	0.990
3:4313404:C:G	F221L	0.990
3:4313480:T:C	F247L	0.989
3:4313482:T:A	F247L	0.989
3:4313482:T:G	F247L	0.989
3:4316368:T:C	F393L	0.989
3:4316370:T:A	F393L	0.989
3:4316370:T:G	F393L	0.989
3:4313430:T:C	L230P	0.988
3:4313231:T:C	F164L	0.986
3:4313233:T:A	F164L	0.986
3:4313233:T:G	F164L	0.986
3:4316488:G:C	A433P	0.986
3:4313202:G:C	R154P	0.985
3:4316359:T:C	F390L	0.984
3:4316361:C:A	F390L	0.984
3:4316361:C:G	F390L	0.984
3:4313192:T:A	W151R	0.983
3:4313192:T:C	W151R	0.983
3:4313370:T:A	V210D	0.983
3:4313448:G:C	R236P	0.983
3:4316519:T:A	V443D	0.983
3:4313171:T:C	F144L	0.982
3:4313173:C:A	F144L	0.982
3:4313173:C:G	F144L	0.982
3:4313481:T:C	F247S	0.981
3:4313366:T:C	F209L	0.978

dbSNP variants (sampled 300 via entrez): RS1000042683 (3:4312736 G>A), RS1000083070 (3:4315598 T>C), RS1000231050 (3:4307081 C>G), RS1000520027 (3:4312439 AATAC>A), RS1000687364 (3:4314221 A>T), RS1000691409 (3:4308023 T>C,G), RS1001205827 (3:4313958 C>G,T), RS1001296700 (3:4302816 G>C), RS1001348193 (3:4307518 G>A), RS1001472969 (3:4302744 T>C), RS1001558253 (3:4306505 G>A), RS1001629170 (3:4312150 A>G), RS1001709685 (3:4317594 A>C), RS1002082289 (3:4313238 G>A,C,T), RS1002142140 (3:4311910 T>C)

Disease associations

OMIM: gene MIM:609834 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002129_8	Periodontitis (DPAL)	8.000000e-06
GCST004283_1	Midgestational circulating levels of PCBs	1.000000e-07
GCST004283_14	Midgestational circulating levels of PCBs	1.000000e-07
GCST004283_17	Midgestational circulating levels of PCBs	9.000000e-08
GCST004283_19	Midgestational circulating levels of PCBs	2.000000e-07
GCST004283_2	Midgestational circulating levels of PCBs	9.000000e-08
GCST006291_3	Spherical equivalent or myopia (age of diagnosis)	9.000000e-09
GCST010002_413	Refractive error	3.000000e-16
GCST010516_2	Fractures (paediatric)	1.000000e-07
GCST012616_17	Spondylosis	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007042	polychlorinated biphenyls measurement
EFO:0007964	gestational serum measurement
EFO:0004847	age at onset

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2189111 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	4
Cisplatin	increases expression	2
Valproic Acid	affects expression, decreases expression, decreases methylation	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
trichostatin A	affects expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	affects binding, increases reaction	1
CPG-oligonucleotide	increases expression	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Resveratrol	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases response to substance	1
Acetaminophen	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2209105	Binding	Inhibition of SETMAR using histone H3 as substrate preincubated for 10 mins followed by addition of [3H]SAM and incubated for 60 mins	Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. — ACS Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TK78	HAP1 SETMAR (-) 1	Cancer cell line	Male
CVCL_TK79	HAP1 SETMAR (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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