SETD7

Summary

SETD7 (SET domain containing 7, histone lysine methyltransferase, HGNC:30412) is a protein-coding gene on chromosome 4q31.1, encoding Histone-lysine N-methyltransferase SETD7 (Q8WTS6). Histone methyltransferase that specifically monomethylates ‘Lys-4’ of histone H3.

Enables histone H3 methyltransferase activity; p53 binding activity; and protein-lysine N-methyltransferase activity. Involved in peptidyl-lysine dimethylation and peptidyl-lysine monomethylation. Acts upstream of or within DNA damage response and heterochromatin organization. Located in chromosome and nucleolus.

Source: NCBI Gene 80854 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 40 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_030648

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30412
Approved symbol	SETD7
Name	SET domain containing 7, histone lysine methyltransferase
Location	4q31.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1717, SET7, SET7/9, Set9, KMT7
Ensembl gene	ENSG00000145391
Ensembl biotype	protein_coding
OMIM	606594
Entrez	80854

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000274031, ENST00000404104, ENST00000406354, ENST00000506866, ENST00000515101, ENST00000608795, ENST00000608958, ENST00000913016, ENST00000954983, ENST00000954984

RefSeq mRNA: 3 — MANE Select: NM_030648 NM_001306199, NM_001306200, NM_030648

CCDS: CCDS3748, CCDS77961, CCDS82956

Canonical transcript exons

ENST00000274031 — 8 exons

Exon	Start	End
ENSE00001192306	139506038	139511843
ENSE00001643989	139533165	139533366
ENSE00001663487	139520277	139520394
ENSE00001671090	139529031	139529220
ENSE00001802218	139523354	139523435
ENSE00001831410	139556098	139556219
ENSE00003569499	139546920	139547049
ENSE00003674982	139517885	139518042

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.25.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.6230 / max 290.2020, expressed in 1761 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54068	22.2488	1742
54070	4.9162	1480
54073	1.4580	571
54067	1.4352	880
54069	0.4273	214
54075	0.4102	196
54071	0.2275	101
54074	0.1830	71
54072	0.1372	47
54080	0.1182	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	99.25	gold quality
deltoid	UBERON:0001476	99.18	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.17	gold quality
left ventricle myocardium	UBERON:0006566	98.83	gold quality
upper arm skin	UBERON:0004263	98.77	gold quality
quadriceps femoris	UBERON:0001377	98.53	gold quality
biceps brachii	UBERON:0001507	98.51	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.51	gold quality
vastus lateralis	UBERON:0001379	98.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.38	gold quality
decidua	UBERON:0002450	98.12	gold quality
synovial joint	UBERON:0002217	97.94	gold quality
layer of synovial tissue	UBERON:0007616	97.88	gold quality
myocardium	UBERON:0002349	97.80	gold quality
skeletal muscle tissue	UBERON:0001134	97.73	gold quality
mammary duct	UBERON:0001765	97.56	gold quality
epithelium of mammary gland	UBERON:0003244	97.53	gold quality
saphenous vein	UBERON:0007318	97.23	gold quality
pericardium	UBERON:0002407	97.22	gold quality
tibia	UBERON:0000979	97.17	gold quality
muscle tissue	UBERON:0002385	97.14	gold quality
heart right ventricle	UBERON:0002080	96.88	gold quality
body of tongue	UBERON:0011876	96.72	gold quality
urethra	UBERON:0000057	96.70	gold quality
vena cava	UBERON:0004087	96.63	gold quality
cardia of stomach	UBERON:0001162	96.61	gold quality
skin of hip	UBERON:0001554	96.40	gold quality
tongue	UBERON:0001723	95.95	gold quality
ganglionic eminence	UBERON:0004023	95.56	gold quality
embryo	UBERON:0000922	95.55	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, MBD2, PDX1, STAT3, TCF12, TP53

miRNA regulators (miRDB)

249 targeting SETD7, 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-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-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
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-5696	99.98	72.36	4487
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-4482-3P	99.98	72.50	3147

Literature-anchored findings (GeneRIF, showing 40)

• purification and functional characterization of a histone H3-lysine 4-specific methyltransferase (PMID:11779497)
• crystal structure of human SET7/9 shows residues essential for catalytic activity with histone H3 (PMID:12372304)
• Crystal structure and catalytic mechanism of the human histone methyltransferase SET7/9 (PMID:12540855)
• This enzyme and human Sin3 deacetylase are tethered together selectively by the cell-proliferation factor HCF-1. (PMID:12670868)
• SET7/9 recognizes a conserved K/R-S/T/A motif preceding the lysine substrate and has a propensity to bind aspartates and asparagines on the C-terminal side of the lysine target (PMID:16415881)
• RBP2 associates with MRG15 complex to maintain reduced H3K4 methylation at transcribed regions, which may ensure the transcriptional elongation state (PMID:17573780)
• Results suggest that the cross talk between lysine methylation and acetylation is critical for p53 activation in response to DNA damage and that Set7/9 may play an important role in tumor suppression. (PMID:17646389)
• Results show that estrogen receptor alpha is directly methylated at lysine 302 (K302) by the SET7 methyltransferase. (PMID:18471979)
• This report shows that H3K9 monomethylation is dependent upon the PR-Set7 H4K20 monomethyltransferase but independent of its catalytic function, indicating that PR-Set7 recruits an H3K9 monomethyltransferase to establish the trans-tail histone code. (PMID:18474616)
• a novel role for SET7/9 in inflammation and diabetes. (PMID:18650421)
• Data show that lysine methyltransferase Set9 physically associates with RelA in vitro and in vivo in response to TNF-alpha. (PMID:19262565)
• signaling through SET7 represents a means of DNMT1 enzyme turnover (PMID:19282482)
• These data may lead to a new insight into PCAF functions and provide additional information to identify unknown targets of Set9. (PMID:19351588)
• the binding of two SET domain-containing proteins, ALL1 and SET7, to chromatin substrates was studied. (PMID:19752191)
• Set7/9-KMT7 associates with the HIV promoter in vivo and monomethylates lysine 51, a highly conserved residue located in the RNA-binding domain of Tat. (PMID:20227666)
• SET7/9 catalytic mutants reveal the role of active site water molecules in lysine multiple methylation (PMID:20675860)
• Data show that STAT3 binds to the SOCS3 promoter, and S727 is then phosphorylated, followed by the coincident binding of SET9 and dimethylation of K140, and lastly by the binding of LSD1. (PMID:21098664)
• results reveal that Set7/9 is a critical regulator of the SIRT1-p53 interaction and suggest that Set7/9 can modulate p53 function indirectly in addition to acting through a methylation-dependent mechanism (PMID:21245319)
• Set9 directly acts on AR at the amino acid level. Chromatin recruitment of Set9 to AREs is suggestive of its additional role as a transcriptional coactivator. (PMID:21273441)
• Direct evidence for methyl group coordination by carbon-oxygen hydrogen bonds in the lysine methyltransferase SET7/9. (PMID:21454678)
• genetic association studies in a Finnish population with type I diabetes: No associations were found between SNPs in SETD7 and the diabetic complications studied. (PMID:21896933)
• simulations show that while the wild-type SET7/9 is a monomethylase, the Y245–>A mutation increases the ability of the enzyme to add more methyl groups on the target lysine (PMID:22242964)
• The response to hyperglycemia in vascular endothelial cells involves Set7 mediated changes in chromatin remodeling and gene expression. (PMID:22403242)
• H3K4me3 level defines unrecognized subsets of heptaocellular carcinoma patients with distinct epigenetic phenotype and clinical outcome and can thus be a novel predictor for poor prognosis of heptaocellular carcinoma patients (PMID:22406368)
• The methyltransferase Set9 directly methylates FoxO3 in vitro and in cells. The modulation of FoxO3 stability and activity by methylation may be critical for fine-tuning cellular responses to stress stimuli. (PMID:22820736)
• Methylation of SUV39H1 by SET7/9 results in heterochromatin relaxation and genome instability. (PMID:23509280)
• The crystal structures presented here provide information about the binding of both AdoMet-analogue inhibitors and peptides by the SET domain of SET7/9. (PMID:23519668)
• study indicates that Set7/9 prevents the histone deacetylase activity of SirT1, potentiating euchromatin formation on the promoter site of COL2A1 and resulting in morphology-dependent COL2A1 gene transactivation. (PMID:23873758)
• Vesicular stomatitis virus and influenza A virus increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-alpha reduced IFITM3-K88me1 levels. (PMID:24129573)
• Set7-dependent gene expression changes that occurred independent of H3K4m1 may involve transcription factor lysine methylation events. (PMID:24875254)
• Results show Set7 efficiently monomethylates Sox2 at K119 residue controling its stability. (PMID:25042802)
• Set7/9 is a potential biomarker in tumour cells and is associated with overexpressed E2F1 activity. (PMID:25124555)
• Set7-induced epigenetic changes contribute to vascular dysfunction in patients with T2DM. (PMID:25472959)
• SET9 enriches at hypoxia response elements sites of HIF-1 responsive glycolytic genes and stabilizes HIF-1alpha at these sites in hypoxia. (PMID:25637186)
• Results show that histone-lysine N-methyltransferase Set7 facilitates hepatitis C virus (HCV) replication through the attenuation of interferon-alpha (IFN-alpha) signaling pathways and IFN-related effectors. (PMID:25681344)
• Based on our results miR-153 inhibits proliferation and suppresses EMT and the invasive potential of ovarian cancer cells through downregulation of SET7 and ZEB2, supporting the pursuit of miR-153 as a potential target for ovarian cancer intervention. (PMID:25954928)
• Findings indicate the regulation of Wnt/beta-catenin signaling and the role of SET domain-containing protein 7/9 (SET7/9) in cancer cells. (PMID:26116705)
• Unleashed expression of Mdm2 in cancer patients with diminished expression of Set7/9 is associated with poor survival outcome. (PMID:26317544)
• Lysine methylation by SETD7 is important for the fine-tuning of reactive oxygen species signaling through its regulation on pro-inflammatory responses. (PMID:26435321)
• Reduced expression of SET7 is associated with gastric cancer progression. (PMID:26701885)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	setd7	ENSDARG00000038858
mus_musculus	Setd7	ENSMUSG00000037111
rattus_norvegicus	Setd7	ENSRNOG00000013045

Paralogs (7): MORN1 (ENSG00000116151), MORN3 (ENSG00000139714), RSPH10B (ENSG00000155026), RSPH1 (ENSG00000160188), RSPH10B2 (ENSG00000169402), ALS2CL (ENSG00000178038), MORN2 (ENSG00000188010)

Protein

Protein identifiers

Histone-lysine N-methyltransferase SETD7 — Q8WTS6 (reviewed: Q8WTS6)

Alternative names: Histone H3-K4 methyltransferase SETD7, Lysine N-methyltransferase 7, SET domain-containing protein 7, SET7/9

All UniProt accessions (5): B5MCZ8, D6RJA0, Q8WTS6, V9GY19, V9GYG1

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase that specifically monomethylates ‘Lys-4’ of histone H3. H3 ‘Lys-4’ methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Also has methyltransferase activity toward non-histone proteins such as CGAS, p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates ‘Lys-189’ of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates ‘Lys-372’ of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation. Monomethylates ‘Lys-491’ of CGAS, promoting interaction between SGF29 and CGAS.

Subunit / interactions. Interacts with IPF1/PDX-1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Widely expressed. Expressed in pancreatic islets.

Domain organisation. The SET domain is necessary but not sufficient for histone methyltransferase activity.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET7 subfamily.

RefSeq proteins (3): NP_001293128, NP_001293129, NP_085151* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR003409	MORN	Repeat
IPR017155	Hist-Lys_N-MeTrfase_SETD7	Family
IPR044436	SETD7_SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR054533	SETD7_N	Domain

Pfam: PF00856, PF02493, PF22648

Enzyme classification (BRENDA):

• EC 2.1.1.364 — [histone H3]-lysine4 N-methyltransferase (BRENDA: 2 organisms, 46 substrates, 4 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 2 shown:

• L-lysyl-[protein] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine + H(+) (RHEA:51736)
• L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60264)

UniProt features (59 total): strand 28, mutagenesis site 6, helix 6, site 5, turn 5, binding site 4, repeat 3, chain 1, domain 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
2F69	X-RAY DIFFRACTION	1.3
3M58	X-RAY DIFFRACTION	1.4
3CBP	X-RAY DIFFRACTION	1.42
3M55	X-RAY DIFFRACTION	1.55
5EG2	X-RAY DIFFRACTION	1.55
4J7F	X-RAY DIFFRACTION	1.59
3M54	X-RAY DIFFRACTION	1.6
4J8O	X-RAY DIFFRACTION	1.63
3CBO	X-RAY DIFFRACTION	1.65
3M56	X-RAY DIFFRACTION	1.65
3CBM	X-RAY DIFFRACTION	1.69
3OS5	X-RAY DIFFRACTION	1.69
5YLT	X-RAY DIFFRACTION	1.69
1N6A	X-RAY DIFFRACTION	1.7
3M57	X-RAY DIFFRACTION	1.7
3M59	X-RAY DIFFRACTION	1.7
4J83	X-RAY DIFFRACTION	1.7
4JDS	X-RAY DIFFRACTION	1.7
1O9S	X-RAY DIFFRACTION	1.75
1XQH	X-RAY DIFFRACTION	1.75
3M5A	X-RAY DIFFRACTION	1.75
3M53	X-RAY DIFFRACTION	1.85
4JLG	X-RAY DIFFRACTION	1.9
4E47	X-RAY DIFFRACTION	2
3VV0	X-RAY DIFFRACTION	2
5AYF	X-RAY DIFFRACTION	2
1H3I	X-RAY DIFFRACTION	2.1
1MT6	X-RAY DIFFRACTION	2.2
1MUF	X-RAY DIFFRACTION	2.26
1N6C	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WTS6-F1	94.51	0.87

Functional residue map

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

Catalytic / active sites (5): 256 (histone h3k4 binding); 266 (histone h3k4 binding); 317 (histone h3k4 binding); 335 (histone h3k4 binding); 245 (histone h3k4 binding)

Ligand- & substrate-binding residues (4): 226–228; 296; 297; 356

Mutagenesis-validated functional residues (6):

Position	Phenotype
220	increases near-attack conformations.
228	increases near-attack conformations.
245	significantly reduces the monomethyltransferase activity but increases the dimethyltransferase activity.
294	significantly reduces the catalytic activity.
297	abolishes methyltransferase activity.
317	induces a reduction in methyltransferase activity toward taf10 but an increased methyltransferase activity for h3 and p5

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: 220 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, AAGCAAT_MIR137, TTTGTAG_MIR520D, AAGCCAT_MIR135A_MIR135B, TACAATC_MIR508, CTATGCA_MIR153, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_PEPTIDYL_LYSINE_MODIFICATION, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, NF1_Q6_01, GROSS_HYPOXIA_VIA_ELK3_UP, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN, CAATGCA_MIR33, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE

GO Biological Process (14): DNA repair (GO:0006281), chromatin organization (GO:0006325), DNA damage response (GO:0006974), peptidyl-lysine monomethylation (GO:0018026), peptidyl-lysine dimethylation (GO:0018027), response to ethanol (GO:0045471), negative regulation of DNA repair (GO:0045738), positive regulation of DNA-templated transcription (GO:0045893), heterochromatin organization (GO:0070828), regulation of DNA repair (GO:0006282), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), methylation (GO:0032259), response to alcohol (GO:0097305)

GO Molecular Function (9): p53 binding (GO:0002039), chromatin binding (GO:0003682), protein-lysine N-methyltransferase activity (GO:0016279), histone methyltransferase activity (GO:0042054), histone H3 methyltransferase activity (GO:0140938), histone H3K4 monomethyltransferase activity (GO:0140945), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730)

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
peptidyl-lysine methylation	2
DNA repair	2
DNA-templated transcription	2
chromatin organization	2
binding	2
protein methyltransferase activity	2
nuclear lumen	2
intracellular membraneless organelle	2
DNA metabolic process	1
DNA damage response	1
cellular component organization	1
cellular response to stress	1
response to alcohol	1
regulation of DNA repair	1
negative regulation of response to stimulus	1
negative regulation of DNA metabolic process	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
metabolic process	1
response to oxygen-containing compound	1
protein binding	1
lysine N-methyltransferase activity	1
histone modifying activity	1
histone methyltransferase activity	1
histone H3K4 methyltransferase activity	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2586 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SETD7	SMYD2	Q9NRG4	857
SETD7	KMT5A	Q9NQR1	838
SETD7	TBX21	Q9UL17	836
SETD7	DNMT1	P26358	836
SETD7	H3-7	Q5TEC6	834
SETD7	H3-5	Q6NXT2	834
SETD7	H3C14	Q71DI3	834
SETD7	H3C1	P02295	833
SETD7	H3-4	Q16695	833
SETD7	H3-3A	P06351	831
SETD7	EHMT2	Q96KQ7	816
SETD7	SIRT1	Q96EB6	806
SETD7	KDM1A	O60341	797
SETD7	MYOD1	P15172	713
SETD7	SETD2	Q9BYW2	709

IntAct

91 interactions, top by confidence:

A	B	Type	Score
TP53	SETD7	psi-mi:“MI:0407”(direct interaction)	0.920
SETD7	TP53	psi-mi:“MI:0407”(direct interaction)	0.920
TP53	SETD7	psi-mi:“MI:0213”(methylation reaction)	0.920
SETD7	TP53	psi-mi:“MI:0213”(methylation reaction)	0.920
TP53	SETD7	psi-mi:“MI:0915”(physical association)	0.920
SETD7	DNMT1	psi-mi:“MI:0213”(methylation reaction)	0.740
SETD7	DNMT1	psi-mi:“MI:0407”(direct interaction)	0.740
DNMT1	SETD7	psi-mi:“MI:0915”(physical association)	0.740
RELA	SETD7	psi-mi:“MI:0213”(methylation reaction)	0.740
DNMT1	SETD7	psi-mi:“MI:0407”(direct interaction)	0.740
DNMT1	SETD7	psi-mi:“MI:0213”(methylation reaction)	0.740
SETD7	RELA	psi-mi:“MI:0213”(methylation reaction)	0.740
RELA	SETD7	psi-mi:“MI:0915”(physical association)	0.740
SETD7	RELA	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (142): ESR1 (Biochemical Activity), SETD7 (Biochemical Activity), SETD7 (Affinity Capture-MS), SETD7 (Affinity Capture-MS), SETD7 (Affinity Capture-MS), SETD7 (Affinity Capture-MS), SETD7 (Proximity Label-MS), SETD7 (Affinity Capture-MS), SETD7 (Reconstituted Complex), SETD7 (Affinity Capture-MS), SMAD7 (Biochemical Activity), RNF111 (Affinity Capture-Western), SMURF1 (Affinity Capture-Western), SMURF2 (Affinity Capture-Western), SETD7 (Affinity Capture-MS)

ESM2 similar proteins: A0A3L7I2I8, A2AGL3, A6H7H7, B0LPN4, E9Q401, F1LNJ2, O60733, O75643, O89000, P30957, P59723, P97443, P97570, P97819, Q14353, Q15413, Q28007, Q28943, Q32PP3, Q4QQN5, Q59H18, Q5F361, Q5GIG6, Q5HZ68, Q5RER6, Q5RF15, Q6DHG0, Q6NRC7, Q6NU47, Q6P4T2, Q6PBF6, Q7L273, Q7TQP6, Q7TSV3, Q7ZXG7, Q8BM85, Q8CA95, Q8CHR6, Q8N165, Q8NB12

Diamond homologs: Q4QQN5, Q6DHG0, Q7Z0G7, Q8VHL1, Q8WTS6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
chromatin organization	5	16.0×	1e-03
transcription by RNA polymerase II	6	13.7×	1e-03
negative regulation of gene expression	5	11.1×	4e-03
negative regulation of apoptotic process	6	6.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1591 predictions. Top by Δscore:

Variant	Effect	Δscore
4:139517880:CTT:C	donor_loss	1.0000
4:139517881:TTA:T	donor_loss	1.0000
4:139517882:TACAT:T	donor_loss	1.0000
4:139517883:A:AC	donor_gain	1.0000
4:139517884:C:CT	donor_gain	1.0000
4:139517884:CA:C	donor_gain	1.0000
4:139517884:CAT:C	donor_gain	1.0000
4:139517884:CATA:C	donor_gain	1.0000
4:139517884:CATAT:C	donor_gain	1.0000
4:139518038:TCAAC:T	acceptor_gain	1.0000
4:139518039:CAAC:C	acceptor_gain	1.0000
4:139518039:CAACC:C	acceptor_gain	1.0000
4:139518040:AAC:A	acceptor_gain	1.0000
4:139518041:AC:A	acceptor_gain	1.0000
4:139518041:ACC:A	acceptor_gain	1.0000
4:139518042:CC:C	acceptor_gain	1.0000
4:139518042:CCTG:C	acceptor_loss	1.0000
4:139518042:CCTGC:C	acceptor_gain	1.0000
4:139518043:C:CC	acceptor_gain	1.0000
4:139518043:C:CG	acceptor_loss	1.0000
4:139518046:C:CT	acceptor_gain	1.0000
4:139518047:A:T	acceptor_gain	1.0000
4:139523349:ATTAC:A	donor_loss	1.0000
4:139523350:TTACC:T	donor_loss	1.0000
4:139523351:TA:T	donor_loss	1.0000
4:139523352:ACCT:A	donor_loss	1.0000
4:139523353:C:CA	donor_loss	1.0000
4:139523353:CCTTT:C	donor_gain	1.0000
4:139523436:C:CC	acceptor_gain	1.0000
4:139523436:CTGA:C	acceptor_loss	1.0000

AlphaMissense

2413 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:139517896:G:C	C303W	0.999
4:139520299:C:T	G247E	0.999
4:139546978:C:G	G38R	0.999
4:139546978:C:T	G38R	0.999
4:139511710:A:G	W352R	0.998
4:139511710:A:T	W352R	0.998
4:139533355:C:T	G61E	0.998
4:139533356:C:A	G61W	0.998
4:139533356:C:G	G61R	0.998
4:139533356:C:T	G61R	0.998
4:139533361:A:G	L59P	0.998
4:139546977:C:T	G38E	0.998
4:139546978:C:A	G38W	0.998
4:139511708:C:A	W352C	0.997
4:139511708:C:G	W352C	0.997
4:139511766:A:T	V333D	0.997
4:139517923:C:A	K294N	0.997
4:139517923:C:G	K294N	0.997
4:139517930:C:T	G292E	0.997
4:139517931:C:G	G292R	0.997
4:139517931:C:T	G292R	0.997
4:139520300:C:G	G247R	0.997
4:139520300:C:T	G247R	0.997
4:139546983:A:G	F36S	0.997
4:139517897:C:T	C303Y	0.996
4:139517898:A:G	C303R	0.996
4:139517913:A:G	S298P	0.996
4:139518025:C:A	W260C	0.996
4:139518025:C:G	W260C	0.996
4:139518027:A:G	W260R	0.996

dbSNP variants (sampled 300 via entrez): RS1000109954 (4:139519601 T>C), RS10001652 (4:139549530 C>T), RS1000185675 (4:139501833 G>A), RS1000245470 (4:139499284 G>A), RS1000271773 (4:139549617 T>C), RS1000315346 (4:139530644 A>C), RS1000367127 (4:139543668 A>C), RS1000381826 (4:139499555 C>A,G), RS1000417464 (4:139533870 T>C), RS1000438582 (4:139536947 G>A,C), RS1000528195 (4:139524419 A>G), RS1000533799 (4:139544220 G>C), RS1000542107 (4:139544557 A>G), RS1000576148 (4:139518303 A>G), RS1000743529 (4:139543237 G>A)

Disease associations

OMIM: gene MIM:606594 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000349_5	Smoking behavior	8.000000e-06
GCST003433_1	Serum lycopene concentrations	5.000000e-09
GCST005041_1	Diastolic blood pressure in combination therapy (beta blocker and thiazide diuretic)	3.000000e-07
GCST008024_2	Salty taste perception in obesity with metabolic syndrome	4.000000e-06
GCST008153_11	Lean body mass	3.000000e-06
GCST012145_19	Ferritin levels	7.000000e-06

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0007801	lycopene measurement
EFO:0006336	diastolic blood pressure
EFO:0007766	response to beta blocker
EFO:0004995	lean body mass
EFO:0004459	ferritin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5523 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 43,654 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL516	CYPROHEPTADINE	4	17,487
CHEMBL1214186	SINEFUNGIN	2	2,165
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL152408	PIMETHIXENE	2	479

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)

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
(R)-PFI-2	Inhibition	9.48	pKi

ChEMBL bioactivities

28 potent at pChembl≥5 of 74 total, top 23 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.48	Ki	0.33	nM	CHEMBL3414622
8.70	IC50	2	nM	CHEMBL3414622
8.70	IC50	2	nM	CHEMBL4789678
8.38	Kd	4.2	nM	CHEMBL4789678
8.38	Kd	4.2	nM	CHEMBL3414622
7.75	Kd	18	nM	CHEMBL4789678
6.96	IC50	110	nM	CHEMBL5712041
6.00	IC50	1000	nM	CYPROHEPTADINE
6.00	IC50	1000	nM	CHEMBL5712060
5.71	IC50	1960	nM	SCUTELLAREIN
5.66	IC50	2200	nM	CHEMBL3414624
5.62	IC50	2380	nM	SINEFUNGIN
5.60	IC50	2500	nM	CHEMBL5184605
5.60	IC50	2500	nM	SINEFUNGIN
5.47	IC50	3400	nM	CYPROHEPTADINE
5.37	IC50	4300	nM	PIMETHIXENE
5.34	IC50	4590	nM	CHEMBL3623751
5.31	IC50	4880	nM	CHEMBL3623770
5.22	IC50	6020	nM	MORIN
5.22	IC50	6080	nM	LUTEOLIN
5.14	IC50	7200	nM	CHEMBL3809236
5.04	IC50	9100	nM	SINEFUNGIN
5.00	IC50	9930	nM	CHEMBL3238424

PubChem BioAssay actives

23 with measured affinity, of 433 total; 15 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-fluoro-N-[(2R)-1-oxo-1-pyrrolidin-1-yl-3-[3-(trifluoromethyl)phenyl]propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide	1199174: Inhibition of full-length human SETD7 expressed in Escherichia coli BL21 (DE3) using biotinylated histone H3 (1 to 25) as substrate after 1 hr by Flash Plate assay in presence of [3H]-SAM	ki	0.0003	uM
5-[(3aR,4S,6aS)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-N-[2-[2-[2-[2-[3-[6-[4-[[4-[4-[(2R)-2-[(8-fluoro-1,2,3,4-tetrahydroisoquinolin-6-yl)sulfonylamino]-3-oxo-3-pyrrolidin-1-ylpropyl]benzoyl]phenoxy]methyl]triazol-1-yl]hexylamino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethyl]pentanamide	2186959: Inhibition of wildtype full length human SETD7 (1 to 366 residues) expressed in Escherichia coli BL21 (DE3) V2R-pRARE using biotinylated H3 (1-25) peptide as substrate incubated for 1 hrs in presence of 3H-SAM by radioactivity based assay	ic50	0.1100	uM
Cyproheptadine	1302504: Inhibition of recombinant Set7/9 (unknown origin) expressed in Escherichia coli BL21 (DE3) using biotinylated histone H3-derived peptide/SAM as substrate by alphaLISA	ic50	1.0000	uM
8-fluoro-N-[(2S)-1-oxo-1-pyrrolidin-1-yl-3-[3-(trifluoromethyl)phenyl]propan-2-yl]-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide	2186959: Inhibition of wildtype full length human SETD7 (1 to 366 residues) expressed in Escherichia coli BL21 (DE3) V2R-pRARE using biotinylated H3 (1-25) peptide as substrate incubated for 1 hrs in presence of 3H-SAM by radioactivity based assay	ic50	1.0000	uM
5,6,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one	1667216: Inhibition of human SET7 overexpressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by addition of SAM as substrate and biotinylated Histone H3 (1-50) peptide measured after 30 mins by AlphaLISA assay relative to control	ic50	1.9600	uM
(2S,5S)-2-amino-6-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]-5-(propylamino)hexanoic acid	1199205: Inhibition of full-length human SETD7 using histamine H3 (1 to 21) as substrate assessed as transfer of [3H]-Me of [3H-Me]-SAM to peptide substrate after 3 hrs by scintillation counting analysis	ic50	2.2000	uM
(2S,5R)-2,5-diamino-6-[(2S,3R,4S,5S)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]hexanoic acid	1882356: Inhibition of SET7 (unknown origin)	ic50	2.5000	uM
(2S,5S)-2,5-diamino-6-[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]hexanoic acid	476874: Inhibition of GST-fused human recombinant SET7 after 90 mins by SDS-PAGE based scintillation counting	ic50	2.5000	uM
1-methyl-4-thioxanthen-9-ylidenepiperidine	1311948: Inhibition of recombinant SET7/9 (unknown origin) using biotinylated histone H3-derived peptide/SAM as substrate after 60 mins by AlphaLISA assay	ic50	4.3000	uM
ethyl 2-amino-4-methyl-5-[(3-nitrophenyl)carbamoyl]thiophene-3-carboxylate	1251545: Competitive inhibition of SET7 (unknown origin) after 60 mins by AlphaLISA method in presence of SAM	ic50	4.5900	uM
methyl 2-amino-4-methyl-5-[(3-nitrophenyl)carbamoyl]thiophene-3-carboxylate	1251545: Competitive inhibition of SET7 (unknown origin) after 60 mins by AlphaLISA method in presence of SAM	ic50	4.8800	uM
2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one	1667216: Inhibition of human SET7 overexpressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by addition of SAM as substrate and biotinylated Histone H3 (1-50) peptide measured after 30 mins by AlphaLISA assay relative to control	ic50	6.0200	uM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one	1667216: Inhibition of human SET7 overexpressed in Escherichia coli BL21 (DE3) cells preincubated for 15 mins followed by addition of SAM as substrate and biotinylated Histone H3 (1-50) peptide measured after 30 mins by AlphaLISA assay relative to control	ic50	6.0800	uM
1-ethyl-4-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenylidene)piperidine	1302504: Inhibition of recombinant Set7/9 (unknown origin) expressed in Escherichia coli BL21 (DE3) using biotinylated histone H3-derived peptide/SAM as substrate by alphaLISA	ic50	7.2000	uM
3-[[3-[4-[4-(trifluoromethyl)phenyl]indol-1-yl]phenyl]methylamino]benzoic acid	1125539: Inhibition of methyl-transferase activity in GST-tagged recombinant SET7/9 (unknown origin) expressed in Escherichia coli BL21 using H3(1-20)-cys-biotin as substrate preincubated for 5 mins followed by substrate addition by ELISA	ic50	9.9300	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	5
trichostatin A	affects cotreatment, increases expression, affects expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Doxorubicin	affects binding, increases stability, increases reaction, increases expression, increases response to substance (+4 more)	2
Estradiol	increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression, increases abundance	2
methylmercuric chloride	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Berberine	increases expression	1

ChEMBL screening assays

165 unique, capped per target: 163 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1023893	Binding	Inhibition of Set7/9 lysine methyltransferase	N-Benzyl-1-heteroaryl-3-(trifluoromethyl)-1H-pyrazole-5-carboxamides as inhibitors of co-activator associated arginine methyltransferase 1 (CARM1). — Bioorg Med Chem Lett
CHEMBL5723168	Functional	Affinity Biochemical interaction: (inhibition of histone H3(1-21) methylation) EUB0002319a SETD7	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2F4	Abcam HeLa SETD7 KO	Cancer cell line	Female
CVCL_B8PA	Abcam HCT 116 SETD7 KO	Cancer cell line	Male
CVCL_B9BF	Abcam MCF-7 SETD7 KO	Cancer cell line	Female
CVCL_B9RN	Abcam A-549 SETD7 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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