SUV39H2

Summary

SUV39H2 (SUV39H2 histone lysine methyltransferase, HGNC:17287) is a protein-coding gene on chromosome 10p13, encoding Histone-lysine N-methyltransferase SUV39H2 (Q9H5I1). Histone methyltransferase that specifically mediates trimethylation of ‘Lys-9’ of histone H3 (H3K9me3) using monomethylated H3 ‘Lys-9’ (H3K9me1) as substrate.

Enables cation binding activity; histone H3K9 methyltransferase activity; and ubiquitin-like ligase-substrate adaptor activity. Involved in epigenetic programming in the zygotic pronuclei. Acts upstream of or within cellular response to hypoxia and negative regulation of transcription by RNA polymerase II. Located in chromatin. Is active in nucleus.

Source: NCBI Gene 79723 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• Druggable target: yes
• MANE Select transcript: NM_001193424

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17287
Approved symbol	SUV39H2
Name	SUV39H2 histone lysine methyltransferase
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ23414, KMT1B
Ensembl gene	ENSG00000152455
Ensembl biotype	protein_coding
OMIM	606503
Entrez	79723

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 8 protein_coding, 1 nonsense_mediated_decay

ENST00000313519, ENST00000354919, ENST00000358298, ENST00000378325, ENST00000378331, ENST00000412254, ENST00000420416, ENST00000433779, ENST00000876681

RefSeq mRNA: 5 — MANE Select: NM_001193424 NM_001193424, NM_001193425, NM_001193426, NM_001193427, NM_024670

CCDS: CCDS53493, CCDS53494, CCDS7104

Canonical transcript exons

ENST00000354919 — 6 exons

Exon	Start	End
ENSE00001815292	14902406	14904315
ENSE00001932261	14878866	14878919
ENSE00003470012	14881500	14881645
ENSE00003479270	14899539	14899685
ENSE00003512484	14896846	14897517
ENSE00003616442	14901133	14901262

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 95.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.8872 / max 823.0704, expressed in 1705 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103985	17.4601	1697
103984	0.2247	77
103983	0.2025	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	95.73	gold quality
secondary oocyte	CL:0000655	95.45	gold quality
male germ cell	CL:0000015	91.76	gold quality
left testis	UBERON:0004533	91.20	gold quality
right testis	UBERON:0004534	90.78	gold quality
testis	UBERON:0000473	89.98	gold quality
ventricular zone	UBERON:0003053	89.97	gold quality
ganglionic eminence	UBERON:0004023	89.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.26	gold quality
oocyte	CL:0000023	88.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.63	gold quality
adrenal tissue	UBERON:0018303	84.29	gold quality
cortical plate	UBERON:0005343	81.74	gold quality
endothelial cell	CL:0000115	80.04	silver quality
stromal cell of endometrium	CL:0002255	78.62	gold quality
islet of Langerhans	UBERON:0000006	77.61	gold quality
endometrium	UBERON:0001295	77.45	gold quality
rectum	UBERON:0001052	76.73	gold quality
calcaneal tendon	UBERON:0003701	76.55	gold quality
gingival epithelium	UBERON:0001949	75.84	silver quality
vermiform appendix	UBERON:0001154	75.64	gold quality
Brodmann (1909) area 23	UBERON:0013554	75.38	silver quality
tibia	UBERON:0000979	74.89	gold quality
bone marrow	UBERON:0002371	74.86	gold quality
esophagus mucosa	UBERON:0002469	74.54	gold quality
bone element	UBERON:0001474	74.32	gold quality
esophagus squamous epithelium	UBERON:0006920	74.32	gold quality
mucosa of sigmoid colon	UBERON:0004993	74.20	gold quality
monocyte	CL:0000576	74.18	gold quality
palpebral conjunctiva	UBERON:0001812	74.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.19
E-GEOD-99795	no	141.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

120 targeting SUV39H2, 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-3163	100.00	77.23	8605
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642

Literature-anchored findings (GeneRIF, showing 18)

• a novel SUV39H2 polymorphism may have a role in lung cancer susceptibility for smokers (PMID:16774942)
• The SUV39H2 gene is found in tetrapods (e.g., human, mouse and frog) but not in zebrafish, suggesting that this gene is generated by a tetrapod lineage-specific gene duplication event. (PMID:18231586)
• findings suggest that Suv39H1 and Suv39H2 are key hypoxia-induced methyltransferases; their decline in fetal lung during late gestation is critical for epigenetic changes resulting in the developmental induction of SP-A (PMID:21402781)
• genetic association studies in a Finnish population with type I diabetes: The minor T allele of exonic SNP rs17353856 in SUV39H2 is associated with diabetic retinopathy (in a larger meta-analysis); thus an genetic variation may be protective. (PMID:21896933)
• Expression of JHDM2A was significantly increased but HDAC2, HDAC7, and SUV39H2 were significantly down-regulated in Systemic Sclerosis B cells relative to controls (PMID:23891737)
• We also demonstrate that the N324K mutant in the SET domain of SUV39H2 that has been shown to cause an inherited nasal skin disease in Labrador Retrievers renders SUV39H2 inactive (PMID:25459750)
• Our results reveal the regulatory mechanism of LSD1 protein through its lysine methylation by SUV39H2 in human cancer cells (PMID:26183527)
• Our finding unveils a novel autoregulatory mechanism of SUV39H2 through lysine automethylation (PMID:26988914)
• data cannot finally exclude H2AX methylation of SUV39H2 in cells, additional experimental evidence is required to validate this claim. (PMID:27177470)
• SUV39H2 functioned cooperatively with MAGE-A11 to increase androgen-dependent AR transcriptional activity. (PMID:28042025)
• histone H3 lysine 9 methylation reduction, which may be due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C, was found in CD4(+) T lymphocytes of Latent autoimmune diabetes in adults patients (PMID:28396876)
• Our data show that the differential expression of SUV39H1 and SUV39H2 is associated with genomic instability and that the modulation of these HMTases can be an attractive approach to prevent CLL evolution (PMID:28833505)
• Study revealed that high SUV39H2 expression positively predicted poor prognosis of CRC patients. Moreover, SUV39H2 promoted CRC proliferation in a SLIT1-dependent manner. (PMID:29458143)
• Results discovered that SUV39H2 is a potential oncogene in lung adenocarcinoma, whose expression was elevated in tumor tissues. SUV39H2 could potentiate the tumorigenesis and invasion of lung adenocarcinoma cells, probably by repressing OPTN and STOM. (PMID:30348215)
• Knockdown of SUV39H2 expression by specific siRNAs in human osteosarcoma cell lines markedly suppressed cancer cell growth and caused an increase in the population of cells in G1 phase and induced apoptosis. Overexpression of SUV39H2 promoted cell proliferation, which indicated that SUV39H2 may possess oncogenic activity in human osteosarcoma. (PMID:30542727)
• SUV39H2 elevation contributes to the progression of nasopharyngeal carcinoma via regulation of NRIP1 (PMID:30709585)
• Epigenetic hallmarks of age-related macular degeneration are recapitulated in a photosensitive mouse model. (PMID:32691052)
• N6-methyadenosine modified SUV39H2 regulates homologous recombination through epigenetic repression of DUSP6 in gastric cancer. (PMID:36806557)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
mus_musculus	Suv39h2	ENSMUSG00000026646
rattus_norvegicus	Suv39h2	ENSRNOG00000015585
drosophila_melanogaster	Set2	FBGN0030486
drosophila_melanogaster	CG4565	FBGN0037841
drosophila_melanogaster	G9a	FBGN0040372
caenorhabditis_elegans	set-32	WBGENE00008062
caenorhabditis_elegans		WBGENE00008206
caenorhabditis_elegans		WBGENE00008527
caenorhabditis_elegans	met-1	WBGENE00016603
caenorhabditis_elegans		WBGENE00018023
caenorhabditis_elegans		WBGENE00019584
caenorhabditis_elegans		WBGENE00019690
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), SETDB2 (ENSG00000136169), SETD1B (ENSG00000139718), SETDB1 (ENSG00000143379), NSD3 (ENSG00000147548), SETBP1 (ENSG00000152217), NSD1 (ENSG00000165671), KMT2D (ENSG00000167548), EHMT1 (ENSG00000181090), SETD2 (ENSG00000181555), EHMT2 (ENSG00000204371), KMT2B (ENSG00000272333)

Protein

Protein identifiers

Histone-lysine N-methyltransferase SUV39H2 — Q9H5I1 (reviewed: Q9H5I1)

Alternative names: Histone H3-K9 methyltransferase 2, Lysine N-methyltransferase 1B, Suppressor of variegation 3-9 homolog 2

All UniProt accessions (6): Q9H5I1, C9IYH9, C9JMB4, G5E9A8, H0Y306, Q5JSS2

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase that specifically mediates trimethylation of ‘Lys-9’ of histone H3 (H3K9me3) using monomethylated H3 ‘Lys-9’ (H3K9me1) as substrate. H3 ‘Lys-9’ trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 ‘Lys-9’ trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H2 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as cell cycle regulation, transcriptional repression and regulation of telomere length. May participate in regulation of higher-order chromatin organization during spermatogenesis. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 ‘Lys-9’ trimethylation.

Subunit / interactions. Interacts with SMAD5. The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex. Interacts with ZNF152B; this interaction initiates heterochromatin formation.

Subcellular location. Nucleus. Chromosome. Centromere.

Post-translational modifications. Ubiquitinated by the DCX(DCAF13) E3 ubiquitin ligase complex, leading to its degradation.

Domain organisation. Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity. The SET domain also participates in stable binding to heterochromatin. 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. Histone-lysine methyltransferase family. Suvar3-9 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H5I1-1	3	yes
Q9H5I1-2	1
Q9H5I1-3	2

RefSeq proteins (5): NP_001180353, NP_001180354, NP_001180355, NP_001180356, NP_078946 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR001214	SET_dom	Domain
IPR003616	Post-SET_dom	Domain
IPR007728	Pre-SET_dom	Domain
IPR011381	H3-K9_MeTrfase_SUV39H1/2-like	Family
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR023779	Chromodomain_CS	Conserved_site
IPR023780	Chromo_domain	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050973	H3K9_Histone-Lys_N-MTase	Family

Pfam: PF00385, PF00856, PF05033

Catalyzed reactions (Rhea), 2 shown:

• N(6)-methyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60284)
• 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 (55 total): binding site 20, strand 15, helix 7, domain 4, modified residue 3, splice variant 2, turn 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2R3A	X-RAY DIFFRACTION	2
6P0R	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H5I1-F1	89.65	0.73

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): 201; 202; 229; 229; 233; 235; 239; 261–263; 330–331; 333; 372; 398 …

Post-translational modifications (3): 381, 384, 388

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: 199 (showing top): GOBP_CIRCADIAN_RHYTHM, ATF_B, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, AP4_Q6, CREBP1_Q2, CAGCTG_AP4_Q5, ATGTTAA_MIR302C, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, chr10p13, MODULE_205, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_LEVELS, ATF1_Q6, GOBP_RESPONSE_TO_OXYGEN_LEVELS, BLALOCK_ALZHEIMERS_DISEASE_UP, KEGG_LYSINE_DEGRADATION

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), circadian rhythm (GO:0007623), cell differentiation (GO:0030154), methylation (GO:0032259), epigenetic programming in the zygotic pronuclei (GO:0044725), negative regulation of gene expression, epigenetic (GO:0045814), negative regulation of DNA-templated transcription (GO:0045892), cellular response to hypoxia (GO:0071456), rhythmic process (GO:0048511)

GO Molecular Function (16): transcription cis-regulatory region binding (GO:0000976), zinc ion binding (GO:0008270), histone H3K9 methyltransferase activity (GO:0046974), histone H3 methyltransferase activity (GO:0140938), histone H3K9 trimethyltransferase activity (GO:0140949), S-adenosyl-L-methionine binding (GO:1904047), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), 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), transferase activity (GO:0016740), histone methyltransferase activity (GO:0042054), metal ion binding (GO:0046872), histone modifying activity (GO:0140993)

GO Cellular Component (5): chromosome, centromeric region (GO:0000775), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694)

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
methyltransferase activity	3
cation binding	2
catalytic activity, acting on a protein	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cellular component organization	1
chromatin organization	1
rhythmic process	1
cellular developmental process	1
metabolic process	1
epigenetic programming of gene expression	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
biological_process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
transition metal ion binding	1
protein-lysine N-methyltransferase activity	1
histone H3 methyltransferase activity	1
histone methyltransferase activity	1
histone H3K9 methyltransferase activity	1
sulfur compound binding	1
enzyme-substrate adaptor activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
protein methyltransferase activity	1
histone modifying activity	1
chromatin remodeling	1
chromosomal region	1
chromosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SUV39H2	DNMT1	P26358	752
SUV39H2	KMT5C	Q86Y97	726
SUV39H2	KMT5B	Q4FZB7	724
SUV39H2	SMYD2	Q9NRG4	641
SUV39H2	PRMT3	O60678	637
SUV39H2	H3-3A	P06351	634
SUV39H2	EZH2	Q15910	634
SUV39H2	H3C14	Q71DI3	634
SUV39H2	H3-5	Q6NXT2	634
SUV39H2	H3C1	P02295	634
SUV39H2	H3-4	Q16695	634
SUV39H2	H3-7	Q5TEC6	634
SUV39H2	SETD7	Q8WTS6	632
SUV39H2	KDM1A	O60341	628
SUV39H2	SMYD3	Q9H7B4	623

IntAct

72 interactions, top by confidence:

A	B	Type	Score
APPL2	SUV39H2	psi-mi:“MI:0915”(physical association)	0.740
SUV39H2	APPL2	psi-mi:“MI:0915”(physical association)	0.740
PNMA1	SUV39H2	psi-mi:“MI:0915”(physical association)	0.700
SUV39H2	PNMA1	psi-mi:“MI:0915”(physical association)	0.700
HEL25	SUV39H2	psi-mi:“MI:0915”(physical association)	0.560
SUV39H2	HEL25	psi-mi:“MI:0915”(physical association)	0.560
SUV39H2	CEP70	psi-mi:“MI:0915”(physical association)	0.550
SUV39H2	RASSF1	psi-mi:“MI:0915”(physical association)	0.550
CEP70	SUV39H2	psi-mi:“MI:0915”(physical association)	0.550
RASSF1	SUV39H2	psi-mi:“MI:0915”(physical association)	0.550
CDCA4	SUV39H2	psi-mi:“MI:0915”(physical association)	0.510
SUV39H2	KCTD17	psi-mi:“MI:0915”(physical association)	0.510
SUV39H2	KLHDC4	psi-mi:“MI:0915”(physical association)	0.510
SUV39H2	MRFAP1	psi-mi:“MI:0915”(physical association)	0.510
SUV39H2	PHF19	psi-mi:“MI:0915”(physical association)	0.510
ZNF212	SUV39H2	psi-mi:“MI:0915”(physical association)	0.510
MRFAP1	SUV39H2	psi-mi:“MI:0915”(physical association)	0.510

BioGRID (114): SUV39H2 (Two-hybrid), SUV39H2 (Two-hybrid), SUV39H2 (Two-hybrid), EHMT1 (Affinity Capture-MS), EHMT2 (Affinity Capture-MS), AP4E1 (Affinity Capture-MS), CBX1 (Affinity Capture-MS), CBX5 (Affinity Capture-MS), NARS (Affinity Capture-MS), ZNF644 (Affinity Capture-MS), SUV39H2 (Two-hybrid), SUV39H2 (Synthetic Lethality), AP4E1 (Affinity Capture-MS), CBX5 (Affinity Capture-MS), ZNF644 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L7TZE5, A0A559KX76, A1C7E4, A1CS00, A1DHW6, A2QCU8, A6SDQ3, A7F045, B0XTS1, B2WKR4, B6Q4Z5, B8M7Q5, B8NGT5, O22781, O43463, O54864, P0CY36, P93025, P97443, Q00659, Q0CY32, Q0E908, Q0VD24, Q28CQ7, Q2NL30, Q2UES9, Q2UFN8, Q32PH7, Q4IJ84, Q4R3E0, Q4WVM1, Q4X0A9, Q5BHD6, Q5E9N5, Q5F3W5, Q5I0M0, Q5PP37, Q5RB81, Q60649, Q6DGD3

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 54 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Downstream signal transduction	5	57.7×	4e-06
DAP12 signaling	5	55.8×	4e-06
FCGR3A-mediated phagocytosis	5	28.4×	3e-05
VEGFA-VEGFR2 Pathway	5	21.1×	1e-04
Axon guidance	5	6.8×	6e-03
Nervous system development	5	6.5×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1194 predictions. Top by Δscore:

Variant	Effect	Δscore
10:14880574:TC:T	donor_gain	1.0000
10:14881498:AGCTT:A	acceptor_gain	1.0000
10:14881499:GCTTG:G	acceptor_gain	1.0000
10:14881641:TAAAG:T	donor_loss	1.0000
10:14881642:AAAG:A	donor_loss	1.0000
10:14881643:AAGG:A	donor_loss	1.0000
10:14881644:AGG:A	donor_loss	1.0000
10:14881645:GGT:G	donor_loss	1.0000
10:14881646:G:T	donor_loss	1.0000
10:14881647:T:A	donor_loss	1.0000
10:14896843:AAG:A	acceptor_gain	1.0000
10:14899537:A:AG	acceptor_gain	1.0000
10:14899537:AG:A	acceptor_gain	1.0000
10:14899538:G:GT	acceptor_gain	1.0000
10:14899538:GG:G	acceptor_gain	1.0000
10:14899538:GGT:G	acceptor_gain	1.0000
10:14899538:GGTA:G	acceptor_gain	1.0000
10:14899614:GACTA:G	donor_gain	1.0000
10:14899658:C:T	donor_gain	1.0000
10:14899682:CAGC:C	donor_gain	1.0000
10:14899683:AGC:A	donor_gain	1.0000
10:14899684:GC:G	donor_gain	1.0000
10:14899684:GCG:G	donor_gain	1.0000
10:14899686:G:GG	donor_gain	1.0000
10:14899693:GACA:G	donor_gain	1.0000
10:14899696:A:AG	donor_gain	1.0000
10:14899696:A:G	donor_gain	1.0000
10:14899700:G:GG	donor_gain	1.0000
10:14901131:A:AG	acceptor_gain	1.0000
10:14901131:AGTGT:A	acceptor_gain	1.0000

AlphaMissense

2704 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:14897353:T:A	C229S	1.000
10:14897353:T:C	C229R	1.000
10:14897354:G:C	C229S	1.000
10:14897455:T:A	W263R	1.000
10:14897455:T:C	W263R	1.000
10:14897457:G:C	W263C	1.000
10:14897457:G:T	W263C	1.000
10:14897498:T:A	V277D	1.000
10:14897506:T:C	Y280H	1.000
10:14897512:G:A	G282R	1.000
10:14897512:G:C	G282R	1.000
10:14897513:G:A	G282E	1.000
10:14897513:G:T	G282V	1.000
10:14899567:G:C	R293P	1.000
10:14899603:T:C	L305P	1.000
10:14899605:T:C	F306L	1.000
10:14899607:T:A	F306L	1.000
10:14899607:T:G	F306L	1.000
10:14899612:T:C	L308P	1.000
10:14899657:G:A	G323D	1.000
10:14899661:T:A	N324K	1.000
10:14899661:T:G	N324K	1.000
10:14899668:C:G	H327D	1.000
10:14899671:T:C	F328L	1.000
10:14899673:T:A	F328L	1.000
10:14899673:T:G	F328L	1.000
10:14899680:C:G	H331D	1.000
10:14899682:C:A	H331Q	1.000
10:14899682:C:G	H331Q	1.000
10:14901133:T:C	C333R	1.000

dbSNP variants (sampled 300 via entrez): RS1000053246 (10:14902331 A>G,T), RS1000216570 (10:14883379 A>G), RS1000407858 (10:14878713 G>A), RS1000513871 (10:14901580 C>A), RS1000615671 (10:14895098 GA>G,GAA), RS1000782495 (10:14878638 C>T), RS1000927363 (10:14882698 C>G), RS1001104714 (10:14888724 A>G), RS1001321281 (10:14881827 A>C), RS1001333778 (10:14887935 C>G), RS1001512136 (10:14901386 G>C), RS1001615897 (10:14888761 G>C), RS1001669317 (10:14881393 T>C), RS1001673016 (10:14900094 A>G), RS1001725309 (10:14900557 T>C)

Disease associations

OMIM: gene MIM:606503 | disease phenotypes: MIM:602450, MIM:603554

GenCC curated gene-disease

Mondo (2): severe combined immunodeficiency due to DCLRE1C deficiency (MONDO:0011225), Omenn syndrome (MONDO:0011338)

Orphanet (2): Severe combined immunodeficiency due to DCLRE1C deficiency (Orphanet:275), Omenn syndrome (Orphanet:39041)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008359_6	Response to cognitive-behavioural therapy in anxiety disorder	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1795177 (SINGLE PROTEIN)

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
example 203 [WO2017058503A1]	Inhibition	8.75	pIC50

Binding affinities (BindingDB)

1 measured of 2 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-2-amino-N-[2-[5-chloro-2-(hydroxymethyl)-4-methoxyphenyl]imidazo[1,2-a]pyridin-7-yl]-3-(1H-indol-3-yl)propanamide	IC50	42.7 nM	US-10508109

ChEMBL bioactivities

767 potent at pChembl≥5 of 770 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.75	IC50	1.77	nM	CHEMBL4587289
8.75	IC50	1.78	nM	CHEMBL4553838
8.75	IC50	1.77	nM	CHEMBL5917854
8.73	IC50	1.88	nM	CHEMBL4563069
8.71	IC50	1.97	nM	CHEMBL4520078
8.70	IC50	2	nM	CHEMBL4551654
8.68	IC50	2.07	nM	CHEMBL4556599
8.66	IC50	2.2	nM	CHEMBL4556449
8.66	IC50	2.2	nM	CHEMBL5889747
8.57	IC50	2.71	nM	CHEMBL4457187
8.57	IC50	2.71	nM	CHEMBL5813669
8.54	IC50	2.9	nM	CHEMBL4534136
8.54	IC50	2.9	nM	CHEMBL5889567
8.52	IC50	3	nM	CHEMBL4551056
8.52	IC50	3	nM	CHEMBL5833321
8.51	IC50	3.1	nM	CHEMBL4547529
8.51	IC50	3.1	nM	CHEMBL5802370
8.48	IC50	3.27	nM	CHEMBL4589569
8.48	IC50	3.33	nM	CHEMBL4558804
8.48	IC50	3.27	nM	CHEMBL5821250
8.48	IC50	3.33	nM	CHEMBL6039206
8.47	IC50	3.35	nM	CHEMBL4514527
8.47	IC50	3.35	nM	CHEMBL6002706
8.46	IC50	3.49	nM	CHEMBL4569911
8.46	IC50	3.5	nM	CHEMBL4536861
8.46	IC50	3.49	nM	CHEMBL5882142
8.45	IC50	3.53	nM	CHEMBL4557178
8.45	IC50	3.53	nM	CHEMBL5990392
8.43	IC50	3.71	nM	CHEMBL4543316
8.43	IC50	3.71	nM	CHEMBL5752280
8.42	IC50	3.81	nM	CHEMBL4532138
8.42	IC50	3.81	nM	CHEMBL4534069
8.42	IC50	3.81	nM	CHEMBL6058730
8.40	IC50	3.95	nM	CHEMBL4542129
8.40	IC50	3.95	nM	CHEMBL5778265
8.39	IC50	4.11	nM	CHEMBL4513598
8.39	IC50	4.03	nM	CHEMBL4483505
8.39	IC50	4.11	nM	CHEMBL5982126
8.38	IC50	4.16	nM	CHEMBL4546702
8.38	IC50	4.16	nM	CHEMBL6035731
8.37	IC50	4.31	nM	CHEMBL4531530
8.37	IC50	4.31	nM	CHEMBL5783478
8.36	IC50	4.35	nM	CHEMBL4521461
8.36	IC50	4.4	nM	CHEMBL4545245
8.36	IC50	4.33	nM	CHEMBL4540137
8.36	IC50	4.35	nM	CHEMBL4515775
8.36	IC50	4.35	nM	CHEMBL6054950
8.36	IC50	4.4	nM	CHEMBL6019346
8.36	IC50	4.33	nM	CHEMBL5874588
8.36	IC50	4.35	nM	CHEMBL6033942

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression, decreases methylation	2
Aflatoxin B1	increases expression, decreases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
beta-glycerophosphoric acid	affects cotreatment, decreases expression	1
cylindrospermopsin	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	decreases expression	1
Ascorbic Acid	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	decreases expression	1
Copper	decreases expression, affects binding	1

ChEMBL screening assays

62 unique, capped per target: 61 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1832597	Binding	Inhibition of SUV39H2 assessed as hydrolysis of S-adenosyl-L-homocysteine after 2 mins by SAHH-coupled fluorescence assay	Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines. — J Med Chem
CHEMBL5723318	Functional	Affinity Biochemical interaction: (Competitive inhibition of methylation of histone substrate in the presence of radioactive methyl donor) EUB0002792aFA SUV39H2	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0Z2	Abcam U2OS SUV39H2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT01186913	Not specified	ENROLLING_BY_INVITATION	Natural History Study of SCID Disorders
NCT01346150	Not specified	UNKNOWN	Patients Treated for SCID (1968-Present)