PRMT2

Summary

PRMT2 (protein arginine methyltransferase 2, HGNC:5186) is a protein-coding gene on chromosome 21q22.3, encoding Protein arginine N-methyltransferase 2 (P55345). Arginine methyltransferase that methylates the guanidino nitrogens of arginyl residues in proteins such as STAT3, FBL, histone H4.

Enables several functions, including nuclear receptor binding activity; peroxisome proliferator activated receptor binding activity; and protein homodimerization activity. Involved in positive regulation of apoptotic process; regulation of DNA-templated transcription; and regulation of androgen receptor signaling pathway. Located in cytosol and nucleoplasm.

Source: NCBI Gene 3275 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_206962

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5186
Approved symbol	PRMT2
Name	protein arginine methyltransferase 2
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC111373
Ensembl gene	ENSG00000160310
Ensembl biotype	protein_coding
OMIM	601961
Entrez	3275

Gene structure

Transcript identifiers

Ensembl transcripts: 65 — 60 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000291705, ENST00000334494, ENST00000355680, ENST00000397628, ENST00000397637, ENST00000397638, ENST00000440086, ENST00000451211, ENST00000455177, ENST00000458387, ENST00000481861, ENST00000482508, ENST00000486520, ENST00000491389, ENST00000498151, ENST00000889215, ENST00000889216, ENST00000889217, ENST00000889218, ENST00000889219, ENST00000889220, ENST00000889221, ENST00000889222, ENST00000889223, ENST00000889224, ENST00000889225, ENST00000889226, ENST00000889227, ENST00000889228, ENST00000889229, ENST00000889230, ENST00000889231, ENST00000889232, ENST00000889233, ENST00000889234, ENST00000889235, ENST00000889236, ENST00000889237, ENST00000889238, ENST00000889239, ENST00000889240, ENST00000889241, ENST00000889242, ENST00000889243, ENST00000889244, ENST00000938198, ENST00000938199, ENST00000938200, ENST00000938201, ENST00000938202, ENST00000938203, ENST00000938204, ENST00000938205, ENST00000945429, ENST00000945430, ENST00000945431, ENST00000945432, ENST00000945433, ENST00000945434, ENST00000945435, ENST00000945436, ENST00000945437, ENST00000945438, ENST00000945439, ENST00000945440

RefSeq mRNA: 8 — MANE Select: NM_206962 NM_001242864, NM_001242865, NM_001242866, NM_001286676, NM_001286677, NM_001286678, NM_001535, NM_206962

CCDS: CCDS13737, CCDS56219, CCDS56220, CCDS68230, CCDS68231, CCDS74806

Canonical transcript exons

ENST00000355680 — 12 exons

Exon	Start	End
ENSE00001051359	46660833	46660962
ENSE00001299450	46661800	46661936
ENSE00001336411	46636896	46636990
ENSE00001414070	46636439	46636547
ENSE00001529463	46635674	46635763
ENSE00001728083	46664295	46665124
ENSE00003472918	46644306	46644488
ENSE00003480025	46649575	46649739
ENSE00003541221	46658745	46658920
ENSE00003542955	46643535	46643639
ENSE00003595101	46648458	46648619
ENSE00003636111	46663383	46663554

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.3812 / max 576.1547, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
189730	57.2313	1823
189731	1.1499	569

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.44	gold quality
right coronary artery	UBERON:0001625	97.99	gold quality
ganglionic eminence	UBERON:0004023	97.97	gold quality
nerve	UBERON:0001021	97.80	gold quality
tibial nerve	UBERON:0001323	97.80	gold quality
spinal cord	UBERON:0002240	97.80	gold quality
popliteal artery	UBERON:0002250	97.73	gold quality
tibial artery	UBERON:0007610	97.73	gold quality
aorta	UBERON:0000947	97.57	gold quality
granulocyte	CL:0000094	97.48	gold quality
thoracic aorta	UBERON:0001515	97.46	gold quality
ascending aorta	UBERON:0001496	97.44	gold quality
ventricular zone	UBERON:0003053	97.37	gold quality
lower esophagus	UBERON:0013473	97.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.37	gold quality
descending thoracic aorta	UBERON:0002345	97.36	gold quality
gall bladder	UBERON:0002110	97.34	gold quality
endocervix	UBERON:0000458	97.30	gold quality
left coronary artery	UBERON:0001626	97.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.26	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.25	gold quality
body of uterus	UBERON:0009853	97.23	gold quality
hypothalamus	UBERON:0001898	97.18	gold quality
left ovary	UBERON:0002119	97.08	gold quality
mucosa of stomach	UBERON:0001199	96.97	gold quality
cingulate cortex	UBERON:0003027	96.91	gold quality
right ovary	UBERON:0002118	96.90	gold quality
anterior cingulate cortex	UBERON:0009835	96.89	gold quality
coronary artery	UBERON:0001621	96.83	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.06
E-CURD-112	yes	7.55
E-MTAB-7303	no	1330.05
E-GEOD-106540	no	1321.19

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

22 targeting PRMT2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6735-5P	98.24	65.36	1488
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-4776-5P	97.14	66.63	405
HSA-MIR-4491	96.53	66.20	935
HSA-MIR-4657	96.53	66.57	895
HSA-MIR-6760-3P	96.35	68.31	1001

Literature-anchored findings (GeneRIF, showing 23)

• PRMT2 is a novel ERalpha coactivator. (PMID:12039952)
• PRMT2 inhibits NF-kappa B function and promotes apoptosis. (PMID:16648481)
• ligand-dependent AR conformation is essential for the recruitment and nuclear translocation of PMRT2 which acts as AR-coactivator, presumably by arginine methylation. (PMID:17587566)
• Here we report methylation activity from PRMT2 and compare it with PRMT1 activity using UPLC-MS/MS (ultra-performance liquid chromatography-tandem MS), gel electrophoresis, and thin-layer chromatography (PMID:19405910)
• Data suggest that post-transcriptional processing mechanism as alternative polyadenylation and splicing may play a crucial role in regulating human PRMT2 gene expression. (PMID:21820040)
• the SH3 domain may mediate an interaction between PRMT1 and -2 in a methylation-dependent fashion (PMID:21851090)
• characterization of 3 PRMT2 splice variants (PRMT2alpha, PRMT2beta, and PRMT2gamma) from breast cancer; these variants bind to ERalpha in vitro/in vivo; overall PRMT2 expression is upregulated in breast cancer and associated w/ ERalpha positivity (PMID:22093364)
• This study uncovers the molecular mechanism of PRMT2 regulating the expression of CCND1 in invasive ductal breast carcinoma. (PMID:24292672)
• This study demonstrates the role and significant correlation between a histone methyltransferase (PRMT2)-dependent signature, RORgamma, the cell-cycle regulation, DNA repair circuits, and breast cancer survival outcomes. (PMID:24911119)
• The PRMT2 interacts with SAM68 in cells and regulates its subcellular localization via the SH3 domain of PRMT2, prompting us to investigate the potential role of PRMT2 in BCL-X alternative splicing. (PMID:28057797)
• Low splice variant of PRMT2 expression is associated with breast cancer. (PMID:28677794)
• Results show that tamoxifen resistance in breast cancer cells is connected with the downregulation of PRMT2 and the upregulation of ER-alpha36. Moreover, PRMT2 was able to interact with ER-alpha36 directly, suppress ER-alpha36 and downstream PI3K/Akt and MAPK/ERK signaling, reversing the tamoxifen resistance of breast cancer cells. (PMID:29620287)
• Cobl-mediated dendritic arborization required PRMT2, complex formation with PRMT2, and PRMT2’s catalytic activity (PMID:29689199)
• PRMT2 acts as a transcriptional co-activator for oncogenic gene expression programs in glioblastoma pathogenesis. (PMID:30382083)
• PRMT2beta suppressed glycolytic pathway in MCF7 cells. (PMID:30883646)
• PRMT2 accelerates tumorigenesis of hepatocellular carcinoma by activating Bcl2 via histone H3R8 methylation. (PMID:32574605)
• Loss of PRMT2 in myeloid cells in normoglycemic mice phenocopies impaired regression of atherosclerosis in diabetic mice. (PMID:35835907)
• PRMT2 promotes RCC tumorigenesis and metastasis via enhancing WNT5A transcriptional expression. (PMID:37173306)
• Protein arginine N-methyltransferase 2 plays a noncatalytic role in the histone methylation activity of PRMT1. (PMID:37863263)
• PRMT2 promotes HIV-1 latency by preventing nucleolar exit and phase separation of Tat into the Super Elongation Complex. (PMID:37949879)
• Advances in Research on Protein Arginine Methyltransferase 2: Functions and Diseases. (PMID:38155464)
• Human C15orf39 Inhibits Inflammatory Response via PRMT2 in Human Microglial HMC3 Cell Line. (PMID:38892217)
• Protein arginine methyltransferase 2 controls inflammatory signaling in acute myeloid leukemia. (PMID:38902349)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	prmt2	ENSDARG00000063212
mus_musculus	Prmt2	ENSMUSG00000020230
rattus_norvegicus	Prmt2	ENSRNOG00000001297
drosophila_melanogaster	Art8	FBGN0032329

Paralogs (7): PRMT8 (ENSG00000111218), PRMT1 (ENSG00000126457), PRMT7 (ENSG00000132600), CARM1 (ENSG00000142453), PRMT9 (ENSG00000164169), PRMT3 (ENSG00000185238), PRMT6 (ENSG00000198890)

Protein

Protein identifiers

Protein arginine N-methyltransferase 2 — P55345 (reviewed: P55345)

Alternative names: Histone-arginine N-methyltransferase PRMT2

All UniProt accessions (4): P55345, A0A0S2Z3N3, A8MXR3, H7C2H9

UniProt curated annotations — full annotation on UniProt →

Function. Arginine methyltransferase that methylates the guanidino nitrogens of arginyl residues in proteins such as STAT3, FBL, histone H4. Acts as a coactivator (with NCOA2) of the androgen receptor (AR)-mediated transactivation. Acts as a coactivator (with estrogen) of estrogen receptor (ER)-mediated transactivation. Enhances PGR, PPARG, RARA-mediated transactivation. May inhibit NF-kappa-B transcription and promote apoptosis. Represses E2F1 transcriptional activity (in a RB1-dependent manner). May be involved in growth regulation. Involved in C15ORF39-mediated inhibition of the microglial inflammatory responses through suppression of NF-kappa-B signaling, thereby reducing the production of pro-inflammatory cytokines.

Subunit / interactions. Self-associates. Interacts with RB1 and E2F1. Interacts with NCOA6 coactivator. Interacts (via SH3 domain) with PRMT8. Interacts with AR. Interacts with NFKBIA. Interacts with ESR1, ESR2, PGR, PPARG, RARA, RXRA and THRB. Interacts with HNRNPUL1. Interacts with C15ORF39.

Subcellular location. Cytoplasm. Nucleus Nucleus Cytoplasm. Nucleus. Nucleolus Nucleus Cytoplasm.

Tissue specificity. Widely expressed. Highly expressed in androgen target organs such as heart, prostate, skeletal muscle, ovary and spinal cord.

Miscellaneous. Higher expression in breast cancer tissues. Higher expression in breast cancer tissues. Doesn’t interact with ESR1. Higher expression in breast cancer tissues.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.

Isoforms (7)

UniProt ID	Names	Canonical?
P55345-1	1	yes
P55345-2	2
P55345-3	3
P55345-4	PRMT2Alpha
P55345-5	PRMT2Beta
P55345-6	PRMT2Gamma
P55345-7	PRMT2L2

RefSeq proteins (8): NP_001229793, NP_001229794, NP_001229795, NP_001273605, NP_001273606, NP_001273607, NP_001526, NP_996845* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR007848	Small_mtfrase_dom	Domain
IPR025799	Arg_MeTrfase	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR055135	PRMT_dom	Domain

Pfam: PF00018, PF05175, PF22528

Enzyme classification (BRENDA):

• EC 2.1.1.319 — type I protein arginine methyltransferase (BRENDA: 13 organisms, 109 substrates, 121 inhibitors, 26 Km, 24 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[HISTONE H2A]-L-ARGININE	0.0005–0.128	3
[HISTONE H3]-L-ARGININE	0.001–0.0282	3
[HISTONE H4]-L-ARGININE	0.0017–0.0388	3
[GRGGFGGRGGFRGGRGG]-L-ARGININE	0.0003–0.0008	2
[HISTONE H4(1-22) PEPTIDE]-L-ARGININE3	0.0002–0.0008	2
FYSGFNS-DIMETHYL-R8-P-DIMETHYL-R10-GRVYATSWY	0.0222	1
FYSGFNS-DIMETHYL-R8-PRG-DIMETHYL-R12-VYATSWY	0.0007	1
FYSGFNS-DIMETHYL-R8-PRGRVYATSWY	0.0006	1
FYSGFNSRP-DIMETHYL-R10-G-DIMETHYL-R12-VYATSWY	0.008	1
FYSGFNSRP-METHYL-R10-GRVYATSWY	0.0007	1
[HISTONE H4(1-16) PEPTIDE]-L-ARGININE3	0.0003	1
[PABPN1 MUTANT DELTAC20]-L-ARGININE	0.0004	1
[PABPN1 MUTANT DELTAC27]-L-ARGININE	0.0001	1
[PABPN1 MUTANT DELTAC33]-L-ARGININE	—	1
[PABPN1 MUTANT DELTAC40]-L-ARGININE	0.0032	1

Catalyzed reactions (Rhea), 1 shown:

• L-arginyl-[protein] + 2 S-adenosyl-L-methionine = N(omega),N(omega)-dimethyl-L-arginyl-[protein] + 2 S-adenosyl-L-homocysteine + 2 H(+) (RHEA:48096)

UniProt features (31 total): splice variant 8, binding site 5, region of interest 5, strand 4, domain 2, modified residue 2, sequence conflict 2, active site 2, chain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1X2P	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55345-F1	92.23	0.88

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 (2): 211; 220

Ligand- & substrate-binding residues (5): 112; 121; 145; 168; 197

Post-translational modifications (2): 61, 72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 262 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_ANDROGEN_RECEPTOR_SIGNALING_PATHWAY, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1

GO Biological Process (15): chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), protein methylation (GO:0006479), signal transduction (GO:0007165), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), positive regulation of apoptotic process (GO:0043065), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), developmental cell growth (GO:0048588), negative regulation of inflammatory response (GO:0050728), regulation of androgen receptor signaling pathway (GO:0060765), negative regulation of G1/S transition of mitotic cell cycle (GO:2000134), peptidyl-arginine methylation (GO:0018216), methylation (GO:0032259)

GO Molecular Function (17): transcription coactivator activity (GO:0003713), protein-arginine N-methyltransferase activity (GO:0016274), nuclear estrogen receptor binding (GO:0030331), nuclear progesterone receptor binding (GO:0033142), protein-arginine omega-N asymmetric methyltransferase activity (GO:0035242), histone methyltransferase activity (GO:0042054), protein homodimerization activity (GO:0042803), nuclear retinoic acid receptor binding (GO:0042974), peroxisome proliferator activated receptor binding (GO:0042975), protein-containing complex binding (GO:0044877), nuclear thyroid hormone receptor binding (GO:0046966), nuclear androgen receptor binding (GO:0050681), histone H3R8 methyltransferase activity (GO:0140592), histone H3 methyltransferase activity (GO:0140938), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear receptor binding	5
DNA-templated transcription	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
protein methyltransferase activity	2
protein-arginine N-methyltransferase activity	2
binding	2
nuclear lumen	2
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein alkylation	1
macromolecule methylation	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cell growth	1
cell development	1
developmental growth	1
inflammatory response	1
negative regulation of defense response	1
negative regulation of response to external stimulus	1
regulation of inflammatory response	1
androgen receptor signaling pathway	1
regulation of intracellular steroid hormone receptor signaling pathway	1
G1/S transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
protein methylation	1

Protein interactions and networks

STRING

2093 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRMT2	HNRNPA1	P09651	706
PRMT2	DDAH2	O95865	617
PRMT2	S100B	P04271	601
PRMT2	HNRNPDL	O14979	593
PRMT2	HNRNPUL1	Q9BUJ2	589
PRMT2	DIP2A	Q14689	585
PRMT2	CTNNB1	P35222	551
PRMT2	MPZL1	O95297	549
PRMT2	HNRNPC	P07910	521
PRMT2	NCOA1	Q15788	502
PRMT2	SNRPB	P14678	501
PRMT2	PRMT8	Q9NR22	485
PRMT2	SLCO6A1	Q86UG4	481
PRMT2	IFNAR1	P17181	475
PRMT2	PRMT1	Q99873	472

IntAct

83 interactions, top by confidence:

A	B	Type	Score
PRMT2	ESR1	psi-mi:“MI:0403”(colocalization)	0.750
PRMT2	ESR1	psi-mi:“MI:0407”(direct interaction)	0.750
PRMT2	ESR1	psi-mi:“MI:0915”(physical association)	0.750
ESR1	PRMT2	psi-mi:“MI:0915”(physical association)	0.750
PRMT2	SHANK3	psi-mi:“MI:0915”(physical association)	0.660
PRMT2	HTT	psi-mi:“MI:0915”(physical association)	0.660
HTT	PRMT2	psi-mi:“MI:0915”(physical association)	0.660
FASLG	PRMT2	psi-mi:“MI:0914”(association)	0.640
PRMT2	SAMD1	psi-mi:“MI:0914”(association)	0.640
PRMT2	CBLB	psi-mi:“MI:0915”(physical association)	0.560
PRMT2	RBM12	psi-mi:“MI:0915”(physical association)	0.560
BAG6	PRMT2	psi-mi:“MI:0915”(physical association)	0.550
RB1	PRMT2	psi-mi:“MI:0407”(direct interaction)	0.540
PRMT2	RB1	psi-mi:“MI:0915”(physical association)	0.540
PRMT2	AKR1B1	psi-mi:“MI:0403”(colocalization)	0.460
PRMT2	AKR1B1	psi-mi:“MI:0915”(physical association)	0.460
E2F1	PRMT2	psi-mi:“MI:0915”(physical association)	0.400
PSRC1	PRMT2	psi-mi:“MI:0915”(physical association)	0.400
ESR2	PRMT2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (142): PRMT2 (Affinity Capture-MS), UBB (Affinity Capture-MS), SALL2 (Affinity Capture-MS), GET4 (Affinity Capture-MS), SHANK3 (Affinity Capture-MS), HTT (Affinity Capture-MS), TAB1 (Affinity Capture-MS), KANK2 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), PLEKHH3 (Affinity Capture-MS), POM121 (Affinity Capture-MS), SF1 (Affinity Capture-MS), L3MBTL3 (Affinity Capture-MS), TIGD5 (Affinity Capture-MS), KSR1 (Affinity Capture-MS)

ESM2 similar proteins: A2ADA5, A4PCD4, A6H611, D3ZDM7, F6PHZ6, O75344, P04053, P09838, P17256, P36195, P47823, P55345, Q01992, Q03426, Q08602, Q0V8R7, Q13144, Q1L8I0, Q3MIT2, Q4KM92, Q4QQT0, Q5CZL1, Q5E9Z1, Q5I0L3, Q5M7T9, Q5M934, Q5RFE6, Q5XGM5, Q64350, Q6GQ53, Q7L3T8, Q80W22, Q86YJ6, Q8BYL4, Q8C0D0, Q8CHW4, Q8N0Z8, Q8WWH5, Q91XW8, Q92089

Diamond homologs: A0A3Q0KHE7, A0A411EW25, A0JMU5, A2AV36, A2Y953, A2YPT7, A2Z0C0, A3KPF2, A6QQV6, A8IEF3, B0JYW5, B0W3L6, B3DLB3, B3M1E1, B3P4N5, B4GZ20, B4HJC0, B4JXV2, B4KA23, B4LVS8, B4MNL1, B4NKI9, B4PVH6, B4QVW6, D9IVE5, O13648, O60678, O70467, O82210, P38074, P55345, Q08A71, Q0J2C6, Q174R2, Q28F07, Q29B63, Q3U3W5, Q4AE70, Q54EF2, Q54HI0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
SUMOylation of intracellular receptors	6	49.1×	3e-07
Nuclear Receptor transcription pathway	7	34.2×	3e-07
Dengue Virus-Host Interactions	7	7.8×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2245 predictions. Top by Δscore:

Variant	Effect	Δscore
21:46644476:C:G	donor_gain	1.0000
21:46648453:TCCA:T	acceptor_loss	1.0000
21:46648454:CCA:C	acceptor_loss	1.0000
21:46648455:CA:C	acceptor_loss	1.0000
21:46648456:A:T	acceptor_loss	1.0000
21:46648457:GA:G	acceptor_gain	1.0000
21:46648457:GAA:G	acceptor_gain	1.0000
21:46648457:GAAA:G	acceptor_gain	1.0000
21:46648615:GAGCG:G	donor_gain	1.0000
21:46648616:AGCGG:A	donor_loss	1.0000
21:46648617:GCG:G	donor_gain	1.0000
21:46648618:CGGTG:C	donor_loss	1.0000
21:46648620:GTGA:G	donor_loss	1.0000
21:46648621:T:A	donor_loss	1.0000
21:46649701:G:GT	donor_gain	1.0000
21:46658733:A:AG	acceptor_gain	1.0000
21:46658743:A:AG	acceptor_gain	1.0000
21:46658743:AGTTT:A	acceptor_gain	1.0000
21:46658744:G:GG	acceptor_gain	1.0000
21:46658744:GTT:G	acceptor_gain	1.0000
21:46658744:GTTT:G	acceptor_gain	1.0000
21:46658744:GTTTG:G	acceptor_gain	1.0000
21:46658916:CTGAA:C	donor_gain	1.0000
21:46658917:TGAA:T	donor_gain	1.0000
21:46658918:GAA:G	donor_gain	1.0000
21:46658918:GAAG:G	donor_gain	1.0000
21:46658919:AA:A	donor_gain	1.0000
21:46658921:G:GG	donor_gain	1.0000
21:46658922:TAAG:T	donor_loss	1.0000
21:46661937:G:GG	donor_gain	1.0000

AlphaMissense

2859 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:46644465:T:C	Y102H	1.000
21:46648474:T:C	M115T	1.000
21:46648474:T:G	M115R	1.000
21:46648475:G:A	M115I	1.000
21:46648475:G:C	M115I	1.000
21:46648475:G:T	M115I	1.000
21:46648568:T:G	C146W	1.000
21:46648569:G:T	G147W	1.000
21:46648575:G:T	G149W	1.000
21:46648576:G:A	G149E	1.000
21:46648584:A:C	S152R	1.000
21:46648586:T:A	S152R	1.000
21:46648586:T:G	S152R	1.000
21:46649717:A:T	E211V	1.000
21:46649719:T:A	W212R	1.000
21:46649719:T:C	W212R	1.000
21:46649725:G:A	G214R	1.000
21:46649725:G:C	G214R	1.000
21:46649725:G:T	G214W	1.000
21:46658745:T:C	F219L	1.000
21:46658747:T:A	F219L	1.000
21:46658747:T:G	F219L	1.000
21:46658749:A:T	E220V	1.000
21:46658756:G:A	M222I	1.000
21:46658756:G:C	M222I	1.000
21:46658756:G:T	M222I	1.000
21:46658883:T:A	W265R	1.000
21:46658883:T:C	W265R	1.000
21:46661866:T:C	F343L	1.000
21:46661868:T:A	F343L	1.000

dbSNP variants (sampled 300 via entrez): RS1000056257 (21:46659215 T>C), RS1000068805 (21:46635721 C>T), RS1000081676 (21:46640149 C>T), RS1000088438 (21:46659495 A>C,G), RS1000341565 (21:46647114 A>G), RS1000343074 (21:46646914 A>G), RS1000404070 (21:46652061 T>A,C), RS1000623176 (21:46658299 C>T), RS1000778768 (21:46649023 C>T), RS1000817694 (21:46642774 G>A,C), RS1000987355 (21:46656750 C>A,T), RS1001042801 (21:46660769 G>T), RS1001085007 (21:46645547 G>A), RS1001177216 (21:46651607 C>T), RS1001193617 (21:46665496 G>A)

Disease associations

OMIM: gene MIM:601961 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006479_7	Diverticular disease	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009959	diverticular disease

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 2.1.1.- Protein arginine N-methyltransferases

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	decreases expression, affects cotreatment	2
Tretinoin	increases expression	2
Valproic Acid	decreases expression	2
bisphenol F	affects cotreatment, decreases expression	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
kojic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
ethylene dichloride	increases expression	1
avobenzone	increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
obeticholic acid	affects binding, increases reaction	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Berberine	increases expression	1
Calcitriol	increases expression	1
Cisplatin	increases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Demecolcine	increases expression	1

Clinical trials (associated diseases)

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