PRDM2

Summary

PRDM2 (PR/SET domain 2, HGNC:9347) is a protein-coding gene on chromosome 1p36.21, encoding PR domain zinc finger protein 2 (Q13029). S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates ‘Lys-9’ of histone H3.

This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7799 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 295 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 3 cancer types
• Transcription factor: yes — 14 downstream targets (CollecTRI)
• MANE Select transcript: NM_001393986

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9347
Approved symbol	PRDM2
Name	PR/SET domain 2
Location	1p36.21
Locus type	gene with protein product
Status	Approved
Aliases	RIZ, RIZ1, RIZ2, KMT8, MTB-ZF, HUMHOXY1, KMT8A
Ensembl gene	ENSG00000116731
Ensembl biotype	protein_coding
OMIM	601196
Entrez	7799

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 10 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000235372, ENST00000311066, ENST00000343137, ENST00000376048, ENST00000407521, ENST00000413440, ENST00000484063, ENST00000487453, ENST00000491134, ENST00000491815, ENST00000502724, ENST00000502727, ENST00000503842, ENST00000505823

RefSeq mRNA: 7 — MANE Select: NM_001393986 NM_001007257, NM_001135610, NM_001393986, NM_001393987, NM_001393988, NM_012231, NM_015866

CCDS: CCDS150, CCDS30603, CCDS44061

Canonical transcript exons

ENST00000311066 — 10 exons

Exon	Start	End
ENSE00001377373	13778418	13782831
ENSE00001644268	13731000	13731117
ENSE00001703660	13732779	13732882
ENSE00002300421	13715541	13715614
ENSE00003252186	13823159	13825079
ENSE00003473435	13742005	13742157
ENSE00003545519	13816427	13816570
ENSE00003684939	13773078	13773188
ENSE00003687392	13749361	13749487
ENSE00003932516	13700188	13700300

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 95.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.6884 / max 2066.9205, expressed in 1805 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
769	34.0444	1792
762	7.2181	1579
768	4.0229	1485
763	0.2227	81
767	0.1803	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.86	gold quality
secondary oocyte	CL:0000655	95.68	gold quality
buccal mucosa cell	CL:0002336	95.63	gold quality
middle temporal gyrus	UBERON:0002771	95.12	gold quality
colonic epithelium	UBERON:0000397	94.63	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.07	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.97	gold quality
cortical plate	UBERON:0005343	93.93	gold quality
frontal pole	UBERON:0002795	93.67	gold quality
bone marrow cell	CL:0002092	93.54	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.50	gold quality
superior frontal gyrus	UBERON:0002661	93.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.18	gold quality
prefrontal cortex	UBERON:0000451	93.12	gold quality
right frontal lobe	UBERON:0002810	93.11	gold quality
primary visual cortex	UBERON:0002436	93.00	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.86	gold quality
tendon	UBERON:0000043	92.75	gold quality
frontal cortex	UBERON:0001870	92.75	gold quality
frontal lobe	UBERON:0016525	92.75	gold quality
postcentral gyrus	UBERON:0002581	92.63	gold quality
neocortex	UBERON:0001950	92.38	gold quality
gastrocnemius	UBERON:0001388	92.18	gold quality
orbitofrontal cortex	UBERON:0004167	92.15	gold quality
parietal lobe	UBERON:0001872	92.02	gold quality
tonsil	UBERON:0002372	91.88	gold quality
muscle of leg	UBERON:0001383	91.76	gold quality
tendon of biceps brachii	UBERON:0008188	91.71	gold quality
calcaneal tendon	UBERON:0003701	91.70	gold quality
occipital lobe	UBERON:0002021	91.66	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9221	yes	19.33
E-MTAB-6379	no	291.11
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

Target	Regulation
HMOX1	Activation
IGF1	Repression
IL10
IL2
KMT5A	Unknown
LHB
MYC	Repression
NFATC1	Unknown
PRDM2
SFTPC
SWI5
TKT
TRIB3
TSC1

Upstream regulators (CollecTRI, top): PRDM2, TP53, YY1

miRNA regulators (miRDB)

105 targeting PRDM2, 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-340-5P	100.00	72.50	4437
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093

Literature-anchored findings (GeneRIF, showing 40)

• loss of RIZ1 mRNA in human cancers is associated with DNA methylation of its promoter CpG island. (PMID:11719434)
• These findings suggest that RIZ may be a possible target of structural alteration leading to leukemia. (PMID:12002276)
• Frameshift mutations of RIZ, but no point mutations, were found in RIZ1 exons in malignant melanomas with deletions in 1p36. RIZ has potential role in the multi-step tumor forming process of malignant melanoma of the skin. (PMID:12082534)
• RIZ1 in gastric neoplasms undergoes biallelic inactivation. (PMID:14534544)
• Tumor suppressor RIZ1 (PRDM2) methylates histone H3 on lysine 9, and this activity is reduced by mutations in the PR domain found in human cancers. (PMID:14633678)
• Frameshift mutations of RIZ may play an important role in gastric cancers with microsatellite instability. (PMID:15309726)
• the presented results indicated that the Zn-finger domain could be endowed with the putative oncogenic activity of RIZ2 gene product. (PMID:15488642)
• RIZ1 may be a new candidate gene for involvement in the variation seen in bone mineral density. (PMID:15579774)
• recurrent inactivation of the tumour suppressor RIZ1 suggests that this event may be a significant contributing factor to tumour development in pheochromocytomas and abdominal paragangliomas (PMID:15809732)
• Forced RIZ1 expression in CML-BC cell lines decreases IGF-1 receptor activation and activation of downstream signaling components extracellular signal-regulated kinase 1/2 and AKT (PMID:16953217)
• The current study suggested an important role for RIZ1 expression in thyroid tumorigenesis. (PMID:17103461)
• A563G variant not found in diffuse large B-cell lymphomas. (PMID:17205536)
• the ERalpha cofactor RIZ gene has a prominent effect on bone marrow density(BMD), and the P704 genotype modulates the impact of estradiol on BMD (PMID:17356055)
• RIZ polymorphisms may be important predictive markers for lung cancer susceptibility. (PMID:17693662)
• Reduced expression of RIZ1 may play an important role in the pathogenesis and/or development of epithelial ovarian carcinoma, and is considered to be caused in part by aberrant DNA methylation. (PMID:17922684)
• The proliferation, migration induction and apoptosis inhibition activities of SMYD3 in hepatocellular carcinoma may be mediated through RIZ1 CpG promoter hypermethylation. (PMID:17963297)
• observed no association of the RIZ1 Pro704 insertion-deletion polymorphism with BMD or fracture risk (PMID:18037365)
• Silencing of YY1 downregulates RIZ1 promoter in human osteosarcoma. (PMID:18488713)
• Results suggest that the inactivation of the RIZ1 by DNA methylation at its promoter region is involved in the tumorigenesis of hepatocellular carcinoma, particularly in the early stage of disease. (PMID:18712668)
• methyl-balanced diet conferred additional survival benefits compared to a tumor-inducing methyl-imbalanced diet only in mice with wild type RIZ1 but not in mice deficient in RIZ1 (PMID:18852888)
• Loss of RIZ1 expression will lead to an increase in myeloid blast cell population resulting in CML progression. (PMID:19602237)
• RIZ1 is expressed in normal prostate epithelial cells and down-regulated in cancer cells, with a switch of its localization from the nucleus to the cytoplasm upon cancer grade progression. RIZ1 levels were modulated by DHT or E2 treatment in vitro. (PMID:19746436)
• Reduced expression of RIZ1 may play an important role in the pathogenesis and/or development of cervical cancer, and is considered to be caused in part by aberrant DNA methylation (PMID:20159667)
• RIZ1 negatively regulated the cell proliferation of monocytic leukemia cells via activation of p53. (PMID:20594067)
• promoter methylation and H3K9 modifications work together to silence the RIZ1 gene in hepatocellular carcinoma (HCC). (PMID:20675009)
• Results suggest that the RIZ1 gene is inactivated in MDS and AML in part by methylation, whereas another mechanism should be involved in others. (PMID:20828818)
• RIZ1 promoter methylation is not a common event in neuroblastoma. (PMID:20878080)
• RIZ1 might play an important role in tumor metastasis, and the PR domain alone possessed anticancer activity. (PMID:21369371)
• Acting as a negative regulator of RIZ1 function, PRFM2 mediates effect of cell proliferation by estrogen via regulation of cell survival and differentiating gene expression. (PMID:21503890)
• Aberrant methylation and decreased expression of the RIZ1 gene are frequent in adult acute lymphoblastic leukemia of T-cell phenotype (PMID:22300346)
• Data suggest that promoter methylation may play an important role in the epigenetic silencing of RIZ1 gene expression in human esophageal squamous cell carcinoma. (PMID:22363126)
• RIZ1 may be a potential tumor suppressor in human esophageal squamous cell cancer. (PMID:22372344)
• RIZ1 expression is significantly downregulated as the formation of meningiomas progressed, and suggest that RIZ1 may represent a promising candidate tumor suppressor gene that contributes to malignant meningiomas. (PMID:22614009)
• Reduction of RIZ1 expression aggravates the progression of liver fluke-related cholangiocarcinoma (PMID:23098508)
• The development and progression of esophageal squamous cell carcinoma are related to the inactivation of RIZ1. (PMID:24115813)
• PRDM2, PRDM5, PRDM16 promoters are methylated and their expression is suppressed in lung cancer cells. (PMID:24966940)
• Results suggest that high expression of SMYD3 is related to the occurrence of esophageal squamous cell carcinoma. Also, its suppression promoted the expression of RIZ1 suggesting a signal transduction pathway between SMYD3 and RIZ1. (PMID:24993551)
• PRDM2 downregulation may play a role in dopamine-agonist resistance and tumor recurrence in prolactinomas. (PMID:25884948)
• Loss of RIZ1 expression due to methylation is associated with Renal Cell Carcinoma. (PMID:25987089)
• RIZ1 expression is negatively correlated with glioma differentiation and can serve as a predictor of glioma prognosis and thus could be a potential therapeutic target for patients with gliomas. (PMID:26690953)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdm2b	ENSDARG00000076451
mus_musculus	Prdm2	ENSMUSG00000057637
rattus_norvegicus	Prdm2	ENSRNOG00000033522

Paralogs (51): WIZ (ENSG00000011451), ZNF416 (ENSG00000083817), MYNN (ENSG00000085274), PRDM4 (ENSG00000110851), ZBTB17 (ENSG00000116809), ZNF644 (ENSG00000122482), GZF1 (ENSG00000125812), ZNF426 (ENSG00000130818), ZNF287 (ENSG00000141040), ZNF697 (ENSG00000143067), ZNF687 (ENSG00000143373), ZNF214 (ENSG00000149050), ZNF547 (ENSG00000152433), ZNF776 (ENSG00000152443), ZNF230 (ENSG00000159882), ZNF222 (ENSG00000159885), ZNF233 (ENSG00000159915), ZNF333 (ENSG00000160961), ZNF319 (ENSG00000166188), ZNF592 (ENSG00000166716), ZNF646 (ENSG00000167395), ZNF507 (ENSG00000168813), ZNF768 (ENSG00000169957), ZNF417 (ENSG00000173480), ZNF408 (ENSG00000175213), ZBTB41 (ENSG00000177888), ZNF223 (ENSG00000178386), ZNF852 (ENSG00000178917), ZNF784 (ENSG00000179922), ZNF572 (ENSG00000180938), ZNF707 (ENSG00000181135), ZNF746 (ENSG00000181220), ZNF467 (ENSG00000181444), ZNF530 (ENSG00000183647), ZNF17 (ENSG00000186272), ZNF527 (ENSG00000189164), ZKSCAN7 (ENSG00000196345), ZNF34 (ENSG00000196378), ZNF774 (ENSG00000196391), ZNF777 (ENSG00000196453)

Protein

Protein identifiers

PR domain zinc finger protein 2 — Q13029 (reviewed: Q13029)

Alternative names: GATA-3-binding protein G3B, Lysine N-methyltransferase 8, MTB-ZF, MTE-binding protein, PR domain-containing protein 2, Retinoblastoma protein-interacting zinc finger protein, Zinc finger protein RIZ

All UniProt accessions (6): Q13029, D6RAA0, D6RED5, D6RJM6, H0Y9J3, S4R3F7

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates ‘Lys-9’ of histone H3. May function as a DNA-binding transcription factor. Binds to the macrophage-specific TPA-responsive element (MTE) of the HMOX1 (heme oxygenase 1) gene and may act as a transcriptional activator of this gene.

Subunit / interactions. Binds to the retinoblastoma protein (RB). Interacts with GATA3.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in retinoblastoma cell lines and in brain tumors. Also expressed in a number of other cell lines and in brain, heart, skeletal muscle, liver and spleen. Isoform 1 is expressed in testis at much higher level than isoform 3.

Miscellaneous. Produced by alternative initiation at Met-202 of isoform 1.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q13029-1	1, RIZ1	yes
Q13029-2	2, MTB-Zf
Q13029-3	3, RIZ2
Q13029-4	4
Q13029-5	5

RefSeq proteins (7): NP_001007258, NP_001129082, NP_001380915, NP_001380916, NP_001380917, NP_036363, NP_056950 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR009170	PRDM2	Family
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR044414	PRDM2_PR-SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF13912, PF21549

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:60276)

UniProt features (101 total): compositionally biased region 17, sequence conflict 14, region of interest 11, cross-link 11, strand 11, zinc finger region 8, modified residue 6, helix 6, splice variant 5, short sequence motif 3, mutagenesis site 3, sequence variant 2, turn 2, chain 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2QPW	X-RAY DIFFRACTION	1.79
2JV0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13029-F1	47.51	0.03

Functional residue map

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

Post-translational modifications (17): 421, 643, 743, 781, 785, 796, 347, 651, 690, 692, 774, 866, 879, 1147, 1151, 1257, 1281

Mutagenesis-validated functional residues (3):

Position	Phenotype
106	reduced histone methyltransferase activity.
159	reduced histone methyltransferase activity.
188	loss of histone methyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, ZHAN_MULTIPLE_MYELOMA_PR_DN, TTTGTAG_MIR520D, CTATGCA_MIR153, GTGCCTT_MIR506, TCF4_Q5, DOANE_RESPONSE_TO_ANDROGEN_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GROSS_HYPOXIA_VIA_ELK3_DN, AAAGGGA_MIR204_MIR211, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_DETERMINATION_OF_ADULT_LIFESPAN, SENESE_HDAC1_TARGETS_UP, GOBP_CHROMATIN_REMODELING, GOBP_METHYLATION

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), determination of adult lifespan (GO:0008340), methylation (GO:0032259), positive regulation of transcription by RNA polymerase II (GO:0045944), chromatin remodeling (GO:0006338)

GO Molecular Function (14): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), histone H3K9 trimethyltransferase activity (GO:0140949), DNA binding (GO:0003677), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), histone methyltransferase activity (GO:0042054), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
intracellular membrane-bounded organelle	2
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
multicellular organismal process	1
metabolic process	1
positive regulation of DNA-templated transcription	1
chromatin organization	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
transition metal ion binding	1
DNA binding	1
histone H3K9 methyltransferase activity	1
nucleic acid binding	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
protein methyltransferase activity	1
histone modifying activity	1
cation binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1

Protein interactions and networks

STRING

1234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM2	FOXG1	P55315	634
PRDM2	CTBP1	Q13363	625
PRDM2	MSH3	P20585	601
PRDM2	CAMKMT	Q7Z624	599
PRDM2	PRDM8	Q9NQV8	595
PRDM2	WTAP	Q15007	594
PRDM2	SETDB1	Q15047	591
PRDM2	ZFP1	Q6P2D0	589
PRDM2	SUV39H1	O43463	585
PRDM2	EHMT2	Q96KQ7	583
PRDM2	NSD1	Q96L73	560
PRDM2	SUV39H2	Q9H5I1	556
PRDM2	DNMT3B	Q9UBC3	556
PRDM2	POU4F2	Q12837	540
PRDM2	SETDB2	Q96T68	527
PRDM2	EHMT1	Q9H9B1	527

IntAct

20 interactions, top by confidence:

A	B	Type	Score
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
PRDM2	HNRNPU	psi-mi:“MI:0915”(physical association)	0.400
Rpl35	RPS6	psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
HMGN5	SMCHD1	psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350
SMARCA1	CBX1	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
CTBP1	SEC16A	psi-mi:“MI:2364”(proximity)	0.270
KLF12		psi-mi:“MI:2364”(proximity)	0.270
KLF3	MCRIP1	psi-mi:“MI:2364”(proximity)	0.270
KLF8	USP27X	psi-mi:“MI:2364”(proximity)	0.270
GPKOW	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SMNDC1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
NSUN2	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
FMR1	PRDM2	psi-mi:“MI:0915”(physical association)	0.000
SOD2	PRDM2	psi-mi:“MI:0915”(physical association)	0.000
	PRDM2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (55): HIST1H3A (Biochemical Activity), PRDM2 (Affinity Capture-MS), PRDM2 (Affinity Capture-MS), PRDM2 (Biochemical Activity), PRDM2 (Affinity Capture-MS), PRDM2 (Affinity Capture-MS), PRDM2 (Affinity Capture-MS), PRDM2 (Affinity Capture-Western), ESR1 (Two-hybrid), PRDM2 (Reconstituted Complex), RB1 (Affinity Capture-Western), PRDM2 (Affinity Capture-MS), PRDM2 (Proximity Label-MS), PRDM2 (Proximity Label-MS), PRDM2 (Proximity Label-MS)

ESM2 similar proteins: A0A0A6YY25, A6NGG8, A6X8Z5, B2RQL2, B2RXH4, D3ZMK9, D3ZUE1, E9Q7F2, O08696, O14513, P59598, P97691, Q05860, Q05AH6, Q08050, Q0GGX2, Q0VET5, Q13029, Q2M1Z3, Q3U0P1, Q571I4, Q5PSV9, Q5SSG4, Q5U2M8, Q5VV67, Q63755, Q66H04, Q68DA7, Q69ZL1, Q6DIA7, Q6JPI3, Q6P1D7, Q6PAC4, Q6PG16, Q71F56, Q76N32, Q811R2, Q86YN6, Q86YV5, Q8BJS7

Diamond homologs: A0A163UT06, A2A935, A2AGX3, A2AJ77, B8A5Y1, E9Q3T6, O75626, P0C6Y7, P14404, Q03112, Q13029, Q3UZD5, Q60636, Q63755, Q6P2A1, Q8BZ97, Q96EQ9, Q9GZV8, Q9H4Q4, Q9HAZ2, Q9NQV5, Q9NQV7, Q9NQV8, Q9NQW5, B7ZRM8, B7ZRU9, Q22024, Q8I7Z8, A6QPM3, Q9CXE0, Q9NQX0, Q9NQX1, E9PZZ1, Q9H4Q3, A2BID7, Q6DCW1, Q9VH70, B4F6U4, E9Q8T2, I7HJS4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRDM2	“up-regulates quantity by expression”	HMOX1	“transcriptional regulation”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 3 cancer types — HCC, NBL, PRCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	227
Likely benign	12
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
816819	NM_001393986.1(PRDM2):c.4283_4295del (p.Leu1428fs)	Likely pathogenic

SpliceAI

3281 predictions. Top by Δscore:

Variant	Effect	Δscore
1:13715616:T:G	donor_loss	1.0000
1:13716675:A:G	donor_gain	1.0000
1:13730990:T:TA	acceptor_gain	1.0000
1:13730995:TGCA:T	acceptor_loss	1.0000
1:13730996:GCAG:G	acceptor_loss	1.0000
1:13730997:CAG:C	acceptor_loss	1.0000
1:13730998:A:AG	acceptor_gain	1.0000
1:13730998:A:AT	acceptor_loss	1.0000
1:13730999:G:GG	acceptor_gain	1.0000
1:13730999:GAAC:G	acceptor_gain	1.0000
1:13731075:G:GT	donor_gain	1.0000
1:13731113:GATTG:G	donor_gain	1.0000
1:13731115:TTGGT:T	donor_loss	1.0000
1:13731116:TGG:T	donor_loss	1.0000
1:13731118:G:GG	donor_gain	1.0000
1:13731118:GTGAG:G	donor_loss	1.0000
1:13731119:T:A	donor_loss	1.0000
1:13731120:GAGT:G	donor_loss	1.0000
1:13731121:AGTGC:A	donor_loss	1.0000
1:13742153:TAAAG:T	donor_loss	1.0000
1:13742154:AAAGG:A	donor_loss	1.0000
1:13742155:AAGG:A	donor_loss	1.0000
1:13742156:AG:A	donor_loss	1.0000
1:13742157:GG:G	donor_loss	1.0000
1:13742158:GTA:G	donor_loss	1.0000
1:13742159:T:G	donor_loss	1.0000
1:13773071:GTTTC:G	acceptor_loss	1.0000
1:13773072:TTTCA:T	acceptor_loss	1.0000
1:13773073:TTCAG:T	acceptor_loss	1.0000
1:13773074:TCA:T	acceptor_loss	1.0000

AlphaMissense

11077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:13732877:T:A	W76R	1.000
1:13732877:T:C	W76R	1.000
1:13778888:T:C	C365R	1.000
1:13778889:G:A	C365Y	1.000
1:13778969:T:C	C392R	1.000
1:13778990:T:C	F399L	1.000
1:13778992:T:A	F399L	1.000
1:13778992:T:G	F399L	1.000
1:13779017:C:G	H408D	1.000
1:13779248:T:C	C485R	1.000
1:13779257:T:C	C488R	1.000
1:13779258:G:A	C488Y	1.000
1:13779259:T:G	C488W	1.000
1:13779269:T:C	F492L	1.000
1:13779271:T:A	F492L	1.000
1:13779271:T:G	F492L	1.000
1:13779296:C:A	H501N	1.000
1:13779296:C:G	H501D	1.000
1:13779298:T:A	H501Q	1.000
1:13779298:T:G	H501Q	1.000
1:13779302:C:A	R503S	1.000
1:13779307:A:C	R504S	1.000
1:13779307:A:T	R504S	1.000
1:13781372:T:C	C1193R	1.000
1:13781798:T:A	C1335S	1.000
1:13781798:T:C	C1335R	1.000
1:13781799:G:A	C1335Y	1.000
1:13781799:G:C	C1335S	1.000
1:13781800:C:G	C1335W	1.000
1:13781807:T:A	C1338S	1.000

dbSNP variants (sampled 300 via entrez): RS1000001936 (1:13769354 G>A), RS1000005767 (1:13728055 A>G), RS1000038734 (1:13728398 C>G,T), RS1000044675 (1:13807157 C>T), RS1000050586 (1:13788915 G>A), RS1000080279 (1:13709700 G>A), RS1000126583 (1:13707852 A>G), RS1000144928 (1:13752969 A>G), RS1000192899 (1:13823353 C>T), RS1000201336 (1:13721901 T>C), RS1000211552 (1:13758805 A>G), RS1000222612 (1:13702496 G>A), RS1000286031 (1:13753219 A>C), RS1000291972 (1:13709392 C>T), RS1000313025 (1:13751962 T>C)

Disease associations

OMIM: gene MIM:601196 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002938_23	Copper levels	3.000000e-06
GCST003059_1	Parkinson’s disease	1.000000e-06
GCST003074_1	Cerebral amyloid deposition in APOEe4 non-carriers (PET imaging)	2.000000e-07
GCST004353_1	Left ventricular function change in anthracycline treatment	7.000000e-07
GCST006995_1	Logical memory (delayed recall) in Alzheimer’s disease dementia	5.000000e-07
GCST007354_20	Intracranial aneurysm	4.000000e-13
GCST007576_106	Chronotype	2.000000e-11
GCST010002_352	Refractive error	2.000000e-09
GCST010570_1	Polycystic ovary syndrome (reproductive subtype)	2.000000e-10
GCST010993_2	Anti-drug antibodies in autoimmune disease (time to event)	6.000000e-07
GCST011743_11	HDL cholesterol levels in HIV infection	1.000000e-05
GCST012310_13	Schizophrenia x sex interaction	3.000000e-06
GCST012311_21	Schizophrenia x sex interaction	3.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007707	cerebral amyloid deposition measurement
EFO:0004295	left ventricular function
EFO:0005257	response to anthracycline-based chemotherapy
EFO:0004874	memory performance
EFO:0008328	chronotype measurement
EFO:0010559	anti-drug antibody measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5214862 (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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects binding, affects folding, decreases reaction, increases expression, affects cotreatment	4
Ozone	increases expression, increases abundance, affects expression, affects cotreatment	3
trichostatin A	affects cotreatment, decreases expression	2
sodium arsenite	affects expression, decreases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
bisphenol S	affects cotreatment, increases methylation, affects binding, decreases reaction	2
bisphenol AF	affects binding, affects folding, decreases reaction, increases reaction	2
Acetaminophen	increases expression	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, affects expression	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
terbufos	increases methylation	1
cobaltous chloride	increases expression	1
arsenic disulfide	decreases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	decreases expression	1
Decitabine	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5214670	Binding	Selectivity interaction (Methyltransferase panel (DSF assay)) EUB0000234b PRDM2	Selectivity Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

4 cell lines: 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5Q2	SEES3-1V human PRDM2, clone1	Embryonic stem cell	Male
CVCL_A5Q3	SEES3-1V human PRDM2, clone2	Embryonic stem cell	Male
CVCL_A5Q4	SEES3-1V human PRDM2, clone3	Embryonic stem cell	Male
CVCL_XV73	HEK293 eGFP-PRDM2	Transformed cell line	Female

Clinical trials (associated diseases)

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