PRDM1

Summary

PRDM1 (PR/SET domain 1, HGNC:9346) is a protein-coding gene on chromosome 6q21, encoding PR domain zinc finger protein 1 (O75626). Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of p….

This gene encodes a protein that acts as a repressor of beta-interferon gene expression. The protein binds specifically to the PRDI (positive regulatory domain I element) of the beta-IFN gene promoter. Transcription of this gene increases upon virus induction. Two alternatively spliced transcript variants that encode different isoforms have been reported.

Source: NCBI Gene 639 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 111 total
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 5 cancer types
• Transcription factor: yes — 74 downstream targets (CollecTRI)
• MANE Select transcript: NM_001198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9346
Approved symbol	PRDM1
Name	PR/SET domain 1
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	PRDI-BF1, Blimp-1
Ensembl gene	ENSG00000057657
Ensembl biotype	protein_coding
OMIM	603423
Entrez	639

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 retained_intron

ENST00000369089, ENST00000369091, ENST00000369096, ENST00000424894, ENST00000450060, ENST00000481163, ENST00000489365, ENST00000648754, ENST00000651185, ENST00000652320, ENST00000967211

RefSeq mRNA: 2 — MANE Select: NM_001198 NM_001198, NM_182907

CCDS: CCDS34505, CCDS5054

Canonical transcript exons

ENST00000369096 — 7 exons

Exon	Start	End
ENSE00000359739	106095615	106095734
ENSE00000761561	106099300	106099552
ENSE00001512799	106106911	106109938
ENSE00002243998	106106371	106106499
ENSE00002258316	106104825	106105933
ENSE00002286410	106086336	106086595
ENSE00003550915	106088201	106088449

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 95.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.0197 / max 684.1177, expressed in 1271 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69088	10.7292	956
69089	6.0178	881
69098	2.8913	413
69099	0.8774	176
69096	0.6724	176
69097	0.6114	163
69090	0.5680	178
69093	0.1630	73
69092	0.1603	93
69091	0.1128	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	95.33	gold quality
esophagus squamous epithelium	UBERON:0006920	93.42	gold quality
colonic epithelium	UBERON:0000397	91.94	gold quality
oral cavity	UBERON:0000167	91.88	gold quality
epithelium of esophagus	UBERON:0001976	91.22	gold quality
pharyngeal mucosa	UBERON:0000355	90.92	gold quality
esophagus mucosa	UBERON:0002469	90.74	gold quality
stromal cell of endometrium	CL:0002255	90.16	gold quality
rectum	UBERON:0001052	88.83	gold quality
upper leg skin	UBERON:0004262	88.29	gold quality
blood	UBERON:0000178	87.47	gold quality
squamous epithelium	UBERON:0006914	87.40	gold quality
vagina	UBERON:0000996	87.00	gold quality
bone marrow cell	CL:0002092	86.83	gold quality
superficial temporal artery	UBERON:0001614	86.40	gold quality
endometrium	UBERON:0001295	86.33	gold quality
epithelium of nasopharynx	UBERON:0001951	85.99	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.94	gold quality
tonsil	UBERON:0002372	85.44	gold quality
granulocyte	CL:0000094	85.34	gold quality
ectocervix	UBERON:0012249	85.29	gold quality
gingiva	UBERON:0001828	85.27	gold quality
penis	UBERON:0000989	84.66	gold quality
amniotic fluid	UBERON:0000173	84.63	gold quality
gall bladder	UBERON:0002110	84.26	gold quality
buccal mucosa cell	CL:0002336	84.02	gold quality
uterine cervix	UBERON:0000002	84.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.78	gold quality
lymph node	UBERON:0000029	83.56	gold quality
mouth mucosa	UBERON:0003729	83.41	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	966.56
E-MTAB-11121	yes	577.68
E-GEOD-109979	yes	435.66
E-MTAB-6386	yes	124.44
E-MTAB-7008	yes	97.40
E-CURD-122	yes	37.59
E-MTAB-8410	yes	37.43
E-ANND-3	yes	32.47
E-CURD-46	yes	29.86
E-MTAB-9543	yes	21.65
E-CURD-112	yes	15.38
E-HCAD-35	yes	7.45
E-GEOD-110499	no	3758.62
E-MTAB-10137	no	2755.60

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

74 targets.

Target	Regulation
ADAM2
AP1	Repression
BCL6	Unknown
BMP5
CAMK4
CCL2	Repression
CCL8	Repression
CD27
CD4	Repression
CD40
CD74
CD8A
CHRD	Repression
CIITA	Repression
CSF2	Activation
CXCR5
DUSP16
EHMT2
EIF3K
ESR1	Repression
FASTK
FCER2	Repression
FOS	Repression
GCSAM	Repression
GHRHR
GZMB	Activation
HAND1
HLA-E
HSPA5
ID3

JASPAR motifs

Motif	Name	Family
MA0508.1	PRDM1	More than 3 adjacent zinc fingers
MA0508.2	PRDM1	More than 3 adjacent zinc fingers
MA0508.3	PRDM1	More than 3 adjacent zinc fingers
MA0508.4	PRDM1	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:20421211, PMID:28473536

Upstream regulators (CollecTRI, top): AHR, AP1, BACH2, BCL6, CEBPB, E2F1, EBF1, EGR1, FOS, GLI1, HAND1, IRF4, IRF5, IRF6, JUN, MAFB, MAFK, PAX5, PRDM1, SP1, SP3, SPI1, SPIB, STAT3, TP53

miRNA regulators (miRDB)

274 targeting PRDM1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
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-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-223-3P	99.99	70.14	1140

Literature-anchored findings (GeneRIF, showing 40)

• were expressed by human PCs following a gradient of increasing maturity in the direction: tonsil–>blood–>BM (PMID:11877292)
• Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program (PMID:12150891)
• BCL-6 regulates the Blimp-1 promoter through a novel mechanism involving AP-1 elements. (PMID:12165517)
• Premature Blimp-1 expression coupled to altered and deficient Pax5 expression causes some proliferating B cells to prematurely differentiate to plasma cells in MM. (PMID:12453881)
• PRDI-BF1 beta is abundantly expressed in myeloma cell lines through alternative transcription initiation, has a disrupted PR domain and a significantly impaired transcription repressor function on multiple target genes. (PMID:12626569)
• PRDI-BF1 mediates silencing of interferon-beta gene transcription via recruitment of the histone H3 methyltransferase G9a. (PMID:14985713)
• Transcriptional regulator PRD1-BF1 governing B-cell terminal cellular differentiation provides multiple myeloma- and other tumor- and nonmalignant-associated cytotoxic T-lymphocyte epitopes. (PMID:16002735)
• identifies PRDM1 inactivation as a recurrent genetic defect in diffuse large B-cell lymphomas cells and establishes PRDM1 as a potential tumor suppressor gene. (PMID:16424392)
• Blimp1 is a tumor suppressor gene, whose inactivation may contribute to lymphomagenesis by blocking post-germinal center differentiation of B cells toward plasma cells. (PMID:16492805)
• tetanus toxoid (tet) (+) plasma cell (PC)expressed several times more positive regulatory domain I- binding factor 1/B lymphocyte-induced maturation protein 1 transcription factor than the tetC(-) PC (PMID:16547239)
• diffuse large B-cell lymphoma cases with increased PRDM1 expression co-expressed BCL-6 and MUM1/IRF4, confirming that PRDM1 expression is insufficient to drive the full genetic program associated with plasmacytic differentiation (PMID:16585013)
• In addition to silencing expression of major histocompatibility class II transactivator protein (CIITA) promoter III in B lymphocytes, PRDI-BF1 is capable of binding and suppressing CIITA promoter type IV. (PMID:16765445)
• Results identify Viperin as a tightly regulated ISGF3 target gene, which is counter-regulated by PRDI-BF1. (PMID:16849320)
• Normal human plasma cells have significantly lower levels of PRDI-BF1beta expression than plasma cells isolated from multiple myeloma patients. (PMID:17043021)
• Altered expression of BLIMP1 may cause neoplastic B-cell proliferation; BLIMP1 is a pivotal molecule in the pathogenesis of diffuse large B-cell lymphoma. (PMID:17213024)
• Suppression of p53 transcription is a crucial function of endogenous BLIMP1 and is essential for normal cell growth. (PMID:17264218)
• both PRDM1alpha and PRDM1beta transcripts were expressed in microdissected lymphoma cells only in the non-germinal center B-cell-like (non-GCB) subtype of DLBCL (PMID:17379744)
• Repression of PRDM1 by BSAP reveals an autoregulatory negative-feedback loop that could play a relevant role in controlling human PC differentiation. (PMID:17682124)
• Blimp-1 could directly repress the expression of c-myc in 2ME2-mediated differentiation induction of multiple myeloma cells. (PMID:17877160)
• Blimp-1 expression is controlled by the same cgammaC cytokines that regulate T cell homeostasis suggesting a direct link between the extrinsic and intrinsic arms of the process. (PMID:18071884)
• Blimp-1 ensures the survival of transformed plasma cells. (PMID:18089822)
• that transcription factors Xbp-1, Blimp-1, and PAX-5-encoded BSAP play important roles in the regulation of plasmacytic differentiation and exert their effects on differentiation induced by low 2ME2 concentrations (PMID:18192112)
• bortezomib down-regulation of PRDM1beta preceded decreased IRF4 and c-MYC expression (PMID:18235046)
• reporter assays demonstrated that Bach2 and Bcl6 cooperate to repress Prdm1 through its intron enhancer region (PMID:18256039)
• STAT3 activation functionally mimicked IL-21 treatment and that STAT3-mediated BLIMP1 up-regulation occurred despite high BCL6 expression levels (PMID:18354204)
• In spite of some commonalities, different targets and regulators of Blimp-1 in B and T cells suggest intriguing evolutionary divergence of this regulatory machinery. (PMID:18370921)
• By chromatin immunoprecipitation and assays using an inducible Spi-B construct BLIMP1 and XBP-1 were identified as direct target genes of Spi-B mediated repression. (PMID:18552212)
• MiRNA-mediated down-regulation of PRDM1/Blimp-1 may contribute to the phenotype maintenance and pathogenesis of Hodgkin/Reed-Sternberg cells (PMID:18583325)
• PRDM1 may be a tumor suppressor in some primary central nervous system lymphoma and contribute to lymphomagenesis by impairing terminal differentiation (PMID:18596541)
• the basal activity of the human PRDM1 promoter, through which several factors, including SP1, SP3 and early growth response 1, modulate its expression through a conserved GC-box. (PMID:18604866)
• Blimp-1Delta7 interferes with endogenous Blimp-1 expression, suggesting an auto-regulatory mechanism of Blimp-1 activation. (PMID:18845144)
• BLIMP1 and PRMT5 were expressed and arginine dimethylation of histones H2A and H4 was detected in human male gonocytes and intratubular germ cell neoplasia unclassified and most seminomas, while downregulated in embryonal carcinoma. (PMID:18992153)
• GC-enriched hsa-miR-125b down-regulates the expression of IRF4 and PRDM1/BLIMP1, and memory B cell-enriched hsa-miR-223 down-regulates the expression of LMO2. (PMID:19047678)
• tumor-promoting effect of deletion in 6q21, that included genes PRDM1, ATG5 and AIM1 (PMID:19194464)
• Blimp-1 is a key regulator of Toll-like receptor-mediated and differentiation-associated reduction of nucleotide-binding domain, leucine-rich repeat family pyrin domain-containing (NLRP)12 protein in human myeloid-monocytic cells. (PMID:19234190)
• regulates the contraction phase of CD8+ T cell response via IL-2 transcription inhibition (PMID:19269192)
• the induction of Blimp1 represents a novel mechanism whereby the RelB NF-kappaB subunit mediates repression, specifically of ERalpha, thereby promoting a more migratory phenotype in breast cancer cells (PMID:19433448)
• Data provide evidence that hsa-miR-127 is involved in B-cell differentiation process through posttranscriptional regulation of BLIMP1 and XBP1. (PMID:19530237)
• Low dose 2-methoxyestradiol can up-regulate the expression of PRDMlalpha and PRDM1beta in myeloma cells. (PMID:19563034)
• C/EBPbeta directly bound to the promoter region of IRF4, BLIMP1, and BCL2. (PMID:19717648)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prdm1a	ENSDARG00000002445
mus_musculus	Prdm1	ENSMUSG00000038151
rattus_norvegicus	Prdm1	ENSRNOG00000000323
drosophila_melanogaster	Blimp-1	FBGN0035625
caenorhabditis_elegans	blmp-1	WBGENE00003847

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), SNAI3 (ENSG00000185669), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

PR domain zinc finger protein 1 — O75626 (reviewed: O75626)

Alternative names: BLIMP-1, Beta-interferon gene positive regulatory domain I-binding factor, PR domain-containing protein 1, Positive regulatory domain I-binding factor 1

All UniProt accessions (5): O75626, A0A3B3IU23, B2REA4, B2REA5, Q5T4E8

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of proteins that promote the egress of tissue-resident T-cell populations from non-lymphoid organs. Plays a role in the development, retention and long-term establishment of adaptive and innate tissue-resident lymphocyte T cell types in non-lymphoid organs, such as the skin and gut, but also in other nonbarrier tissues like liver and kidney, and therefore may provide immediate immunological protection against reactivating infections or viral reinfection. Binds specifically to the PRDI element in the promoter of the beta-interferon gene. Drives the maturation of B-lymphocytes into Ig secreting cells. Associates with the transcriptional repressor ZNF683 to chromatin at gene promoter regions. Binds to the promoter and acts as a transcriptional repressor of IRF8, thereby promotes transcription of osteoclast differentiation factors such as NFATC1 and EEIG1.

Subunit / interactions. Interacts with PRMT5. Interacts with FBXO10. Interacts with FBXO11. Interacts with multiple nuclear sumoylation E3 ligases, including CBX4, PIAS1, PIAS2, PIAS3, PIAS4, PML and RNF4, but not RANBP2. Interacts with LDB1, SMARCD3 and SMARCC1. Interacts with EEIG1; following TNFSF11/RANKL stimulation in bone marrow-derived macrophages, the interaction promotes the binding of PRDM1/BLIMP1 to the gene promoter of IRF8.

Subcellular location. Nucleus. Cytoplasm.

Post-translational modifications. Sumoylation at Lys-816 by PIAS1 augments transcriptional repressor activity, and is critical for plasma cell differentiation. Can be sumoylated with SUMO1 and SUMO2 by PML. Degradation of the wild-type protein mostly depends upon sumoylation, rather than ubiquitination. Desumoylated by SENP1 and SENP6. Ubiquitinated by the SCF(FBXO11) complex, leading to its degradation by the proteasome.

Disease relevance. In certain aggressive cases of activated B cell-like diffuse large B-cell lymphoma (ABC-DLBCL), PRDM1 protein instability has been observed. This instability, which impairs B-cell differentiation, is caused by N-terminal misfolding mutations, including those occurring at positions Pro-84 and Ile-107, and results in PRDM1 protein sequestration in the cytoplasm, followed by proteasomal degradation via a heat shock protein 70 HSPA1A-SYNV1/HRD1 pathway. These N-terminal mutations do not affect PRDM1 transcription regulation activity. HSPA1A inhibition restores PRDM1 nuclear localization and transcriptional activity in lymphoma cell lines and suppresses tumor growth in xenografts, more efficiently than proteasome inhibition.

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

Isoforms (3)

UniProt ID	Names	Canonical?
O75626-1	1	yes
O75626-2	2
O75626-3	3

RefSeq proteins (2): NP_001189, NP_878911 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR013087	Znf_C2H2_type	Domain
IPR016608	PRDM1	Family
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR044413	PRDM1_PR-SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily
IPR050331	Zinc_finger_PRDM4/PRDM1/PRDM14	Family

Pfam: PF00096, PF13912, PF21549

UniProt features (37 total): strand 10, helix 5, sequence variant 4, zinc finger region 4, splice variant 3, cross-link 2, mutagenesis site 2, turn 2, region of interest 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3DAL	X-RAY DIFFRACTION	1.65
9Q33	ELECTRON MICROSCOPY	3.2
9Q1G	X-RAY DIFFRACTION	3.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75626-F1	56.73	0.15

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 (2): 816, 816

Mutagenesis-validated functional residues (2):

Position	Phenotype
84	protein instability caused by increased susceptibility to proteasomal degradation.
107	protein instability caused by increased susceptibility to proteasomal degradation.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6804754	Regulation of TP53 Expression
R-HSA-9701898	STAT3 nuclear events downstream of ALK signaling
R-HSA-9827857	Specification of primordial germ cells

MSigDB gene sets: 657 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, AAGCAAT_MIR137, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, HNF3ALPHA_Q6, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, PAX4_01, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, MODULE_255, GOBP_EPITHELIAL_CELL_DEVELOPMENT

GO Biological Process (33): negative regulation of transcription by RNA polymerase II (GO:0000122), morphogenesis of a branching structure (GO:0001763), kidney development (GO:0001822), maternal placenta development (GO:0001893), adaptive immune response (GO:0002250), heart valve development (GO:0003170), ventricular septum development (GO:0003281), regulation of transcription by RNA polymerase II (GO:0006357), germ cell development (GO:0007281), post-embryonic development (GO:0009791), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), methylation (GO:0032259), regulation of natural killer cell differentiation (GO:0032823), regulation of extrathymic T cell differentiation (GO:0033082), aorta development (GO:0035904), regulation of cell population proliferation (GO:0042127), eye photoreceptor cell development (GO:0042462), innate immune response (GO:0045087), cell fate commitment (GO:0045165), artery morphogenesis (GO:0048844), regulation of NK T cell differentiation (GO:0051136), retinal bipolar neuron differentiation (GO:0060040), intestinal epithelial cell development (GO:0060576), trophoblast giant cell differentiation (GO:0060707), coronary vasculature development (GO:0060976), sebum secreting cell proliferation (GO:1990654), in utero embryonic development (GO:0001701), embryonic placenta development (GO:0001892), immune system process (GO:0002376), cardiac septum development (GO:0003279), cellular developmental process (GO:0048869)

GO Molecular Function (15): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), methyltransferase activity (GO:0008168), zinc ion binding (GO:0008270), histone methyltransferase binding (GO:1990226), sequence-specific double-stranded DNA binding (GO:1990837), promoter-specific chromatin binding (GO:1990841), transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), protein binding (GO:0005515), transferase activity (GO:0016740), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Regulation of TP53 Expression and Degradation	1
Signaling by ALK	1
Reproduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
multicellular organismal process	2
developmental process involved in reproduction	2
anatomical structure development	2
immune response	2
regulation of DNA-templated transcription	2
gene expression	2
regulation of gene expression	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription cis-regulatory region binding	2
nuclear lumen	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
anatomical structure morphogenesis	1
animal organ development	1
renal system development	1
placenta development	1
maternal process involved in female pregnancy	1
heart development	1
cardiac ventricle development	1
cardiac septum development	1
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
multicellular organism development	1
macromolecule biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
metabolic process	1
natural killer cell differentiation	1
regulation of natural killer cell activation	1
regulation of lymphocyte differentiation	1
extrathymic T cell differentiation	1
regulation of T cell differentiation	1
artery development	1
cell population proliferation	1
regulation of cellular process	1
eye photoreceptor cell differentiation	1
photoreceptor cell development	1

Protein interactions and networks

STRING

2716 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM1	IRF4	Q15306	928
PRDM1	PAX5	Q02548	908
PRDM1	XBP1	P17861	858
PRDM1	SDC1	P18827	826
PRDM1	EHMT2	Q96KQ7	805
PRDM1	DPPA3	Q6W0C5	802
PRDM1	BACH2	Q9BYV9	798
PRDM1	BATF	Q16520	790
PRDM1	AICDA	Q9GZX7	780
PRDM1	TBX21	Q9UL17	776
PRDM1	CD40	P25942	770
PRDM1	STAT3	P40763	749
PRDM1	IL7R	P16871	727
PRDM1	CD19	P15391	726
PRDM1	PRMT5	O14744	723

IntAct

35 interactions, top by confidence:

A	B	Type	Score
PIAS1	PRDM1	psi-mi:“MI:0915”(physical association)	0.520
NFIA	PRDM1	psi-mi:“MI:0915”(physical association)	0.470
PRDM1	ST13	psi-mi:“MI:0915”(physical association)	0.400
NFIB	PRDM1	psi-mi:“MI:0915”(physical association)	0.400
NFIC	PRDM1	psi-mi:“MI:0915”(physical association)	0.400
PRDM1	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.400
CDC37	PRDM1	psi-mi:“MI:0915”(physical association)	0.400
FBXO11	PRDM1	psi-mi:“MI:0915”(physical association)	0.400
FBXO10	PRDM1	psi-mi:“MI:0915”(physical association)	0.400
PRDM1	SUMO1	psi-mi:“MI:0915”(physical association)	0.400
PRDM1	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CFTR	PRDM1	psi-mi:“MI:0915”(physical association)	0.370
PRDM1	IFNL1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
PRDM1	HSPD1	psi-mi:“MI:0914”(association)	0.350
KIZ	PRDM1	psi-mi:“MI:0914”(association)	0.350
PRDM1	SRC	psi-mi:“MI:0914”(association)	0.350
PRDM1	ZNF609	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	PRDM1	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	PRDM1	psi-mi:“MI:2364”(proximity)	0.270
SPOP	PRDM1	psi-mi:“MI:2364”(proximity)	0.270
PRDM1	SPOP	psi-mi:“MI:2364”(proximity)	0.270
PRDM1	EGFR	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (110): PRDM1 (Affinity Capture-Western), PRDM1 (Affinity Capture-Western), IKZF3 (Affinity Capture-Western), PRDM1 (Affinity Capture-Western), IKZF3 (Reconstituted Complex), GTF2I (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), IKZF3 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), DPYSL3 (Affinity Capture-MS), BMX (Affinity Capture-MS), SRC (Affinity Capture-MS), RRAS (Affinity Capture-MS), UBE4A (Affinity Capture-MS)

ESM2 similar proteins: A0JPB4, A1L1J6, A2VDW9, A4IFJ6, O00409, O08876, O08900, O13089, O15060, O15062, O42410, O57415, O60315, O75626, O89091, P14404, P25932, P36197, P37275, P55878, P55879, P81183, Q03267, Q0VDT2, Q13422, Q33BP8, Q3BJS3, Q3UH06, Q499D0, Q5R9W9, Q5T0B9, Q5ZLR2, Q5ZM39, Q60636, Q62255, Q62947, Q64318, Q6DBW0, Q6NRM0, Q6XDT4

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, A6QPM3, E9Q8T2, P57071, Q5R5M1, Q80V63, Q9NQX0, Q9QZP2, Q9UKN5, Q9CXE0, Q9NQX1, A2BID7, B4F6U4, Q3UTQ7, Q5RAX9, Q9NQV6, E9PZZ1

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
PIAS1	up-regulates	PRDM1	sumoylation
PRDM1	“down-regulates quantity by repression”	MYC	“transcriptional regulation”
PRDM1	“down-regulates quantity by repression”	FCER2	“transcriptional regulation”
PRDM1	“down-regulates quantity by repression”	PAX5	“transcriptional regulation”
PRDM1	“down-regulates quantity by repression”	CIITA	“transcriptional regulation”
PAX5	“down-regulates quantity”	PRDM1	“transcriptional regulation”
PRDM1	“down-regulates quantity”	PAX5	“transcriptional regulation”
SOX17/POU5F1	“up-regulates quantity by expression”	PRDM1	“transcriptional regulation”
PRDM1	up-regulates	Pluripotency
PRDM1	“down-regulates quantity by repression”	CCL2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 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
Diseases of signal transduction by growth factor receptors and second messengers	5	14.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein stabilization	5	14.5×	1e-03
negative regulation of apoptotic process	7	10.6×	6e-04
protein ubiquitination	5	9.0×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 5 cancer types — AML, DLBCLNOS, NHL, PCM, PROSTATE.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	9
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

915 predictions. Top by Δscore:

Variant	Effect	Δscore
6:106088197:CCAG:C	acceptor_loss	1.0000
6:106088198:CAGGC:C	acceptor_loss	1.0000
6:106088199:A:AG	acceptor_gain	1.0000
6:106088199:A:T	acceptor_loss	1.0000
6:106088200:G:GA	acceptor_loss	1.0000
6:106088200:G:GG	acceptor_gain	1.0000
6:106088200:GGCT:G	acceptor_gain	1.0000
6:106095611:TTA:T	acceptor_loss	1.0000
6:106095613:A:AG	acceptor_gain	1.0000
6:106095613:A:AT	acceptor_loss	1.0000
6:106095613:AG:A	acceptor_gain	1.0000
6:106095614:G:GA	acceptor_gain	1.0000
6:106095614:GG:G	acceptor_gain	1.0000
6:106095614:GGT:G	acceptor_gain	1.0000
6:106095614:GGTT:G	acceptor_gain	1.0000
6:106095719:G:GT	donor_gain	1.0000
6:106095730:GGAGG:G	donor_gain	1.0000
6:106095731:GAGG:G	donor_gain	1.0000
6:106095731:GAGGG:G	donor_gain	1.0000
6:106095732:AGG:A	donor_gain	1.0000
6:106095733:GG:G	donor_gain	1.0000
6:106095733:GGG:G	donor_gain	1.0000
6:106095734:GG:G	donor_gain	1.0000
6:106095735:G:C	donor_loss	1.0000
6:106095735:G:GG	donor_gain	1.0000
6:106095736:T:G	donor_loss	1.0000
6:106097025:G:GT	donor_gain	1.0000
6:106099293:T:A	acceptor_gain	1.0000
6:106099294:G:A	acceptor_gain	1.0000
6:106099297:CA:C	acceptor_loss	1.0000

AlphaMissense

5460 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:106105889:T:C	C577R	1.000
6:106105898:T:C	C580R	1.000
6:106105910:T:C	F584L	1.000
6:106105912:C:A	F584L	1.000
6:106105912:C:G	F584L	1.000
6:106105929:T:C	L590P	1.000
6:106106378:T:C	L594P	1.000
6:106106410:T:C	C605R	1.000
6:106106431:T:C	F612L	1.000
6:106106432:T:C	F612S	1.000
6:106106433:T:A	F612L	1.000
6:106106433:T:G	F612L	1.000
6:106106450:T:C	L618P	1.000
6:106106494:T:C	C633R	1.000
6:106106914:T:C	C636R	1.000
6:106106926:T:C	F640L	1.000
6:106106927:T:C	F640S	1.000
6:106106928:T:A	F640L	1.000
6:106106928:T:G	F640L	1.000
6:106106945:T:C	L646P	1.000
6:106106953:C:G	H649D	1.000
6:106106955:C:A	H649Q	1.000
6:106106955:C:G	H649Q	1.000
6:106106957:T:C	L650P	1.000
6:106106989:T:C	C661R	1.000
6:106106998:T:C	C664R	1.000
6:106107010:T:C	F668L	1.000
6:106107011:T:C	F668S	1.000
6:106107012:C:A	F668L	1.000
6:106107012:C:G	F668L	1.000

dbSNP variants (sampled 300 via entrez): RS1000001855 (6:106046230 C>G), RS1000005531 (6:106092555 C>G,T), RS1000047613 (6:106030770 G>A), RS1000154830 (6:106100443 GAAGAA>G), RS1000192093 (6:106050723 G>A), RS1000198536 (6:106106263 T>A), RS1000233255 (6:106004459 A>C), RS1000240109 (6:106016849 T>G), RS1000245048 (6:105992694 T>C), RS1000248754 (6:106025377 A>G), RS1000301126 (6:106010523 A>G), RS1000324480 (6:106010207 T>A,C), RS1000374427 (6:106046413 G>A,T), RS1000424238 (6:106064713 C>T), RS1000475413 (6:106016958 A>G)

Disease associations

OMIM: gene MIM:603423 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000507_12	Systemic lupus erythematosus	5.000000e-12
GCST000879_55	Crohn’s disease	4.000000e-08
GCST001795_22	Systemic lupus erythematosus	4.000000e-06
GCST001999_6	Adverse response to chemotherapy (neutropenia/leucopenia) (paclitaxel)	1.000000e-06
GCST002001_11	Adverse response to chemotherapy (neutropenia/leucopenia) (all antimicrotubule drugs)	3.000000e-06
GCST003155_3	Systemic lupus erythematosus	5.000000e-14
GCST003156_8	Systemic lupus erythematosus	5.000000e-14
GCST003622_31	Systemic lupus erythematosus	4.000000e-12
GCST003622_47	Systemic lupus erythematosus	3.000000e-06
GCST003996_46	Monobrow	5.000000e-14
GCST004202_1	Systemic sclerosis	7.000000e-10
GCST004483_2	Multiple myeloma	9.000000e-15
GCST004867_8	Systemic lupus erythematosus	7.000000e-10
GCST004878_14	Sjögren’s syndrome	3.000000e-06
GCST005351_6	Carboplatin disposition in epthelial ovarian cancer	7.000000e-06
GCST005537_197	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	6.000000e-10
GCST005752_41	Systemic lupus erythematosus	2.000000e-06
GCST006627_1	Diastolic blood pressure	4.000000e-11
GCST009173_2	Response to (pegylated) interferon in HBeAG-positive hepatitis B	4.000000e-06
GCST010244_345	Triglyceride levels	3.000000e-08
GCST011956_20	Systemic lupus erythematosus	6.000000e-39

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005260	response to antimicrotubule agent
EFO:0007906	synophrys measurement
EFO:0006336	diastolic blood pressure
EFO:0007859	response to interferon
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5214860 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs548234	PRDM1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, affects cotreatment, increases expression, decreases expression	8
(+)-JQ1 compound	affects cotreatment, decreases expression	5
Benzo(a)pyrene	increases expression, increases methylation	4
Cadmium Chloride	decreases expression, increases expression	4
methylmercuric chloride	increases expression, decreases expression	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects methylation, increases expression	3
Cisplatin	affects expression, decreases expression, increases expression	3
Asbestos, Crocidolite	increases expression	3
4-phenylenediamine	increases expression, decreases reaction, increases reaction	2
mercuric bromide	increases expression, affects cotreatment	2
Zoledronic Acid	increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Vehicle Emissions	affects cotreatment, decreases expression, increases methylation	2
Dinitrochlorobenzene	decreases reaction, increases expression, increases reaction	2
Estradiol	decreases expression, increases expression	2
Oxygen	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	increases methylation, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
chloroacetaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
alpha-naphthoflavone	decreases expression, decreases reaction	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
CHEMBL5214667	Binding	Selectivity interaction (Methyltransferase panel (DSF assay)) EUB0000234b PRDM1	Selectivity Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

7 cell lines: 3 embryonic stem cell, 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5P6	SEES3-1V human PRDM1, clone1	Embryonic stem cell	Male
CVCL_A5P7	SEES3-1V human PRDM1, clone2	Embryonic stem cell	Male
CVCL_A5P8	SEES3-1V human PRDM1, clone3	Embryonic stem cell	Male
CVCL_B8MY	Abcam HCT 116 PRDM1 KO	Cancer cell line	Male
CVCL_B9AJ	Abcam MCF-7 PRDM1 KO	Cancer cell line	Female
CVCL_B9Q7	Abcam A-549 PRDM1 KO	Cancer cell line	Male
CVCL_HC88	HEK293 eGFP-PRDM1	Transformed cell line	Female

Clinical trials (associated diseases)

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