PRDM7

Summary

PRDM7 (PR/SET domain 7, HGNC:9351) is a protein-coding gene on chromosome 16q24.3, encoding Histone-lysine N-methyltransferase PRDM7 (Q9NQW5). Histone methyltransferase that selectively methylates ‘Lys-4’ of dimethylated histone H3 (H3K4me2) to produce trimethylated ‘Lys-4’ histone H3 (H3K4me3).

This gene encodes a member of a family of proteins that may have roles in transcription and other nuclear processes. The encoded protein contains a KRAB (Kruppel-associated box) domain -A box and a SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain and may function as a histone methyltransferase.

Source: NCBI Gene 11105 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 70 total
• Druggable target: yes
• MANE Select transcript: NM_001098173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9351
Approved symbol	PRDM7
Name	PR/SET domain 7
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	ZNF910
Ensembl gene	ENSG00000126856
Ensembl biotype	protein_coding
OMIM	609759
Entrez	11105

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000325921, ENST00000449207, ENST00000564210, ENST00000568473, ENST00000569206

RefSeq mRNA: 1 — MANE Select: NM_001098173 NM_001098173

CCDS: CCDS45557

Canonical transcript exons

ENST00000449207 — 11 exons

Exon	Start	End
ENSE00002500383	90060341	90060623
ENSE00002525756	90056566	90058534
ENSE00003486013	90075351	90075474
ENSE00003488323	90066861	90066910
ENSE00003567620	90061921	90062192
ENSE00003621307	90074916	90075023
ENSE00003636806	90062401	90062502
ENSE00003653773	90063612	90063768
ENSE00003679586	90061452	90061519
ENSE00003821970	90077226	90077331
ENSE00003824701	90075842	90075995

Expression profiles

Bgee: expression breadth broad, 77 present calls, max score 79.52.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.52	gold quality
tendon of biceps brachii	UBERON:0008188	73.71	silver quality
right testis	UBERON:0004534	67.74	gold quality
left testis	UBERON:0004533	65.86	gold quality
testis	UBERON:0000473	64.89	gold quality
buccal mucosa cell	CL:0002336	54.88	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	54.75	gold quality
right uterine tube	UBERON:0001302	52.54	gold quality
monocyte	CL:0000576	50.81	gold quality
lower esophagus mucosa	UBERON:0035834	50.71	gold quality
leukocyte	CL:0000738	50.44	gold quality
body of pancreas	UBERON:0001150	45.12	gold quality
right ovary	UBERON:0002118	44.14	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
ovary	UBERON:0000992	43.25	gold quality
bone marrow	UBERON:0002371	43.23	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	42.45	gold quality
left ovary	UBERON:0002119	42.35	silver quality
pharyngeal mucosa	UBERON:0000355	42.29	gold quality
adult mammalian kidney	UBERON:0000082	42.20	gold quality
kidney	UBERON:0002113	42.20	silver quality
pancreas	UBERON:0001264	42.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	41.60	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
biceps brachii	UBERON:0001507	41.30	gold quality
oviduct epithelium	UBERON:0004804	41.27	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	11.42
E-ANND-3	yes	4.24
E-GEOD-111727	no	222.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting PRDM7, 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-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3150B-3P	98.81	67.21	1728

Literature-anchored findings (GeneRIF, showing 2)

• Evolutionary analysis suggests that human PRDM7 and PRDM9 genes, a pair of close paralogs corresponding to a single mouse gene Prdm9, were generated by a recent gene duplication event after the divergence of the ancestors of human and mouse. (PMID:18231586)
• These studies indicate that after a single serine to tyrosine mutation at residue 357 (S357Y), PRDM7 regains the substrate specificities and catalytic activities similar to its evolutionary predecessor, including the ability to efficiently methylate H3K36. (PMID:27129774)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prdm9	ENSMUSG00000051977
rattus_norvegicus	Prdm9	ENSRNOG00000021493
caenorhabditis_elegans		WBGENE00011887

Paralogs (1): PRDM11 (ENSG00000019485)

Protein

Protein identifiers

Histone-lysine N-methyltransferase PRDM7 — Q9NQW5 (reviewed: Q9NQW5)

Alternative names: PR domain zinc finger protein 7, PR domain-containing protein 7, [histone H3]-lysine4 N-methyltransferase PRDM7

All UniProt accessions (3): Q9NQW5, A4Q9G9, H3BUJ3

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase that selectively methylates ‘Lys-4’ of dimethylated histone H3 (H3K4me2) to produce trimethylated ‘Lys-4’ histone H3 (H3K4me3). May play a role in epigenetic regulation of gene expression by defining an active chromatin state.

Subcellular location. Nucleus. Chromosome.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NQW5-3	1	yes
Q9NQW5-2	2, B
Q9NQW5-1	3, A

RefSeq proteins (1): NP_001091643* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001214	SET_dom	Domain
IPR001909	KRAB	Domain
IPR003655	aKRAB	Domain
IPR019041	SSXRD_motif	Conserved_site
IPR036051	KRAB_dom_sf	Homologous_superfamily
IPR044417	PRDM7_9_PR-SET	Domain
IPR046341	SET_dom_sf	Homologous_superfamily

Pfam: PF01352, PF09514, PF21549

Enzyme classification (BRENDA):

• EC 2.1.1.354 — [histone H3]-lysine4 N-trimethyltransferase (BRENDA: 18 organisms, 22 substrates, 3 inhibitors, 20 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ART(KME1)QTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0002–0.002	5
ART(KME2)QTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0003–0.004	5
ARTKQTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0002–0.0017	5
S-ADENOSYL-L-METHIONINE	0.014–0.9	5

Catalyzed reactions (Rhea), 1 shown:

• N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60272)

UniProt features (18 total): splice variant 4, sequence variant 3, mutagenesis site 3, domain 2, region of interest 2, compositionally biased region 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQW5-F1	60.59	0.27

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
289	gains the ability to sequentially mono-, di-, and tri-methylate both ’lys-4’ and ’lys-36’ of histone h3, albeit with low
312	gains the ability to sequentially mono-, di-, and tri-methylate both ’lys-4’ and ’lys-36’ of histone h3, albeit with low
357	substantially increases histone-lysine n-methyltransferase activity. gains the catalytic competency of prdm9. sequential

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-212436	Generic Transcription Pathway

MSigDB gene sets: 28 (showing top): NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, GOBP_CHROMATIN_REMODELING, GOBP_METHYLATION, GOMF_N_METHYLTRANSFERASE_ACTIVITY, YKACATTT_UNKNOWN, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, ROYLANCE_BREAST_CANCER_16Q_COPY_NUMBER_UP, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, GOMF_LYSINE_N_METHYLTRANSFERASE_ACTIVITY, GOMF_HISTONE_H3K4_METHYLTRANSFERASE_ACTIVITY, GOMF_HISTONE_METHYLTRANSFERASE_ACTIVITY, MIR6867_5P, MIR6830_3P, MIR6852_3P

GO Biological Process (4): regulation of DNA-templated transcription (GO:0006355), methylation (GO:0032259), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (5): histone H3K4 methyltransferase activity (GO:0042800), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), histone methyltransferase activity (GO:0042054)

GO Cellular Component (2): nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
metabolic process	1
cellular component organization	1
chromatin organization	1
protein-lysine N-methyltransferase activity	1
histone H3 methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
protein methyltransferase activity	1
histone modifying activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRDM7	PRDM13	Q9H4Q3	510
PRDM7	RNF212	Q495C1	494
PRDM7	CXXC1	Q9P0U4	461
PRDM7	PRDM5	Q9NQX1	447
PRDM7	A0A087WTH5	A0A087WTH5	447
PRDM7	H3-4	Q16695	434
PRDM7	MSH4	O15457	427
PRDM7	SETD3	Q86TU7	426
PRDM7	SETD4	Q9NVD3	420
PRDM7	SPO11	Q9Y5K1	418
PRDM7	SMYD1	Q8NB12	406
PRDM7	SMYD2	Q9NRG4	404
PRDM7	DBNDD1	Q9H9R9	403
PRDM7	AMACR	Q9UHK6	393
PRDM7	SETMAR	Q53H47	385

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PRDM7	TRAF1	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	PRDM7	psi-mi:“MI:0915”(physical association)	0.560
PRDM7	TUBB2B	psi-mi:“MI:0915”(physical association)	0.400
PRDM7	SNRPD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): PRDM7 (Two-hybrid), PRDM7 (Affinity Capture-MS), PRDM7 (Proximity Label-MS), PRDM7 (Affinity Capture-MS), PRDM7 (Affinity Capture-MS), PRDM7 (Affinity Capture-MS), PRDM7 (Affinity Capture-MS), PRDM7 (Affinity Capture-MS), PRDM7 (Affinity Capture-MS), PRDM7 (Affinity Capture-MS), TUBB2B (Affinity Capture-MS), PRDM7 (Protein-peptide), PRDM7 (Affinity Capture-MS), PRDM7 (Affinity Capture-MS), PRDM7 (Affinity Capture-RNA)

ESM2 similar proteins: A0A5K7RLP0, A1YEX3, A2AGX3, A2AKB4, A7YWH3, A8MVX0, C9JSJ3, O08715, O88286, O88884, P24278, P97303, P97432, Q17RG1, Q1XFL1, Q3KNY0, Q3USH1, Q495C1, Q4V7B1, Q501R9, Q562E2, Q5SYB0, Q5VT97, Q5XIN1, Q6P2K3, Q6PCP7, Q6ZSG2, Q7TSX9, Q80SU3, Q80TL0, Q80W88, Q80XI1, Q8BLK9, Q8BSV3, Q8BW86, Q8K3E9, Q8K451, Q8N7W2, Q8NE31, Q8NFN8

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, B1AUS7, O60224, O60225, Q16384, Q16385, Q7RTT3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1437 predictions. Top by Δscore:

Variant	Effect	Δscore
16:90061446:CCTTA:C	donor_loss	1.0000
16:90061447:CTTAC:C	donor_loss	1.0000
16:90061448:TTA:T	donor_loss	1.0000
16:90061449:TA:T	donor_loss	1.0000
16:90061450:A:C	donor_loss	1.0000
16:90061451:C:CT	donor_loss	1.0000
16:90061520:C:CC	acceptor_gain	1.0000
16:90061528:C:CT	acceptor_gain	1.0000
16:90061919:A:AC	donor_gain	1.0000
16:90061920:C:CC	donor_gain	1.0000
16:90062399:A:AC	donor_gain	1.0000
16:90062400:C:CC	donor_gain	1.0000
16:90074910:TCTTA:T	donor_loss	1.0000
16:90074911:CTTAC:C	donor_loss	1.0000
16:90074912:TTA:T	donor_loss	1.0000
16:90074913:TA:T	donor_loss	1.0000
16:90074914:ACCT:A	donor_loss	1.0000
16:90074915:CCTTG:C	donor_gain	1.0000
16:90075024:C:CC	acceptor_gain	1.0000
16:90075342:T:TA	donor_gain	1.0000
16:90075353:A:AC	donor_gain	1.0000
16:90075354:C:CC	donor_gain	1.0000
16:90075387:T:A	donor_gain	1.0000
16:90061445:GCCTT:G	donor_loss	0.9900
16:90061519:TCT:T	acceptor_loss	0.9900
16:90061520:C:CG	acceptor_loss	0.9900
16:90061521:T:G	acceptor_loss	0.9900
16:90061525:T:C	acceptor_gain	0.9900
16:90061529:A:T	acceptor_gain	0.9900
16:90061919:ACTAG:A	donor_gain	0.9900

AlphaMissense

3256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:90074998:G:C	F73L	0.961
16:90074998:G:T	F73L	0.961
16:90075000:A:G	F73L	0.961
16:90075439:G:C	F35L	0.955
16:90075439:G:T	F35L	0.955
16:90075441:A:G	F35L	0.955
16:90062131:A:C	F224L	0.939
16:90062131:A:T	F224L	0.939
16:90062133:A:G	F224L	0.939
16:90075426:A:G	W40R	0.927
16:90075426:A:T	W40R	0.927
16:90061984:A:C	F273L	0.917
16:90061984:A:T	F273L	0.917
16:90061986:A:G	F273L	0.917
16:90075460:G:C	F28L	0.913
16:90075460:G:T	F28L	0.913
16:90075462:A:G	F28L	0.913
16:90062080:A:C	S241R	0.912
16:90062080:A:T	S241R	0.912
16:90062082:T:G	S241R	0.912
16:90062167:G:C	F212L	0.904
16:90062167:G:T	F212L	0.904
16:90062169:A:G	F212L	0.904
16:90061459:A:G	W315R	0.900
16:90061459:A:T	W315R	0.900
16:90075424:C:A	W40C	0.891
16:90075424:C:G	W40C	0.891
16:90060554:G:C	F340L	0.889
16:90060554:G:T	F340L	0.889
16:90060556:A:G	F340L	0.889

dbSNP variants (sampled 300 via entrez): RS1000043404 (16:90069350 A>G), RS1000050610 (16:90072829 T>C), RS1000206069 (16:90074946 A>T), RS1000294305 (16:90062726 T>G), RS1001021262 (16:90056786 A>G), RS1001270383 (16:90057356 G>C,T), RS1001387037 (16:90063202 T>C), RS1001418261 (16:90063424 T>C), RS1001811152 (16:90074474 A>C,G), RS1001922051 (16:90068508 GC>G), RS1002063349 (16:90070153 A>G), RS1002115568 (16:90074275 T>A), RS1002292400 (16:90068265 C>T), RS1003933468 (16:90065464 G>A), RS1004011215 (16:90058816 G>T)

Disease associations

OMIM: gene MIM:609759 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005790_42	Rosacea symptom severity	1.000000e-06
GCST005897_5	Low tan response	4.000000e-139
GCST010703_280	Brain morphology (MOSTest)	2.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0009180	rosacea severity measurement
EFO:0004279	suntan
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5214861 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases response to substance	1
Lipopolysaccharides	affects cotreatment, increases expression	1
S-Adenosylmethionine	affects binding	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5214664	Binding	Selectivity interaction (Methyltransferase panel (DSF assay)) EUB0000234b PRDM7	Selectivity Literature for EUbOPEN Chemogenomics Library wave 3

Clinical trials (associated diseases)

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