PRDM9
PR/SET Domain 9: A Key Regulator of Meiotic Recombination and Genome Stability
Gene Information Card
| Symbol | PRDM9 |
|---|---|
| Full Name | PR/SET Domain 9 |
| Gene Type | Protein coding |
| Chromosomal Location | 5p14.2 |
| NCBI Gene ID | 56979 ncbi.nlm.nih.gov/gene/56979 |
| Ensembl ID | ENSG00000164256 |
| UniProt ID | Q9NQV7 |
| OMIM ID | 609760 |
| HGNC ID | 13994 |
| Aliases | MEISETZ, PFM6, ZNF899 |
Description
PRDM9 (PR/SET Domain 9) encodes a histone methyltransferase that specifically trimethylates histone H3 at lysine 4 (H3K4me3) and lysine 36 (H3K36me3). It is a key regulator of meiotic recombination, directing the placement of double-strand breaks (DSBs) at recombination hotspots. PRDM9 contains a PR/SET domain responsible for methyltransferase activity and a C-terminal zinc finger array that determines DNA-binding specificity. Variants in PRDM9 are associated with altered recombination landscapes, infertility, and susceptibility to certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male Infertility (Azoospermia) | Loss-of-function mutations impair meiotic recombination, leading to meiotic arrest and spermatogenic failure. | ClinVar, OMIM |
| Female Infertility | Disruption of PRDM9 activity reduces oocyte quality and meiotic progression. | OMIM, PubMed |
| Cancer Susceptibility (e.g., Breast, Colorectal) | Altered PRDM9 activity may influence genomic instability and recombination errors, increasing cancer risk. | COSMIC, PubMed |
| Genomic Instability | Defective PRDM9 leads to aberrant DSB repair and chromosomal rearrangements. | NCBI, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | High |
| Ovary | 3.8 | Medium |
| Lymph Node | 1.1 | Low |
| Brain | 0.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 2.3 | Low expression |
| K562 | 0.8 | Not detected |
| HeLa | 1.5 | Low expression |
| Testicular germ cells | 12.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1015C>T (p.Arg339*) | Nonsense | Rare | Loss of function; associated with azoospermia |
| c.1234G>A (p.Gly412Arg) | Missense | Rare | Reduced methyltransferase activity; linked to infertility |
| c.1685_1686insA | Frameshift | Very rare | Truncated protein; loss of zinc finger domain |
| c.2002C>T (p.Arg668Cys) | Missense | Rare | Altered DNA binding specificity |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg339*, c.1685_1686insA) result in truncated, non-functional PRDM9 protein, impairing H3K4me3 deposition and meiotic DSB formation.
Gain of Function (GOF)
Not well documented; no clear gain-of-function variants reported in literature.
Dominant Negative (DN)
Missense mutations in the zinc finger domain (e.g., p.Arg668Cys) may produce a protein that interferes with wild-type PRDM9 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GO:0005634 (GO:0005634) | • GO:0008270 (GO:0008270) |
| • GO:0018024 (GO:0018024) | • GO:0007129 (GO:0007129) |
| • GO:0007131 (GO:0007131) | • GO:0046982 (GO:0046982) |
Pathways
• Meiotic recombination (Reactome: R-HSA-912446)
• Chromatin modifying enzymes (Reactome: R-HSA-3247509)
Protein Summary
PRDM9 is a 1,118-amino acid protein containing an N-terminal PR/SET domain with histone methyltransferase activity and a C-terminal tandem zinc finger array that binds specific DNA sequences. It catalyzes H3K4me3 and H3K36me3 at meiotic recombination hotspots, recruiting the SPO11 complex to initiate double-strand breaks. PRDM9 expression is predominantly in the testis and ovary, with low levels in other tissues. Its zinc finger array is highly polymorphic, leading to variation in hotspot localization across individuals and populations.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRDM9 Knockout HEK293 Cell Line | EDJ-KQ14887 | Human | 56979 | Details Get a Quote |
| PRDM9 Knockout HeLa Cell Line | EDJ-KQ56783 | Human | 56979 | Details Get a Quote |
| PRDM9 Knockout A-549 Cell Line | EDJ-KQ65286 | Human | 56979 | Details Get a Quote |
| PRDM9 Knockout HCT 116 Cell Line | EDJ-KQ73729 | Human | 56979 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
