GeneBe

PRDM9

protein-coding

PR/SET domain 9, the group of Lysine methyltransferases|PR/SET domain family|Zinc fingers C2H2-type

Gene summary

The protein encoded by this gene is a zinc finger protein with histone methyltransferase activity that catalyzes histone H3 lysine 4 trimethylation (H3K4me3) during meiotic prophase. This protein contains multiple domains, including a Kruppel-associated box (KRAB) domain, an SSX repression domain (SSXRD), a PRD1-BF1 and RIZ homologous region, a subclass of SET (PR/SET) domain, and a tandem array of C2H2 zinc fingers. The zinc finger array recognizes a short sequence motif, leading to local H3K4me3, and meiotic recombination hotspot activity. The observed allelic variation alters the DNA-binding sequence specificity of the protein, resulting in distinct meiotic recombination hotspots amongst individuals and populations. Multiple alternate alleles of this gene have been described. [provided by RefSeq, Jul 2015]

Previous symbols:
  • MSBP3

MANE transcript

NM_020227.4

Inheritance

AD

ClinVar variants

P:3U:140B:21

Top phenotype

primary ovarian failure

gnomAD constraint

pLI —, LoF o/e 1.01

Max pathogenic AF

—

Genomic locus

chr5:23,443,586-23,528,093

External References & Databases

Ensembl (ENSG00000164256)NCBI Gene (56979)OMIM (609760)HGNC:13994GenCCUniProt (Q9NQV7)AlphaFoldClinVar (PRDM9)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~84.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

primary ovarian failureSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0005387

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRDM9 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 140
not providedTotal: 12
PRDM9-related disorderTotal: 6
Genetic non-acquired premature ovarian failureTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020227.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
6
clinvar
2
clinvar
 8
missense
2
clinvar
138
clinvar
13
clinvar
 153
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total30140192164

Highest pathogenic variant AF is 0.0000260264

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_020227.4RefSeqNP_064612.210MANE Select
ENST00000296682.4EnsemblENSP00000296682.410MANE Select
NM_001376900.1RefSeqNP_001363829.110Standard
ENST00000502755.6EnsemblENSP00000425471.210Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Lysine degradation - Homo sapiens (human)
  • Reproduction
  • PKMTs methylate histone lysines
  • Chromatin modifying enzymes
  • Meiotic recombination

Biological Process

  • meiotic gene conversion
  • regulation of transcription by RNA polymerase II
  • positive regulation of reciprocal meiotic recombination
  • nucleosome positioning
  • histone H3-K4 methylation

Molecular Function

  • RNA polymerase II regulatory region sequence-specific DNA binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • DNA-binding transcription factor activity
  • recombination hotspot binding
  • histone-lysine N-methyltransferase activity

Cellular Component

  • nucleus
  • nucleoplasm
  • chromosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000296682
Coding exons
10
Length
21443
Individuals with no LoFs
125516
Homozygous LoFs
0
Heterozygous LoFs
231
Defined
125747
p
0.000919
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.7465074621.100.00002545781
Missense (PolyPhen)103116.40.884861397
Synonymous-0.7341831711.070.000008671637
Loss of Function-0.08324039.41.010.00000215485

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00620.0059notable
Latino/Admixed American0.00120.0012notable
Ashkenazi Jewish0.00130.0013notable
East Asian0.00100.00071notable
Finnish0.0000920.000092rare
European (Non-Finnish)0.000430.00042rare
South Asian0.000490.00049rare
Other0.000830.00081rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Histone methyltransferase that specifically trimethylates 'Lys-4' of histone H3 during meiotic prophase and is essential for proper meiotic progression. Does not have the ability to mono- and dimethylate 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes during early meiotic prophase (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool
0.973
RVIS EVS
1.32
RVIS percentile EVS
94.07

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
K
Indispensability pred.
N
Indispensability score
0.0231

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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