PRDM9 (PR/SET domain 9)

Gene

• Entrez ID: 56979
• Gene name: PR/SET domain 9
• Gene symbol: PRDM9
• Synonyms (NCBI Gene): KMT8B, MEISETZ, MSBP3, PFM6, ZNF899
• Chromosome: 5
• Chromosome location: 5p14.2
• 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 b

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1260376	hsa-miR-183	CLIP-seq
MIRT1260377	hsa-miR-2467-3p	CLIP-seq
MIRT1260378	hsa-miR-3150b-3p	CLIP-seq
MIRT1260379	hsa-miR-4282	CLIP-seq
MIRT1260380	hsa-miR-4459	CLIP-seq
MIRT1260381	hsa-miR-4695-5p	CLIP-seq
MIRT1260382	hsa-miR-4773	CLIP-seq
MIRT1260383	hsa-miR-4784	CLIP-seq
MIRT1260384	hsa-miR-885-3p	CLIP-seq
MIRT1260385	hsa-miR-922	CLIP-seq
MIRT2076687	hsa-miR-4667-5p	CLIP-seq
MIRT2076688	hsa-miR-4700-5p	CLIP-seq
MIRT2076687	hsa-miR-4667-5p	CLIP-seq
MIRT2076688	hsa-miR-4700-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000976	Function	Transcription cis-regulatory region binding	IMP	29072575
GO:0003677	Function	DNA binding	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0005654	Component	Nucleoplasm	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0006311	Process	Meiotic gene conversion	IDA	21750151
GO:0006325	Process	Chromatin organization	IEA
GO:0006338	Process	Chromatin remodeling	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0007129	Process	Homologous chromosome pairing at meiosis	ISS
GO:0007292	Process	Female gamete generation	ISS
GO:0008168	Function	Methyltransferase activity	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0010468	Process	Regulation of gene expression	IBA
GO:0010844	Function	Recombination hotspot binding	IBA
GO:0010844	Function	Recombination hotspot binding	IDA	26833727, 29072575
GO:0010844	Function	Recombination hotspot binding	IEA
GO:0010844	Function	Recombination hotspot binding	IMP	20044539
GO:0010845	Process	Positive regulation of reciprocal meiotic recombination	IBA
GO:0010845	Process	Positive regulation of reciprocal meiotic recombination	IEA
GO:0010845	Process	Positive regulation of reciprocal meiotic recombination	IMP	21750151
GO:0016279	Function	Protein-lysine N-methyltransferase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0032259	Process	Methylation	IEA
GO:0035825	Process	Homologous recombination	IEA
GO:0042054	Function	Histone methyltransferase activity	IEA
GO:0042800	Function	Histone H3K4 methyltransferase activity	IBA
GO:0042800	Function	Histone H3K4 methyltransferase activity	IDA	24095733, 26833727
GO:0042800	Function	Histone H3K4 methyltransferase activity	IEA
GO:0042800	Function	Histone H3K4 methyltransferase activity	IMP	24634223
GO:0042803	Function	Protein homodimerization activity	ISS
GO:0043066	Process	Negative regulation of apoptotic process	ISS
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0046975	Function	Histone H3K36 methyltransferase activity	IBA
GO:0046975	Function	Histone H3K36 methyltransferase activity	IEA
GO:0046975	Function	Histone H3K36 methyltransferase activity	IMP	24634223
GO:0046975	Function	Histone H3K36 methyltransferase activity	ISS
GO:0048232	Process	Male gamete generation	ISS
GO:0051321	Process	Meiotic cell cycle	IEA
GO:0061982	Process	Meiosis I cell cycle process	IEA
GO:0140941	Function	Histone H4K20me methyltransferase activity	IEA
GO:0140944	Function	Histone H4K20 monomethyltransferase activity	IEA
GO:0140949	Function	Histone H3K9 trimethyltransferase activity	IEA
GO:0140955	Function	Histone H3K36 trimethyltransferase activity	IEA
GO:0140999	Function	Histone H3K4 trimethyltransferase activity	IEA
GO:1905516	Process	Positive regulation of fertilization	ISS
GO:1990918	Process	Double-strand break repair involved in meiotic recombination	ISS

Other IDs

• MIM: 609760
• HGNC: 13994
• e!Ensembl: ENSG00000164256

Protein

• UniProt ID: Q9NQV7
• Protein name: Histone-lysine N-methyltransferase PRDM9 (PR domain zinc finger protein 9) (PR domain-containing protein 9) (Protein-lysine N-methyltransferase PRDM9) (EC 2.1.1.-) ([histone H3]-lysine36 N-trimethyltransferase PRDM9) (EC 2.1.1.359) ([histone H3]-lysine4 N
• Protein function: Histone methyltransferase that sequentially mono-, di-, and tri-methylates both 'Lys-4' (H3K4) and 'Lys-36' (H3K36) of histone H3 to produce respectively trimethylated 'Lys-4' (H3K4me3) and trimethylated 'Lys-36' (H3K36me3) histone H3 and plays
• PDB: 4IJD, 5EGB, 5EH2, 5EI9, 6NM4
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01352	KRAB	27 → 65	KRAB box	Family
  PF00856	SET	65 → 358	SET domain	Family
  PF09514	SSXRD	171 → 201	SSXRD motif	Motif
  PF00096	zf-C2H2	552 → 574	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	580 → 602	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	608 → 630	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	636 → 658	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	664 → 686	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	692 → 714	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	720 → 742	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	748 → 770	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	776 → 798	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	804 → 826	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	832 → 854	Zinc finger, C2H2 type	Domain
  PF00096	zf-C2H2	860 → 882	Zinc finger, C2H2 type	Domain

• Sequence:

  MSPEKSQEESPEEDTERTERKPMVKDAFKDISIYFTKEEWAEMGDWEKTRYRNVKRNYNA
  LITIGLRATRPAFMCHRRQAIKLQVDDTEDSDEEWTPRQQVKPPWMALRVEQRKHQKGMP
  KASFSNESSLKELSRTANLLNASGSEQAQKPVSPSGEASTSGQHSRLKLELRKKETERKM
  YSLRERKGHAYKEVSEPQDDDYLYCEMCQNFFIDSCAAHGPPTFVKDSAVDKGHPNRSAL
  SLPPGLRIGPSGIPQAGLGVWNEASDLPLGLHFGPYEGRITEDEEAANNGYSWLITKGRN
  CYEYVDGKDKSWANWMRYVNCARDDEEQNLVAFQYHRQIFYRTCRVIRPGCELLVWYGDE
  YGQELGIKWGSKWKKELMAGREPKPEIHPCPSCCLAFSSQKFLSQHVERNHSSQNFPGPS
  ARKLLQPENPCPGDQNQEQQYPDPHSRNDKTKGQEIKERSKLLNKRTWQREISRAFSSPP
  KGQMGSCRVGKRIMEEESRTGQKVNPGNTGKLFVGVGISRIAKVKYGECGQGFSVKSDVI
  THQRTHTGEKLYVCRECGRGFSWKSHLLIHQRIHTGEKPYVCRECGRGFSWQSVLLTHQR
  THTGEKPYVCRECGRGFSRQSVLLTHQRRHTGEKPYVCRECGRGFSRQSVLLTHQRRHTG
  EKPYVCRECGRGFSWQSVLLTHQRTHTGEKPYVCRECGRGFSWQSVLLTHQRTHTGEKPY
  VCRECGRGFSNKSHLLRHQRTHTGEKPYVCRECGRGFRDKSHLLRHQRTHTGEKPYVCRE
  CGRGFRDKSNLLSHQRTHTGEKPYVCRECGRGFSNKSHLLRHQRTHTGEKPYVCRECGRG
  FRNKSHLLRHQRTHTGEKPYVCRECGRGFSDRSSLCYHQRTHTGEKPYVCREDE

• Sequence length: 894

Pathways

KEGG:

Lysine degradation
Metabolic pathways

Reactome:

PKMTs methylate histone lysines

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Genetic non-acquired premature ovarian failure	Pathogenic	rs201284800, rs747527740, rs2126427825	RCV001780386 RCV001780387 RCV001780388	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONOTRUNCAL HEART MALFORMATIONS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EARLY-ONSET ALZHEIMERS DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HUNTINGTON DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRDM9-related disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	23222848, 26201965		★☆☆☆☆ Found in Text Mining only
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	26201965		★☆☆☆☆ Found in Text Mining only
Aneuploidy	Aneuploidy	Pubtator	23222848	Associate	★☆☆☆☆ Found in Text Mining only
Azoospermia	Azoospermia	BEFREE	18941885		★☆☆☆☆ Found in Text Mining only
Azoospermia	Azoospermia	Pubtator	18941885, 19168450, 36688188	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases	Bone disease	Pubtator	33420361	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	16322686, 21406404, 24391143, 30990809, 35850772, 39395300	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	18172012, 28418882, 33339442, 36831256, 37237385	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	35054776	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	27656834, 32964965, 37371098	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Merkel Cell	Merkel cell carcinoma	Pubtator	37037414	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Pancreatic Ductal	Pancreatic ductal carcinoma	Pubtator	29409480	Associate	★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	26201965		★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	34880125	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	23001792, 25549357, 27259240, 33323965, 35748228	Associate	★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	28978636		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	BEFREE	22258617		★☆☆☆☆ Found in Text Mining only
Cystic kidney	Cystic Kidney Disease	BEFREE	22258617		★☆☆☆☆ Found in Text Mining only
DiGeorge Syndrome	DiGeorge Syndrome	BEFREE	22643917		★☆☆☆☆ Found in Text Mining only
DiGeorge Syndrome	Digeorge syndrome	Pubtator	28059126	Associate	★☆☆☆☆ Found in Text Mining only
Dystonia	Dystonia	Pubtator	27992417	Associate	★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	28418882	Associate	★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	Pubtator	29408993	Associate	★☆☆☆☆ Found in Text Mining only
GATA2 Deficiency	Gata2 deficiency	Pubtator	23529930	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	21836617	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	20018718, 26902498, 31611394	Associate	★☆☆☆☆ Found in Text Mining only
Head and Neck Neoplasms	Head and neck neoplasm	Pubtator	27002147	Associate	★☆☆☆☆ Found in Text Mining only
Heart Defects Congenital	Congenital heart defect	Pubtator	30342662	Associate	★☆☆☆☆ Found in Text Mining only
Hepatitis C	Hepatitis c	Pubtator	32001678	Associate	★☆☆☆☆ Found in Text Mining only
Hydatidiform Mole	Hydatidiform mole	Pubtator	27998939	Associate	★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	21836617	Stimulate	★☆☆☆☆ Found in Text Mining only
Infertility	Infertility	Pubtator	19168450	Associate	★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	23222848, 36688188	Associate	★☆☆☆☆ Found in Text Mining only
Intracranial Aneurysm	Intracranial Aneurysm	BEFREE	26186006		★☆☆☆☆ Found in Text Mining only
Intracranial Aneurysm	Intracranial aneurysm	Pubtator	26186006	Associate	★☆☆☆☆ Found in Text Mining only
Isodicentric Chromosome 15 Syndrome	Isodicentric Chromosome 15 Syndrome	BEFREE	23649991		★☆☆☆☆ Found in Text Mining only
Kabuki syndrome	Kabuki syndrome	Pubtator	21658225	Associate	★☆☆☆☆ Found in Text Mining only
Kleefstra Syndrome	Kleefstra syndrome	Pubtator	37257768	Associate	★☆☆☆☆ Found in Text Mining only
Latent Autoimmune Diabetes in Adults	Latent autoimmune diabetes in adults	Pubtator	28396876	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	15941828, 16449642, 20332322, 23744037, 26541578	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	18566324, 28301528, 29066607, 32293500, 32634241, 36450243	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	31042721, 34219384, 37121971	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	Pubtator	22740705, 33530253	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma Follicular	Lymphoma	Pubtator	21796119, 28430172	Associate	★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25738358		★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	Pubtator	22820256	Associate	★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	24850177, 32269030, 32512705	Associate	★☆☆☆☆ Found in Text Mining only
Mesothelioma	Mesothelioma	Pubtator	37369845	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	18172012, 22972034, 26272979, 31649247	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	38009194	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31843273		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	20018718, 34016720	Associate	★☆☆☆☆ Found in Text Mining only
Oligospermia	Oligospermia	BEFREE	23190393		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	28901481	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Diseases	Ovarian diseases	Pubtator	36318113	Associate	★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	24335192, 31092221	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	22536950, 23807219, 29229751, 35350907	Associate	★☆☆☆☆ Found in Text Mining only
Prader-Willi Syndrome	Prader-Willi Syndrome	BEFREE	22643917		★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	BEFREE	23222848		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	15817459, 22797064, 24289559, 24556744, 25535400, 27268279, 27323813, 33976366, 36924677	Associate	★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	Pubtator	32366932	Associate	★☆☆☆☆ Found in Text Mining only
Shprintzen syndrome	Shprintzen Syndrome	BEFREE	22643917		★☆☆☆☆ Found in Text Mining only
Shprintzen-Goldberg syndrome	Shprintzen-Goldberg Syndrome	BEFREE	22643917		★☆☆☆☆ Found in Text Mining only
Skin Erosion	Skin Erosion	BEFREE	29109225		★☆☆☆☆ Found in Text Mining only
Sotos Syndrome	Sotos syndrome	Pubtator	20018718	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	27002147, 27323410	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	BEFREE	27323410		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	27572307	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	27227949, 30990809, 32244385, 37970920	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	30984543	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	36594087	Associate	★☆☆☆☆ Found in Text Mining only
Weaver syndrome	Weaver syndrome	Pubtator	26694085, 29802153	Associate	★☆☆☆☆ Found in Text Mining only
Williams Syndrome	Williams Syndrome	BEFREE	22643917		★☆☆☆☆ Found in Text Mining only