PRDM2

protein-coding

PR/SET domain 2, the group of PR/SET domain family|Lysine methyltransferases

Gene summary

This tumor suppressor gene is a member of a nuclear histone/protein methyltransferase superfamily. It encodes a zinc finger protein that can bind to retinoblastoma protein, estrogen receptor, and the TPA-responsive element (MTE) of the heme-oxygenase-1 gene. Although the functions of this protein have not been fully characterized, it may (1) play a role in transcriptional regulation during neuronal differentiation and pathogenesis of retinoblastoma, (2) act as a transcriptional activator of the heme-oxygenase-1 gene, and (3) be a specific effector of estrogen action. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

MANE transcript

NM_001393986.1

Inheritance

—

ClinVar variants

P:1U:284B:15

Top phenotype

Flexion contracture

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr1:13,700,188-13,825,079

External References & Databases

Ensembl (ENSG00000116731)

Transcript & Mutation Effects

hg38 • Region Span ~124.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PRDM2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 246

not providedTotal: 10

Flexion contractureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001393986.1. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	6 clinvar		13
missense			272 clinvar	7 clinvar	2 clinvar	281
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar	3 clinvar			4
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	284	13	2	300

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001393986.1	RefSeq	NP_001380915.1	8	MANE Select
ENST00000311066.10	Ensembl	ENSP00000312352.6	8	MANE Select
NM_001007257.3	RefSeq	NP_001007258.1	3	Standard
NM_001135610.2	RefSeq	NP_001129082.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysine degradation - Homo sapiens (human)
Histone Modifications

Biological Process

regulation of transcription, DNA-templated
determination of adult lifespan
histone lysine methylation
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA-binding transcription factor activity
zinc ion binding

Cellular Component

nucleus
Golgi apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000235372
Coding exons: 8
Length: 124882
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.08	845	938	0.900	0.0000515	11243
Missense (PolyPhen)		180	245.13	0.73431		2946
Synonymous	-2.06	415	365	1.14	0.0000217	3407
Loss of Function	6.29	7	59.3	0.118	0.00000350	752

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00012	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00017	rare
South Asian	0.000098	0.000098	rare
Other	0.00019	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: S-adenosyl-L-methionine-dependent histone methyltransferase that specifically methylates 'Lys-9' of histone H3. May function as a DNA-binding transcription factor. Binds to the macrophage-specific TPA-responsive element (MTE) of the HMOX1 (heme oxygenase 1) gene and may act as a transcriptional activator of this gene. {ECO:0000269|PubMed:14633678}.;

Recessive Scores

pRec: 0.215

Intolerance Scores

LoFtool: 0.554
RVIS EVS: -0.55
RVIS percentile EVS: 19.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.730

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium