PEG3

protein-coding

paternally expressed 3, the group of Zinc fingers C2H2-type|SCAN domain containing

Gene summary

In human, ZIM2 and PEG3 are treated as two distinct genes though they share multiple 5' exons and a common promoter and both genes are paternally expressed (PMID:15203203). Alternative splicing events connect their shared 5' exons either with the remaining 4 exons unique to ZIM2, or with the remaining 2 exons unique to PEG3. In contrast, in other mammals ZIM2 does not undergo imprinting and, in mouse, cow, and likely other mammals as well, the ZIM2 and PEG3 genes do not share exons. Human PEG3 protein belongs to the Kruppel C2H2-type zinc finger protein family. PEG3 may play a role in cell proliferation and p53-mediated apoptosis. PEG3 has also shown tumor suppressor activity and tumorigenesis in glioma and ovarian cells. Alternative splicing of this PEG3 gene results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Sep 2009]

MANE transcript

NM_006210.3

Inheritance

—

ClinVar variants

U:207B:61

Top phenotype

PEG3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr19:56,810,077-56,840,728

External References & Databases

Ensembl (ENSG00000198300)

Transcript & Mutation Effects

hg38 • Region Span ~30.7 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 PEG3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 233

not providedTotal: 37

PEG3-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006210.3. 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				6 clinvar	8 clinvar	14
missense			207 clinvar	36 clinvar	10 clinvar	253
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	207	43	18	268

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006210.3	RefSeq	NP_006201.1	7	MANE Select
ENST00000326441.15	Ensembl	ENSP00000326581.7	7	MANE Select
NM_001146184.2	RefSeq	NP_001139656.1	7	Standard
NM_001146185.2	RefSeq	NP_001139657.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TNFalpha

Biological Process

negative regulation of transcription by RNA polymerase II
apoptotic process
positive regulation of transcription by RNA polymerase II

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
nucleic acid binding
metal ion binding

Cellular Component

nucleus
autophagosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000326441
Coding exons: 7
Length: 30652
Individuals with no LoFs: 125537
Homozygous LoFs: 0
Heterozygous LoFs: 211
Defined: 125748
p: 0.000839

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.954	957	877	1.09	0.0000498	10620
Missense (PolyPhen)		222	226.33	0.98086		2900
Synonymous	-0.194	324	320	1.01	0.0000186	2907
Loss of Function	4.43	18	52.7	0.341	0.00000298	685

Population LoF Frequency

Population	CAF	p-value	Status
African	0.017	0.0054	notable
Latino/Admixed American	0.0014	0.00046	notable
Ashkenazi Jewish	0.00033	0.00030	rare
East Asian	0.0034	0.0033	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00020	0.00017	rare
South Asian	0.00059	0.00059	rare
Other	0.0015	0.00081	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Induces apoptosis in cooperation with SIAH1A. Acts as a mediator between p53/TP53 and BAX in a neuronal death pathway that is activated by DNA damage. Acts synergistically with TRAF2 and inhibits TNF induced apoptosis through activation of NF-kappa-B (By similarity). Possesses a tumor suppressing activity in glioma cells. {ECO:0000250, ECO:0000269|PubMed:11260267}.;

Recessive Scores

pRec: 0.203

Intolerance Scores

LoFtool: 0.696
RVIS EVS: 1.51
RVIS percentile EVS: 95.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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