TREX2

protein-coding

three prime repair exonuclease 2, the group of Exonucleases

Gene summary

This gene encodes a nuclear protein with 3' to 5' exonuclease activity. The encoded protein participates in double-stranded DNA break repair, and may interact with DNA polymerase delta. [provided by RefSeq, Nov 2012]

MANE transcript

NM_080701.4

Inheritance

—

ClinVar variants

U:45B:14

Top phenotype

Abnormality of neuronal migration

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chrX:153,444,473-153,470,587

External References & Databases

Ensembl (ENSG00000183479)

Transcript & Mutation Effects

hg38 • Region Span ~26.1 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 TREX2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 11

Abnormality of neuronal migrationTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080701.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	7 clinvar	1 clinvar	9
missense			44 clinvar	5 clinvar		49
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	45	13	1	59

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080701.4	RefSeq	NP_542432.2	1	MANE Select
ENST00000370231.3	Ensembl	ENSP00000359251.2	1	MANE Select
ENST00000330912.7	Ensembl	ENSP00000333441.2	1	Standard
ENST00000334497.7	Ensembl	ENSP00000334993.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA metabolic process
DNA repair
nucleic acid phosphodiester bond hydrolysis

Molecular Function

magnesium ion binding
nucleic acid binding
3'-5'-exodeoxyribonuclease activity
exodeoxyribonuclease III activity
protein homodimerization activity

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000330912
Coding exons: 1
Length: 25868
Individuals with no LoFs: 124026
Homozygous LoFs: 47
Heterozygous LoFs: 153
Defined: 124226
p: 0.000805

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.658	125	106	1.18	0.0000106	1451
Missense (PolyPhen)		39	33.389	1.1681		560
Synonymous	-1.24	59	48.1	1.23	0.00000454	527
Loss of Function	1.15	0	1.53	0.00	9.64e-8	35

Population LoF Frequency

Population	CAF	p-value	Status
African	0.014	0.010	notable
Latino/Admixed American	0.0010	0.00081	notable
Ashkenazi Jewish	0.00046	0.00030	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000069	0.000045	rare
South Asian	0.000060	0.000033	rare
Other	0.00071	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Exonuclease with a preference for double-stranded DNA with mismatched 3' termini. May play a role in DNA repair. {ECO:0000269|PubMed:11279105}.;

Intolerance Scores

LoFtool: 0.646
RVIS EVS: 0.48
RVIS percentile EVS: 79.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.777

Gene Damage Prediction

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