EXD2

protein-coding

exonuclease 3'-5' domain containing 2

Gene summary

Enables 3'-5' exonuclease activity; metal ion binding activity; and protein homodimerization activity. Involved in DNA double-strand break processing; double-strand break repair via homologous recombination; and replication fork processing. Located in mitochondrial outer membrane and site of DNA damage. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C14orf114
EXDL2

MANE transcript

NM_001193360.2

Inheritance

—

ClinVar variants

U:102B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr14:69,191,498-69,244,020

External References & Databases

Ensembl (ENSG00000081177)

Transcript & Mutation Effects

hg38 • Region Span ~52.5 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 EXD2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 96

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001193360.2. 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	1 clinvar		2
missense			95 clinvar	2 clinvar		97
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	102	3	0	105

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001193360.2	RefSeq	NP_001180289.1	8	MANE Select
ENST00000685843.1	Ensembl	ENSP00000510642.1	8	MANE Select
NM_001193361.2	RefSeq	NP_001180290.1	8	Standard
NM_001193362.2	RefSeq	NP_001180291.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

double-strand break repair via homologous recombination
DNA double-strand break processing
double-strand break repair
nucleic acid phosphodiester bond hydrolysis

Molecular Function

nucleic acid binding
protein binding
single-stranded DNA 3'-5' exodeoxyribonuclease activity
3'-5' exonuclease activity
exodeoxyribonuclease I activity

Cellular Component

nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409018
Coding exons: 8
Length: 50848
Individuals with no LoFs: 125691
Homozygous LoFs: 0
Heterozygous LoFs: 57
Defined: 125748
p: 0.000227

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.933	295	344	0.858	0.0000194	4035
Missense (PolyPhen)		101	129.73	0.77855		1453
Synonymous	2.22	101	134	0.756	0.00000723	1239
Loss of Function	1.07	21	27.0	0.778	0.00000146	324

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00038	0.00038	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00034	0.00028	rare
South Asian	0.00016	0.00016	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Exonuclease required for double-strand breaks resection and efficient homologous recombination. Plays a key role in controlling the initial steps of chromosomal break repair, it is recruited to chromatin in a damage-dependent manner and functionally interacts with the MRN complex to accelerate resection through its 3'-5' exonuclease activity, which efficiently processes double-stranded DNA substrates containing nicks. {ECO:0000269|PubMed:20603073, ECO:0000269|PubMed:26807646}.;

Intolerance Scores

LoFtool: 0.937
RVIS EVS: 0.02
RVIS percentile EVS: 55.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.129

Gene Damage Prediction

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