EXD3

protein-coding

exonuclease 3'-5' domain containing 3

Gene summary

Predicted to enable 3'-5' exonuclease activity; metal ion binding activity; and nucleic acid binding activity. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_017820.5

Inheritance

—

ClinVar variants

U:211B:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr9:137,306,896-137,423,211

External References & Databases

Ensembl (ENSG00000187609)

Transcript & Mutation Effects

hg38 • Region Span ~116.3 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 EXD3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 204

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017820.5. 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			3 clinvar	1 clinvar		4
missense			198 clinvar	15 clinvar		213
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	211	16	0	227

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 91 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017820.5	RefSeq	NP_060290.3	21	MANE Select
ENST00000340951.9	Ensembl	ENSP00000340474.4	21	MANE Select
NM_001286823.2	RefSeq	NP_001273752.1	7	Standard
ENST00000460390.6	Ensembl	ENSP00000436717.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

nucleic acid phosphodiester bond hydrolysis

Molecular Function

nucleic acid binding
protein binding
3'-5' exonuclease activity
metal ion binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000340951
Coding exons: 21
Length: 116367
Individuals with no LoFs: 124282
Homozygous LoFs: 0
Heterozygous LoFs: 151
Defined: 124433
p: 0.000607

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0412	535	538	0.995	0.0000356	5504
Missense (PolyPhen)		125	135.22	0.92445		1600
Synonymous	0.328	239	246	0.973	0.0000178	1825
Loss of Function	1.56	30	40.7	0.737	0.00000183	445

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00094	0.00091	rare
Latino/Admixed American	0.0012	0.0011	notable
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.0013	0.0013	notable
Finnish	0.00024	0.00019	rare
European (Non-Finnish)	0.00056	0.00054	rare
South Asian	0.00015	0.00013	rare
Other	0.00091	0.00083	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possesses 3'-5' exoribonuclease activity. Required for 3'-end trimming of AGO1-bound miRNAs (By similarity). {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.895
RVIS EVS: 2.95
RVIS percentile EVS: 99.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.877

Gene Damage Prediction

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