EXD1
protein-codingexonuclease 3'-5' domain containing 1
Gene summary
Predicted to enable RNA binding activity and protein homodimerization activity. Predicted to be involved in piRNA processing. Predicted to be located in P granule. Predicted to be part of PET complex. [provided by Alliance of Genome Resources, Jul 2025]
- EXDL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~48.0 kbGenCC 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 EXD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001286441.2. 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 | 3 | 3 | ||||
| missense | 68 | 3 | 71 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 72 | 3 | 0 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001273370.1 | 11 | MANE Select | |
| Ensembl | ENSP00000415056.2 | 11 | MANE Select | |
| RefSeq | NP_001371965.1 | 10 | Standard | |
| RefSeq | NP_689809.2 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- gene silencing by RNA
- piRNA metabolic process
- meiotic cell cycle
- nucleic acid phosphodiester bond hydrolysis
Molecular Function
- RNA binding
- protein binding
- 3'-5' exonuclease activity
- protein homodimerization activity
Cellular Component
- P granule
- PET complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000314992
- Coding exons
- 10
- Length
- 48019
- Individuals with no LoFs
- 125623
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 124
- Defined
- 125747
- p
- 0.000493
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.112 | 267 | 262 | 1.02 | 0.0000130 | 3363 |
| Missense (PolyPhen) | 80 | 76.051 | 1.0519 | 929 | ||
| Synonymous | -0.0775 | 97 | 96.0 | 1.01 | 0.00000466 | 982 |
| Loss of Function | 0.534 | 22 | 24.9 | 0.884 | 0.00000126 | 308 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00041 | 0.00040 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00054 | 0.00054 | rare |
| Finnish | 0.0011 | 0.0010 | notable |
| European (Non-Finnish) | 0.00034 | 0.00033 | rare |
| South Asian | 0.0010 | 0.00098 | notable |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: RNA-binding component of the PET complex, a multiprotein complex required for the processing of piRNAs during spermatogenesis. The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposable elements, preventing their mobilization, which is essential for the germline integrity (By similarity). The PET complex is required during the secondary piRNAs metabolic process for the PIWIL2 slicing- triggered loading of PIWIL4 piRNAs. In the PET complex, EXD1 probably acts as an RNA adapter. EXD1 is an inactive exonuclease (By similarity). {ECO:0000250|UniProtKB:H9IUR0, ECO:0000250|UniProtKB:Q8CDF7}.;
Intolerance Scores
- RVIS EVS
- -0.47
- RVIS percentile EVS
- 23.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.302
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |