APLF
protein-codingaprataxin and PNKP like factor, the group of Zinc fingers
Gene summary
Enables several functions, including nuclease activity; poly-ADP-D-ribose binding activity; and protein folding chaperone. Involved in DNA repair; DNA repair-dependent chromatin remodeling; and protein localization to chromatin. Located in nucleoplasm. Is active in site of double-strand break. [provided by Alliance of Genome Resources, Jun 2026]
- C2orf13
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~188.3 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 APLF variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173545.3. 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 | 1 | 1 | ||||
| missense | 71 | 2 | 73 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 73 | 3 | 0 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_775816.1 | 10 | MANE Select | |
| Ensembl | ENSP00000307004.4 | 10 | MANE Select | |
| Ensembl | ENSP00000393403.1 | 7 | Standard | |
| Ensembl | ENSP00000432297.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DNA-PK pathway in nonhomologous end joining
Biological Process
- single strand break repair
- double-strand break repair
- cellular response to DNA damage stimulus
- regulation of isotype switching
- positive regulation of DNA ligation
Molecular Function
- nucleotide binding
- DNA-(apurinic or apyrimidinic site) endonuclease activity
- endodeoxyribonuclease activity
- protein binding
- 3'-5' exonuclease activity
Cellular Component
- nucleus
- nucleoplasm
- cytosol
- site of double-strand break
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000303795
- Coding exons
- 10
- Length
- 163312
- Individuals with no LoFs
- 125571
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 170
- Defined
- 125741
- p
- 0.000676
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.102 | 239 | 243 | 0.982 | 0.0000114 | 3367 |
| Missense (PolyPhen) | 54 | 57.964 | 0.93161 | 876 | ||
| Synonymous | -0.335 | 90 | 86.0 | 1.05 | 0.00000422 | 922 |
| Loss of Function | -0.460 | 26 | 23.6 | 1.10 | 0.00000107 | 325 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0017 | 0.0016 | notable |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00055 | 0.00054 | rare |
| Finnish | 0.00034 | 0.00032 | rare |
| European (Non-Finnish) | 0.00064 | 0.00062 | rare |
| South Asian | 0.0017 | 0.0017 | notable |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Nuclease involved in single-strand and double-strand DNA break repair. Recruited to sites of DNA damage through interaction with poly(ADP-ribose), a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Displays apurinic- apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro. Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage. {ECO:0000269|PubMed:17353262, ECO:0000269|PubMed:17396150}.;
Recessive Scores
- pRec
- 0.0732
Intolerance Scores
- LoFtool
- 0.957
- RVIS EVS
- 1.07
- RVIS percentile EVS
- 91.61
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0121
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |