PADI2
protein-codingpeptidyl arginine deiminase 2, the group of Peptidyl arginine deiminases
Gene summary
This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. The type II enzyme is the most widely expressed family member. Known substrates for this enzyme include myelin basic protein in the central nervous system and vimentin in skeletal muscle and macrophages. This enzyme is thought to play a role in the onset and progression of neurodegenerative human disorders, including Alzheimer disease and multiple sclerosis, and it has also been implicated in glaucoma pathogenesis. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~52.7 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 PADI2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007365.3. 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 | 5 | 6 | |||
| missense | 103 | 3 | 106 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 104 | 5 | 5 | 114 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_031391.2 | 16 | MANE Select | |
| Ensembl | ENSP00000364635.4 | 16 | MANE Select | |
| Ensembl | ENSP00000364630.1 | 11 | Standard | |
| Ensembl | ENSP00000364630.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| padi2 | Danio rerio | Structure: ocular blood vessel Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neutrophil degranulation
- Chromatin modifying enzymes
- Innate Immune System
- Immune System
- Chromatin organization
Biological Process
- regulation of chromatin disassembly
- protein citrullination
- substantia nigra development
- intracellular estrogen receptor signaling pathway
- histone H3-R26 citrullination
Molecular Function
- protein-arginine deiminase activity
- calcium ion binding
- estrogen receptor binding
- protein homodimerization activity
Cellular Component
- extracellular region
- nucleus
- cytoplasm
- cytosol
- transcriptionally active chromatin
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375486
- Coding exons
- 16
- Length
- 52693
- Individuals with no LoFs
- 125211
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 536
- Defined
- 125747
- p
- 0.00213
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.490 | 385 | 413 | 0.932 | 0.0000256 | 4346 |
| Missense (PolyPhen) | 144 | 167.25 | 0.86101 | 1792 | ||
| Synonymous | 0.167 | 172 | 175 | 0.984 | 0.0000119 | 1295 |
| Loss of Function | 2.07 | 22 | 35.3 | 0.624 | 0.00000193 | 386 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0016 | 0.0015 | notable |
| Latino/Admixed American | 0.0011 | 0.0011 | notable |
| Ashkenazi Jewish | 0.0011 | 0.0011 | notable |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.0013 | 0.0013 | notable |
| European (Non-Finnish) | 0.0031 | 0.0031 | notable |
| South Asian | 0.0022 | 0.0022 | notable |
| Other | 0.00098 | 0.00098 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the deimination of arginine residues of proteins. {ECO:0000269|PubMed:12392711, ECO:0000269|PubMed:25621824}.;
Recessive Scores
- pRec
- 0.140
Intolerance Scores
- LoFtool
- 0.800
- RVIS EVS
- -0.5
- RVIS percentile EVS
- 21.81
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.260
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |