PADI4
protein-codingpeptidyl arginine deiminase 4, the group of Peptidyl arginine deiminases
Gene summary
This gene is a member of a gene family which encodes enzymes responsible for the conversion of arginine residues to citrulline residues. This gene may play a role in granulocyte and macrophage development leading to inflammation and immune response. [provided by RefSeq, Jul 2008]
- PADI5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~55.8 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 PADI4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012387.3. 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 | 2 | 8 | ||
| missense | 97 | 12 | 6 | 115 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 98 | 17 | 8 | 123 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036519.2 | 16 | MANE Select | |
| Ensembl | ENSP00000364597.4 | 16 | MANE Select | |
| Ensembl | ENSP00000364602.1 | 4 | Standard | |
| Ensembl | ENSP00000810545.1 | 16 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Chromatin modifying enzymes
- Chromatin organization
- protein citrullination
Biological Process
- chromatin organization
- nucleosome assembly
- chromatin remodeling
- cellular protein modification process
- protein citrullination
Molecular Function
- protein-arginine deiminase activity
- calcium ion binding
- protein binding
- arginine deiminase activity
- arginine binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375448
- Coding exons
- 16
- Length
- 55810
- Individuals with no LoFs
- 125564
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 183
- Defined
- 125748
- p
- 0.000732
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0775 | 396 | 392 | 1.01 | 0.0000222 | 4358 |
| Missense (PolyPhen) | 182 | 169.89 | 1.0713 | 1867 | ||
| Synonymous | 0.565 | 165 | 175 | 0.946 | 0.0000117 | 1294 |
| Loss of Function | 0.933 | 27 | 32.8 | 0.824 | 0.00000156 | 373 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0039 | 0.0039 | notable |
| Latino/Admixed American | 0.0016 | 0.0016 | notable |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00050 | 0.00049 | rare |
| Finnish | 0.00018 | 0.00018 | rare |
| European (Non-Finnish) | 0.00021 | 0.00020 | rare |
| South Asian | 0.00088 | 0.00085 | rare |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg- 54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1. {ECO:0000269|PubMed:15339660, ECO:0000269|PubMed:15345777, ECO:0000269|PubMed:15731352, ECO:0000269|PubMed:16567635, ECO:0000269|PubMed:18209087, ECO:0000269|PubMed:21245532}.;
- Disease
- DISEASE: Rheumatoid arthritis (RA) [MIM:180300]: An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. {ECO:0000269|PubMed:12833157}. Note=The gene represented in this entry may be involved in disease pathogenesis. The association to rheumatoid arthritis was initially thought to result from increased citrullination of target proteins (PubMed:12833157). However, variants that have been associated to rheumatoid arthritis (Ser-55, Ala-82 and Ala-112) do not affect the catalytic activity or the citrullination activity of PADI4, suggesting that these variants may affect the mRNA stability rather than the protein (PubMed:21245532). {ECO:0000269|PubMed:12833157, ECO:0000269|PubMed:21245532}.;
Intolerance Scores
- LoFtool
- 0.911
- RVIS EVS
- 2.23
- RVIS percentile EVS
- 98.17
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.732
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |