PADI4
peptidyl arginine deiminase 4, the group of Peptidyl arginine deiminases
Basic information
Region (hg38): 1:17308195-17364004
Previous symbols: [ "PADI5" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (94 variants)
- PADI4-related_disorder (11 variants)
- not_provided (7 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PADI4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000012387.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | |||||
| missense | 86 | 11 | 103 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 86 | 16 | 8 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PADI4 | protein_coding | protein_coding | ENST00000375448 | 16 | 55810 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.60e-16 | 0.0852 | 125564 | 1 | 183 | 125748 | 0.000732 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.0775 | 396 | 392 | 1.01 | 0.0000222 | 4358 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00558 | 0.00552 |
| Ashkenazi Jewish | 0.000199 | 0.000198 |
| East Asian | 0.000501 | 0.000489 |
| Finnish | 0.000185 | 0.000185 |
| European (Non-Finnish) | 0.000208 | 0.000202 |
| Middle Eastern | 0.000501 | 0.000489 |
| South Asian | 0.000880 | 0.000850 |
| Other | 0.000342 | 0.000326 |
dbNSFP
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}.;
- Pathway
- Chromatin modifying enzymes;Chromatin organization;protein citrullination
(Consensus)
Intolerance Scores
- loftool
- 0.911
- rvis_EVS
- 2.23
- rvis_percentile_EVS
- 98.17
Haploinsufficiency Scores
- pHI
- 0.0813
- hipred
- N
- hipred_score
- 0.341
- ghis
- 0.409
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.732
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Padi4
- Phenotype
- immune system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype; hematopoietic system phenotype;
Gene ontology
- Biological process
- chromatin organization;nucleosome assembly;chromatin remodeling;cellular protein modification process;protein citrullination;arginine deiminase pathway;stem cell population maintenance;histone H3-R26 citrullination;histone citrullination;innate immune response
- Cellular component
- nucleus;nucleoplasm;cytoplasm;cytosol;protein-containing complex
- Molecular function
- protein-arginine deiminase activity;calcium ion binding;protein binding;arginine deiminase activity;arginine binding;protein homodimerization activity