PADI4 Gene (Peptidylarginine Deiminase 4): Function, Disease Associations, and Expression
A comprehensive biomedical overview of PADI4, including genomic context, protein function, disease links, tissue expression, and mutation landscape.
Gene Information Card
| Symbol | PADI4 |
|---|---|
| Full Name | Peptidylarginine deiminase 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 23569 ncbi.nlm.nih.gov/gene/23569 |
| Ensembl ID | ENSG00000159339 |
| UniProt ID | Q9UM07 |
| OMIM ID | 605347 |
| HGNC ID | 18368 |
| Aliases | PAD4, PADI5, PDI4 |
Description
PADI4 encodes peptidylarginine deiminase 4, an enzyme that catalyzes the conversion of arginine residues to citrulline in a calcium-dependent manner. This post-translational modification, known as citrullination, affects protein structure and function, playing roles in gene regulation, immune responses, and apoptosis. PADI4 is implicated in autoimmune diseases, particularly rheumatoid arthritis, and has been studied in cancer contexts.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Rheumatoid Arthritis | PADI4 citrullinates proteins, generating autoantigens that trigger immune response in genetically susceptible individuals. SNPs in PADI4 are associated with increased disease risk. | OMIM 605347; multiple case-control studies (e.g., Suzuki et al., 2003) |
| Systemic Lupus Erythematosus | PADI4-mediated citrullination may contribute to autoantigen generation and immune dysregulation, though evidence is less robust than for RA. | OMIM 605347; some association studies |
| Cancer (various) | PADI4 overexpression in certain tumors may promote tumor progression via citrullination of histones and other proteins, affecting gene expression and apoptosis. | COSMIC; literature reports (e.g., Chang et al., 2009) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.2 | Medium |
| Spleen | 10.1 | Medium |
| Lymph Node | 8.5 | Low |
| Whole Blood | 6.3 | Low |
| Lung | 4.2 | Low |
| Brain | 1.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 15.3 | High expression; used in studies of citrullination |
| K-562 (chronic myelogenous leukemia) | 8.7 | Moderate expression |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
| A549 (lung carcinoma) | 1.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Arg89Gly (rs11203366) | Missense | ~20% in East Asian populations | Associated with increased PADI4 activity and RA risk |
| p.Gly112Ser (rs11203367) | Missense | ~20% in East Asian populations | Linked to RA susceptibility; may affect protein stability |
| p.Val347Ala (rs1748033) | Missense | ~15% in European populations | Reported in some RA cohorts; functional impact unclear |
Mutation functional classification
Loss of Function (LOF)
Rare loss-of-function mutations have been reported in PADI4, but they are not well characterized in disease contexts. Such mutations would reduce citrullination activity, potentially affecting immune regulation.
Gain of Function (GOF)
Certain SNPs (e.g., p.Arg89Gly) are associated with increased enzymatic activity, leading to enhanced citrullination and autoantigen production, contributing to autoimmune pathology.
Dominant Negative (DN)
No dominant-negative mutations have been documented for PADI4 in the literature.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding | • protein-arginine deiminase activity |
| • citrullination | • chromatin organization |
| • regulation of gene expression | • immune response |
Pathways
• Citrullination pathway
• Rheumatoid arthritis pathogenesis
• Neutrophil extracellular trap (NET) formation
Protein Summary
PADI4 is a 663-amino acid protein that requires calcium for activity. It is primarily localized in the nucleus and cytoplasm, where it citrullinates histone H3 and other proteins, influencing chromatin structure and gene expression. PADI4 is highly expressed in hematopoietic cells and is involved in immune regulation. Its dysregulation is linked to autoimmune diseases and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PADI4 Knockout HEK293 Cell Line | EDJ-KQ8071 | Human | 23569 | Details Get a Quote |
| PADI4 Knockout HeLa Cell Line | EDJ-KQ55775 | Human | 23569 | Details Get a Quote |
| PADI4 Knockout A-549 Cell Line | EDJ-KQ64270 | Human | 23569 | Details Get a Quote |
| PADI4 Knockout HCT 116 Cell Line | EDJ-KQ72716 | Human | 23569 | Details Get a Quote |
