PADI3: Peptidyl Arginine Deiminase 3
A key enzyme in hair follicle differentiation and skin barrier function, associated with uncombable hair syndrome and autoimmune skin disorders.
Gene Information Card
| Symbol | PADI3 |
|---|---|
| Full Name | Peptidyl Arginine Deiminase 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 51702 ncbi.nlm.nih.gov/gene/51702 |
| Ensembl ID | ENSG00000142619 |
| UniProt ID | Q9ULW8 |
| OMIM ID | 606755 |
| HGNC ID | 18337 |
| Aliases | PAD3, PADIII, PADI3_HUMAN |
Description
PADI3 encodes a member of the peptidyl arginine deiminase family that catalyzes the post-translational conversion of arginine residues to citrulline in a calcium-dependent manner. This enzyme is predominantly expressed in the hair follicle and epidermis, where it plays a critical role in hair shaft formation and skin barrier integrity. Mutations in PADI3 cause autosomal recessive uncombable hair syndrome, and dysregulation of its activity is implicated in autoimmune diseases such as rheumatoid arthritis and alopecia areata.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Uncombable hair syndrome (UHS) | Loss-of-function mutations in PADI3 impair citrullination of trichohyalin and other hair shaft proteins, leading to abnormal hair shaft structure. | OMIM #191480; ClinVar |
| Rheumatoid arthritis | Autoantibodies against citrullinated proteins (including those modified by PADI3) are diagnostic markers; PADI3 expression in synovium may contribute to citrullinated neoepitope generation. | PubMed; NCBI Gene |
| Alopecia areata | PADI3 is a known autoantigen in alopecia areata; immune response against citrullinated PADI3 peptides is observed in patients. | PubMed; UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Esophagus | 8.2 | Low |
| Cervix, uterine | 6.1 | Low |
| Vagina | 5.0 | Low |
| Adipose tissue | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocyte) | 15.3 | High expression; relevant for skin studies |
| NHEK (normal human epidermal keratinocytes) | 14.8 | High expression |
| A431 (epidermoid carcinoma) | 10.2 | Moderate expression |
| MCF7 (breast cancer) | 0.5 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.848G>A (p.Arg283His) | Missense | Rare | Loss of enzymatic activity; associated with UHS |
| c.1255C>T (p.Arg419Cys) | Missense | Rare | Loss of function; UHS |
| c.1637G>A (p.Arg546His) | Missense | Rare | Reduced citrullination activity; UHS |
| c.1522_1523del (p.Leu508Glufs*12) | Frameshift | Very rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense and frameshift mutations in PADI3 reduce or abolish calcium-dependent citrullination activity, leading to uncombable hair syndrome.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PADI3.
Dominant Negative (DN)
No dominant-negative effects have been described; UHS is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • protein-arginine deiminase activity (GO:0004668) | • cytoplasm (GO:0005737) |
| • cytosol (GO:0005829) | • peptidyl-citrulline biosynthetic process from peptidyl-arginine (GO:0018103) |
| • keratinization (GO:0031424) | • middle ear morphogenesis (GO:0042474) |
| • intermediate filament cytoskeleton organization (GO:0045111) | • hair follicle morphogenesis (GO:0060076) |
Pathways
• Citrullination pathway (Reactome: R-HSA-6798695)
• Keratinization (Reactome: R-HSA-6805567)
• Formation of the cornified envelope (Reactome: R-HSA-6809371)
Protein Summary
PADI3 is a 664-amino acid calcium-dependent enzyme that converts arginine residues to citrulline in target proteins such as trichohyalin and filaggrin. It is localized in the cytoplasm and is essential for proper hair shaft formation and epidermal barrier function. The protein contains a conserved PAD domain and requires calcium for catalytic activity. Structural studies show that mutations in the calcium-binding or active-site regions disrupt function, leading to hair shaft defects.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PADI3 Knockout HEK293 Cell Line | EDJ-KQ11193 | Human | 51702 | Details Get a Quote |
| PADI3 Knockout A-549 Cell Line | EDJ-KQ39247 | Human | 51702 | Details Get a Quote |
| PADI3 Knockout HeLa Cell Line | EDJ-KQ56349 | Human | 51702 | Details Get a Quote |
| PADI3 Knockout HCT 116 Cell Line | EDJ-KQ73283 | Human | 51702 | Details Get a Quote |
