ITCH Gene
E3 Ubiquitin-Protein Ligase Itchy Homolog
Gene Information Card
| Symbol | ITCH |
|---|---|
| Full Name | Itchy E3 Ubiquitin Protein Ligase |
| Gene Type | Protein coding |
| Chromosomal Location | 20q11.22 |
| NCBI Gene ID | 83737 ncbi.nlm.nih.gov/gene/83737 |
| Ensembl ID | ENSG00000078747 |
| UniProt ID | Q96J02 |
| OMIM ID | 606409 |
| HGNC ID | 13890 |
| Aliases | AIP4, ADMFD, NAPP2, dJ468O1.1 |
Description
The ITCH gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. The protein ubiquitinates target proteins, regulating their stability, localization, and activity. ITCH plays critical roles in immune regulation, cell growth, and apoptosis. Mutations in ITCH are associated with syndromic multisystem autoimmune disease and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Syndromic multisystem autoimmune disease (ADMFD) | Loss-of-function mutations impair ubiquitination of immune regulators, leading to dysregulated T-cell responses and autoimmunity. | OMIM #606409; ClinVar |
| Hepatocellular carcinoma | Reduced ITCH expression correlates with poor prognosis; ITCH targets p73 for degradation, affecting apoptosis. | COSMIC; NCBI Gene |
| Breast cancer | ITCH overexpression promotes degradation of p53 family members, contributing to tumor progression. | COSMIC; PubMed |
| Colorectal cancer | Altered ITCH expression linked to Wnt/β-catenin pathway dysregulation. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 15.2 | Medium |
| Spleen | 12.8 | Medium |
| Testis | 10.5 | Medium |
| Brain (cerebellum) | 8.3 | Low |
| Liver | 6.1 | Low |
| Heart | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 18.4 | High expression |
| HeLa | 12.1 | Medium expression |
| Jurkat | 14.6 | Medium expression |
| MCF7 | 9.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2221C>T (p.Arg741*) | Nonsense | Rare | Loss of function; truncation of HECT domain |
| c.1669G>A (p.Gly557Arg) | Missense | Rare | Impaired catalytic activity |
| c.2530_2531del (p.Leu844fs) | Frameshift | Rare | Loss of function; premature stop |
| c.1000A>G (p.Thr334Ala) | Missense | Rare | Reduced substrate binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and missense mutations that disrupt the HECT domain or catalytic activity, leading to impaired ubiquitination and immune dysregulation.
Gain of Function (GOF)
Not well documented; overexpression in some cancers may act as a gain-of-function by promoting degradation of tumor suppressors.
Dominant Negative (DN)
Not reported for ITCH.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Notch signaling pathway (Reactome: R-HSA-157118)
• TGF-beta signaling pathway (Reactome: R-HSA-170834)
• p53 pathway (Reactome: R-HSA-5633007)
Protein Summary
The ITCH protein (Q96J02) is a 903-amino acid E3 ubiquitin-protein ligase containing an N-terminal C2 domain, four WW domains, and a C-terminal HECT domain. It mediates ubiquitination of target proteins such as p73, p63, Notch, and JunB, thereby regulating cell proliferation, differentiation, and immune responses. Subcellularly localized to the cytoplasm and membrane, ITCH is widely expressed in immune tissues.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITCH Knockout HEK293 Cell Line | EDJ-KQ1468 | Human | 83737 | Details Get a Quote |
| ITCH Knockout A-549 Cell Line | EDJ-KQ21035 | Human | 83737 | Details Get a Quote |
| ITCH Knockout HCT 116 Cell Line | EDJ-KQ21036 | Human | 83737 | Details Get a Quote |
| ITCH Knockout HeLa Cell Line | EDJ-KQ18236 | Human | 83737 | Details Get a Quote |
| ITCH Knockout HAP1 Cell Line | EDC08101 | Human | 83737 | Details Get a Quote |
