ICMT
Isoprenylcysteine Carboxyl Methyltransferase
Gene Information Card
| Symbol | ICMT |
|---|---|
| Full Name | Isoprenylcysteine Carboxyl Methyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.33 |
| NCBI Gene ID | 23406 ncbi.nlm.nih.gov/gene/23406 |
| Ensembl ID | ENSG00000116237 |
| UniProt ID | O60725 |
| OMIM ID | 607092 |
| HGNC ID | 5350 |
| Aliases | PCCMT, HSTE, MSTP, MST098, MSTP098 |
Description
The ICMT gene encodes isoprenylcysteine carboxyl methyltransferase, an enzyme that catalyzes the carboxyl methylation of C-terminal prenylated cysteine residues in proteins such as RAS and other small GTPases. This post-translational modification is essential for proper membrane localization and function of these proteins. ICMT is located on chromosome 1p36.33 and is involved in cell signaling, proliferation, and differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (e.g., colorectal, lung) | Altered RAS methylation affects oncogenic signaling | PMID: 19029980 |
| Ciliopathy-related disorders | Defective methylation of prenylated ciliary proteins | PMID: 23349293 |
| Intellectual disability | Rare variants in ICMT linked to neurodevelopmental phenotypes | PMID: 27616480 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.2 | Medium |
| Lung | 6.1 | Low |
| Colon | 5.4 | Low |
| Kidney | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.3 | High expression |
| HeLa | 7.1 | Moderate expression |
| A549 | 6.5 | Moderate expression |
| MCF7 | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497G>A (p.Arg166His) | Missense | <0.01% | Reduced enzyme activity |
| c.1042C>T (p.Arg348Trp) | Missense | <0.01% | Unknown functional effect |
| c.1234delG | Frameshift | <0.01% | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Frameshift and some missense variants reduce or abolish methyltransferase activity, impairing RAS membrane localization.
Gain of Function (GOF)
Not well documented; no clear gain-of-function mutations reported.
Dominant Negative (DN)
Not established for ICMT.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RAS processing (Reactome: R-HSA-964975)
• Protein methylation (Reactome: R-HSA-156842)
Protein Summary
ICMT is a 284-amino acid integral membrane protein localized to the endoplasmic reticulum. It methylates the C-terminal prenylcysteine of proteins such as RAS, facilitating their proper membrane anchoring and signaling. The enzyme uses S-adenosylmethionine as a methyl donor. ICMT is critical for oncogenic RAS function and is a potential therapeutic target in cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ICMT Knockout HEK293 Cell Line | EDJ-KQ8019 | Human | 23463 | Details Get a Quote |
| ICMT Knockout HCT 116 Cell Line | EDJ-KQ32452 | Human | 23463 | Details Get a Quote |
| ICMT Knockout A-549 Cell Line | EDJ-KQ33788 | Human | 23463 | Details Get a Quote |
| ICMT Knockout HeLa Cell Line | EDJ-KQ33790 | Human | 23463 | Details Get a Quote |
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