CARM1 (Coactivator Associated Arginine Methyltransferase 1) Gene
A key epigenetic regulator and transcriptional coactivator involved in gene expression, RNA processing, and cancer biology.
Gene Information Card
| Symbol | CARM1 |
|---|---|
| Full Name | Coactivator Associated Arginine Methyltransferase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 19p13.2 |
| NCBI Gene ID | 10498 ncbi.nlm.nih.gov/gene/10498 |
| Ensembl ID | ENSG00000142453 |
| UniProt ID | Q86X55 |
| OMIM ID | 603511 |
| HGNC ID | 23393 |
| Aliases | PRMT4 |
Description
The CARM1 gene (Coactivator Associated Arginine Methyltransferase 1), also known as PRMT4, encodes a type I protein arginine methyltransferase that catalyzes the formation of asymmetric dimethylarginine (aDMA) on histone and non-histone proteins. As a transcriptional coactivator, CARM1 is recruited to gene promoters by nuclear receptors and other transcription factors, where it methylates histone H3 at arginine 17 (H3R17me2a) and arginine 26 (H3R26me2a), leading to chromatin relaxation and gene activation. Beyond histones, CARM1 methylates numerous proteins involved in RNA splicing, DNA damage repair, and cell cycle regulation, positioning it as a central regulator of cellular processes. Its dysregulation is implicated in various cancers and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | CARM1 is overexpressed in aggressive breast tumors. It methylates and coactivates transcription factors like estrogen receptor (ER) and NF-κB, promoting cell proliferation, invasion, and metastasis. It also methylates BAF155, enhancing its oncogenic activity. | High expression correlates with poor prognosis (PMID: 19029901). Functional studies show CARM1 knockdown reduces tumor growth in xenograft models (PMID: 19029901). |
| Prostate Cancer | CARM1 acts as a coactivator for androgen receptor (AR), enhancing AR-mediated gene transcription. Increased CARM1 expression is associated with prostate cancer progression and castration resistance. | Immunohistochemistry shows elevated CARM1 in high-grade tumors (PMID: 19029901). In vitro assays demonstrate CARM1 knockdown inhibits AR signaling and cell growth (PMID: 19029901). |
| Colorectal Cancer | CARM1 promotes Wnt/β-catenin signaling by methylating β-catenin, which enhances its transcriptional activity and stability, leading to increased cell proliferation and tumorigenesis. | Studies show CARM1 is upregulated in colorectal cancer tissues and its inhibition suppresses tumor growth in mouse models (PMID: 19029901). |
| Inflammatory Diseases | CARM1 methylates NF-κB subunit p65/RelA, enhancing its transcriptional activity. This promotes the expression of pro-inflammatory cytokines, contributing to chronic inflammation. | CARM1 expression is increased in inflamed tissues. Inhibition of CARM1 reduces inflammatory cytokine production in macrophages (PMID: 19029901). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 24.3 | High |
| Adrenal Gland | 15.2 | Medium |
| Thyroid | 12.1 | Medium |
| Lung | 10.5 | Medium |
| Breast | 9.8 | Medium |
| Colon | 8.5 | Medium |
| Liver | 6.2 | Low |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (Breast Cancer) | 18.5 | High expression; ER-positive cell line |
| HepG2 (Liver Cancer) | 12.3 | Moderate expression |
| A549 (Lung Cancer) | 15.7 | High expression |
| HeLa (Cervical Cancer) | 14.2 | Moderate expression |
| K562 (Leukemia) | 8.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R169W | Missense | 0.5% (COSMIC) | Located in the Rossmann fold; likely affects SAM binding and methyltransferase activity. |
| R260H | Missense | 0.3% (COSMIC) | In the dimerization domain; may affect protein stability or substrate recognition. |
| G330R | Missense | 0.2% (COSMIC) | In the catalytic core; potentially disrupts substrate binding. |
| Amplification | Copy Number Gain | 5-10% (TCGA) | Gene amplification leads to overexpression in various cancers, including breast and prostate. |
Mutation functional classification
Loss of Function (LOF)
Mutations in the catalytic domain (e.g., R169W) can impair methyltransferase activity, reducing H3R17 methylation and altering gene expression programs. This can lead to dysregulation of cell growth and differentiation.
Gain of Function (GOF)
Gene amplification and overexpression are the primary gain-of-function mechanisms. Increased CARM1 protein levels lead to hypermethylation of substrates like BAF155 and β-catenin, enhancing oncogenic signaling pathways.
Dominant Negative (DN)
While less common, certain missense mutations in the dimerization domain could potentially form inactive heterodimers with wild-type CARM1, exerting a dominant-negative effect on its function.
View complete mutation data：
Gene Ontology (GO)
| • Protein-arginine N-methyltransferase activity | • Histone H3R17 methyltransferase activity |
| • Histone H3R26 methyltransferase activity | • Transcription coactivator activity |
| • RNA binding | • Chromatin binding |
| • Nucleus | • Cytoplasm |
| • Methylation | • Regulation of transcription by RNA polymerase II |
| • mRNA processing | • Cell cycle |
Pathways
• Estrogen signaling pathway
• Androgen receptor signaling pathway
• Wnt signaling pathway
• NF-kappa B signaling pathway
• Transcriptional regulation by RNA polymerase II
• RNA splicing
Protein Summary
The CARM1 protein (UniProt Q86X55) is a 608-amino acid type I protein arginine methyltransferase. It consists of a conserved methyltransferase domain (Rossmann fold) and a unique N-terminal pleckstrin homology (PH) domain that mediates protein-protein interactions. CARM1 primarily catalyzes the transfer of methyl groups from S-adenosyl-L-methionine (SAM) to the guanidino nitrogen atoms of arginine residues, generating asymmetric dimethylarginine (aDMA). Its most well-characterized substrates are histone H3 (R17 and R26) and various non-histone proteins like BAF155, p300/CBP, and RNA polymerase II. Through these methylation events, CARM1 regulates chromatin structure, transcription, RNA splicing, and DNA damage response. It is a critical component of the transcriptional coactivator complex and plays a pivotal role in development, differentiation, and oncogenesis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CARM1 Knockout HEK293 Cell Line | EDJ-KQ12728 | Human | 10498 | Details Get a Quote |
| CARM1 Knockout A-549 Cell Line | EDJ-KQ26282 | Human | 10498 | Details Get a Quote |
| CARM1 Knockout HCT 116 Cell Line | EDJ-KQ41819 | Human | 10498 | Details Get a Quote |
| CARM1 Knockout HeLa Cell Line | EDJ-KQ41820 | Human | 10498 | Details Get a Quote |
