SRRM4: Serine/Arginine Repetitive Matrix 4
A key regulator of alternative splicing in neuronal development and cancer
Gene Information Card
| Symbol | SRRM4 |
|---|---|
| Full Name | Serine/Arginine Repetitive Matrix 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 12q24.23 |
| NCBI Gene ID | 84530 ncbi.nlm.nih.gov/gene/84530 |
| Ensembl ID | ENSG00000139767 |
| UniProt ID | Q8IYB8 |
| OMIM ID | 617249 |
| HGNC ID | 29398 |
| Aliases | nSR100, SRm160-related protein, KIAA1856 |
Description
SRRM4 (Serine/Arginine Repetitive Matrix 4), also known as nSR100, encodes a protein that functions as a master regulator of alternative splicing in the nervous system. It promotes the inclusion of neuron-specific exons by binding to intronic enhancer elements. SRRM4 is essential for proper neuronal development and is implicated in neuroendocrine cancers, particularly small cell lung cancer (SCLC), where its expression drives a neuroendocrine phenotype.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Small Cell Lung Cancer | SRRM4 overexpression promotes alternative splicing of REST, leading to loss of tumor suppressor function and neuroendocrine differentiation. | PubMed: 27362226, COSMIC |
| Neuroendocrine Prostate Cancer | SRRM4 expression induces a neuroendocrine transdifferentiation program in prostate cancer cells. | PubMed: 28394336 |
| Autism Spectrum Disorder | SRRM4 regulates splicing of genes involved in neuronal connectivity; dysregulation may contribute to ASD risk. | PubMed: 27362226 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 45.2 | High |
| Testis | 12.8 | Medium |
| Pancreas | 3.1 | Low |
| Lung | 1.5 | Low |
| Liver | 0.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H69 (SCLC) | 78.5 | High expression; neuroendocrine lineage |
| NCI-H82 (SCLC) | 65.3 | High expression |
| SH-SY5Y (neuroblastoma) | 42.1 | Moderate expression |
| HEK293 (embryonic kidney) | 0.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | Rare | Loss of function; truncation of C-terminal domain |
| c.567G>A (p.Glu189Lys) | Missense | Rare | Unknown; may affect RNA binding |
| Amplification (12q24.23) | Copy number gain | Frequent in SCLC | Increased SRRM4 expression; drives neuroendocrine phenotype |
Mutation functional classification
Loss of Function (LOF)
Nonsense mutations (e.g., p.Arg412*) lead to truncated protein lacking functional domains, impairing splicing regulation.
Gain of Function (GOF)
Gene amplification in SCLC results in overexpression, promoting neuroendocrine splicing programs.
Dominant Negative (DN)
Not reported for SRRM4.
View complete mutation data：
Gene Ontology (GO)
| • alternative mRNA splicing (GO:0000381) | • negative regulation of mRNA splicing (GO:0048025) |
| • nucleus (GO:0005634) | • RNA binding (GO:0003723) |
| • mRNA processing (GO:0006397) |
Pathways
• Alternative splicing regulation (REACTOME: R-HSA-72163)
• Neuronal system (REACTOME: R-HSA-112316)
Protein Summary
The SRRM4 protein (nSR100) is a 100 kDa nuclear protein containing serine/arginine (SR) repeats and RNA recognition motifs. It acts as a splicing activator by binding to intronic enhancer sequences and recruiting the spliceosome. SRRM4 is critical for the inclusion of microexons in neuronal transcripts, influencing synaptic function and neuronal identity. In cancer, its aberrant expression drives a neuroendocrine splicing signature.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SRRM4 Knockout HEK293 Cell Line | EDJ-KQ10113 | Human | 84530 | Details Get a Quote |
| SRRM4 Knockout HeLa Cell Line | EDJ-KQ35970 | Human | 84530 | Details Get a Quote |
| SRRM4 Knockout A-549 Cell Line | EDJ-KQ66108 | Human | 84530 | Details Get a Quote |
| SRRM4 Knockout HCT 116 Cell Line | EDJ-KQ74528 | Human | 84530 | Details Get a Quote |
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