DPYSL2 (Dihydropyrimidinase Like 2)
A key regulator of neuronal development and axonal guidance, implicated in neuropsychiatric disorders and cancer.
Gene Information Card
| Symbol | DPYSL2 |
|---|---|
| Full Name | dihydropyrimidinase like 2 |
| Gene Type | protein coding |
| Chromosomal Location | 8p21.2 |
| NCBI Gene ID | 1808 ncbi.nlm.nih.gov/gene/1808 |
| Ensembl ID | ENSG00000092964 |
| UniProt ID | Q16555 |
| OMIM ID | 602463 |
| HGNC ID | 3014 |
| Aliases | CRMP2, DRP2, ULIP2, DHPRP2, N2A3 |
Description
DPYSL2 (Dihydropyrimidinase Like 2), also known as CRMP2 (Collapsin Response Mediator Protein 2), is a protein-coding gene located on chromosome 8p21.2. It encodes a cytoplasmic phosphoprotein that plays a critical role in neuronal development, including axonal guidance, neuronal polarity, and synaptic plasticity. DPYSL2 is involved in microtubule assembly and is a key mediator of semaphorin 3A signaling. It has been implicated in various neuropsychiatric disorders, including schizophrenia and bipolar disorder, as well as in cancer progression and neurodegenerative diseases. The gene is expressed predominantly in the brain and nervous system, with lower expression in other tissues.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered DPYSL2 expression and splicing variants affect neuronal migration and synaptic function, contributing to disease susceptibility. | Genetic association studies and post-mortem brain analyses (NCBI, OMIM). |
| Bipolar Disorder | DPYSL2 variants may influence neuronal plasticity and neurotransmitter signaling, linked to mood regulation. | Association studies and gene expression profiling (OMIM, NCBI). |
| Alzheimer's Disease | Aberrant phosphorylation of CRMP2 (DPYSL2) leads to neurofibrillary tangle formation and axonal degeneration. | Immunohistochemistry and biochemical studies (UniProt, NCBI). |
| Lung Cancer | DPYSL2 overexpression promotes cell migration and invasion, potentially via regulation of cytoskeletal dynamics. | Expression analysis in tumor tissues and cell lines (COSMIC, NCBI). |
| Colorectal Cancer | DPYSL2 may act as a tumor suppressor or oncogene depending on context; altered expression correlates with metastasis. | Gene expression and functional studies (COSMIC, NCBI). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 25.3 | High |
| Adrenal Gland | 8.1 | Medium |
| Lung | 4.2 | Low |
| Liver | 2.5 | Low |
| Kidney | 3.1 | Low |
| Testis | 6.7 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 30.2 | High expression; used in neuronal differentiation studies |
| A549 (lung carcinoma) | 12.4 | Moderate expression; associated with invasive phenotype |
| HCT116 (colorectal carcinoma) | 8.9 | Moderate expression; linked to metastasis |
| HEK293 (embryonic kidney) | 5.3 | Low expression; used for recombinant studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs3743160 (C→T) | SNP | ~30% in East Asian populations | Associated with altered splicing and increased schizophrenia risk |
| c.1516A>G (p.Thr506Ala) | Missense | Rare (<1%) | May affect protein stability and function; reported in neurodevelopmental disorders |
| c.1690C>T (p.Arg564Cys) | Missense | Rare (<0.5%) | Potential impact on phosphorylation sites; linked to bipolar disorder |
| Copy number variations (CNVs) | CNV | Variable | Deletions/duplications at 8p21.2 associated with intellectual disability and schizophrenia |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in DPYSL2 are rare but may lead to impaired axonal growth and neuronal migration, contributing to neurodevelopmental phenotypes.
Gain of Function (GOF)
Gain-of-function mutations or overexpression can enhance cell motility and invasion in cancers, promoting metastasis.
Dominant Negative (DN)
Dominant-negative effects have been suggested for certain missense variants that disrupt CRMP2 dimerization, interfering with microtubule assembly.
View complete mutation data：
Gene Ontology (GO)
| • microtubule binding | • hydrolase activity |
| • protein homodimerization activity | • axon guidance |
| • neuron projection development | • semaphorin receptor binding |
| • cytoskeleton organization | • synaptic transmission |
Pathways
• Semaphorin signaling
• Axon guidance
• Neurotrophin signaling
• Microtubule cytoskeleton regulation
• Rho GTPase signaling
Protein Summary
The DPYSL2 protein, also known as CRMP2, is a 572-amino-acid cytoplasmic protein that belongs to the dihydropyrimidinase family. It is highly expressed in the developing and adult nervous system. CRMP2 mediates semaphorin 3A-induced growth cone collapse by regulating microtubule dynamics. It interacts with tubulin heterodimers and promotes microtubule assembly, essential for axonal elongation and neuronal polarity. Phosphorylation by kinases such as Cdk5 and GSK3β modulates its activity. In addition to its role in neurodevelopment, CRMP2 is involved in cancer cell migration and invasion, and its aberrant regulation is linked to neurodegenerative diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DPYSL2 Knockout HEK293 Cell Line | EDJ-KQ3136 | Human | 1808 | Details Get a Quote |
| DPYSL2 Knockout A-549 Cell Line | EDJ-KQ24513 | Human | 1808 | Details Get a Quote |
| DPYSL2 Knockout HCT 116 Cell Line | EDJ-KQ24514 | Human | 1808 | Details Get a Quote |
| DPYSL2 Knockout HeLa Cell Line | EDJ-KQ24515 | Human | 1808 | Details Get a Quote |
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