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GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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DPYSL2
dihydropyrimidinase like 2
Chromosome 8 · 8p21.2
NCBI Gene: 1808Ensembl: ENSG00000092964.18HGNC: HGNC:3014UniProt: A0A1C7CYX9
221PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
endocytosismembranemicrotubule cytoskeletoncytosolhypertensionautosomal dominant non-syndromic intellectual disabilityovarian neoplasmglomerulonephritis
✦AI Summary

DPYSL2 (dihydropyrimidinase-like 2) encodes CRMP2, a microtubule-stabilizing protein essential for neuronal development and function. The protein plays critical roles in neurogenesis, axonal growth, and cellular projection formation 1. DPYSL2 is highly expressed in sensory neurons including nociceptors and dorsal root ganglion neurons, where it contributes to axonal growth and regeneration 2. The gene generates multiple isoforms with distinct functions - knockout of the DPYSL2-B isoform reduces dendritic length by up to 58% and disrupts mTOR signaling pathways 1. DPYSL2 localizes to centrosomes where it promotes ciliogenesis through interaction with USP21, which prevents its proteasomal degradation via deubiquitination 3. The protein is implicated in psychiatric disorders, with genetic variants associated with schizophrenia and alcohol dependence 45. In disease contexts, DPYSL2 dysfunction affects cellular projections, immune function, calcium signaling, and cholesterol biosynthesis 1. The gene also shows altered expression in cancer metastasis, suggesting broader roles in cellular migration and invasion 6. DPYSL2's involvement in mTOR signaling and neurodevelopmental processes makes it a key player in both normal brain function and psychiatric pathogenesis.

Sources cited
1
DPYSL2 is expressed in sensory neurons and contributes to axonal growth/regeneration
PMID: 37044067
2
DPYSL2 encodes microtubule-stabilizing protein, DPYSL2-B knockout reduces dendritic length and disrupts mTOR signaling
PMID: 37479784
3
DPYSL2 localizes to centrosomes, interacts with USP21 for deubiquitination, and promotes ciliogenesis
PMID: 40619097
4
DPYSL2 variants are associated with schizophrenia and affect mTOR signaling
PMID: 27801893
5
DPYSL2 genetic variants are associated with alcohol dependence
PMID: 23846846
6
DPYSL2 shows altered expression in cancer metastasis
PMID: 38057344
Disease Associationsⓘ20
hypertensionOpen Targets
0.44Moderate
autosomal dominant non-syndromic intellectual disabilityOpen Targets
0.37Weak
ovarian neoplasmOpen Targets
0.31Weak
glomerulonephritisOpen Targets
0.31Weak
metabolic diseaseOpen Targets
0.30Weak
cardiovascular diseaseOpen Targets
0.30Weak
genetic disorderOpen Targets
0.27Weak
Abruptio PlacentaeOpen Targets
0.25Weak
Intellectual disabilityOpen Targets
0.19Weak
Aplasia/Hypoplasia of the corpus callosumOpen Targets
0.18Weak
Sjogren syndromeOpen Targets
0.12Weak
fungal infectious diseaseOpen Targets
0.11Weak
Alzheimer diseaseOpen Targets
0.11Weak
autism spectrum disorderOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
Huntington diseaseOpen Targets
0.08Suggestive
Pathogenic Variants1
NM_001197293.3(DPYSL2):c.357C>A (p.Ser119Arg)Likely pathogenic
Inborn genetic diseases
★☆☆☆2013→ Residue 119
View on ClinVar ↗
Related Genes
UMPSProtein interaction100%PLXNA2Protein interaction100%PLXNA3Protein interaction100%PLXNA4Protein interaction100%PLXNA1Protein interaction100%GRIN2BProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Heart
21%
Lung
20%
Ovary
13%
Liver
4%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
DPYSL2UMPSPLXNA2PLXNA3PLXNA4PLXNA1GRIN2B
PROTEIN STRUCTURE
Preparing viewer…
PDB5LXX · 1.25 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.29Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.18 [0.11–0.29]
RankingsWhere DPYSL2 stands among ~20K protein-coding genes
  • #1,854of 20,598
    Most Researched221 · top 10%
  • #4,716of 5,498
    Most Pathogenic Variants1
  • #1,063of 17,882
    Most Constrained (LOEUF)0.29 · top 10%
Genes detectedDPYSL2
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Scalable generation of sensory neurons from human pluripotent stem cells.
PMID: 37044067
Stem Cell Reports · 2023
1.00
2
Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.
PMID: 35685361
Comput Struct Biotechnol J · 2022
0.90
3
The DPYSL2 gene connects mTOR and schizophrenia.
PMID: 27801893
Transl Psychiatry · 2016
0.80
4
DPYSL2/CRMP2 isoform B knockout in human iPSC-derived glutamatergic neurons confirms its role in mTOR signaling and neurodevelopmental disorders.
PMID: 37479784
Mol Psychiatry · 2023
0.70
5
Celastrol inhibits the DPYSL2-JAK/STAT pathway by targeting mito-IDHs mediated mitochondrial metabolism to exhaust breast cancer.
PMID: 40274961
Acta Pharmacol Sin · 2025
0.60