DPYSL3

Chr 5

dihydropyrimidinase like 3

Also known as: CRMP-4, CRMP4, DRP-3, DRP3, LCRMP, ULIP, ULIP-1

NCBI Gene: 1809ENSG00000113657UniProt: Q14195

Enables filamin binding activity. Predicted to be involved in several processes, including actin filament organization; regulation of plasma membrane bounded cell projection organization; and response to axon injury. Predicted to act upstream of or within nervous system development. Predicted to be located in several cellular components, including exocytic vesicle; growth cone; and lamellipodium. Predicted to be part of filamentous actin. Predicted to be active in cytosol and synapse. [provided by Alliance of Genome Resources, Apr 2025]

85
ClinVar variants
12
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DPYSL3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 62 VUS of 85 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.22LOEUF
pLI 0.999
Z-score 4.60
OE 0.07 (0.03–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.48Z-score
OE missense 0.66 (0.59–0.73)
271 obs / 412.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.66 (0.59–0.73)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 2 / 28.5Missense obs/exp: 271 / 412.6Syn Z: 0.73

ClinVar Variant Classifications

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS62
Likely Benign7
Benign4
12
Pathogenic
62
VUS
7
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
57
5
0
62
Likely Benign
0
1
3
3
7
Benign
0
0
2
2
4
Total05822585

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DPYSL3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Dihydropyrimidinase-like 3 is a putative hepatocellular carcinoma tumor suppressor.
Oya H et al.·J Gastroenterol
2015
Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma.
Liang PI et al.·BMC Cancer
2023
DPYSL3 modulates mitosis, migration, and epithelial-to-mesenchymal transition in claudin-low breast cancer.
Matsunuma R et al.·Proc Natl Acad Sci U S A
2018
Silencing immune-infiltrating biomarker CCDC80 inhibits malignant characterization and tumor formation in gastric cancer.
Yu M et al.·BMC Cancer
2024
A novel efferocytosis-related gene signature for predicting prognosis and therapeutic response in bladder cancer.
Yu W et al.·Sci Rep
2025
A rare motor neuron deleterious missense mutation in the DPYSL3 (CRMP4) gene is associated with ALS.
Blasco H et al.·Hum Mutat
2013
Spatial Transcriptomics in a Case of Follicular Thyroid Carcinoma Reveals Clone-Specific Dysregulation of Genes Regulating Extracellular Matrix in the Invading Front.
Condello V et al.·Endocr Pathol
2024Case report
Regulation of Dihydropyrimidinase-like 3 Gene Expression by MicroRNAs in PC12 Cells with Induced Ischaemia and Hypothermia.
Kwon K et al.·Folia Biol (Praha)
2023
Enhancing DPYSL3 gene expression via a promoter-targeted small activating RNA approach suppresses cancer cell motility and metastasis.
Li C et al.·Oncotarget
2016
Serum levels of ANOS1 serve as a diagnostic biomarker of gastric cancer: a prospective multicenter observational study.
Kanda M et al.·Gastric Cancer
2020
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools