DPYSL5

Chr 2AD

dihydropyrimidinase like 5

Also known as: CRAM, CRMP-5, CRMP5, CV2, RTSC4, Ulip6

NCBI Gene: 56896ENSG00000157851UniProt: Q9BPU6OMIM: 608383

This protein negatively regulates dendrite outgrowth during neural development and is highly intolerant to loss-of-function variants (pLI 1.0, LOEUF 0.11). Mutations cause Ritscher-Schinzel syndrome 4, a neurodevelopmental disorder with autosomal dominant inheritance that affects brain development and other organ systems.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.111 OMIM phenotype
Clinical Summary— DPYSL5
⚡
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.
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 4.76
OE 0.00 (0.00–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.08Z-score
OE missense 0.55 (0.49–0.62)
206 obs / 373.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.11)
0≤0.351.4
Missense OE0.55 (0.49–0.62)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 0 / 26.3Missense obs/exp: 206 / 373.7Syn Z: 0.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongDPYSL5-related developmental disorderOTHERAD
DN
0.3991th %ile
GOF
0.5367th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.11

Literature Evidence

LOFIn 8 additional patients with a similar neurodevelopmental disorder with features of RTSC4, Jeanne et al. (2021) identified a recurrent de novo heterozygous missense mutation in the DPYSL5 gene (E41K; 608383.0002). The mutations were found by exome sequencing; neither was present in the gnomAD databPMID:33894126

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DPYSL5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Contribution of the dihydropyrimidinase-like proteins family in synaptic physiology and in neurodevelopmental disorders
Desprez F et al.·Front Neurosci
2023
Integrative genomic and spatial transcriptomic analysis elucidates the oligodendrocyte-mediated etiology of epileptic cortical thinning.
Zhang D et al.·Epilepsia Open
2026
Comparative molecular landscapes of immature neurons in the mammalian dentate gyrus across species reveal special features in humans.
Zhou Y et al.·bioRxiv
2025
Nicotine Exposure in a Phencyclidine-Induced Mice Model of Schizophrenia: Sex-Selective Medial Prefrontal Cortex Protein Markers of the Combined Insults in Adolescent Mice
Rodríguez-Vega A et al.·Int J Mol Sci
2023Functional
Expanding the pre- and postnatal phenotype of WASHC5 and CCDC22 -related Ritscher-Schinzel syndromes.
Neri S et al.·Eur J Med Genet
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients