DSTYK

Chr 1

dual serine/threonine and tyrosine protein kinase

Also known as: CAKUT1, DustyPK, HDCMD38P, RHDNS1, RIP5, RIPK5, SPG23

NCBI Gene: 25778ENSG00000133059UniProt: Q6XUX3

This dual serine/threonine and tyrosine protein kinase acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor receptor activation and regulates both caspase-dependent apoptosis and caspase-independent cell death pathways. Mutations cause autosomal recessive spastic paraplegia 23 and congenital anomalies of kidney and urinary tract, as well as autosomal dominant forms of renal and urinary tract malformations. The gene shows significant constraint against loss-of-function variants (LOEUF 0.37), suggesting intolerance to complete protein loss.

ResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 0.37
Clinical Summary— DSTYK
🧬
Gene-Disease Validity (ClinGen)
complex hereditary spastic paraplegia · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.51) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 160 VUS of 310 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.513
Z-score 4.90
OE 0.22 (0.13–0.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.59Z-score
OE missense 0.81 (0.75–0.87)
434 obs / 537.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.13–0.37)
0≤0.351.4
Missense OE0.81 (0.75–0.87)
0≤0.61.4
Synonymous OE1.02
0≤1.21.6
LoF obs/exp: 10 / 45.8Missense obs/exp: 434 / 537.5Syn Z: -0.17

ClinVar Variant Classifications

310 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic5
VUS160
Likely Benign59
Benign26
Conflicting8
16
Pathogenic
5
Likely Pathogenic
160
VUS
59
Likely Benign
26
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
14
0
16
Likely Pathogenic
3
1
1
0
5
VUS
6
148
5
1
160
Likely Benign
0
5
16
38
59
Benign
0
3
18
5
26
Conflicting
—8
Total111575444274

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

View in ClinVar →

Protein Context — Lollipop Plot

DSTYK · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 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
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