DYRK4

Chr 12

dual specificity tyrosine phosphorylation regulated kinase 4

DYRK4 encodes a serine/threonine protein kinase that regulates cell differentiation, proliferation, survival, and development, with a possible role in spermiogenesis. Mutations cause autosomal dominant developmental delay with impaired language, autism spectrum disorder, and seizures, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants, suggesting intolerance to haploinsufficiency.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
57
P/LP submissions
0%
P/LP missense
1.51
LOEUF
Mechanism
Clinical SummaryDYRK4
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
57 unique Pathogenic / Likely Pathogenic· 74 VUS of 157 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.51LOEUF
pLI 0.000
Z-score -0.40
OE 1.09 (0.801.51)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.25Z-score
OE missense 1.04 (0.951.15)
295 obs / 283.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.09 (0.801.51)
00.351.4
Missense OE1.04 (0.951.15)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 26 / 23.9Missense obs/exp: 295 / 283.1Syn Z: 0.72

ClinVar Variant Classifications

157 submitted variants in ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic5
VUS74
Likely Benign5
52
Pathogenic
5
Likely Pathogenic
74
VUS
5
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
52
0
52
Likely Pathogenic
0
0
5
0
5
VUS
0
67
7
0
74
Likely Benign
0
4
0
1
5
Benign
0
0
0
0
0
Total071641136

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

View in ClinVar →

Protein Context — Lollipop Plot

DYRK4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗