HIPK3

Chr 11

homeodomain interacting protein kinase 3

Also known as: DYRK6, FIST3, PKY, YAK1

The protein is a serine/threonine kinase that regulates transcription, apoptosis, and steroidogenic gene expression by phosphorylating key targets including JUN, RUNX2, and NR5A1. Mutations cause autosomal recessive intellectual disability with developmental delay, seizures, and dysmorphic features. This gene is highly constrained against loss-of-function variants (LOEUF 0.367), suggesting that complete loss of protein function is likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
14
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.37
LOEUF
Mechanism
Clinical SummaryHIPK3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.37LOEUF
pLI 0.277
Z-score 5.35
OE 0.23 (0.150.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.73Z-score
OE missense 0.81 (0.750.87)
519 obs / 642.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.23 (0.150.37)
00.351.4
Missense OE0.81 (0.750.87)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 13 / 56.3Missense obs/exp: 519 / 642.1Syn Z: -0.17

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HIPK3 · 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.

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Clinical Literature
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