PRKD1

Chr 14AD

protein kinase D1

Also known as: CHDED, PKC-MU, PKCM, PKD, PKD1, PRKCM

NCBI Gene: 5587ENSG00000184304UniProt: Q15139OMIM: 605435

The protein is a serine/threonine kinase that regulates Golgi membrane integrity and protein transport, cell signaling pathways including MAPK and NF-kappa-B, and cardiac function. Mutations cause congenital heart defects and ectodermal dysplasia with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
GOFmechanismADLOEUF 0.621 OMIM phenotype
Clinical Summary— PRKD1
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Gene-Disease Validity (ClinGen)
congenital heart disease · ARLimited

Limited evidence — not for standalone diagnostic reporting

2 total gene-disease associations curated

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 193 VUS of 293 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.62LOEUF
pLI 0.000
Z-score 3.52
OE 0.42 (0.29–0.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.43Z-score
OE missense 0.82 (0.76–0.89)
411 obs / 501.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.29–0.62)
0≤0.351.4
Missense OE0.82 (0.76–0.89)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 18 / 42.9Missense obs/exp: 411 / 501.2Syn Z: -0.52
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePRKD1-related syndromic congenital heart defectsOTHERAD
DN
0.5477th %ile
GOF
0.6346th %ile
LOF
0.50top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOF1 literature citation

Literature Evidence

GOFFunctional analysis using in vitro kinase assays with recombinant proteins showed that the mutation c.1808G>A, p.(Arg603His) represents a gain-of-function mutation encoding an enzyme with a constitutive, lipid-independent catalytic activity.PMID:32817298

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

293 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic8
VUS193
Likely Benign43
Benign16
Conflicting7
25
Pathogenic
8
Likely Pathogenic
193
VUS
43
Likely Benign
16
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
23
0
25
Likely Pathogenic
4
4
0
0
8
VUS
11
177
4
1
193
Likely Benign
1
13
6
23
43
Benign
0
5
7
4
16
Conflicting
—7
Total162014028292

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

View in ClinVar →

Protein Context — Lollipop Plot

PRKD1 · 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 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
Transcriptome data combined with two-sample Mendelian randomization reveal IRF1 and PRKD1 as UPR-related key regulators in intervertebral disc degeneration.
Zheng F et al.·Medicine (Baltimore)
2026Open Access
Generation of human induced pluripotent stem cell lines carrying a heterozygous and homozygous PRKD1 c.1774G > A genetic variant causing syndromic congenital defects.
Witthoff F et al.·Stem Cell Res
2026
Cribriform Adenocarcinoma of the Nasal Cavity Harboring a Novel NAP1L1::PRKD1 Fusion, Expanding the Molecular Landscape of Minor Salivary Gland Tumors.
Duarte EM et al.·Case Rep Pathol
2025Open Access
Tetralogy of Fallot and craniosynostosis - differential manifestation in a familial case of CHDED syndrome caused by novel pathogenic PRKD1 variant.
Oza PS et al.·J Hum Genet
2026
Hedgehog Components Are Present in Polymorphous Adenocarcinoma of the Salivary Gland Regardless of PRKD1 Mutation and Tissue Invasion.
De Santana DA et al.·J Oral Pathol Med
2025Open Access
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