PRKRA

Chr 2AR

protein activator of interferon induced protein kinase EIF2AK2

Also known as: DYT16, HSD14, PACT, RAX

NCBI Gene: 8575ENSG00000180228UniProt: O75569

This gene encodes a protein kinase activated by double-stranded RNA which mediates the effects of interferon in response to viral infection. Mutations in this gene have been associated with dystonia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

Primary Disease Associations & Inheritance

Dystonia 16MIM #612067
AR
231
ClinVar variants
33
Pathogenic / LP
0.42
pLI score
0
Active trials
Clinical Summary— PRKRA
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 95 VUS of 231 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.56LOEUF
pLI 0.417
Z-score 2.71
OE 0.22 (0.10–0.56)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.58Z-score
OE missense 0.65 (0.55–0.76)
103 obs / 159.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.10–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.55–0.76)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 3 / 13.9Missense obs/exp: 103 / 159.0Syn Z: 0.97

ClinVar Variant Classifications

231 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic6
VUS95
Likely Benign76
Benign21
Conflicting6
27
Pathogenic
6
Likely Pathogenic
95
VUS
76
Likely Benign
21
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
26
0
27
Likely Pathogenic
1
3
2
0
6
VUS
5
56
32
2
95
Likely Benign
1
6
48
21
76
Benign
1
2
16
2
21
Conflicting
—6
Total96712425231

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

View in ClinVar →

Protein Context — Lollipop Plot

PRKRA · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Dystonia 16

MIM #612067

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — PRKRA
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetics and Pathogenesis of Dystonia.
Thomsen M et al.·Annu Rev Pathol
2024Review
Dystonia.
Morgante F et al.·Continuum (Minneap Minn)
2013Review
Dystonia-plus syndromes.
Asmus F et al.·Eur J Neurol
2010Review
Early onset primary dystonia.
Zorzi G et al.·Eur J Paediatr Neurol
2009Review
Combined dystonias: clinical and genetic updates.
Weissbach A et al.·J Neural Transm (Vienna)
2021Review
Update on the Genetics of Dystonia.
Lohmann K et al.·Curr Neurol Neurosci Rep
2017Review
Genotype-Phenotype Relations for Isolated Dystonia Genes: MDSGene Systematic Review.
Lange LM et al.·Mov Disord
2021Review
The monogenic primary dystonias.
Müller U·Brain
2009Review
Complicated recessive dystonia parkinsonism syndromes.
Schneider SA et al.·Mov Disord
2009Review
Decreased protein activator of interferon induced protein kinase (PRKRA) involved in menopause-related cholesterol metabolic disorders by regulating cholesterol biosynthesis.
Xu L et al.·Lipids Health Dis
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools