PRRT2

Chr 16AD

proline rich transmembrane protein 2

Also known as: BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA, ICCA, IFITMD1

NCBI Gene: 112476ENSG00000167371UniProt: Q7Z6L0

This gene encodes a transmembrane protein containing a proline-rich domain in its N-terminal half. Studies in mice suggest that it is predominantly expressed in brain and spinal cord in embryonic and postnatal stages. Mutations in this gene are associated with episodic kinesigenic dyskinesia-1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Primary Disease Associations & Inheritance

Convulsions, familial infantile, with paroxysmal choreoathetosisMIM #602066
AD
Episodic kinesigenic dyskinesia 1MIM #128200
AD
Seizures, benign familial infantile, 2MIM #605751
AD
691
ClinVar variants
233
Pathogenic / LP
0.58
pLI score
2
Active trials
Clinical Summary— PRRT2
🧬
Gene-Disease Validity (ClinGen)
infantile convulsions and choreoathetosis · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.58) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
233 Pathogenic / Likely Pathogenic· 276 VUS of 691 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

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 0.579
Z-score 2.55
OE 0.18 (0.07–0.56)
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.
0.23Z-score
OE missense 0.96 (0.85–1.07)
213 obs / 222.5 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.0.18 (0.07–0.56)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.85–1.07)
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.1.00
0≤1.21.6
LoF obs/exp: 2 / 11.2Missense obs/exp: 213 / 222.5Syn Z: -0.00

ClinVar Variant Classifications

691 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic197
Likely Pathogenic36
VUS276
Likely Benign149
Benign3
Conflicting30
197
Pathogenic
36
Likely Pathogenic
276
VUS
149
Likely Benign
3
Benign
30
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
52
4
141
0
197
Likely Pathogenic
16
11
9
0
36
VUS
8
249
17
2
276
Likely Benign
2
29
14
104
149
Benign
0
0
2
1
3
Conflicting
—30
Total78293183107691

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

View in ClinVar →

Protein Context — Lollipop Plot

PRRT2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PRRT2-related intellectual developmental disorder

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗
frameshift variant

PRRT2-related benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Convulsions, familial infantile, with paroxysmal choreoathetosis

MIM #602066

Molecular basis of disorder known

Autosomal dominant

Episodic kinesigenic dyskinesia 1

MIM #128200

Molecular basis of disorder known

Autosomal dominant

Seizures, benign familial infantile, 2

MIM #605751

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — PRRT2
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Episodic Ataxias: Primary and Secondary Etiologies, Treatment, and Classification Approaches.
Hassan A·Tremor Other Hyperkinet Mov (N Y)
2023Case report
Familial hemiplegic migraine.
Villar-Martinez MD et al.·Handb Clin Neurol
2024Review
Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.
Lindy AS et al.·Epilepsia
2018Cohort
Recommendations for the diagnosis and treatment of paroxysmal kinesigenic dyskinesia: an expert consensus in China.
Cao L et al.·Transl Neurodegener
2021Review
Dystonia.
Morgante F et al.·Continuum (Minneap Minn)
2013Review
Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort.
Symonds JD et al.·Brain
2019Cohort
Expanding the genotypes and phenotypes for 19 rare diseases by exome sequencing performed in pediatric intensive care unit.
Liu J et al.·Hum Mutat
2021
Genome sequencing of 320 Chinese children with epilepsy: a clinical and molecular study.
Zou D et al.·Brain
2021
Genetics in dystonia.
Klein C·Parkinsonism Relat Disord
2014Review
Paroxysmal Dyskinesias.
McGuire S et al.·Semin Pediatr Neurol
2018Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
A Case of Atypical Presentation of Paroxysmal Movement Disorder, Contributed to PRRT2 Gene Variant.
Pace M et al.·J Child Neurol
2026
Clinical and neuroimaging features of PRRT2-related epilepsy in adult patients.
Yan Y et al.·Epilepsy Behav
2026Cohort
Motor-planning cerebello-cerebral network alterations in PRRT2-related paroxysmal kinesigenic dyskinesia.
Liao W et al.·Parkinsonism Relat Disord
2026
Multiple phenotypic traits including developmental impairment in a Chinese family with infantile convulsion and choreoathetosis syndrome: a case study expanding the clinical spectrum of prrt2-related syndrome.
Wu R et al.·BMC Pediatr
2025🔓 Open Access
Functional Characterization and Pathogenicity Classification of PRRT2 Splice Variants in PRRT2-Related Disorders.
Xu JJ et al.·Ann Clin Transl Neurol
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
DystoniaDystonia; IdiopathicDystonia, Primary

Dystonia Genotype-Phenotype Correlation

RECRUITING
NCT03428009University of Texas Southwestern Medical CenterStarted 2018-03-01
Magnetic Resonance Imaging
Paroxysmal Dyskinesia

Neural Correlates of Movement Disorders Associated With PRRT2 Related Paroxysmal Kinesigenic Dyskinesia - an Ancillary Study of AMEDYST Research

RECRUITING
NCT06701851Phase NAInstitut National de la Santé Et de la Recherche Médicale, FranceStarted 2025-01-21
Voluntary and involuntary conditions

External Resources

Links to major genomics databases and tools