PRRT2

Chr 16AD

proline rich transmembrane protein 2

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

NCBI Gene: 112476 ENSG00000167371 UniProt: Q7Z6L0 OMIM: 614386

The protein is a transmembrane protein with a proline-rich domain that is predominantly expressed in brain and spinal cord during embryonic and postnatal development. Mutations cause autosomal dominant episodic kinesigenic dyskinesia, benign familial infantile seizures, and familial infantile convulsions with paroxysmal choreoathetosis. The pathogenic mechanism involves haploinsufficiency, as suggested by the low LOEUF score indicating intolerance to loss-of-function variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Convulsions, familial infantile, with paroxysmal choreoathetosisMIM #602066

Episodic kinesigenic dyskinesia 1MIM #128200

Seizures, benign familial infantile, 2MIM #605751

Clinical highlights

Management implications

Paroxysmal kinesigenic dyskinesia responds dramatically to low-dose carbamazepine.A low-dose sodium-channel blocker (oxcarbazepine or carbamazepine) is exquisitely effective for PRRT2 PKD.

PRRT2: treatable — low-dose oxcarbazepine or carbamazepine

Gene–disease validity (ClinGen · GenCC)

Definitive · infantile convulsions and choreoathetosis · AD · ClinGen 2020
Definitive · PRRT2-associated paroxysmal movement disorder · AD · Ambry Genetics
Definitive · hereditary neurological disease · AR · Ambry Genetics
Strong · seizures, benign familial infantile, 2 · AD · Genomics England PanelApp

+7 more curated pairs

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.56

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — PRRT2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Treatment implicationsTreatable

PRRT2-related paroxysmal kinesigenic dyskinesia / benign familial infantile epilepsy

A low-dose sodium-channel blocker (oxcarbazepine or carbamazepine) is exquisitely effective for PRRT2 PKD.

Paroxysmal kinesigenic dyskinesia responds dramatically to low-dose carbamazepine.

Treatment of choice

low-dose oxcarbazepine or carbamazepine

Ebrahimi-Fakhari et al. 2015 (GeneReviews). Confirm with a neurologist and current guidelines. Functional class (GOF/LOF) is from published functional/segregation data, never inferred from the variant. As of 2026-10. Curated from the clinical genetics/neurology literature (cited per gene). Decision-support, not prescribing.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.23Z-score

OE missense 0.96 (0.85–1.07)

213 obs / 222.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.18 (0.07–0.56)

0≤0.351.4

Missense OE?0.96 (0.85–1.07)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 2 / 11.2Missense obs/exp: 213 / 222.5Syn Z: -0.00

Background carrier burden — how many people carry a rare variant somewhere in PRRT2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

660 rare PASS variants

Rare truncating (LoF)

1 in 440

65 rare PASS variants

Rare synonymous (reference)

1 in 250

217 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRRT2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 500
South Asian	~43k	1 in 94	1 in 660
Remaining (unassigned)	~30k	1 in 88	1 in 570
European (Finnish)	~27k	1 in 290	1 in 390
Admixed American	~22k	1 in 110	1 in 1,400
African / African American	~21k	1 in 90	1 in 380
East Asian	~20k	1 in 72	1 in 530
Ashkenazi Jewish	~13k	1 in 300	1 in 760
Middle Eastern	~2,884	1 in 90	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓