PRRT2

proline rich transmembrane protein 2, the group of interferon induced transmembrane protein domain containing

Basic information

Region (hg38): 16:29811382-29815892

Previous symbols: [ "ICCA", "DYT10" ]

Links

ENSG00000167371 ∙ NCBI:112476 ∙ OMIM:614386 ∙ HGNC:30500 ∙ Uniprot:Q7Z6L0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• infantile convulsions and choreoathetosis (Definitive), mode of inheritance: AD
• seizures, benign familial infantile, 2 (Strong), mode of inheritance: AD
• episodic kinesigenic dyskinesia 1 (Strong), mode of inheritance: AD
• infantile convulsions and choreoathetosis (Strong), mode of inheritance: AD
• familial or sporadic hemiplegic migraine (Supportive), mode of inheritance: AD
• benign familial infantile epilepsy (Supportive), mode of inheritance: AD
• infantile convulsions and choreoathetosis (Supportive), mode of inheritance: AD
• episodic kinesigenic dyskinesia 1 (Supportive), mode of inheritance: AD
• paroxysmal nonkinesigenic dyskinesia 1 (Supportive), mode of inheritance: AD
• childhood onset GLUT1 deficiency syndrome 2 (Supportive), mode of inheritance: AD
• seizures, benign familial infantile, 2 (Strong), mode of inheritance: AD
• episodic kinesigenic dyskinesia 1 (Strong), mode of inheritance: AD
• infantile convulsions and choreoathetosis (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Episodic kinesigenic dyskinesia 1	AD	Neurologic	In Episodic kinesigenic dyskinesia, treatment with carbamazepine has been shown to particularly effective in affected individuals	Neurologic	22101681; 22120146; 22243967; 22543779; 22832103; 22870186; 23535490; 28331464
As with other disorders that manifest with seizures, maximal seizure control is beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRRT2 gene.

• Episodic kinesigenic dyskinesia (68 variants)
• not provided (21 variants)
• Episodic kinesigenic dyskinesia 1 (11 variants)
• Infantile convulsions and choreoathetosis (8 variants)
• Seizures, benign familial infantile, 2 (5 variants)
• Inborn genetic diseases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRRT2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	102	2	107
missense	4	9	227	25	1	266
nonsense	21	2				23
start loss			1			1
frameshift	56	17				73
inframe indel	2		7			9
splice donor/acceptor (+/-2bp)	4	1	6			11
splice region			6	8		14
non coding			3	30	3	36
Total	87	29	247	157	6

Highest pathogenic variant AF is 0.00000706

Variants in PRRT2

This is a list of pathogenic ClinVar variants found in the PRRT2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-29812021-T-C			Benign (Apr 16, 2019)
16-29812298-GGAGCTGTCCGGAGGCCGGCGTCGAGGTGA-G		not specified	Likely benign (Sep 12, 2017)
16-29812324-G-A			Uncertain significance (Aug 14, 2014)
16-29812342-G-A			Likely benign (May 23, 2018)
16-29812954-C-CCCTCCTCACCCCAAGCCTATCT		not specified	Likely benign (Jan 11, 2017)
16-29812974-TCTC-T			Likely benign (Nov 23, 2022)
16-29812987-C-CA			Uncertain significance (May 17, 2018)
16-29812989-G-A		Seizures, benign familial infantile, 2	Pathogenic (Jan 13, 2022)
16-29812997-C-T		not specified	Likely benign (Apr 06, 2017)
16-29812998-G-A		not specified	Likely benign (Aug 12, 2016)
16-29813023-C-T		not specified	Likely benign (Feb 12, 2016)
16-29813025-T-C			Benign/Likely benign (Aug 30, 2018)
16-29813029-GGCTCTCTCCCCTCTCCCATCTCAAGATGGCAGCCAGCA-G		Episodic kinesigenic dyskinesia	Uncertain significance (Aug 09, 2022)
16-29813030-G-C		not specified	Likely benign (Aug 31, 2016)
16-29813036-T-TC			Likely benign (Apr 05, 2018)
16-29813059-C-A		Episodic kinesigenic dyskinesia	Uncertain significance (Jan 25, 2023)
16-29813062-C-G		Episodic kinesigenic dyskinesia • not specified	Uncertain significance (Feb 04, 2020)
16-29813066-C-A		Episodic kinesigenic dyskinesia	Uncertain significance (Oct 22, 2021)
16-29813068-G-C		Episodic kinesigenic dyskinesia	Uncertain significance (Sep 14, 2023)
16-29813069-C-T		Episodic kinesigenic dyskinesia	Likely benign (Sep 10, 2020)
16-29813068-G-GCTCTGAGAT		Episodic kinesigenic dyskinesia • Episodic kinesigenic dyskinesia 1	Uncertain significance (Apr 14, 2023)
16-29813071-C-T		Episodic kinesigenic dyskinesia	Uncertain significance (Aug 31, 2023)
16-29813073-G-A		Episodic kinesigenic dyskinesia	Uncertain significance (Nov 06, 2023)
16-29813080-C-CT		Episodic kinesigenic dyskinesia	Pathogenic (Mar 08, 2023)
16-29813081-T-G			Likely benign (Jul 04, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRRT2	protein_coding	protein_coding	ENST00000567659	2	4025

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.579	0.419	125675	0	5	125680	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.225	213	222	0.957	0.0000115	2477
Missense in Polyphen		61	74.552	0.81823		842
Synonymous	-0.00263	95	95.0	1.00	0.00000529	904
Loss of Function	2.55	2	11.2	0.178	6.83e-7	119

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000626	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000563	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.0000563	0.0000544
South Asian	0.0000988	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As a component of the outer core of AMPAR complex, may be involved in synaptic transmission in the central nervous system. In hippocampal neurons, in presynaptic terminals, plays an important role in the final steps of neurotransmitter release, possibly by regulating Ca(2+)-sensing. In the cerebellum, may inhibit SNARE complex formation and downregulate short-term facilitation. {ECO:0000250|UniProtKB:E9PUL5}.
• Disease: DISEASE: Episodic kinesigenic dyskinesia 1 (EKD1) [MIM:128200]: An autosomal dominant neurologic condition characterized by recurrent and brief attacks of abnormal involuntary movements, triggered by sudden voluntary movement. These attacks usually have onset during childhood or early adulthood and can involve dystonic postures, chorea, or athetosis. {ECO:0000269|PubMed:22101681, ECO:0000269|PubMed:22120146, ECO:0000269|PubMed:22131361, ECO:0000269|PubMed:22209761, ECO:0000269|PubMed:25915028, ECO:0000269|PubMed:27172900}. Note=The disease is caused by mutations affecting the gene represented in this entry. Disease- causing mutations that produce truncation of the C-terminus of the protein alter subcellular location, from plasma membrane to cytoplasm (PubMed:22101681). {ECO:0000269|PubMed:22101681}.; DISEASE: Convulsions, familial infantile, with paroxysmal choreoathetosis (ICCA) [MIM:602066]: A syndrome characterized by clinical features of benign familial infantile seizures and episodic kinesigenic dyskinesia. Benign familial infantile seizures is a disorder characterized by afebrile seizures occurring during the first year of life, without neurologic sequelae. Paroxysmal choreoathetosis is a disorder of involuntary movements characterized by attacks that occur spontaneously or are induced by a variety of stimuli. {ECO:0000269|PubMed:22243967, ECO:0000269|PubMed:22832103}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Seizures, benign familial infantile, 2 (BFIS2) [MIM:605751]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS2 inheritance is autosomal dominant. {ECO:0000269|PubMed:22243967, ECO:0000269|PubMed:22399141, ECO:0000269|PubMed:22623405}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0808

Intolerance Scores

• loftool: 0.475
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.38

Haploinsufficiency Scores

• pHI: 0.307
• hipred: N
• hipred_score: 0.145
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.896

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Prrt2
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: synaptic vesicle fusion to presynaptic active zone membrane;negative regulation of SNARE complex assembly;neuromuscular process controlling posture;negative regulation of short-term synaptic potentiation
• Cellular component: plasma membrane;synaptic vesicle;postsynaptic density;membrane;integral component of membrane;cell junction;synaptic vesicle membrane;vesicle;presynaptic membrane;dendritic spine;axon terminus;postsynaptic membrane;presynapse
• Molecular function: syntaxin-1 binding