PRRT2

Summary

PRRT2 (proline rich transmembrane protein 2, HGNC:30500) is a protein-coding gene on chromosome 16p11.2, encoding Proline-rich transmembrane protein 2 (Q7Z6L0). As a component of the outer core of AMPAR complex, may be involved in synaptic transmission in the central nervous system. It is haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 112476 — RefSeq curated summary.

At a glance

• Gene–disease (curated): infantile convulsions and choreoathetosis (Definitive, ClinGen) — +9 more curated relationships
• Clinical variants (ClinVar): 31 total — 13 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 132
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_145239

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30500
Approved symbol	PRRT2
Name	proline rich transmembrane protein 2
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25513, DKFZp547J199, IFITMD1, FICCA, DSPB3, PKC, EKD1
Ensembl gene	ENSG00000167371
Ensembl biotype	protein_coding
OMIM	614386
Entrez	112476

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000300797, ENST00000358758, ENST00000562148, ENST00000567551, ENST00000567659, ENST00000568516, ENST00000572820, ENST00000636001, ENST00000636019, ENST00000636131, ENST00000636246, ENST00000636619, ENST00000636902, ENST00000637064, ENST00000637290, ENST00000637403, ENST00000637425, ENST00000637542, ENST00000637565, ENST00000637596, ENST00000647876, ENST00000861878

RefSeq mRNA: 3 — MANE Select: NM_145239 NM_001256442, NM_001256443, NM_145239

CCDS: CCDS10654, CCDS58445, CCDS58446

Canonical transcript exons

ENST00000358758 — 4 exons

Exon	Start	End
ENSE00001242697	29812990	29813933
ENSE00001321240	29814333	29814465
ENSE00001434189	29814628	29815881
ENSE00003793477	29812193	29812323

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0745 / max 784.6513, expressed in 1112 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153522	7.4503	774
153521	5.9185	872
153529	2.2195	210
153530	0.3857	142
153534	0.3258	127
153535	0.2605	115
153532	0.1213	43
153523	0.1052	53
153533	0.0859	41
153531	0.0717	31

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	99.48	gold quality
cerebellar hemisphere	UBERON:0002245	99.44	gold quality
cerebellar cortex	UBERON:0002129	99.43	gold quality
cerebellum	UBERON:0002037	99.25	gold quality
cerebellar vermis	UBERON:0004720	98.54	gold quality
right frontal lobe	UBERON:0002810	98.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.70	gold quality
primary visual cortex	UBERON:0002436	97.56	gold quality
cortical plate	UBERON:0005343	97.52	gold quality
middle temporal gyrus	UBERON:0002771	97.16	gold quality
prefrontal cortex	UBERON:0000451	97.05	gold quality
superior frontal gyrus	UBERON:0002661	96.97	gold quality
frontal cortex	UBERON:0001870	96.94	gold quality
frontal lobe	UBERON:0016525	96.94	gold quality
nucleus accumbens	UBERON:0001882	96.85	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.84	gold quality
neocortex	UBERON:0001950	96.75	gold quality
anterior cingulate cortex	UBERON:0009835	96.72	gold quality
postcentral gyrus	UBERON:0002581	96.56	gold quality
caudate nucleus	UBERON:0001873	96.51	gold quality
parietal lobe	UBERON:0001872	96.34	gold quality
putamen	UBERON:0001874	96.34	gold quality
occipital lobe	UBERON:0002021	96.28	gold quality
amygdala	UBERON:0001876	96.23	gold quality
left ovary	UBERON:0002119	96.18	gold quality
cerebral cortex	UBERON:0000956	96.16	gold quality
telencephalon	UBERON:0001893	95.93	gold quality
temporal lobe	UBERON:0001871	95.81	gold quality
forebrain	UBERON:0001890	95.57	gold quality
brain	UBERON:0000955	95.42	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	7.74
E-MTAB-6108	no	168.46
E-ANND-3	no	1.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting PRRT2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia (PMID:22101681)
• identified PRRT2 as the first causative gene of paroxysmal kinesigenic dyskinesias (PMID:22120146)
• The present study identifies PRRT2 as the gene mutated in a subset of Paroxysmal kinesigenic choreoathetosis (PKC), and suggests that PKC is genetically heterogeneous. (PMID:22131361)
• study shows that kinesigenic paroxysmal dyskinesia, paroxysmal choreoa and some other paroxysmal dyskinesia-related phenotypes are part of the same phenotypic spectrum, caused by mutations in PRRT2; this underscores the complexity of the phenotypic consequences of PRRT2 mutations (PMID:22209761)
• Mutations in PRRT2 cause both epilepsy and a movement disorder. Furthermore, PRRT2 mutations elicited pleiotropy in terms of both age of expression (infancy versus later childhood) and anatomical substrate (cortex versus basal ganglia). (PMID:22243967)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• This study identified 2 mutations of PRRT2 gene in this study. c.573dupT is novel. c.649dupC is the hot-spot mutation in Chinese paroxysmal kinesigenic dyskinesias patients. (PMID:22386217)
• Direct sequencing revealed that two mutations, c.649dupC and c.748C>T, were detected in all members of the paroxysmal kinesigenic dyskinesias (PKD) and benign familial infantile convulsions (BFIC) families. (PMID:22399141)
• This study reported a family diagnosed with infantile convulsions and paroxysmal choreoathetosis syndrome with an Arg217STOP mutation. (PMID:22464846)
• PRRT2 as the major gene for benign familial infantile seizures alone (PMID:22623405)
• Prevalence of PRRT2 mutations is selected for study in a European population of unrelated patients diagnosed with paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions with choreoathetosis (ICCA) syndrome. (PMID:22744660)
• PRRT2 mutations co-segregated with Paroxysmal dyskinesia in two families and occurred in two sporadic cases of Paroxysmal dyskinesia. (PMID:22752065)
• The results of this study confirmed that PRRT2 mutations cause PKD and ICPC in multi-ethnic populations including German, Turkish, and Russian (PMID:22782515)
• Mutants associated with paroxysmal kinesigenic dyskinesia with infantile convulsions C lead to dramatically reduced PRRT2 levels. (PMID:22832103)
• We propose that PRRT2 is a new gene for hemiplegic migraine. (PMID:22845787)
• PRRT2 mutations account for 61.5% (8 out of 13) of familial PKD/IC and 33.3% (5 out of 15) of apparently sporadic PKD/IC in the Taiwanese cohort. Most patients with the PRRT2 p.R217Pfs*8 mutation in Taiwan likely descend from a single common ancestor (PMID:22870186)
• PRRT2 mutations are the major cause of PKD or ICCA, but they do not seem to be involved in the etiology of febrile convulsions and migraine. (PMID:22875091)
• PRRT2 mutation c.649dupC is a frequent cause of benign familial infantile convulsions in families without paroxysmal kinesigenic dyskinesia. (PMID:22877996)
• We describe a family with characteristic Paroxysmal dyskinesia and a nonsense PRRT2 mutation (PMID:22902309)
• Our findings emphasize that PRRT2 mutations might be responsible of both benign familial infantile seizures and infantile convulsions and choreoathetosis (PMID:22902423)
• Heterozygous PRRT2 gene mutations also cause paroxysmal kinesigenic dyskinesia in African-Americans. (PMID:22985072)
• Missense mutations of the PRRT2 gene other than truncate and frameshift mutations were account for mild paroxysmal kinesigenic dyskinesia and/or infantile convulsions (PMID:23063574)
• The results confirm that a mutation of PRRT2,is a hotspot mutation resulting in benign infantile epilepsy or infantile convulsions with choreoathetosis syndrome regardless of the ethnic background. (PMID:23073245)
• PRRT2 mutations can occasionally cause hemiplegic migraine. (PMID:23077016)
• Two novel PRRT2 mutations are detected in families with infantile convulsions and paroxysmal dyskinesia with migraine. (PMID:23077017)
• PRRT2 mutations are present in the majority of benign familial infantile epilepsy and infantile convulsions and choreoathetosis families. (PMID:23077018)
• Mutation in PRRT2 gene is the causal gene in benign familial infantile convulsions without associated paroxysmal dyskinesia. (PMID:23077019)
• PRRT2 mutations are associated with paroxysmal kinesigenic dyskinesia and other episodic neurologic disorders. (PMID:23077024)
• PRRT2 mutations play a predominant role in benign familial infantile seizures, including febrile sizures, childhood absence seizures, migraine and hemiplegic migraine. (PMID:23077026)
• The present family provides novel evidence that homozygous PRRT2 mutations give rise to more severe BFIS/PKD disease and, thus, enlarges the clinical spectrum related to PRRT2 mutations. (PMID:23126439)
• Our study revealed that PRRT2 mutations are common in Japanese patients with benign infantile epilepsy, especially in patients with a family history of paroxysmal kinesigenic dyskinesia (PMID:23131349)
• This study identified the c.649dupC mutation in two cases and a novel c.133-136delCCAG mutation in one case in chinese patient. (PMID:23176561)
• This study demonistrated that Migraine with aura in a family with a PRRT2 mutation. (PMID:23180180)
• The coexistence of paroxysmal kinesigenic dyskinesia and hemiplegic migraine is reported in twins harboring a heterozygous mutation in PRRT2. (PMID:23182655)
• Five novel PRRT2 mutations showed varied inheritance patterns and phenotypes with distinct clinical characteristics in chorea patients. (PMID:23190448)
• This study showed that in one paroxysmal kinesigenic dyskinesia combined with infantile seizures family with mutations are exclusively found in two exons of the PRRT2 gene. (PMID:23299620)
• Review on the role of PRRT2 in benign familial infantile epilepsy, infantile convulsions with choreoathetosis syndrome, and paroxysmal kinesigenic dyskinesia. (PMID:23343561)
• study enlarges the clinical spectrum related to PPRT2 mutations and underscores the complexity of the phenotypic consequences of mutations in this gene (PMID:23352743)
• PRRT2 mutations are clustered in families with benign familial infantile seizures, although it is not found in this study’s series. (PMID:23360469)
• case series provides a detailed clinical description of patients with PRRT2-paroxysmal kinesigenic dyskinesia, and reports a spectrum of disease-causing mutations, thereby expanding both the clinical phenotype and mutation spectrum of disease (PMID:23363396)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prrt2	ENSDARG00000103588
mus_musculus	Prrt2	ENSMUSG00000045114
rattus_norvegicus	Prrt2	ENSRNOG00000029366

Paralogs (4): TRARG1 (ENSG00000184811), PRRT1 (ENSG00000204314), TMEM233 (ENSG00000224982), PRRT1B (ENSG00000283526)

Protein

Protein identifiers

Proline-rich transmembrane protein 2 — Q7Z6L0 (reviewed: Q7Z6L0)

Alternative names: Dispanin subfamily B member 3

All UniProt accessions (10): A0A1B0GTE9, A0A1B0GTP1, A0A1B0GTR2, A0A1B0GTS0, A0A1B0GU25, A0A1B0GU37, A0A1B0GUR0, A0A1B0GUW9, Q7Z6L0, H3BN10

UniProt curated annotations — full annotation on UniProt →

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 down-regulate short-term facilitation.

Subunit / interactions. Component of the outer core of AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing. Interacts with intersectin 1/ITSN1. Interacts with SNARE complex components, including SNAP25, STX1A, SYT1 and SYT2; this interaction may inhibit SNARE complex formation.

Subcellular location. Cell membrane. Presynaptic cell membrane. Synapse. Cell projection. Axon. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle membrane. Postsynaptic density membrane. Dendritic spine.

Disease relevance. Episodic kinesigenic dyskinesia 1 (EKD1) [MIM:128200] An autosomal dominant form of paroxysmal kinesigenic dyskinesia, a 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. The disease is caused by variants 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. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the CD225/Dispanin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z6L0-1	1	yes
Q7Z6L0-2	2
Q7Z6L0-3	3

RefSeq proteins (3): NP_001243371, NP_001243372, NP_660282* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007593	CD225/Dispanin_fam	Family
IPR051423	CD225/Dispanin	Family

Pfam: PF04505

UniProt features (36 total): sequence variant 15, modified residue 6, topological domain 3, sequence conflict 3, compositionally biased region 3, splice variant 2, chain 1, intramembrane region 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z6L0-F1	51.86	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 28, 74, 238, 240, 248, 249

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 392 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, CREL_01, GOBP_REGULATION_OF_VESICLE_FUSION, GOBP_VESICLE_ORGANIZATION, CMYB_01, GOBP_MEMBRANE_FUSION, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, TTGGGAG_MIR150, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION

GO Biological Process (5): synaptic vesicle fusion to presynaptic active zone membrane (GO:0031629), negative regulation of SNARE complex assembly (GO:0035544), neuromuscular process controlling posture (GO:0050884), regulation of calcium-dependent activation of synaptic vesicle fusion (GO:0150037), negative regulation of short-term synaptic potentiation (GO:1905513)

GO Molecular Function (2): syntaxin-1 binding (GO:0017075), protein binding (GO:0005515)

GO Cellular Component (16): plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), membrane (GO:0016020), synaptic vesicle membrane (GO:0030672), vesicle (GO:0031982), presynaptic membrane (GO:0042734), dendritic spine (GO:0043197), axon terminus (GO:0043679), presynapse (GO:0098793), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), axon (GO:0030424), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202), postsynaptic membrane (GO:0045211)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
presynapse	3
cellular anatomical structure	3
synaptic membrane	2
postsynapse	2
synapse	2
synaptic vesicle exocytosis	1
synaptic vesicle membrane organization	1
vesicle fusion to plasma membrane	1
negative regulation of protein-containing complex assembly	1
negative regulation of vesicle fusion	1
SNARE complex assembly	1
regulation of SNARE complex assembly	1
musculoskeletal movement	1
neuromuscular process	1
regulation of synaptic vesicle fusion to presynaptic active zone membrane	1
calcium-dependent activation of synaptic vesicle fusion	1
negative regulation of biological process	1
regulation of short-term synaptic potentiation	1
short-term synaptic potentiation	1
syntaxin binding	1
binding	1
membrane	1
cell periphery	1
exocytic vesicle	1
synaptic vesicle	1
exocytic vesicle membrane	1
membrane-bounded organelle	1
dendrite	1
neuron spine	1
neuron projection terminus	1
distal axon	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
neuron projection	1
cytoplasm	1
intracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

1482 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRRT2	SNAP25	P13795	972
PRRT2	PNKD	Q8N490	963
PRRT2	SCN2A	Q99250	898
PRRT2	SYT1	P21579	802
PRRT2	SCN1A	P35498	720
PRRT2	SCN1B	Q07699	680
PRRT2	ATP1A2	P50993	669
PRRT2	KCNQ2	O43526	663
PRRT2	CACNA1A	P78510	661
PRRT2	PCDH19	Q8TAB3	643
PRRT2	CIZ1	Q9ULV3	624
PRRT2	STX1B	P61266	623
PRRT2	SCN8A	Q9UQD0	620
PRRT2	ATP1A3	P13637	608
PRRT2	KCNT1	Q5JUK3	604

IntAct

27 interactions, top by confidence:

A	B	Type	Score
SMIM5	PRRT2	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	PRRT2	psi-mi:“MI:0915”(physical association)	0.560
PRRT2	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
MFSD14B	PRRT2	psi-mi:“MI:0915”(physical association)	0.560
PRRT2	GPRC5D	psi-mi:“MI:0915”(physical association)	0.560
AQP6	PRRT2	psi-mi:“MI:0915”(physical association)	0.560
PRRT2	NDUFS4	psi-mi:“MI:0914”(association)	0.530
PRRT2	NDUFB3	psi-mi:“MI:0914”(association)	0.530
PRRT2	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
PRRT2	SMIM5	psi-mi:“MI:0915”(physical association)	0.000
PRRT2	SLC10A6	psi-mi:“MI:0915”(physical association)	0.000
PRRT2	TLCD4	psi-mi:“MI:0915”(physical association)	0.000
PRRT2	MFSD14B	psi-mi:“MI:0915”(physical association)	0.000
PRRT2	AQP6	psi-mi:“MI:0915”(physical association)	0.000
PRRT2	GPRC5D	psi-mi:“MI:0915”(physical association)	0.000
SNAP25	PRRT2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): NDUFV3 (Affinity Capture-MS), CALML5 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), NDUFS4 (Affinity Capture-MS), DDI1 (Affinity Capture-MS), LCLAT1 (Affinity Capture-MS), NDUFS4 (Affinity Capture-MS), NDUFB8 (Affinity Capture-MS), DDI1 (Affinity Capture-MS), NDUFB9 (Affinity Capture-MS), LCLAT1 (Affinity Capture-MS), NDUFV3 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RQ45, A0A1B0GWB2, A2A9T0, A6QPA0, A7MCY6, D3ZFB6, E9PUL5, E9Q0B3, F5GYI3, F5H4A9, J3QNX5, O70142, P0C1G7, P81408, P97764, P98077, Q148V8, Q15654, Q2KI80, Q3SX26, Q3SZL6, Q4V9L6, Q5FVJ4, Q5FW56, Q5RAC1, Q5T7N3, Q6DG50, Q6PAJ3, Q6PJ61, Q6ZMQ8, Q6ZNR0, Q6ZRV2, Q75VX8, Q7Z6L0, Q86UK7, Q86VE0, Q8BGW2, Q8BRJ3, Q8BX43, Q8C0R7

Diamond homologs: B4DJY2, D3Z1U7, D3ZFB6, E9PUL5, Q2MHH0, Q5RAC1, Q6DFT4, Q7Z6L0, Q8C838, Q8IXB3, Q91499, Q6ZNR0, Q8C581, A6NMD0, A6NNB3, C9JQL5, O88728, P13164, P26376, Q01628, Q01629, Q8BR26, Q99J93, Q9CQW9, Q9D103

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

31 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	5
Uncertain significance	6
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (18)

Variant ID	HGVS	Classification
1013117	GRCh37/hg19 16p11.2(chr16:29824309-29825959)x1	Pathogenic
1333727	NM_145239.3(PRRT2):c.-65-1G>A	Pathogenic
1460111	NC_000016.9:g.(?29825620)(29825969_?)del	Pathogenic
1802974	NM_145239.3(PRRT2):c.397del (p.Glu133fs)	Pathogenic
1809610	NM_145239.3(PRRT2):c.46G>T (p.Glu16Ter)	Pathogenic
2427334	NC_000016.9:g.(?29824744)(29826559_?)del	Pathogenic
31172	NM_145239.3(PRRT2):c.950G>A (p.Ser317Asn)	Pathogenic
31173	NM_145239.3(PRRT2):c.879+5G>A	Pathogenic
31176	NM_145239.3(PRRT2):c.487C>T (p.Gln163Ter)	Pathogenic
39755	NM_145239.3(PRRT2):c.291del (p.Asn98fs)	Pathogenic
4847055	NC_000016.9:g.(?29823513)(29827203_?)del	Pathogenic
813798	NC_000016.10:g.(?29813054)(29813955_?)del	Pathogenic
872059	GRCh37/hg19 16p11.2(chr16:29824376-29825959)x1	Pathogenic
1707531	NM_145239.3(PRRT2):c.914G>A (p.Gly305Glu)	Likely pathogenic
1709866	NM_145239.3(PRRT2):c.515_516del (p.Leu171_Ser172insTer)	Likely pathogenic
4796776	NM_145239.3(PRRT2):c.827G>A (p.Cys276Tyr)	Likely pathogenic
495288	NC_000016.10:g.(?29824300)(29826034_?)del	Likely pathogenic
976325	NM_145239.3(PRRT2):c.341_342del (p.Val114fs)	Likely pathogenic

SpliceAI

750 predictions. Top by Δscore:

Variant	Effect	Δscore
16:29814462:GGCG:G	donor_gain	1.0000
16:29814463:GCG:G	donor_gain	1.0000
16:29814463:GCGG:G	donor_gain	1.0000
16:29814464:CGGTG:C	donor_loss	1.0000
16:29814465:GGT:G	donor_loss	1.0000
16:29814466:G:GA	donor_loss	1.0000
16:29814466:G:GG	donor_gain	1.0000
16:29814467:T:G	donor_loss	1.0000
16:29812322:AG:A	donor_loss	0.9900
16:29812324:G:A	donor_loss	0.9900
16:29812325:T:G	donor_loss	0.9900
16:29812397:G:T	donor_gain	0.9900
16:29814319:C:CA	acceptor_gain	0.9900
16:29814461:AGGCG:A	donor_gain	0.9900
16:29814462:GGCGG:G	donor_gain	0.9900
16:29814463:GCGGT:G	donor_loss	0.9900
16:29815830:A:AG	acceptor_gain	0.9900
16:29815830:ATGCC:A	acceptor_gain	0.9900
16:29815831:T:G	acceptor_gain	0.9900
16:29815834:C:A	acceptor_gain	0.9900
16:29815835:G:A	acceptor_gain	0.9900
16:29812324:G:GG	donor_gain	0.9800
16:29812398:A:T	donor_gain	0.9800
16:29814319:C:A	acceptor_gain	0.9800
16:29814325:A:AG	acceptor_gain	0.9800
16:29814326:A:G	acceptor_gain	0.9800
16:29814464:CG:C	donor_gain	0.9800
16:29814465:GG:G	donor_gain	0.9800
16:29814468:GA:G	donor_loss	0.9800
16:29815827:T:A	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000293543 (16:29812782 T>A), RS1000752460 (16:29812182 G>A), RS1000923002 (16:29812342 G>A,C), RS1001591175 (16:29812468 C>A,G), RS1001993455 (16:29813593 A>C), RS1002428298 (16:29812669 G>A,C), RS1002696915 (16:29815594 C>T), RS1003215218 (16:29810719 C>G,T), RS1003453664 (16:29811686 TGCCCAGCTCCTCC>T), RS1003692660 (16:29814255 G>C), RS1004449390 (16:29815432 G>A), RS1004492608 (16:29814604 G>A,C), RS1004544963 (16:29814882 C>T), RS1005295619 (16:29811505 T>C), RS1005310278 (16:29811319 G>A,C)

Disease associations

OMIM: gene MIM:614386 | disease phenotypes: MIM:605751, MIM:602066, MIM:128200

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary neurological disease	Definitive	Autosomal recessive
PRRT2-associated paroxysmal movement disorder	Definitive	Autosomal dominant
infantile convulsions and choreoathetosis	Definitive	Autosomal dominant
episodic kinesigenic dyskinesia 1	Strong	Autosomal dominant
seizures, benign familial infantile, 2	Strong	Autosomal dominant
neurodevelopmental disorder	Moderate	Autosomal recessive
benign familial infantile epilepsy	Supportive	Autosomal dominant
familial or sporadic hemiplegic migraine	Supportive	Autosomal dominant
paroxysmal nonkinesigenic dyskinesia 1	Supportive	Autosomal dominant
childhood onset GLUT1 deficiency syndrome 2	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
infantile convulsions and choreoathetosis	Definitive	AD

Mondo (12): seizures, benign familial infantile, 2 (MONDO:0011593), infantile convulsions and choreoathetosis (MONDO:0011178), episodic kinesigenic dyskinesia (MONDO:0044202), episodic kinesigenic dyskinesia 1 (MONDO:0100352), hereditary neurological disease (MONDO:0100545), PRRT2-associated paroxysmal movement disorder (MONDO:0100556), (MONDO:0007494), benign familial infantile epilepsy (MONDO:0017615), familial or sporadic hemiplegic migraine (MONDO:0018925), (MONDO:0007326), childhood onset GLUT1 deficiency syndrome 2 (MONDO:0012805), neurodevelopmental disorder (MONDO:0700092)

Orphanet (3): Self-limited infantile epilepsy (Orphanet:306), Infantile convulsions and choreoathetosis (Orphanet:31709), Paroxysmal kinesigenic dyskinesia (Orphanet:98809)

HPO phenotypes

132 total (30 of 132 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000211	Trismus
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000473	Torticollis
HP:0000575	Scotoma
HP:0000651	Diplopia
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000961	Cyanosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001259	Coma
HP:0001260	Dysarthria
HP:0001266	Choreoathetosis
HP:0001269	Hemiparesis
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001289	Confusion
HP:0001304	Torsion dystonia
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001328	Specific learning disability
HP:0001332	Dystonia
HP:0001337	Tremor

GWAS associations

0 associations (top):

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C565296	Convulsions, Benign Familial Infantile, 2 (supp.)
C564288	Dystonia 18 (supp.)
C537180	Familial paroxysmal dystonia (supp.)
C535522	Infantile convulsions and paroxysmal choreoathetosis, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	3
trichostatin A	affects cotreatment, decreases expression	2
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Estradiol	affects expression	1
Hydrogen Peroxide	affects expression	1
Naphthoquinones	increases expression	1
Phenylmercuric Acetate	affects cotreatment, decreases expression	1
Polychlorinated Biphenyls	affects expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3ZJ	ZZUi022-A	Induced pluripotent stem cell	Male
CVCL_B2C8	Abcam HeLa PRRT2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

204 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06955624	Not specified	RECRUITING	Use of Omics Methods to Classify Variations of Uncertain Significance and Improve Diagnosis of Neurogenetic Diseases
NCT04112862	EARLY_PHASE1	COMPLETED	Sodium Lactate Infusion in GLUT1DS Patients
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism