PRRT1

Summary

PRRT1 (proline rich transmembrane protein 1, HGNC:13943) is a protein-coding gene on chromosome 6p21.32, encoding Proline-rich transmembrane protein 1 (Q99946). Required to maintain a pool of extrasynaptic AMPA-regulated glutamate receptors (AMPAR) which is necessary for synapse development and function.

Enables identical protein binding activity. Predicted to be involved in several processes, including long-term synaptic depression; protein localization to cell surface; and regulation of AMPA receptor activity. Predicted to act upstream of or within several processes, including learning or memory; long-term synaptic potentiation; and synapse organization. Predicted to be located in plasma membrane and synaptic vesicle membrane. Predicted to be active in glutamatergic synapse and postsynaptic density membrane.

Source: NCBI Gene 80863 — RefSeq curated summary.

At a glance

• GWAS associations: 28
• Clinical variants (ClinVar): 27 total
• MANE Select transcript: NM_030651

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13943
Approved symbol	PRRT1
Name	proline rich transmembrane protein 1
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	NG5, IFITMD7, DSPD1, SynDIG4
Ensembl gene	ENSG00000204314
Ensembl biotype	protein_coding
OMIM	618297
Entrez	80863

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000211413, ENST00000375150, ENST00000467780, ENST00000472641, ENST00000495191, ENST00000897965, ENST00000897966

RefSeq mRNA: 2 — MANE Select: NM_030651 NM_001363780, NM_030651

CCDS: CCDS4739

Canonical transcript exons

ENST00000211413 — 4 exons

Exon	Start	End
ENSE00001602962	32150368	32150906
ENSE00001932420	32151809	32151939
ENSE00003843483	32148363	32149398
ENSE00003973528	32149537	32149722

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.02.

FANTOM5 (CAGE): breadth broad, TPM avg 15.2155 / max 678.1095, expressed in 633 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
72893	14.9683	621
72894	0.1421	64
72889	0.0533	30
72890	0.0518	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.02	gold quality
cerebellar hemisphere	UBERON:0002245	97.63	gold quality
cerebellum	UBERON:0002037	97.62	gold quality
cerebellar cortex	UBERON:0002129	97.62	gold quality
superior frontal gyrus	UBERON:0002661	97.55	gold quality
right frontal lobe	UBERON:0002810	97.38	gold quality
primary visual cortex	UBERON:0002436	97.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.69	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.50	gold quality
Ammon’s horn	UBERON:0001954	95.71	gold quality
anterior cingulate cortex	UBERON:0009835	95.71	gold quality
nucleus accumbens	UBERON:0001882	95.53	gold quality
temporal lobe	UBERON:0001871	94.70	gold quality
amygdala	UBERON:0001876	94.65	gold quality
putamen	UBERON:0001874	94.61	gold quality
caudate nucleus	UBERON:0001873	94.33	gold quality
hypothalamus	UBERON:0001898	94.00	gold quality
brain	UBERON:0000955	92.50	gold quality
telencephalon	UBERON:0001893	92.34	gold quality
cerebral cortex	UBERON:0000956	91.78	gold quality
left ovary	UBERON:0002119	90.39	gold quality
right ovary	UBERON:0002118	90.24	gold quality
ovary	UBERON:0000992	89.87	gold quality
substantia nigra	UBERON:0002038	89.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.53	gold quality
adenohypophysis	UBERON:0002196	88.05	gold quality
pituitary gland	UBERON:0000007	87.82	gold quality
frontal cortex	UBERON:0001870	86.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.00	gold quality
mucosa of stomach	UBERON:0001199	83.36	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting PRRT1, 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-548AW	99.99	72.57	3559
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-6893-5P	99.31	66.25	2119

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prrt1	ENSMUSG00000015476
rattus_norvegicus	Prrt1	ENSRNOG00000000433

Paralogs (4): PRRT2 (ENSG00000167371), TRARG1 (ENSG00000184811), TMEM233 (ENSG00000224982), PRRT1B (ENSG00000283526)

Protein

Protein identifiers

Proline-rich transmembrane protein 1 — Q99946 (reviewed: Q99946)

Alternative names: Dispanin subfamily D member 1, Synapse differentiation-induced protein 4

All UniProt accessions (3): Q99946, A0A1U9X8D6, A0A8Z5AAT7

UniProt curated annotations — full annotation on UniProt →

Function. Required to maintain a pool of extrasynaptic AMPA-regulated glutamate receptors (AMPAR) which is necessary for synapse development and function. Regulates basal AMPAR function and synaptic transmission during development but is dispensable at mature hippocampal synapses. Plays a role in regulating basal phosphorylation levels of glutamate receptor GRIA1 and promotes GRIA1 and GRIA2 cell surface expression.

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.

Subcellular location. Cell membrane. Synapse.

Similarity. Belongs to the CD225/Dispanin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99946-1	1	yes
Q99946-2	2

RefSeq proteins (2): NP_001350709, NP_085154* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF04505

UniProt features (15 total): compositionally biased region 4, topological domain 3, sequence conflict 2, chain 1, splice variant 1, sequence variant 1, transmembrane region 1, intramembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99946-F1	53.00	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 150 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_COGNITION, GOBP_BEHAVIOR, XU_GH1_AUTOCRINE_TARGETS_UP, DARWICHE_PAPILLOMA_PROGRESSION_RISK, EFC_Q6, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_LONG_TERM_SYNAPTIC_DEPRESSION, GOBP_NEGATIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION, GOBP_SYNAPTIC_SIGNALING, GOBP_LONG_TERM_SYNAPTIC_POTENTIATION, GOBP_PROTEIN_LOCALIZATION_TO_CELL_SURFACE, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION

GO Biological Process (8): protein phosphorylation (GO:0006468), learning or memory (GO:0007611), protein localization to cell surface (GO:0034394), synapse organization (GO:0050808), long-term synaptic potentiation (GO:0060291), long-term synaptic depression (GO:0060292), regulation of AMPA receptor activity (GO:2000311), intracellular protein localization (GO:0008104)

GO Molecular Function (2): signaling receptor regulator activity (GO:0030545), identical protein binding (GO:0042802)

GO Cellular Component (6): membrane (GO:0016020), synaptic vesicle membrane (GO:0030672), postsynaptic density membrane (GO:0098839), glutamatergic synapse (GO:0098978), plasma membrane (GO:0005886), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of synaptic plasticity	2
phosphorylation	1
protein modification process	1
behavior	1
cognition	1
intracellular protein localization	1
cell junction organization	1
positive regulation of synaptic transmission	1
negative regulation of synaptic transmission	1
AMPA glutamate receptor activity	1
regulation of transmembrane transporter activity	1
regulation of neurotransmitter receptor activity	1
macromolecule localization	1
signaling receptor activity	1
molecular function regulator activity	1
protein binding	1
cellular anatomical structure	1
synaptic vesicle	1
exocytic vesicle membrane	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
synapse	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

947 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRRT1	DXO	O77932	695
PRRT1	GPSM3	Q9Y4H4	641
PRRT1	EGFL8	Q99944	506
PRRT1	ZBTB12	Q9Y330	404
PRRT1	PGGHG	Q32M88	377
PRRT1	FKBPL	Q9UIM3	377
PRRT1	TMEM233	B4DJY2	370
PRRT1	SKIC2	Q15477	367
PRRT1	KRT37	O76014	349
PRRT1	GSG1	Q2KHT4	330
PRRT1	AK9	Q5TCS8	327
PRRT1	PRRT1B	A0A1B0GWB2	324
PRRT1	AK8	Q96MA6	318
PRRT1	PPT2	Q9UMR5	318
PRRT1	PRRT2	Q7Z6L0	304

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PRRT1	ARL6IP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): PRRT1 (Two-hybrid), PRRT1 (Two-hybrid), PRRT1 (Two-hybrid), PRRT1 (Two-hybrid), REEP6 (Affinity Capture-MS), ARL6IP5 (Affinity Capture-MS), C10orf35 (Affinity Capture-MS), PRRT1 (Affinity Capture-MS)

ESM2 similar proteins: E7FBS9, O02754, O08789, O35449, O88470, P02831, P18111, P42128, P43241, P47902, P51179, P55318, P58012, P85037, Q01167, Q04649, Q08DG7, Q2THW0, Q2THW8, Q2THX0, Q3UCQ1, Q3Y598, Q4VUF1, Q5I1X5, Q5VYV0, Q5Y5T5, Q61850, Q63246, Q64733, Q6MG82, Q6NSM8, Q6P4S6, Q6VFT6, Q6VFT7, Q7TQ40, Q8WUF5, Q92570, Q96NZ1, Q96T25, Q99583

Diamond homologs: A0A1B0GWB2, O35449, Q6MG82, Q99946, A2ANU3, A4IFJ1, A6NDD5, Q08DM6, Q3USQ7, Q4R532, Q58DZ9, Q5TZE2, Q6ZNR0, Q8C581, Q9H7V2, Q6DFT4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

315 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32149394:CGCAC:C	acceptor_gain	1.0000
6:32149395:GCAC:G	acceptor_gain	1.0000
6:32149396:CAC:C	acceptor_gain	1.0000
6:32149396:CACC:C	acceptor_gain	1.0000
6:32149397:AC:A	acceptor_gain	1.0000
6:32149397:ACCTA:A	acceptor_loss	1.0000
6:32149398:CC:C	acceptor_gain	1.0000
6:32149398:CCTA:C	acceptor_loss	1.0000
6:32149399:C:CC	acceptor_gain	1.0000
6:32149400:T:A	acceptor_loss	1.0000
6:32149402:C:CT	acceptor_gain	1.0000
6:32149403:G:T	acceptor_gain	1.0000
6:32149532:CCTAC:C	donor_loss	1.0000
6:32149533:CTA:C	donor_loss	1.0000
6:32149534:TA:T	donor_loss	1.0000
6:32149535:A:AC	donor_gain	1.0000
6:32149535:ACCT:A	donor_loss	1.0000
6:32149536:C:CC	donor_gain	1.0000
6:32149536:C:CG	donor_loss	1.0000
6:32149666:C:CT	acceptor_gain	1.0000
6:32149667:G:T	acceptor_gain	1.0000
6:32151804:TTTA:T	donor_loss	1.0000
6:32151806:TA:T	donor_loss	1.0000
6:32151807:A:T	donor_loss	1.0000
6:32151808:C:CA	donor_loss	1.0000
6:32151808:CCTGA:C	donor_gain	1.0000
6:32149412:G:C	acceptor_gain	0.9900
6:32149412:G:GC	acceptor_gain	0.9900
6:32149536:CCT:C	donor_gain	0.9900
6:32149536:CCTG:C	donor_gain	0.9900

AlphaMissense

1913 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32149277:A:G	L289P	1.000
6:32149277:A:T	L289H	1.000
6:32149280:A:T	I288N	1.000
6:32149287:A:G	C286R	1.000
6:32149289:A:G	L285P	1.000
6:32149289:A:T	L285H	1.000
6:32149295:A:C	M283R	1.000
6:32149298:G:T	A282D	1.000
6:32149299:C:G	A282P	1.000
6:32149301:G:T	A281E	1.000
6:32149302:C:G	A281P	1.000
6:32149304:A:T	I280N	1.000
6:32149307:C:A	G279V	1.000
6:32149307:C:T	G279D	1.000
6:32149308:C:A	G279C	1.000
6:32149308:C:G	G279R	1.000
6:32149310:A:T	V278E	1.000
6:32149313:G:T	A277D	1.000
6:32149314:C:G	A277P	1.000
6:32149316:A:G	L276P	1.000
6:32149316:A:T	L276Q	1.000
6:32149319:G:A	S275F	1.000
6:32149319:G:T	S275Y	1.000
6:32149320:A:G	S275P	1.000
6:32149322:A:T	I274N	1.000
6:32149324:G:C	F273L	1.000
6:32149324:G:T	F273L	1.000
6:32149325:A:G	F273S	1.000
6:32149326:A:G	F273L	1.000
6:32149328:G:A	S272F	1.000

dbSNP variants (sampled 300 via entrez): RS1000611882 (6:32151289 A>G), RS1000940084 (6:32151594 T>C,G), RS1001946289 (6:32153513 T>A,G), RS1002397740 (6:32153171 T>G), RS1002690219 (6:32153471 G>A), RS1003077323 (6:32148575 G>A), RS1003108353 (6:32148284 A>T), RS1005386739 (6:32150193 G>T), RS1005768534 (6:32150552 G>T), RS1006359000 (6:32148510 T>C), RS1006534909 (6:32151602 A>G), RS1006753635 (6:32152158 C>G,T), RS1006805041 (6:32148188 G>A,C), RS1007110491 (6:32151822 T>A,G), RS1008484977 (6:32151980 A>C,G,T)

Disease associations

OMIM: gene MIM:618297 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST001812_2	Epstein-Barr virus immune response (EBNA-1)	2.000000e-10
GCST001848_150	IgG glycosylation	4.000000e-06
GCST001848_337	IgG glycosylation	4.000000e-06
GCST001848_607	IgG glycosylation	4.000000e-08
GCST001942_21	Prostate cancer	5.000000e-09
GCST004131_25	Inflammatory bowel disease	2.000000e-31
GCST004133_79	Ulcerative colitis	5.000000e-65
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_118	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_154	Autism spectrum disorder or schizophrenia	3.000000e-08
GCST004521_17	Autism spectrum disorder or schizophrenia	2.000000e-12
GCST004521_170	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_173	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_213	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_226	Autism spectrum disorder or schizophrenia	4.000000e-12
GCST004521_276	Autism spectrum disorder or schizophrenia	5.000000e-10
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_45	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST005542_1	Sarcoidosis (non-Lofgren’s syndrome without extrapulmonary manifestations)	7.000000e-06
GCST005580_265	Intraocular pressure	3.000000e-10
GCST007267_215	Systolic blood pressure	6.000000e-15
GCST012227_766	Hip circumference adjusted for BMI	4.000000e-16
GCST012230_414	Waist-to-hip ratio adjusted for BMI	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement
EFO:0004695	intraocular pressure measurement
EFO:0006335	systolic blood pressure
EFO:0008039	BMI-adjusted hip circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
Valproic Acid	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
ferrous chloride	decreases expression	1
entinostat	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	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	affects methylation, increases abundance	1
Arsenic	affects methylation	1
Camptothecin	increases expression	1
Fonofos	increases methylation	1
Folic Acid	decreases expression	1
Lead	affects expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Testosterone	decreases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	affects methylation, increases abundance	1

Clinical trials (associated diseases)

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