PRRT1

Chr 6

proline rich transmembrane protein 1

NCBI Gene: 80863ENSG00000204314UniProt: Q99946

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

0
ClinVar variants
0
Pathogenic / LP
0.30
pLI score
0
Active trials
Clinical Summary— PRRT1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.77LOEUF
pLI 0.298
Z-score 2.00
OE 0.25 (0.10–0.77)
Tolerant

Typical tolerance to LoF variation

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.
3.03Z-score
OE missense 0.35 (0.28–0.43)
59 obs / 170.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.25 (0.10–0.77)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.35 (0.28–0.43)
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.0.51
0≤1.21.6
LoF obs/exp: 2 / 8.2Missense obs/exp: 59 / 170.1Syn Z: 3.47

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PRRT1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Loss of SynDIG4/PRRT1 alters distribution of AMPA receptors in Rab4- and Rab11-positive endosomes and impairs basal AMPA receptor recycling.
He CW et al.·Front Pharmacol
2025🔓 Open Access
Uncovering the epigenetic regulatory clues of PRRT1 in Alzheimer's disease: a strategy integrating multi-omics analysis with explainable machine learning.
Wang F et al.·Alzheimers Res Ther
2025🔓 Open Access
Mutually Dependent Clustering of SynDIG4/PRRT1 and AMPA Receptor Subunits GluA1 and GluA2 in Heterologous Cells and Primary Neurons.
Plambeck KE et al.·Front Mol Neurosci
2022🔓 Open Access
Interaction and Subcellular Association of PRRT1/SynDIG4 With AMPA Receptors.
Martin EE et al.·Front Synaptic Neurosci
2021🔓 Open Access
PRRT1 regulates basal and plasticity-induced AMPA receptor trafficking.
Troyano-Rodriguez E et al.·Mol Cell Neurosci
2019
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools