PLRG1
Chr 4pleiotropic regulator 1
Also known as: Cwc1, PRL1, PRP46, PRPF46, TANGO4
The protein is a core component of the CDC5L complex within the spliceosome, functioning in pre-mRNA splicing and alternative splice site selection. Mutations cause neurodevelopmental disorders with intellectual disability, seizures, and multiple congenital anomalies, inherited in an autosomal recessive pattern. This gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
97 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 25 | 0 | 25 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 44 | 2 | 0 | 46 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 46 | 31 | 1 | 78 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PLRG1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools