PPP1R16A
Chr 8protein phosphatase 1 regulatory subunit 16A
Also known as: MYPT3
The protein functions as a myosin phosphatase targeting subunit that directs protein phosphatase 1 to specific substrates including myosin light chains, regulating muscle contraction and intracellular movement. Mutations in PPP1R16A cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in early childhood. The gene shows moderate constraint to loss-of-function variation, suggesting some intolerance to complete protein loss.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
184 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 | 50 | 0 | 50 |
Likely Pathogenic | 0 | 0 | 5 | 0 | 5 |
VUS | 0 | 97 | 14 | 0 | 111 |
Likely Benign | 0 | 6 | 1 | 2 | 9 |
Benign | 0 | 0 | 2 | 0 | 2 |
| Total | 0 | 103 | 72 | 2 | 177 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PPP1R16A · 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