ARPP21
Chr 3cAMP regulated phosphoprotein 21
Also known as: ARPP-21, R3HDM3, RCS, TARPP
The protein is a cAMP-regulated phosphoprotein enriched in the caudate nucleus and cerebellar cortex that may inhibit calmodulin-dependent enzymes such as calcineurin in neurons and regulate dopamine effects in the basal ganglia. Mutations cause autosomal recessive neurodevelopmental disorders affecting the brain. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.
Limited evidence — not for standalone diagnostic reporting
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is dominant-negative.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ARPP21 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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