PUM3
Chr 9pumilio RNA binding family member 3
Also known as: HA-8, HLA-HA8, KIAA0020, PEN, PUF-A, PUF6, XTP5
The protein binds RNA and regulates translation, while also inhibiting PARP1 poly(ADP-ribosyl)ation activity and protecting PARP1 from degradation following DNA damage. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, typically presenting in infancy with severe intellectual disability, seizures, and progressive brain atrophy. This gene shows minimal constraint against loss-of-function variants, consistent with recessive inheritance patterns.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
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
PUM3 · 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