GPS2
Chr 17G protein pathway suppressor 2
Also known as: AMF-1
GPS2 encodes a key regulator of inflammation, lipid metabolism and mitochondrial homeostasis that acts by inhibiting the ubiquitin-conjugating enzyme UBE2N/Ubc13 and functions as both a transcriptional coactivator and corepressor depending on cellular context. Mutations cause autosomal recessive intellectual disability with microcephaly, seizures, and growth retardation. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.583), suggesting some tolerance to functional disruption.
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
GPS2 · 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
External Resources
Links to major genomics databases and tools