IQSEC2
Chr XX-linkedIQ motif and Sec7 domain ArfGEF 2
Also known as: BRAG1, IQ-ArfGEF, MRX1, MRX18, MRX78, NEDXSB, XLID1
The protein functions as a guanine nucleotide exchange factor for ARF GTP-binding proteins and is a component of the postsynaptic density at excitatory synapses, where it regulates cytoskeletal and synaptic organization through activation of ARF1 and ARF6. Mutations cause X-linked intellectual developmental disorder, predominantly through loss-of-function mechanisms given the gene's high constraint against such variants (pLI 0.999, LOEUF 0.133). The condition follows X-linked dominant inheritance.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Extremely missense-constrained (top ~0.01%)
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
IQSEC2 · 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