IQSEC2 Gene
IQ Motif and Sec7 Domain 2
Gene Information Card
| Symbol | IQSEC2 |
|---|---|
| Full Name | IQ motif and Sec7 domain 2 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.22 |
| NCBI Gene ID | 23096 ncbi.nlm.nih.gov/gene/23096 |
| Ensembl ID | ENSG00000124313 |
| UniProt ID | Q5JU85 |
| OMIM ID | 300522 |
| HGNC ID | 29059 |
| Aliases | BRAG2, IQ-ArfGEF, KIAA0522, MRX78, MRX1 |
Description
IQSEC2 encodes a guanine nucleotide exchange factor (GEF) for the ADP-ribosylation factor (ARF) family of small GTPases. The protein contains an IQ motif that binds calmodulin, a Sec7 domain responsible for GEF activity, and a pleckstrin homology (PH) domain. It is involved in synaptic vesicle trafficking, dendritic spine morphogenesis, and regulation of AMPA receptor surface expression. Mutations in IQSEC2 are associated with X-linked intellectual disability, epilepsy, and autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability 78 (MRX78) | Loss-of-function mutations impair ARF-GEF activity, disrupting synaptic signaling and plasticity. | ClinVar, OMIM #300522 |
| X-linked intellectual disability with epilepsy | Missense and truncating mutations lead to altered neuronal excitability and synaptic dysfunction. | ClinVar, PubMed |
| Autism spectrum disorder | De novo and inherited variants affect dendritic spine development and glutamatergic transmission. | ClinVar, OMIM |
| Early infantile epileptic encephalopathy | Severe loss-of-function variants cause developmental delay and refractory seizures. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Testis | 3.2 | Medium |
| Adrenal gland | 2.1 | Medium |
| Lung | 1.0 | Low |
| Liver | 0.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 8.4 | Neuronal model |
| HEK293 (embryonic kidney) | 2.1 | Overexpression studies |
| U-87 MG (glioblastoma) | 5.3 | Brain tumor line |
| HepG2 (hepatocellular carcinoma) | 0.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2662C>T (p.Arg888*) | Nonsense | Rare | Loss of function; truncation of PH domain |
| c.2155G>A (p.Glu719Lys) | Missense | Rare | Impaired GEF activity; reduced ARF activation |
| c.1291C>T (p.Arg431Trp) | Missense | Rare | Disrupted calmodulin binding; altered synaptic plasticity |
| c.346_347del (p.Leu116Alafs*5) | Frameshift | Rare | Complete loss of protein function |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic IQSEC2 mutations are loss-of-function, including nonsense, frameshift, and missense variants that reduce or abolish GEF activity, leading to impaired ARF6-mediated endocytosis and synaptic dysfunction.
Gain of Function (GOF)
No gain-of-function mutations have been reported in IQSEC2.
Dominant Negative (DN)
Some missense variants (e.g., p.Glu719Lys) may act in a dominant-negative manner by interfering with wild-type protein function in heterozygous females.
View complete mutation data：
Gene Ontology (GO)
Pathways
• ARF6 signaling pathway
• Synaptic vesicle cycle
• Glutamatergic synapse
• Endocytosis
Protein Summary
IQSEC2 (BRAG2) is a 1488-amino acid protein with an N-terminal IQ motif, a central Sec7 domain, and a C-terminal PH domain. It functions as a guanine nucleotide exchange factor for ARF6, regulating endosomal trafficking and actin cytoskeleton remodeling at synapses. The IQ motif mediates calcium-dependent calmodulin binding, linking neuronal activity to ARF6 activation. The protein is predominantly expressed in brain, especially in cortex, hippocampus, and cerebellum. Mutations cause X-linked intellectual disability and epilepsy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IQSEC2 Knockout HEK293 Cell Line | EDJ-KQ7827 | Human | 23096 | Details Get a Quote |
| IQSEC2 Knockout A-549 Cell Line | EDJ-KQ33364 | Human | 23096 | Details Get a Quote |
| IQSEC2 Knockout HCT 116 Cell Line | EDJ-KQ33365 | Human | 23096 | Details Get a Quote |
| IQSEC2 Knockout HeLa Cell Line | EDJ-KQ33366 | Human | 23096 | Details Get a Quote |
