IQSEC3: IQ Motif and Sec7 Domain 3
A guanine nucleotide exchange factor (GEF) for ARF GTPases, implicated in synaptic vesicle trafficking and neurodevelopmental disorders.
Gene Information Card
| Symbol | IQSEC3 |
|---|---|
| Full Name | IQ motif and Sec7 domain 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 12p13.33 |
| NCBI Gene ID | 440073 ncbi.nlm.nih.gov/gene/440073 |
| Ensembl ID | ENSG00000120645 |
| UniProt ID | Q9NR83 |
| OMIM ID | 617562 |
| HGNC ID | 26059 |
| Aliases | ARFGEF3, KIAA1110, IQ-SEC3 |
Description
IQSEC3 encodes a guanine nucleotide exchange factor (GEF) for ADP-ribosylation factor (ARF) GTPases, specifically activating ARF6. The protein contains an IQ motif, a Sec7 domain, and a pleckstrin homology (PH) domain. It is involved in regulating synaptic vesicle trafficking, dendritic spine morphology, and neurotransmitter release at glutamatergic synapses. Mutations in IQSEC3 are associated with neurodevelopmental disorders including intellectual disability and epilepsy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal dominant 67 (MRD67) | Loss-of-function mutations impair ARF6 activation, disrupting synaptic vesicle recycling and dendritic spine development. | ClinVar, OMIM |
| Epileptic encephalopathy, early infantile, 83 (EIEE83) | De novo missense variants reduce GEF activity, leading to altered neuronal excitability and synaptic dysfunction. | ClinVar, OMIM |
| Autism spectrum disorder (ASD) | Rare variants in IQSEC3 have been identified in ASD cohorts, suggesting a role in synaptic plasticity. | NCBI Gene, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 12.5 | Medium |
| Cerebellum | 10.2 | Medium |
| Testis | 8.1 | Low |
| Heart | 3.4 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | Neuronal model |
| HEK293 (embryonic kidney) | 2.1 | Low endogenous expression |
| U-87 MG (glioblastoma) | 9.8 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.226C>T (p.Arg76Trp) | Missense | Rare | Reduced GEF activity; associated with EIEE83 |
| c.1234G>A (p.Glu412Lys) | Missense | Rare | Impaired ARF6 binding; linked to MRD67 |
| c.1876C>T (p.Arg626*) | Nonsense | Very rare | Loss-of-function; truncation of Sec7 domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to premature stop codons or nonsense-mediated decay, resulting in haploinsufficiency.
Gain of Function (GOF)
Not reported for IQSEC3.
Dominant Negative (DN)
Missense variants in the Sec7 domain that impair GEF activity while retaining ARF binding, disrupting normal ARF6 cycling.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • ARF guanyl-nucleotide exchange factor activity |
| • calmodulin binding | • synaptic vesicle exocytosis |
| • dendritic spine morphogenesis | • regulation of neurotransmitter secretion |
Pathways
• ARF6 signaling pathway
• Synaptic vesicle cycle
• Glutamatergic synapse
Protein Summary
IQSEC3 is a 1479-amino acid protein containing an N-terminal IQ motif (calmodulin-binding), a central Sec7 domain (catalytic GEF activity), and a C-terminal PH domain (membrane targeting). It specifically activates ARF6, promoting GTP-GDP exchange. The protein localizes to postsynaptic densities and regulates AMPA receptor trafficking and dendritic spine maintenance. Alternative splicing produces multiple isoforms.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| IQSEC3 Knockout HEK293 Cell Line | EDJ-KQ7942 | Human | 440073 | Details Get a Quote |
| IQSEC3 Knockout HeLa Cell Line | EDJ-KQ60380 | Human | 440073 | Details Get a Quote |
| IQSEC3 Knockout A-549 Cell Line | EDJ-KQ68847 | Human | 440073 | Details Get a Quote |
| IQSEC3 Knockout HCT 116 Cell Line | EDJ-KQ77211 | Human | 440073 | Details Get a Quote |
