ARFGEF2
ADP Ribosylation Factor Guanine Nucleotide Exchange Factor 2
Gene Information Card
| Symbol | ARFGEF2 |
|---|---|
| Full Name | ADP Ribosylation Factor Guanine Nucleotide Exchange Factor 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 20q13.13 |
| NCBI Gene ID | 10564 ncbi.nlm.nih.gov/gene/10564 |
| Ensembl ID | ENSG00000124208 |
| UniProt ID | Q9Y6D5 |
| OMIM ID | 605371 |
| HGNC ID | 689 |
| Aliases | BIG2, dJ1163J1.1, KIAA0763 |
Description
ARFGEF2 encodes brefeldin A-inhibited guanine nucleotide-exchange protein 2 (BIG2), which activates ADP-ribosylation factors (ARFs) by exchanging GDP for GTP. BIG2 is involved in vesicle trafficking, membrane dynamics, and protein transport between the Golgi apparatus and endosomes. Mutations in ARFGEF2 cause autosomal recessive periventricular heterotopia with microcephaly (PHM), a disorder of neuronal migration.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Periventricular heterotopia with microcephaly (PHM) | Loss-of-function mutations impair ARF activation, disrupting vesicle trafficking and neuronal migration during cortical development. | Multiple families; OMIM #608097 |
| Periventricular nodular heterotopia 6 (PVNH6) | Biallelic ARFGEF2 variants lead to abnormal neuronal positioning and microcephaly. | ClinVar; PMID: 23390182 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Kidney | 7.1 | Low |
| Liver | 5.9 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y | 15.2 | Neuroblastoma cell line |
| HeLa | 10.1 | Cervical carcinoma |
| HEK293 | 9.8 | Embryonic kidney |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1300C>T (p.Arg434Ter) | Nonsense | Rare | Loss of function; truncation of BIG2 protein |
| c.2029C>T (p.Arg677Trp) | Missense | Rare | Impaired GEF activity; associated with PHM |
| c.3589C>T (p.Arg1197Ter) | Nonsense | Rare | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or absent BIG2 protein; cause periventricular heterotopia with microcephaly.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • ARF guanyl-nucleotide exchange factor activity |
| • Golgi membrane | • intracellular protein transport |
| • vesicle-mediated transport | • regulation of ARF protein signal transduction |
Pathways
• ARF6 signaling events
• Vesicle-mediated transport
• Golgi-to-ER retrograde transport
Protein Summary
BIG2 is a 1785-amino acid protein localized to the Golgi apparatus. It contains a Sec7 domain responsible for guanine nucleotide exchange on ARF1 and ARF3. BIG2 regulates membrane trafficking, endosome-to-Golgi transport, and cytokinesis. Its dysfunction leads to impaired neuronal migration and microcephaly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ARFGEF2 Knockout HEK293 Cell Line | EDJ-KQ7091 | Human | 10564 | Details Get a Quote |
| ARFGEF2 Knockout A-549 Cell Line | EDJ-KQ31936 | Human | 10564 | Details Get a Quote |
| ARFGEF2 Knockout HeLa Cell Line | EDJ-KQ31937 | Human | 10564 | Details Get a Quote |
| ARFGEF2 Knockout HCT 116 Cell Line | EDJ-KQ30553 | Human | 10564 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
