SBF1 (SET Binding Factor 1) Gene
A pseudophosphatase involved in endosomal trafficking and Charcot-Marie-Tooth disease
Gene Information Card
| Symbol | SBF1 |
|---|---|
| Full Name | SET binding factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q13.33 |
| NCBI Gene ID | 8895 ncbi.nlm.nih.gov/gene/8895 |
| Ensembl ID | ENSG00000100241 |
| UniProt ID | O95248 |
| OMIM ID | 603560 |
| HGNC ID | 10542 |
| Aliases | MTMR5, CMT4B3 |
Description
SBF1 (SET binding factor 1), also known as MTMR5, encodes a pseudophosphatase member of the myotubularin-related protein family. It lacks phosphatase activity due to a critical cysteine-to-serine substitution in the active site but retains the ability to bind phosphoinositides and interact with other myotubularins. SBF1 functions in endosomal trafficking, autophagy, and cell signaling. Mutations in SBF1 cause autosomal recessive Charcot-Marie-Tooth disease type 4B3 (CMT4B3), a severe demyelinating neuropathy with childhood onset.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 4B3 (CMT4B3) | Loss-of-function mutations in SBF1 disrupt endosomal trafficking and myelin maintenance in peripheral nerves, leading to demyelination and axonal loss. | ClinVar, OMIM |
| Charcot-Marie-Tooth disease type 4B1 (CMT4B1) modifier | SBF1 interacts with MTMR2; mutations may modify disease severity in CMT4B1 caused by MTMR2 mutations. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Low |
| Peripheral nerve | 8.1 | Medium |
| Testis | 12.3 | Medium |
| Skeletal muscle | 3.4 | Low |
| Heart | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 6.8 | Neuronal model |
| HeLa (cervical carcinoma) | 4.5 | Epithelial |
| HEK293 (embryonic kidney) | 5.1 | Common cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2086C>T (p.Arg696*) | Nonsense | Rare | Loss of function; associated with CMT4B3 |
| c.2935C>T (p.Arg979Trp) | Missense | Rare | Loss of function; disrupts phosphoinositide binding |
| c.1123_1124del (p.Leu375Valfs*3) | Frameshift | Rare | Loss of function; premature truncation |
Mutation functional classification
Loss of Function (LOF)
Most SBF1 mutations are loss-of-function, leading to reduced or absent protein function, causing CMT4B3.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • phosphatidylinositol-3-phosphatase activity (inactive) (GO:0004438) | • lipid binding (GO:0008289) |
| • endosomal transport (GO:0016197) | • autophagy (GO:0006914) |
| • myelination (GO:0042552) |
Pathways
• Myotubularin-related protein signaling
• Endosomal trafficking
• Autophagy
Protein Summary
SBF1 (MTMR5) is a 1,208-amino acid pseudophosphatase with an N-terminal PH-GRAM domain, a catalytically inactive phosphatase domain, a coiled-coil region, and a C-terminal SET-binding domain. It heterodimerizes with active myotubularins (e.g., MTMR2) to regulate phosphoinositide levels on endosomal membranes, thereby controlling vesicle trafficking and autophagy. Loss of SBF1 function leads to abnormal endosomal accumulation and impaired myelin maintenance in Schwann cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SBF1 Knockout HEK293T Cell Line | EDJ-KQ157 | Human | 6305 | Details Get a Quote |
| SBF1 Knockout HEK293 Cell Line | EDJ-KQ15173 | Human | 6305 | Details Get a Quote |
| SBF1 Knockout A-549 Cell Line | EDJ-KQ47955 | Human | 6305 | Details Get a Quote |
| SBF1 Knockout HCT 116 Cell Line | EDJ-KQ47957 | Human | 6305 | Details Get a Quote |
| SBF1 Knockout HeLa Cell Line | EDJ-KQ47958 | Human | 6305 | Details Get a Quote |
