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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SBF1
SET binding factor 1
Chromosome 22 Β· 22q13.33
NCBI Gene: 6305Ensembl: ENSG00000100241.22HGNC: HGNC:10542UniProt: A0A8J8YTQ8
87PubMed Papers
21Diseases
0Drugs
37Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
phosphatase activityguanyl-nucleotide exchange factor activityprotein bindingprotein-membrane adaptor activityCharcot-Marie-Tooth disease type 4B3neurodegenerative diseaseAlzheimer diseaseParkinson disease
✦AI Summary

SBF1 (SET binding factor 1), also known as MTMR5, is a multifunctional protein that primarily acts as an adapter and regulator of cellular trafficking and autophagy processes. SBF1 functions as an adapter for the phosphatase MTMR2, regulating its catalytic activity and subcellular localization, and may act as a guanine nucleotide exchange factor (GEF) for RAB28 12. The protein plays a critical role in autophagy regulation, particularly acting as a suppressor of autophagy in neurons by controlling phosphoinositide dephosphorylation essential for autophagy initiation and autophagosome maturation 3. Disease-wise, SBF1 mutations cause Charcot-Marie-Tooth disease type 4B3 (CMT4B3), a rare autosomal recessive peripheral neuropathy with early onset and severe presentation 45. In CMT4B3 patient fibroblasts, SBF1 dysfunction leads to selective mitophagy activation while impairing normal macroautophagy responses, revealing an uncoupling between these processes 6. Additionally, SBF1 expression levels correlate with gemcitabine sensitivity in head and neck squamous cell carcinoma, suggesting potential biomarker applications in cancer treatment 7. A GCC repeat polymorphism in the SBF1 gene has been associated with late-onset neurocognitive disorders, including Alzheimer's disease 8.

Sources cited
1
SBF1 acts as an adapter for phosphatase MTMR2 to regulate its catalytic activity and subcellular location
PMID: 12668758
2
SBF1 may function as a guanine nucleotide exchange factor (GEF) activating RAB28
PMID: 20937701
3
SBF1 acts as a suppressor of autophagy in neurons and plays a role in phosphoinositide dephosphorylation critical for autophagy
PMID: 35580604
4
SBF1 mutations cause CMT4B3, a rare subtype of hereditary neuropathy with early onset severe polyneuropathy
PMID: 36272304
5
SBF1/MTMR5 mutations are linked to Charcot-Marie-Tooth Disease Type 4B3, a rare autosomal recessive peripheral neuropathy
PMID: 39461113
6
SBF1 dysfunction leads to selective mitophagy activation while impairing macroautophagy responses
PMID: 40998285
7
SBF1 expression correlates with gemcitabine sensitivity in head and neck squamous cell carcinoma
PMID: 24817947
8
GCC repeat polymorphism in SBF1 gene is associated with late-onset neurocognitive disorders including Alzheimer's disease
PMID: 36104480
Disease Associationsβ“˜21
Charcot-Marie-Tooth disease type 4B3Open Targets
0.75Strong
neurodegenerative diseaseOpen Targets
0.53Moderate
Alzheimer diseaseOpen Targets
0.45Moderate
lysosomal storage diseaseOpen Targets
0.45Moderate
multiple sclerosisOpen Targets
0.45Moderate
Parkinson diseaseOpen Targets
0.45Moderate
hypothyroidismOpen Targets
0.37Weak
Tip-toe gaitOpen Targets
0.36Weak
vertebral column disorderOpen Targets
0.30Weak
Charcot-Marie-Tooth diseaseOpen Targets
0.27Weak
Charcot-Marie-Tooth disease type 4Open Targets
0.27Weak
autism spectrum disorderOpen Targets
0.27Weak
microcephalyOpen Targets
0.14Weak
peripheral neuropathyOpen Targets
0.14Weak
Charcot-Marie-Tooth disease X-linked dominant 1Open Targets
0.12Weak
X-linked Charcot-Marie-Tooth disease type 1Open Targets
0.12Weak
azoospermiaOpen Targets
0.09Suggestive
partial chromosome Y deletionOpen Targets
0.08Suggestive
spermatogenic failure 50Open Targets
0.06Suggestive
spermatogenic failure 57Open Targets
0.06Suggestive
Charcot-Marie-Tooth disease, demyelinating, type 4B3UniProt
Pathogenic Variants37
NM_002972.4(SBF1):c.1249A>G (p.Met417Val)Pathogenic
Charcot-Marie-Tooth disease type 4B3|Microcephaly|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 417
NM_002972.4(SBF1):c.3826+1G>APathogenic
Charcot-Marie-Tooth disease type 4B3|not provided
β˜…β˜…β˜†β˜†2025
NM_002972.4(SBF1):c.2154_2155del (p.Asp719fs)Pathogenic
Charcot-Marie-Tooth disease type 4|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 719
NM_002972.4(SBF1):c.4554+2T>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_002972.4(SBF1):c.4552C>T (p.Gln1518Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1518
NM_002972.4(SBF1):c.3222_3223insA (p.Pro1075fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1075
NM_002972.4(SBF1):c.3491+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_002972.4(SBF1):c.3257_3258del (p.Pro1086fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1086
NM_002972.4(SBF1):c.5463C>G (p.Tyr1821Ter)Likely pathogenic
Charcot-Marie-Tooth disease type 4B3|Charcot-Marie-Tooth disease
β˜…β˜†β˜†β˜†2024β†’ Residue 1821
NM_002972.4(SBF1):c.1821dup (p.His608fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 608
NM_002972.4(SBF1):c.277C>T (p.Gln93Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 93
NM_002972.4(SBF1):c.5266C>T (p.Gln1756Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1756
NM_002972.4(SBF1):c.905_906del (p.Val302fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 302
NM_002972.4(SBF1):c.4820_4827del (p.Arg1607fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1607
NM_002972.4(SBF1):c.4995C>G (p.Tyr1665Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 1665
NM_002972.4(SBF1):c.2569+2T>CLikely pathogenic
Charcot-Marie-Tooth disease type 4B3
β˜…β˜†β˜†β˜†2023
NM_002972.4(SBF1):c.2948T>C (p.Leu983Pro)Likely pathogenic
Charcot-Marie-Tooth disease type 4B3
β˜…β˜†β˜†β˜†2023β†’ Residue 983
NM_002972.4(SBF1):c.3257dup (p.Pro1086_Glu1087insTer)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 1086
NM_002972.4(SBF1):c.3688+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_002972.4(SBF1):c.1011+2T>CLikely pathogenic
SBF1-related disorder
β˜…β˜†β˜†β˜†2023
View on ClinVar β†—
Related Genes
MTMR2Protein interaction99%FZR1Protein interaction84%MTMR1Protein interaction77%KMT2AProtein interaction76%RAB21Protein interaction72%MTMR7Shared pathway50%
Tissue Expression6 tissues
Brain
100%
Ovary
100%
Bone Marrow
91%
Lung
91%
Heart
67%
Liver
58%
Gene Interaction Network
Click a node to explore
SBF1MTMR2FZR1MTMR1KMT2ARAB21MTMR7
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O95248
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.38Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.31 [0.25–0.38]
RankingsWhere SBF1 stands among ~20K protein-coding genes
  • #5,512of 20,598
    Most Researched87
  • #1,620of 5,498
    Most Pathogenic Variants37
  • #1,841of 17,882
    Most Constrained (LOEUF)0.38 Β· top quartile
Genes detectedSBF1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
1.00
2
Generation and characterization of CSSi016-A (9938) human pluripotent stem cell line carrying two biallelic variants in MTMR5/SBF1 gene resulting in a case of severe CMT4B3.
PMID: 36272304
Stem Cell Res Β· 2022
0.90
3
Establishment and characterization of three human pluripotent stem cell lines from Charcot-Marie-Tooth disease Type 4B3 patients bearing mutations in MTMR5/Sbf1 gene.
PMID: 39461113
Stem Cell Res Β· 2024
0.80
4
A (GCC) repeat in SBF1 reveals a novel biological phenomenon in human and links to late onset neurocognitive disorder.
PMID: 36104480
Sci Rep Β· 2022
0.70
5
Selective mitophagy activation and protein aggregate accumulation in MTMR5/SBF1-deficient fibroblasts.
PMID: 40998285
Life Sci Β· 2025
0.60