SBF1

Chr 22AR

SET binding factor 1

Also known as: CMT4B3, DENND7A, MTMR5

NCBI Gene: 6305ENSG00000100241UniProt: O95248OMIM: 603560

The protein is a pseudophosphatase that contains a guanine nucleotide exchange factor (GEF) domain necessary for cellular growth and differentiation, but lacks catalytic phosphatase activity due to missing amino acids in the catalytic pocket. Mutations cause Charcot-Marie-Tooth disease type 4B3, inherited in an autosomal recessive pattern. The high pLI score (0.999) and low LOEUF score (0.265) indicate the gene is highly intolerant to loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.271 OMIM phenotype
Clinical Summary— SBF1
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Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease type 4B3 · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.999
Z-score 7.32
OE 0.17 (0.12–0.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
0.53Z-score
OE missense 0.96 (0.91–1.00)
1179 obs / 1231.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.12–0.27)
0≤0.351.4
Missense OE0.96 (0.91–1.00)
0≤0.61.4
Synonymous OE1.39
0≤1.21.6
LoF obs/exp: 16 / 91.6Missense obs/exp: 1179 / 1231.0Syn Z: -7.01

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SBF1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Pediatric toe-walking cohort with heterozygous SBF1 variants: A phenotypic description.
Pomarino D et al.·Glob Med Genet
2026Open AccessCohort
Selective mitophagy activation and protein aggregate accumulation in MTMR5/SBF1-deficient fibroblasts.
Zanfardino P et al.·Life Sci
2025
A novel SBF1 missense mutation causes autosomal dominant Charcot-Marie-Tooth disease type 4B3.
Liu H et al.·Front Neurol
2024Open Access
Establishment and characterization of three human pluripotent stem cell lines from Charcot-Marie-Tooth disease Type 4B3 patients bearing mutations in MTMR5/Sbf1 gene.
Jacobs EH et al.·Stem Cell Res
2024Open AccessCohort
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.
Maria Turco E et al.·Stem Cell Res
2022
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients