SBF1

Chr 22AR

SET binding factor 1

Also known as: CMT4B3, DENND7A, MTMR5

NCBI Gene: 6305ENSG00000100241UniProt: O95248

This gene encodes a member of the protein-tyrosine phosphatase family. However, the encoded protein does not appear to be a catalytically active phosphatase because it lacks several amino acids in the catalytic pocket. This protein contains a Guanine nucleotide exchange factor (GEF) domain which is necessary for its role in growth and differentiation. Mutations in this gene have been associated with Charcot-Marie-Tooth disease 4B3. Pseudogenes of this gene have been defined on chromosomes 1 and 8. [provided by RefSeq, Dec 2014]

Primary Disease Associations & Inheritance

Charcot-Marie-Tooth disease, type 4B3MIM #615284
AR
2307
ClinVar variants
14
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SBF1
⚡
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.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 262 VUS of 2307 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.53Z-score
OE missense 0.96 (0.91–1.00)
1179 obs / 1231.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.17 (0.12–0.27)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.91–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.39
0≤1.21.6
LoF obs/exp: 16 / 91.6Missense obs/exp: 1179 / 1231.0Syn Z: -7.01

ClinVar Variant Classifications

2307 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic3
VUS262
Likely Benign193
Conflicting2
11
Pathogenic
3
Likely Pathogenic
262
VUS
193
Likely Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
7
0
11
Likely Pathogenic
3
0
0
0
3
VUS
2
234
25
1
262
Likely Benign
0
0
86
107
193
Benign
0
0
0
0
0
Conflicting
—2
Total9234118108471

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Charcot-Marie-Tooth disease, type 4B3

MIM #615284

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Recent advances in Charcot-Marie-Tooth disease.
Baets J et al.·Curr Opin Neurol
2014Review
Male infertility, impaired spermatogenesis, and azoospermia in mice deficient for the pseudophosphatase Sbf1.
Firestein R et al.·J Clin Invest
2002
MTM1 mutations in X-linked myotubular myopathy.
Laporte J et al.·Hum Mutat
2000Review
SET binding factor 1 (SBF1) mutation causes Charcot-Marie-Tooth disease type 4B3.
Nakhro K et al.·Neurology
2013
Novel SBF1 splice-site null mutation broadens the clinical spectrum of Charcot-Marie-Tooth type 4B3 disease.
Flusser H et al.·Clin Genet
2018Case report
Bi-allelic variants in MTMR5/SBF1 cause Charcot-Marie-Tooth type 4B3 featuring mitochondrial dysfunction.
Berti B et al.·BMC Med Genomics
2021Case report
Potential Candidate Genes for Therapeutic Targeting in Chronic Myeloid Leukemia: A Pilot Study.
Alsamman K et al.·Asian Pac J Cancer Prev
2023
A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres.
Gang Q et al.·J Neurol
2020Case report
Whole-Exome Sequencing (WES) Reveals Novel Sex-Specific Gene Variants in Non-Alcoholic Steatohepatitis (MASH).
Wei J et al.·Genes (Basel)
2024
The mutational landscape and prognostic indicators of pseudomyxoma peritonei originating from the ovary.
Wang B et al.·Int J Cancer
2021
Top 10 resultsSearch 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
2026🔓 Open 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
2024🔓 Open 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
2024🔓 Open 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 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools