SBF1
SET binding factor 1, the group of Myotubularins|Pleckstrin homology domain containing|DENN domain containing
Basic information
Region (hg38): 22:50443218-50483923
Links
Phenotypes
GenCC
Source:
- Charcot-Marie-Tooth disease type 4B3 (Supportive), mode of inheritance: AR
- Charcot-Marie-Tooth disease type 4B3 (Limited), mode of inheritance: AR
- Charcot-Marie-Tooth disease type 4B3 (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Charcot-Marie-Tooth disease, type 4B3 | AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Neurologic | 21210780; 23749797; 24799518 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (1399 variants)
- Charcot-Marie-Tooth disease type 4B3 (100 variants)
- Inborn genetic diseases (59 variants)
- not specified (15 variants)
- Tip-toe gait (3 variants)
- Microcephaly (2 variants)
- Peripheral neuropathy (2 variants)
- Charcot-Marie-Tooth disease X-linked dominant 1 (1 variants)
- Charcot-Marie-Tooth disease type 4 (1 variants)
- Charcot-Marie-Tooth disease (1 variants)
- Autism spectrum disorder (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SBF1 gene is commonly pathogenic or not.
Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
---|---|---|---|---|---|---|
synonymous | 1 | 8 | 354 | 28 | 391 | |
missense | 1 | 1 | 558 | 24 | 3 | 587 |
nonsense | 4 | 4 | 1 | 9 | ||
start loss | 0 | |||||
frameshift | 4 | 14 | 18 | |||
inframe indel | 2 | 2 | 4 | |||
splice variant | 4 | 44 | 64 | 7 | 119 | |
non coding | 7 | 239 | 59 | 305 | ||
Total | 10 | 11 | 634 | 681 | 97 |
Highest pathogenic variant AF is 0.0000394
Variants in SBF1
This is a list of pathogenic ClinVar variants found in the SBF1 region.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
22-50443885-C-T | Inborn genetic diseases | Uncertain significance (Jul 11, 2023) | ||
22-50443886-G-A | Inborn genetic diseases | Uncertain significance (Mar 28, 2023) | ||
22-50443888-C-A | Inborn genetic diseases | Uncertain significance (Dec 06, 2021) | ||
22-50443910-C-T | Inborn genetic diseases | Uncertain significance (Jul 25, 2023) | ||
22-50443999-G-A | Inborn genetic diseases | Uncertain significance (Apr 12, 2022) | ||
22-50444074-G-A | Inborn genetic diseases | Uncertain significance (Jul 13, 2021) | ||
22-50444206-G-C | Inborn genetic diseases | Uncertain significance (Dec 05, 2022) | ||
22-50444214-G-A | Inborn genetic diseases | Likely benign (Sep 13, 2023) | ||
22-50446979-C-CGGGCG | Likely benign (Sep 20, 2019) | |||
22-50447030-G-A | Likely benign (Sep 21, 2018) | |||
22-50447066-A-G | Likely benign (Jul 31, 2018) | |||
22-50447148-G-A | Likely benign (Oct 05, 2022) | |||
22-50447150-CCGACAGGCAG-C | Uncertain significance (Mar 11, 2022) | |||
22-50447151-C-T | Likely benign (Oct 26, 2022) | |||
22-50447152-G-A | Uncertain significance (Sep 13, 2022) | |||
22-50447170-C-T | Inborn genetic diseases | Conflicting interpretations of pathogenicity (Apr 07, 2023) | ||
22-50447171-G-A | Uncertain significance (May 30, 2022) | |||
22-50447187-G-C | Likely benign (Sep 04, 2022) | |||
22-50447190-C-T | Likely benign (Sep 28, 2022) | |||
22-50447191-G-A | Uncertain significance (Jun 19, 2022) | |||
22-50447194-G-A | Likely benign (Nov 01, 2022) | |||
22-50447195-G-A | Uncertain significance (Jan 17, 2022) | |||
22-50447197-A-G | Uncertain significance (Apr 08, 2022) | |||
22-50447198-C-T | Uncertain significance (Sep 24, 2021) | |||
22-50447199-G-A | Charcot-Marie-Tooth disease type 4B3 • not specified | Benign/Likely benign (Oct 19, 2022) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
SBF1 | protein_coding | protein_coding | ENST00000380817 | 41 | 30026 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.999 | 0.000670 | 124863 | 0 | 29 | 124892 | 0.000116 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 0.527 | 1179 | 1.23e+3 | 0.958 | 0.0000893 | 12063 |
Missense in Polyphen | 422 | 528.32 | 0.79876 | 5142 | ||
Synonymous | -7.01 | 740 | 534 | 1.39 | 0.0000391 | 3934 |
Loss of Function | 7.32 | 16 | 91.6 | 0.175 | 0.00000451 | 1002 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.0000582 | 0.0000582 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.000167 | 0.000167 |
Finnish | 0.0000937 | 0.0000928 |
European (Non-Finnish) | 0.000161 | 0.000159 |
Middle Eastern | 0.000167 | 0.000167 |
South Asian | 0.0000656 | 0.0000654 |
Other | 0.000335 | 0.000329 |
dbNSFP
Source:
- Function
- FUNCTION: Probable pseudophosphatase. Lacks several amino acids in the catalytic pocket which renders it catalytically inactive as a phosphatase. The pocket is however sufficiently preserved to bind phosphorylated substrates, and maybe protect them from phosphatases. Inhibits myoblast differentiation in vitro and induces oncogenic transformation in fibroblasts. According to PubMed:20937701, may function as a guanine nucleotide exchange factor (GEF) activating RAB28. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701, ECO:0000269|PubMed:9537414}.;
- Disease
- DISEASE: Charcot-Marie-Tooth disease 4B3 (CMT4B3) [MIM:615284]: A recessive demyelinating form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot- Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4. {ECO:0000269|PubMed:23749797}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Vesicle-mediated transport;Membrane Trafficking;Metabolism of lipids;Metabolism;Synthesis of PIPs at the ER membrane;Rab regulation of trafficking;PI Metabolism;Phospholipid metabolism;RAB GEFs exchange GTP for GDP on RABs
(Consensus)
Recessive Scores
- pRec
- 0.145
Intolerance Scores
- loftool
- 0.0648
- rvis_EVS
- -4.05
- rvis_percentile_EVS
- 0.17
Haploinsufficiency Scores
- pHI
- 0.154
- hipred
- N
- hipred_score
- 0.476
- ghis
- 0.621
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.323
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sbf1
- Phenotype
- cellular phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- protein dephosphorylation;phosphatidylinositol biosynthetic process;spermatogenesis;regulation of GTPase activity
- Cellular component
- cytoplasm;endoplasmic reticulum membrane;cytosol;integral component of membrane;nuclear body
- Molecular function
- protein tyrosine/serine/threonine phosphatase activity;phosphatase activity;Rab guanyl-nucleotide exchange factor activity;phosphatase regulator activity