SBF1

SET binding factor 1, the group of Myotubularins|Pleckstrin homology domain containing|DENN domain containing

Basic information

Region (hg38): 22:50443219-50483923

Links

ENSG00000100241

∙ NCBI:6305 ∙ OMIM:603560 ∙ HGNC:10542 ∙ Uniprot:O95248 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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 (Strong), mode of inheritance: AR
Charcot-Marie-Tooth disease type 4B3 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the SBF1 gene.

not_provided (1770 variants)
not_specified (383 variants)
Charcot-Marie-Tooth_disease_type_4B3 (120 variants)
SBF1-related_disorder (57 variants)
Tip-toe_gait (5 variants)
Peripheral_neuropathy (2 variants)
Microcephaly (2 variants)
Charcot-Marie-Tooth_disease (2 variants)
Charcot-Marie-Tooth_disease_type_4 (1 variants)
Autism_spectrum_disorder (1 variants)
See_cases (1 variants)
Charcot-Marie-Tooth_disease_X-linked_dominant_1 (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. These statistics are base on transcript: NM_000002972.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		7 clinvar	556 clinvar	20 clinvar	584
missense		6 clinvar	748 clinvar	30 clinvar	2 clinvar	786
nonsense	7 clinvar	4 clinvar	1 clinvar			12
start loss						0
frameshift	9 clinvar	5 clinvar	3 clinvar			17
splice donor/acceptor (+/-2bp)		9 clinvar				9
Total	17	24	759	586	22

Highest pathogenic variant AF is 0.000111564

Loading clinvar variants...

GnomAD

Source: gnomAD

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: dbNSFP

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