SBF1

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

Basic information

Region (hg38): 22:50443218-50483923

Links

ENSG00000100241

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

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 (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 (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	Phenotype	Significance	ClinVar
22-50443885-C-T	Inborn genetic diseases	Uncertain significance (Jul 11, 2023)	link
22-50443886-G-A	Inborn genetic diseases	Uncertain significance (Mar 28, 2023)	link
22-50443888-C-A	Inborn genetic diseases	Uncertain significance (Dec 06, 2021)	link
22-50443910-C-T	Inborn genetic diseases	Uncertain significance (Jul 25, 2023)	link
22-50443999-G-A	Inborn genetic diseases	Uncertain significance (Apr 12, 2022)	link
22-50444074-G-A	Inborn genetic diseases	Uncertain significance (Jul 13, 2021)	link
22-50444206-G-C	Inborn genetic diseases	Uncertain significance (Dec 05, 2022)	link
22-50444214-G-A	Inborn genetic diseases	Likely benign (Sep 13, 2023)	link
22-50446979-C-CGGGCG		Likely benign (Sep 20, 2019)	link
22-50447030-G-A		Likely benign (Sep 21, 2018)	link
22-50447066-A-G		Likely benign (Jul 31, 2018)	link
22-50447148-G-A		Likely benign (Oct 05, 2022)	link
22-50447150-CCGACAGGCAG-C		Uncertain significance (Mar 11, 2022)	link
22-50447151-C-T		Likely benign (Oct 26, 2022)	link
22-50447152-G-A		Uncertain significance (Sep 13, 2022)	link
22-50447170-C-T	Inborn genetic diseases	Conflicting interpretations of pathogenicity (Apr 07, 2023)	link
22-50447171-G-A		Uncertain significance (May 30, 2022)	link
22-50447187-G-C		Likely benign (Sep 04, 2022)	link
22-50447190-C-T		Likely benign (Sep 28, 2022)	link
22-50447191-G-A		Uncertain significance (Jun 19, 2022)	link
22-50447194-G-A		Likely benign (Nov 01, 2022)	link
22-50447195-G-A		Uncertain significance (Jan 17, 2022)	link
22-50447197-A-G		Uncertain significance (Apr 08, 2022)	link
22-50447198-C-T		Uncertain significance (Sep 24, 2021)	link
22-50447199-G-A	Charcot-Marie-Tooth disease type 4B3 • not specified	Benign/Likely benign (Oct 19, 2022)	link

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