SBF2

SET binding factor 2, the group of DENN domain containing|Myotubularins|Pleckstrin homology domain containing

Basic information

Region (hg38): 11:9776775-10304877

Previous symbols: [ "CMT4B2" ]

Links

ENSG00000133812 ∙ NCBI:81846 ∙ OMIM:607697 ∙ HGNC:2135 ∙ Uniprot:Q86WG5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease type 4B2 (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4B2 (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4B2 (Definitive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4B2 (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 4B2 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Charcot-Marie-Tooth disease, type 4B2 with early-onset glaucoma	AR	Ophthalmologic; Pharmacogenomic	Open-angle glaucoma is typically asymptomatic until late stages, when irreversible nerve damage has already taken place; As the condition may include early-onset hearing loss, intervention related to speech and language development may be beneficial; Agents that may contribute to glaucoma should be avoided	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	9521281; 10932274; 12687498; 12554688; 15477569; 15304601; 23334996
Several families with CMT4B2 with early-onset glaucoma have been reported; One report has also described homozygous variants associated with Congenital thrombocytopenia, autosomal recessive

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SBF2 gene.

• Charcot-Marie-Tooth disease type 4 (1099 variants)
• not provided (308 variants)
• Inborn genetic diseases (237 variants)
• Charcot-Marie-Tooth disease type 4B2 (179 variants)
• Charcot-Marie-Tooth disease (110 variants)
• not specified (97 variants)
• Tip-toe gait (7 variants)
• SBF2-related condition (5 variants)
• Charcot-Marie-Tooth disease type 4B2 with early-onset glaucoma (2 variants)
• Peripheral neuropathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SBF2 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	244	2	255
missense		1	652	6	2	661
nonsense	21	2	2			25
start loss						0
frameshift	11	6	1			18
inframe indel			6			6
splice donor/acceptor (+/-2bp)	5	15	2			22
splice region			45	43	2	90
non coding			37	212	82	331
Total	37	24	709	462	86

Highest pathogenic variant AF is 0.0000131

Variants in SBF2

This is a list of pathogenic ClinVar variants found in the SBF2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-9778732-C-T		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 13, 2018)
11-9778799-T-G		Charcot-Marie-Tooth disease type 4B2	Benign (Jan 13, 2018)
11-9778903-C-T		Charcot-Marie-Tooth disease type 4B2	Benign (Jan 13, 2018)
11-9778923-A-G		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 12, 2018)
11-9778977-G-A		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 12, 2018)
11-9778979-G-T		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 12, 2018)
11-9779005-T-C		Charcot-Marie-Tooth disease type 4B2	Benign (Jan 12, 2018)
11-9779013-A-G		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 12, 2018)
11-9779019-A-G		Charcot-Marie-Tooth disease type 4B2	Benign (Jan 12, 2018)
11-9779054-G-A		Charcot-Marie-Tooth disease type 4B2	Benign (Jan 13, 2018)
11-9779103-T-G		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Apr 27, 2017)
11-9779163-C-T		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 13, 2018)
11-9779274-T-C		Charcot-Marie-Tooth disease type 4B2	Benign (Jan 13, 2018)
11-9779327-C-T		Charcot-Marie-Tooth disease type 4B2	Likely benign (Jan 12, 2018)
11-9779455-G-A		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 12, 2018)
11-9779536-A-G		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 12, 2018)
11-9779543-C-T		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 13, 2018)
11-9779687-A-T		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 13, 2018)
11-9779688-C-T		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 13, 2018)
11-9779787-A-G		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 12, 2018)
11-9779810-C-G		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 12, 2018)
11-9779904-G-A		Charcot-Marie-Tooth disease type 4B2	Benign (Jan 13, 2018)
11-9779938-C-T		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 13, 2018)
11-9779971-T-A		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 13, 2018)
11-9780000-A-G		Charcot-Marie-Tooth disease type 4B2	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SBF2	protein_coding	protein_coding	ENST00000256190	40	515541

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.38e-10	1.00	125682	0	66	125748	0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.19	849	952	0.891	0.0000507	12151
Missense in Polyphen		197	298.43	0.66013		3792
Synonymous	-0.870	362	342	1.06	0.0000179	3533
Loss of Function	5.98	35	99.3	0.353	0.00000523	1209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000662	0.000662
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000109	0.000109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000282	0.000281
Middle Eastern	0.000109	0.000109
South Asian	0.000360	0.000359
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Guanine nucleotide exchange factor (GEF) which may activate RAB28. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. {ECO:0000269|PubMed:20937701}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Metabolism of lipids;Metabolism;Rab regulation of trafficking;Synthesis of PIPs at the plasma membrane;PI Metabolism;Phospholipid metabolism;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

• pRec: 0.169

Intolerance Scores

• loftool: 0.0995
• rvis_EVS: -2
• rvis_percentile_EVS: 1.73

Haploinsufficiency Scores

• pHI: 0.0582
• hipred: N
• hipred_score: 0.426
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.874

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sbf2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: myelination;regulation of GTPase activity;protein tetramerization
• Cellular component: vacuolar membrane;cytosol;membrane
• Molecular function: protein binding;Rab guanyl-nucleotide exchange factor activity;phosphatase regulator activity;phosphatase binding;phosphatidylinositol binding;protein homodimerization activity