SBF1

Summary

SBF1 (SET binding factor 1, HGNC:10542) is a protein-coding gene on chromosome 22q13.33, encoding Myotubularin-related protein 5 (O95248). Acts as an adapter for the phosphatase MTMR2 to regulate MTMR2 catalytic activity and subcellular location.

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.

Source: NCBI Gene 6305 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease type 4B3 (Strong, GenCC)
• Clinical variants (ClinVar): 2,155 total — 22 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 24
• MANE Select transcript: NM_002972

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10542
Approved symbol	SBF1
Name	SET binding factor 1
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MTMR5, DENND7A
Ensembl gene	ENSG00000100241
Ensembl biotype	protein_coding
OMIM	603560
Entrez	6305

Gene structure

Transcript identifiers

Ensembl transcripts: 80 — 36 protein_coding, 22 retained_intron, 19 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000348911, ENST00000380817, ENST00000399627, ENST00000418590, ENST00000470434, ENST00000473724, ENST00000476293, ENST00000477234, ENST00000684986, ENST00000685180, ENST00000685239, ENST00000685386, ENST00000685390, ENST00000685411, ENST00000685459, ENST00000685592, ENST00000685809, ENST00000685960, ENST00000686029, ENST00000686191, ENST00000686222, ENST00000686321, ENST00000686421, ENST00000686427, ENST00000686717, ENST00000686758, ENST00000686801, ENST00000686826, ENST00000687016, ENST00000687340, ENST00000687704, ENST00000687861, ENST00000687878, ENST00000688030, ENST00000688066, ENST00000688124, ENST00000688381, ENST00000688848, ENST00000688985, ENST00000689095, ENST00000689129, ENST00000689177, ENST00000689763, ENST00000689849, ENST00000689981, ENST00000690155, ENST00000690197, ENST00000690369, ENST00000690590, ENST00000690990, ENST00000691233, ENST00000691306, ENST00000691344, ENST00000691345, ENST00000691792, ENST00000691959, ENST00000692006, ENST00000692076, ENST00000692844, ENST00000692946, ENST00000693052, ENST00000693068, ENST00000693289, ENST00000693440, ENST00000693499, ENST00000693591, ENST00000693675, ENST00000899576, ENST00000931644, ENST00000931645, ENST00000931646, ENST00000931647, ENST00000967446, ENST00000967447, ENST00000967448, ENST00000967449, ENST00000967450, ENST00000967451, ENST00000967452, ENST00000967453

RefSeq mRNA: 4 — MANE Select: NM_002972 NM_001365819, NM_001410794, NM_001410795, NM_002972

CCDS: CCDS14091, CCDS93185, CCDS93186, CCDS93187

Canonical transcript exons

ENST00000380817 — 41 exons

Exon	Start	End
ENSE00000657682	50455481	50455582
ENSE00000657686	50456492	50456673
ENSE00000878874	50456216	50456395
ENSE00000878875	50459255	50459392
ENSE00000878876	50459470	50459666
ENSE00000878877	50459952	50460159
ENSE00000878878	50460272	50460408
ENSE00000878879	50460534	50460712
ENSE00000878883	50461947	50462119
ENSE00000878884	50462205	50462473
ENSE00000878885	50462559	50462717
ENSE00000878886	50462870	50462938
ENSE00000878887	50463283	50463432
ENSE00000878888	50464329	50464441
ENSE00000878889	50464534	50464738
ENSE00000878890	50464819	50464917
ENSE00000878891	50465001	50465129
ENSE00000878892	50465215	50465328
ENSE00000878893	50465763	50465840
ENSE00000878894	50465961	50466074
ENSE00001032912	50467532	50467690
ENSE00001335635	50466150	50466258
ENSE00001362708	50467786	50467923
ENSE00001362926	50474786	50475035
ENSE00001486369	50457034	50457111
ENSE00001540799	50445000	50447240
ENSE00002232849	50461796	50461869
ENSE00002438053	50461159	50461286
ENSE00002709774	50461523	50461718
ENSE00003471756	50447522	50447609
ENSE00003492670	50454512	50454742
ENSE00003499521	50455016	50455142
ENSE00003533209	50467338	50467448
ENSE00003544270	50468376	50468461
ENSE00003588606	50448543	50448650
ENSE00003590156	50455224	50455409
ENSE00003605639	50454814	50454944
ENSE00003620549	50466605	50466710
ENSE00003633790	50448233	50448444
ENSE00003661951	50466350	50466482
ENSE00003692002	50447322	50447453

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 98.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7222 / max 237.9970, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194745	16.7222	1797

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.18	gold quality
right testis	UBERON:0004534	98.16	gold quality
right lobe of thyroid gland	UBERON:0001119	97.88	gold quality
left lobe of thyroid gland	UBERON:0001120	97.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.72	gold quality
right frontal lobe	UBERON:0002810	97.71	gold quality
lower esophagus mucosa	UBERON:0035834	97.49	gold quality
cerebellar hemisphere	UBERON:0002245	97.16	gold quality
cingulate cortex	UBERON:0003027	97.15	gold quality
thyroid gland	UBERON:0002046	97.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.14	gold quality
anterior cingulate cortex	UBERON:0009835	97.13	gold quality
cerebellar cortex	UBERON:0002129	97.06	gold quality
amygdala	UBERON:0001876	96.83	gold quality
prefrontal cortex	UBERON:0000451	96.47	gold quality
spinal cord	UBERON:0002240	96.08	gold quality
cerebellum	UBERON:0002037	95.98	gold quality
testis	UBERON:0000473	95.89	gold quality
frontal cortex	UBERON:0001870	95.53	gold quality
skin of leg	UBERON:0001511	95.48	gold quality
neocortex	UBERON:0001950	95.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.34	gold quality
granulocyte	CL:0000094	95.28	gold quality
skin of abdomen	UBERON:0001416	95.10	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.94	gold quality
nucleus accumbens	UBERON:0001882	94.88	gold quality
Ammon’s horn	UBERON:0001954	94.88	gold quality
adenohypophysis	UBERON:0002196	94.62	gold quality
cerebral cortex	UBERON:0000956	94.48	gold quality
apex of heart	UBERON:0002098	94.47	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.25

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 8)

• MTMR2 interacts with MTMR5 via its coiled-coil domain and that mutations in the coiled-coil domain of either MTMR2 or MTMR5 abrogate this interaction. (PMID:12668758)
• Compound heterozygous mutations in SBF1 appear to be the underlying causes of a novel Charcot-Marie-Tooth disease type 4B subtype (designated as CMT4B3) in a Korean family. (PMID:23749797)
• ZNF195 and SBF1 are potential biomarkers for gemcitabine sensitivity in head and neck squamous cell carcinoma cell lines. (PMID:24817947)
• Novel sequence variants in SBF1 (c.1168C>G and c.2209_2210del) as the potential causative mutations in two siblings with severe axonal neuropathy, hearing loss, facial weakness and bulbar features. (PMID:28005197)
• The novel SBF1 null mutation highlights distinct severe phenotypic manifestations, broadening the clinical spectrum of SBF1-related neuropathies: cerebellar and pyramidal signs evident in the first months of life with peripheral polyneuropathy emerging only toward the end of the first decade, together with unique MRI findings. (PMID:30039846)
• A novel frameshift deletion in autosomal recessive SBF1-related syndromic neuropathy with necklace fibres. (PMID:32444983)
• A (GCC) repeat in SBF1 reveals a novel biological phenomenon in human and links to late onset neurocognitive disorder. (PMID:36104480)
• SBF1 (MTMR5) belongs to the myotubularin family of phosphoinositides phosphatases-like (PMID:9736772)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	sbf1	ENSDARG00000062968
mus_musculus	Sbf1	ENSMUSG00000036529
rattus_norvegicus	Sbf1	ENSRNOG00000008392
drosophila_melanogaster	mtm	FBGN0025742
drosophila_melanogaster	Sbf	FBGN0025802
drosophila_melanogaster	Mtmr6	FBGN0028497
drosophila_melanogaster	CG14411	FBGN0030582
drosophila_melanogaster	CG3632	FBGN0030735
drosophila_melanogaster	CG5026	FBGN0035945
caenorhabditis_elegans	mtm-1	WBGENE00003475
caenorhabditis_elegans		WBGENE00003476
caenorhabditis_elegans		WBGENE00003477
caenorhabditis_elegans		WBGENE00003478
caenorhabditis_elegans		WBGENE00003479
caenorhabditis_elegans	mtm-10	WBGENE00021683

Paralogs (13): MTMR7 (ENSG00000003987), MTMR11 (ENSG00000014914), MTMR1 (ENSG00000063601), MTMR2 (ENSG00000087053), MTMR3 (ENSG00000100330), MTMR8 (ENSG00000102043), MTMR9 (ENSG00000104643), MTMR4 (ENSG00000108389), SBF2 (ENSG00000133812), MTMR6 (ENSG00000139505), MTMR12 (ENSG00000150712), MTMR10 (ENSG00000166912), MTM1 (ENSG00000171100)

Protein

Protein identifiers

Myotubularin-related protein 5 — O95248 (reviewed: O95248)

Alternative names: Inactive phosphatidylinositol 3-phosphatase 5, SET-binding factor 1

All UniProt accessions (40): O95248, A0A8I5KNQ5, A0A8I5KPS7, A0A8I5KR05, A0A8I5KRX8, A0A8I5KS44, A0A8I5KS51, A0A8I5KS68, A0A8I5KS97, A0A8I5KT25, A0A8I5KT60, A0A8I5KTI7, A0A8I5KTN1, A0A8I5KU03, A0A8I5KU87, A0A8I5KUE4, A0A8I5KUL5, A0A8I5KUS0, A0A8I5KUU6, A0A8I5KVF2, A0A8I5KVI6, A0A8I5KVL6, A0A8I5KW56, A0A8I5KWB4, A0A8I5KWI8, A0A8I5KX98, A0A8I5KXH4, A0A8I5KXN1, A0A8I5KXX8, A0A8I5KXX9, A0A8I5KY28, A0A8I5KY61, A0A8I5KYG9, A0A8I5KYT4, A0A8I5KZ29, A0A8I5QJN2, A0A8I5QKN6, A0A8I5QKT8, A0A8J8YTQ8, H0Y5W8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an adapter for the phosphatase MTMR2 to regulate MTMR2 catalytic activity and subcellular location. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form. May function as a guanine nucleotide exchange factor (GEF) activating RAB28. Acts as a suppressor of autophagy in neurons. Together with its binding partner, the phosphatase MTMR2, plays a role in dephosphorylation of phosphoinositides critical for autophagy initiation and autophagosome maturation. Plays a role in positively regulating late-stage radial sorting of large caliber axons, a process leading to myelination by Schwann cells, possibly via regulating endosomal trafficking. Inhibits myoblast differentiation in vitro and induces oncogenic transformation in fibroblasts.

Subunit / interactions. Heterodimer with lipid phosphatase MTMR2. Interacts with SBF2/MTMR13; the interaction seems to be independent of the coiled-coil and PH domain of SBF2/MTMR13 and independent of MTMR2. Interacts with KMT2A/MLL1 (via SET domain). Interacts with SUV39H1.

Subcellular location. Cytoplasm. Perinuclear region. Cell projection. Neuron projection.

Tissue specificity. Expressed in neurons within the frontal cortex, in neurons of the deep cerebellar nuclei, stellate and basket cells of the molecular layer, and Golgi cells of the granular layer (at protein level).

Disease relevance. Charcot-Marie-Tooth disease, demyelinating, type 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal domain mediates interaction with MTMR2.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
O95248-1	1	yes
O95248-4	4
O95248-5	5

RefSeq proteins (4): NP_001352748, NP_001397723, NP_001397724, NP_002963* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001194	cDENN_dom	Domain
IPR001849	PH_domain	Domain
IPR004182	GRAM	Domain
IPR005112	dDENN_dom	Domain
IPR005113	uDENN_dom	Domain
IPR010569	Myotubularin-like_Pase_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR022096	SBF1/SBF2	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR030564	Myotubularin	Family
IPR037516	Tripartite_DENN	Domain
IPR043153	DENN_C	Homologous_superfamily

Pfam: PF00169, PF02141, PF02893, PF03456, PF06602, PF12335

Enzyme classification (BRENDA):

• EC 3.1.3.16 — protein-serine/threonine phosphatase (BRENDA: 92 organisms, 641 substrates, 468 inhibitors, 127 Km, 67 kcat entries)

Substrate kinetics (BRENDA)

59 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.023–0.862	22
4-NITROPHENYL PHOSPHATE	0.0028–12.7	13
P-NITROPHENYL PHOSPHATE	3–200	11
RRAPTVA	0.058–1.954	4
PHOSPHOCASEIN	0.0001–0.002	3
PHOSPHOHISTONE	0.0023–0.0723	3
PHOSPHORYLATED MYOSIN LIGHT CHAIN PEPTIDE	0.01–0.11	3
PHOSPHOSERINE-MYELIN BASIC PROTEIN	0.0004–0.022	3
DLDVPIPGRFDRRVSVAAE	0.0006–0.0138	2
DLDVPIPGRFDRRVY(P)VAAE	0.0025–0.023	2
PHOSPHORYLASE A	0.004–0.021	2
RRA(PT)VA	0.0536–0.308	2
80S-RIBOSOME	0.0027	1
AAAPTVA	0.206	1
AGPALSPVPPV	0.357	1

UniProt features (29 total): domain 6, region of interest 5, compositionally biased region 5, modified residue 4, sequence conflict 4, splice variant 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95248-F1	74.72	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 1121, 1138, 1223, 1747

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1483248	Synthesis of PIPs at the ER membrane
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs
R-HSA-1430728	Metabolism
R-HSA-1483255	PI Metabolism
R-HSA-1483257	Phospholipid metabolism
R-HSA-199991	Membrane Trafficking
R-HSA-556833	Metabolism of lipids
R-HSA-5653656	Vesicle-mediated transport
R-HSA-9007101	Rab regulation of trafficking

MSigDB gene sets: 150 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, TGACATY_UNKNOWN, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P

GO Biological Process (4): protein dephosphorylation (GO:0006470), phosphatidylinositol biosynthetic process (GO:0006661), spermatid development (GO:0007286), spermatogenesis (GO:0007283)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), protein tyrosine/serine/threonine phosphatase activity (GO:0008138), protein-membrane adaptor activity (GO:0043495)

GO Cellular Component (8): cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020), nuclear body (GO:0016604), neuron projection (GO:0043005), perinuclear region of cytoplasm (GO:0048471), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
PI Metabolism	1
Rab regulation of trafficking	1
Phospholipid metabolism	1
Metabolism of lipids	1
Vesicle-mediated transport	1
Metabolism	1
Membrane Trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoplasm	2
dephosphorylation	1
protein modification process	1
biosynthetic process	1
phosphatidylinositol metabolic process	1
germ cell development	1
spermatid differentiation	1
developmental process involved in reproduction	1
male gamete generation	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
phosphoprotein phosphatase activity	1
protein-macromolecule adaptor activity	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
nucleoplasm	1
intracellular membraneless organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SBF1	MTMR2	Q13614	771
SBF1	FIG4	Q92562	612
SBF1	SH3TC2	Q8TF17	610
SBF1	KMT2A	Q03164	609
SBF1	MTMR6	Q9Y217	609
SBF1	FGD4	Q96M96	586
SBF1	PIK3C3	Q8NEB9	577
SBF1	PLEK2	Q9NYT0	567
SBF1	PLEK	P08567	548
SBF1	CHKB	Q9Y259	535
SBF1	NEFL	P07196	521
SBF1	CREBBP	Q92793	514
SBF1	RAB21	Q9UL25	504
SBF1	MTMR14	Q8NCE2	486
SBF1	GDAP1	Q8TB36	475

IntAct

229 interactions, top by confidence:

A	B	Type	Score
MTMR2	CCDC22	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
APBA3	SBF1	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
MTMR1	GMNN	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
TGFBR2	PIK3R2	psi-mi:“MI:0914”(association)	0.530
LRRC4C	DVL2	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
HENMT1	SNX2	psi-mi:“MI:0914”(association)	0.530
RHEX	NOS1AP	psi-mi:“MI:0914”(association)	0.530
RAB6B	SBF1	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
APBA3	CLSTN1	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
SBF1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN3	SBF1	psi-mi:“MI:0407”(direct interaction)	0.440
SBF1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (216): SBF1 (Affinity Capture-MS), SBF1 (Affinity Capture-MS), SBF1 (Affinity Capture-MS), SBF1 (Affinity Capture-MS), SBF1 (Affinity Capture-MS), SBF1 (Two-hybrid), SBF1 (Affinity Capture-MS), SBF1 (Affinity Capture-MS), SBF1 (Affinity Capture-MS), SBF1 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), MTMR1 (Affinity Capture-MS), MTMR2 (Affinity Capture-MS), PRKACA (Affinity Capture-MS), RPAP3 (Affinity Capture-MS)

ESM2 similar proteins: A0JMF6, A2BGG1, A4FU01, B1WC10, E7FAW3, E9PUQ8, E9PXF8, F4JWB3, O00750, O15327, O70167, O70173, O95248, O95876, P0CE43, P97874, Q2I0E5, Q2I6J0, Q32NR9, Q3V1L6, Q4R4D7, Q5PQT2, Q5R991, Q5RA60, Q5U581, Q5ZLG9, Q60760, Q60949, Q68DX3, Q6NTN5, Q6NU08, Q6P1Y8, Q6PJI9, Q6ZPE2, Q6ZS30, Q7TPM9, Q7ZXF1, Q80U56, Q86WG5, Q8C0M0

Diamond homologs: A0JMF6, A2BGG1, A4FU01, O95248, Q13615, Q3V1L6, Q5FVM6, Q5PQT2, Q5R989, Q5U581, Q6NU08, Q6XHA7, Q6ZPE2, Q7TPM9, Q80TA6, Q8K296, Q9C0I1, Q9NXD2, A0A0G2JXT6, A6QLT4, E9PXF8, Q22712, Q5R6F6, Q6NTN5, Q7ZXF1, Q86WG5, Q91XS1, Q96EF0, Q9NYA4, Q9TXP3, Q9Y216, Q9Z2C9, Q2KJ24, Q55E58, Q6AXQ4, Q96QG7, Q9N589, Q9Z2D0, A7MB43, G2WWH6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SBF1	up-regulates	Myelination
SBF1	“up-regulates activity”	MTMR2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 203 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RHO GTPases activate PKNs	5	12.9×	2e-03
Assembly and cell surface presentation of NMDA receptors	6	12.4×	1e-03
Intrinsic Pathway for Apoptosis	5	11.9×	2e-03
Synthesis of PIPs at the plasma membrane	6	10.3×	2e-03
Neurexins and neuroligins	6	9.6×	2e-03
RHOQ GTPase cycle	6	8.8×	2e-03
Apoptosis	6	8.2×	3e-03
Golgi Associated Vesicle Biogenesis	5	8.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	28.7×	2e-08
receptor clustering	6	20.6×	1e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	6	16.3×	3e-04
establishment of protein localization	5	11.9×	9e-03
cell-cell adhesion	10	5.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2155 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	15
Uncertain significance	858
Likely benign	1032
Benign	96

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1120016	NM_002972.4(SBF1):c.2289C>T (p.Arg763=)	Pathogenic
1452526	NM_002972.4(SBF1):c.3179dup (p.Lys1061fs)	Pathogenic
1455151	NM_002972.4(SBF1):c.376C>T (p.Gln126Ter)	Pathogenic
1456060	NM_002972.4(SBF1):c.2848C>T (p.Gln950Ter)	Pathogenic
1458104	NC_000022.10:g.(?50885571)(50906910_?)del	Pathogenic
1899073	NM_002972.4(SBF1):c.4384C>T (p.Gln1462Ter)	Pathogenic
1929321	NM_002972.4(SBF1):c.3228dup (p.Ser1077fs)	Pathogenic
1952532	NM_002972.4(SBF1):c.3317del (p.Pro1106fs)	Pathogenic
2018292	NM_002972.4(SBF1):c.3447del (p.Phe1150fs)	Pathogenic
2018999	NM_002972.4(SBF1):c.5102G>A (p.Trp1701Ter)	Pathogenic
2874544	NM_002972.4(SBF1):c.3257dup (p.Pro1086_Glu1087insTer)	Pathogenic
2880513	NM_002972.4(SBF1):c.4820_4827del (p.Arg1607fs)	Pathogenic
2975329	NM_002972.4(SBF1):c.4995C>G (p.Tyr1665Ter)	Pathogenic
3248099	NC_000022.10:g.(?50885571)(50895560_?)del	Pathogenic
3342220	NM_002972.4(SBF1):c.1821dup (p.His608fs)	Pathogenic
3641149	NM_002972.4(SBF1):c.905_906del (p.Val302fs)	Pathogenic
3644969	NM_002972.4(SBF1):c.5266C>T (p.Gln1756Ter)	Pathogenic
3698557	NM_002972.4(SBF1):c.3257_3258del (p.Pro1086fs)	Pathogenic
4703784	NM_002972.4(SBF1):c.3222_3223insA (p.Pro1075fs)	Pathogenic
4723859	NM_002972.4(SBF1):c.4552C>T (p.Gln1518Ter)	Pathogenic
523853	NM_002972.4(SBF1):c.277C>T (p.Gln93Ter)	Pathogenic
565004	GRCh37/hg19 22q13.33(chr22:50613566-51197838)x1	Pathogenic
1030606	NM_002972.4(SBF1):c.161G>A (p.Trp54Ter)	Likely pathogenic
1065826	NM_002972.4(SBF1):c.2288G>A (p.Arg763His)	Likely pathogenic
1301185	NM_002972.4(SBF1):c.5474_5475del (p.Val1825fs)	Likely pathogenic
1301645	NM_002972.4(SBF1):c.5463C>G (p.Tyr1821Ter)	Likely pathogenic
1690663	NM_002972.4(SBF1):c.2958C>A (p.Cys986Ter)	Likely pathogenic
1805204	NM_002972.4(SBF1):c.2948T>C (p.Leu983Pro)	Likely pathogenic
1805241	NM_002972.4(SBF1):c.2569+2T>C	Likely pathogenic
2124472	NM_002972.4(SBF1):c.4813-1G>T	Likely pathogenic

SpliceAI

7153 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50447320:A:AC	donor_gain	1.0000
22:50447321:C:CC	donor_gain	1.0000
22:50447321:CGT:C	donor_gain	1.0000
22:50447449:CGCAG:C	acceptor_gain	1.0000
22:50447451:CAG:C	acceptor_gain	1.0000
22:50447452:AG:A	acceptor_gain	1.0000
22:50447454:C:CC	acceptor_gain	1.0000
22:50447520:A:AC	donor_gain	1.0000
22:50447521:C:CA	donor_loss	1.0000
22:50447521:C:CC	donor_gain	1.0000
22:50447619:C:CT	acceptor_gain	1.0000
22:50447619:C:T	acceptor_gain	1.0000
22:50447620:A:T	acceptor_gain	1.0000
22:50448230:TACC:T	donor_loss	1.0000
22:50448231:ACCTG:A	donor_loss	1.0000
22:50448232:C:G	donor_loss	1.0000
22:50448526:CA:C	donor_gain	1.0000
22:50448537:A:AC	donor_gain	1.0000
22:50448537:ACTC:A	donor_loss	1.0000
22:50448538:C:CC	donor_gain	1.0000
22:50448538:CT:C	donor_gain	1.0000
22:50448539:TCAC:T	donor_loss	1.0000
22:50448541:A:AC	donor_gain	1.0000
22:50448541:A:AG	donor_loss	1.0000
22:50448542:C:CC	donor_gain	1.0000
22:50448542:C:CT	donor_loss	1.0000
22:50448542:CA:C	donor_gain	1.0000
22:50448542:CACGG:C	donor_gain	1.0000
22:50448646:AGCTC:A	acceptor_gain	1.0000
22:50448647:GCTC:G	acceptor_gain	1.0000

AlphaMissense

12262 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50447178:C:A	W1857C	1.000
22:50447178:C:G	W1857C	1.000
22:50447180:A:G	W1857R	1.000
22:50447180:A:T	W1857R	1.000
22:50447212:A:G	F1846S	1.000
22:50447326:A:G	F1835S	1.000
22:50447452:A:G	L1793P	1.000
22:50447541:A:G	L1786P	1.000
22:50447546:G:C	F1784L	1.000
22:50447546:G:T	F1784L	1.000
22:50447547:A:G	F1784S	1.000
22:50447548:A:G	F1784L	1.000
22:50447561:C:A	W1779C	1.000
22:50447561:C:G	W1779C	1.000
22:50447563:A:G	W1779R	1.000
22:50447563:A:T	W1779R	1.000
22:50447585:C:A	K1771N	1.000
22:50447585:C:G	K1771N	1.000
22:50447587:T:C	K1771E	1.000
22:50455331:A:G	W1458R	1.000
22:50455331:A:T	W1458R	1.000
22:50459975:G:C	N1157K	1.000
22:50459975:G:T	N1157K	1.000
22:50462002:G:C	C839W	1.000
22:50462642:A:G	W683R	1.000
22:50462642:A:T	W683R	1.000
22:50462660:A:G	W677R	1.000
22:50462660:A:T	W677R	1.000
22:50447167:A:T	I1861N	0.999
22:50447179:C:G	W1857S	0.999

dbSNP variants (sampled 300 via entrez): RS1000054851 (22:50473068 A>G,T), RS1000072983 (22:50473433 T>C), RS1000078416 (22:50448355 G>A), RS1000241515 (22:50458402 A>G,T), RS1000291288 (22:50462409 C>T), RS1000303921 (22:50469232 C>CTCCCTG), RS1000416950 (22:50466265 A>G), RS1000445852 (22:50455944 C>T), RS1000596404 (22:50450616 C>T), RS1000691197 (22:50455639 C>G,T), RS1000693302 (22:50477001 G>C), RS1000860502 (22:50455826 C>T), RS1000988084 (22:50458186 T>A), RS1001015434 (22:50476178 GTTTT>G,GT,GTTT,GTTTTTT), RS1001193240 (22:50472839 A>C)

Disease associations

OMIM: gene MIM:603560 | disease phenotypes: MIM:615284, MIM:118220, MIM:302800, MIM:302900

GenCC curated gene-disease

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 4B3	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 4B3	Moderate	AR

Mondo (7): Charcot-Marie-Tooth disease type 4B3 (MONDO:0014117), Charcot-Marie-Tooth disease (MONDO:0015626), peripheral neuropathy (MONDO:0005244), microcephaly (MONDO:0001149), autism spectrum disorder (MONDO:0005258), Charcot-Marie-Tooth disease type 4 (MONDO:0018995), Charcot-Marie-Tooth disease X-linked dominant 1 (MONDO:0010549)

Orphanet (5): Charcot-Marie-Tooth disease type 4B3 (Orphanet:363981), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Charcot-Marie-Tooth disease type 4 (Orphanet:64749), X-linked Charcot-Marie-Tooth disease type 1 (Orphanet:101075), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

24 total (24 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000020	Urinary incontinence
HP:0000252	Microcephaly
HP:0000486	Strabismus
HP:0000602	Ophthalmoplegia
HP:0000762	Decreased nerve conduction velocity
HP:0001159	Syndactyly
HP:0001249	Intellectual disability
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001763	Pes planus
HP:0002505	Loss of ambulation
HP:0002650	Scoliosis
HP:0002936	Distal sensory impairment
HP:0003202	Skeletal muscle atrophy
HP:0003383	Onion bulb formation
HP:0003484	Upper limb muscle weakness
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0004336	Myelin outfoldings
HP:0007340	Lower limb muscle weakness
HP:0009053	Distal lower limb muscle weakness
HP:0010546	Muscle fibrillation
HP:0012444	Brain atrophy

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C564446	Charcot-Marie-Tooth Peroneal Muscular Atrophy and Friedreich Ataxia, Combined (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases abundance	4
Arsenic	affects expression, affects methylation, increases abundance, increases expression	4
Lead	affects splicing, decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases expression	1
methylparaben	increases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	increases abundance, increases expression	1
ochratoxin A	decreases expression	1
cupric chloride	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation, increases ADP-ribosylation	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Caffeine	increases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Dieldrin	decreases expression	1
Manganese	increases abundance, increases expression	1
Ozone	affects expression, increases abundance	1
Rotenone	decreases expression	1
Smoke	decreases expression	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C3RC	CSSi016-A	Induced pluripotent stem cell	Female
CVCL_D7HE	Ubigene HEK293T SBF1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	PHASE3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	PHASE3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	PHASE3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	PHASE3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	PHASE3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	PHASE3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	PHASE3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	PHASE3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	PHASE3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	PHASE3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	PHASE3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	PHASE3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	PHASE3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	PHASE3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy