SPTBN2

spectrin beta, non-erythrocytic 2, the group of Spectrins|Pleckstrin homology domain containing

Basic information

Region (hg38): 11:66682496-66744670

Previous symbols: [ "SCA5" ]

Links

ENSG00000173898 ∙ NCBI:6712 ∙ OMIM:604985 ∙ HGNC:11276 ∙ Uniprot:O15020 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spinocerebellar ataxia 14 (Strong), mode of inheritance: AR
• spinocerebellar ataxia type 5 (Supportive), mode of inheritance: AD
• autosomal recessive spinocerebellar ataxia 14 (Supportive), mode of inheritance: AR
• spinocerebellar ataxia type 5 (Strong), mode of inheritance: AD
• spinocerebellar ataxia type 5 (Strong), mode of inheritance: AD
• autosomal recessive spinocerebellar ataxia 14 (Strong), mode of inheritance: AR
• spinocerebellar ataxia type 5 (Strong), mode of inheritance: AD
• autosomal recessive spinocerebellar ataxia 14 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 5, autosomal dominant; Spinocerebellar ataxia 14, autosomal recessive	AD/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; Ophthalmologic	16429157; 23236289; 23838597

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPTBN2 gene.

• not_provided (1013 variants)
• Inborn_genetic_diseases (308 variants)
• not_specified (141 variants)
• Spinocerebellar_ataxia_type_5 (106 variants)
• Autosomal_dominant_cerebellar_ataxia (68 variants)
• Autosomal_recessive_spinocerebellar_ataxia_14 (66 variants)
• SPTBN2-related_disorder (38 variants)
• See_cases (4 variants)
• Autosomal_recessive_cerebellar_ataxia (4 variants)
• Hereditary_ataxia (2 variants)
• Intellectual_disability (1 variants)
• Cerebellar_ataxia (1 variants)
• Hereditary_spastic_paraplegia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPTBN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006946.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			23	252	33	308
missense	4	24	561	171	11	771
nonsense	9	2	1			12
start loss						0
frameshift	4	4	3			11
splice donor/acceptor (+/-2bp)	5	2	1			8
Total	22	32	589	423	44

Highest pathogenic variant AF is 0.0000830572

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPTBN2	protein_coding	protein_coding	ENST00000533211	36	43979

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000993	1.00	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.63	1209	1.50e+3	0.808	0.000111	15347
Missense in Polyphen		459	664.15	0.69111		6992
Synonymous	-0.589	653	634	1.03	0.0000470	4851
Loss of Function	7.64	34	127	0.268	0.00000763	1257

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000398	0.000398
Ashkenazi Jewish	0.000473	0.000397
East Asian	0.000327	0.000326
Finnish	0.000288	0.000231
European (Non-Finnish)	0.000172	0.000167
Middle Eastern	0.000327	0.000326
South Asian	0.000363	0.000359
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probably plays an important role in neuronal membrane skeleton.
• Disease: DISEASE: Spinocerebellar ataxia, autosomal recessive, 14 (SCAR14) [MIM:615386]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR14 is characterized by delayed psychomotor development, severe early onset gait ataxia, eye movement abnormalities, cerebellar atrophy on brain imaging, and intellectual disability. {ECO:0000269|PubMed:23236289, ECO:0000269|PubMed:23838597}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Developmental Biology;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Interaction between L1 and Ankyrins;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;NCAM signaling for neurite out-growth;L1CAM interactions;COPI-mediated anterograde transport;Axon guidance;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.205

Intolerance Scores

• loftool: 0.469
• rvis_EVS: -4.23
• rvis_percentile_EVS: 0.14

Haploinsufficiency Scores

• pHI: 0.374
• hipred: Y
• hipred_score: 0.644
• ghis: 0.573

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.816

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sptbn2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; limbs/digits/tail phenotype; 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); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: MAPK cascade;endoplasmic reticulum to Golgi vesicle-mediated transport;cytoskeleton organization;axon guidance;synapse assembly;vesicle-mediated transport;antigen processing and presentation of exogenous peptide antigen via MHC class II;cerebellar Purkinje cell layer morphogenesis;adult behavior;multicellular organism growth;actin filament capping;postsynapse organization
• Cellular component: extracellular space;cytosol;spectrin;apical plasma membrane;cell junction;neuronal cell body;parallel fiber to Purkinje cell synapse;presynapse;glutamatergic synapse;postsynaptic spectrin-associated cytoskeleton
• Molecular function: actin binding;Ras guanyl-nucleotide exchange factor activity;structural constituent of cytoskeleton;phospholipid binding;cadherin binding;structural constituent of synapse