SPTBN1

spectrin beta, non-erythrocytic 1, the group of Pleckstrin homology domain containing|Spectrins

Basic information

Region (hg38): 2:54456327-54671446

Links

ENSG00000115306 ∙ NCBI:6711 ∙ OMIM:182790 ∙ HGNC:11275 ∙ Uniprot:Q01082 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental delay, impaired speech, and behavioral abnormalities (Strong), mode of inheritance: AD
• developmental delay, impaired speech, and behavioral abnormalities (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Devlopmental delay, impaired speech, and behavioral abnormalities	AD	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	Craniofacial; Musculoskeletal; Neurologic	34211179

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPTBN1 gene.

• Developmental delay, impaired speech, and behavioral abnormalities (3 variants)
• Inborn genetic diseases (2 variants)
• Pervasive developmental disorder;Intellectual disability, autosomal recessive 53 (1 variants)
• SPTBN1-related disorder (1 variants)
• not provided (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPTBN1 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				17	8	25
missense	2	8	175	18	1	204
nonsense		5	5			10
start loss						0
frameshift	5	3				8
inframe indel	1					1
splice donor/acceptor (+/-2bp)	1	1	2			4
splice region			5		3	8
non coding						0
Total	9	17	182	35	9

Variants in SPTBN1

This is a list of pathogenic ClinVar variants found in the SPTBN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-54526450-A-G			Uncertain significance (Jan 01, 2024)
2-54526489-G-A		Inborn genetic diseases	Uncertain significance (Apr 18, 2023)
2-54526523-C-T			Likely benign (Feb 01, 2023)
2-54526528-C-T		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
2-54526531-G-A		Inborn genetic diseases	Uncertain significance (Aug 17, 2022)
2-54526548-C-T			Uncertain significance (Mar 01, 2024)
2-54558878-C-T			Uncertain significance (Nov 20, 2023)
2-54558889-T-C		SPTBN1-related disorder	Uncertain significance (May 17, 2024)
2-54558897-C-A		SPTBN1-related disorder	Likely benign (Mar 28, 2024)
2-54599092-A-T			Uncertain significance (Jan 09, 2024)
2-54599103-GC-TG			Uncertain significance (Apr 21, 2022)
2-54599108-G-C			Likely benign (Jan 01, 2023)
2-54599119-C-G		Developmental delay, impaired speech, and behavioral abnormalities	Pathogenic (Mar 24, 2022)
2-54599119-C-T		Developmental delay, impaired speech, and behavioral abnormalities	Likely pathogenic (Sep 02, 2021)
2-54599152-G-A		Inborn genetic diseases	Uncertain significance (Oct 21, 2021)
2-54599158-C-G		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
2-54599163-C-T		not specified	Uncertain significance (Nov 24, 2023)
2-54599202-A-T			Uncertain significance (Aug 18, 2017)
2-54599225-C-T			Likely benign (Jul 01, 2024)
2-54612188-A-T		Developmental disorder	Likely benign (Nov 16, 2023)
2-54612190-C-G			Uncertain significance (Aug 01, 2023)
2-54612196-C-T			Benign (Jan 30, 2018)
2-54612260-G-C		SPTBN1-related disorder	Uncertain significance (Dec 20, 2023)
2-54612290-C-T		Developmental delay, impaired speech, and behavioral abnormalities	Uncertain significance (Nov 18, 2022)
2-54612321-T-G			Uncertain significance (Dec 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPTBN1	protein_coding	protein_coding	ENST00000356805	35	213391

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.78e-16	125739	0	9	125748	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.54	931	1.41e+3	0.660	0.0000895	15788
Missense in Polyphen		224	521.25	0.42974		5848
Synonymous	-3.44	671	567	1.18	0.0000389	4329
Loss of Function	9.70	5	119	0.0419	0.00000605	1332

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000149	0.000149
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.0000546	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
• Pathway: TGF-beta Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Developmental Biology;Signal Transduction;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;TGF_beta_Receptor;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;Nephrin family interactions;Cell-Cell communication;TGF-beta receptor signaling (Consensus)

Recessive Scores

• pRec: 0.371

Intolerance Scores

• loftool: 0.131
• rvis_EVS: -3.86
• rvis_percentile_EVS: 0.22

Haploinsufficiency Scores

• pHI: 0.271
• hipred: Y
• hipred_score: 0.825
• ghis: 0.644

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.905

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sptbn1
• Phenotype: embryo phenotype; liver/biliary 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; hearing/vestibular/ear 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); digestive/alimentary phenotype; renal/urinary system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: MAPK cascade;mitotic cytokinesis;endoplasmic reticulum to Golgi vesicle-mediated transport;plasma membrane organization;cytoskeleton organization;common-partner SMAD protein phosphorylation;axon guidance;Golgi to plasma membrane protein transport;actin filament capping;regulation of SMAD protein signal transduction;membrane assembly;protein localization to plasma membrane;positive regulation of interleukin-2 secretion;regulation of protein localization to plasma membrane;positive regulation of protein localization to plasma membrane
• Cellular component: nucleolus;cytoplasm;cytosol;spectrin;postsynaptic density;spectrin-associated cytoskeleton;axolemma;M band;cuticular plate;protein-containing complex;extracellular exosome;glutamatergic synapse
• Molecular function: RNA binding;actin binding;Ras guanyl-nucleotide exchange factor activity;structural constituent of cytoskeleton;protein binding;calmodulin binding;phospholipid binding;ankyrin binding;protein-containing complex binding;cadherin binding;GTPase binding