SPTB

spectrin beta, erythrocytic, the group of Spectrins|Pleckstrin homology domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 14:64746283-64879907

Links

ENSG00000070182 ∙ NCBI:6710 ∙ OMIM:182870 ∙ HGNC:11274 ∙ Uniprot:P11277 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary spherocytosis (Supportive), mode of inheritance: AD
• hereditary elliptocytosis (Supportive), mode of inheritance: AD
• hereditary spherocytosis type 2 (Strong), mode of inheritance: AD
• elliptocytosis 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spherocytosis, type 2; Ellipsocytosis 3	AD/AR	Hematologic	Some individuals may have severe, transfusion-requiring anemia, and splenectomy may also be beneficial	Hematologic	4426130; 7229027; 7119110; 7104494; 4052329; 3276733; 2807277; 2346784; 2070088; 1391962; 8102379; 8226774; 7883966; 8675627; 8844207; 9075575; 9005995; 9163587; 9414314; 9450796; 9609518; 9887280; 11703334; 19538529

ClinVar

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

• not_provided (1058 variants)
• Inborn_genetic_diseases (287 variants)
• Hereditary_spherocytosis_type_2 (139 variants)
• Elliptocytosis (99 variants)
• Spherocytosis,_Dominant (99 variants)
• SPTB-related_disorder (86 variants)
• Elliptocytosis_3 (39 variants)
• not_specified (38 variants)
• Hereditary_spherocytosis (5 variants)
• Familial_hemolytic_anemia (3 variants)
• Spherocytosis (3 variants)
• Pyropoikilocytosis,_hereditary (2 variants)
• Anemia (1 variants)
• Hemolytic_anemia (1 variants)
• Chudley-McCullough_syndrome (1 variants)
• See_cases (1 variants)
• ANEMIA,_PERINATAL_HEMOLYTIC,_FATAL_OR_NEAR-FATAL (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPTB gene is commonly pathogenic or not. These statistics are base on transcript: NM_001355436.2. 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		2	15	131	13	161
missense	7	16	589	72	1	685
nonsense	82	103				185
start loss		1	1			2
frameshift	81	144				225
splice donor/acceptor (+/-2bp)	15	50	1			66
Total	185	316	606	203	14

Highest pathogenic variant AF is 0.000203263

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPTB	protein_coding	protein_coding	ENST00000389722	35	133600

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.95e-12	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.751	1278	1.36e+3	0.943	0.0000939	15320
Missense in Polyphen		426	501.12	0.8501		5895
Synonymous	-2.28	657	587	1.12	0.0000414	4464
Loss of Function	9.03	9	112	0.0802	0.00000574	1250

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.00153	0.00147
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000708	0.0000703
Middle Eastern	0.00153	0.00147
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane.
• Disease: DISEASE: Elliptocytosis 3 (EL3) [MIM:617948]: A Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous hematologic disorder characterized by variable hemolytic anemia and elliptical or oval red cell shape. Inheritance can be autosomal dominant or autosomal recessive. {ECO:0000269|PubMed:1975598, ECO:0000269|PubMed:7883966, ECO:0000269|PubMed:8018926, ECO:0000269|PubMed:8226774}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spherocytosis 2 (SPH2) [MIM:616649]: An autosomal dominant form of hereditary spherocytosis, a group of hematologic disorders characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. Clinical manifestations include chronic hemolytic anemia, jaundice, and splenomegaly, with variable severity. {ECO:0000269|PubMed:19538529, ECO:0000269|PubMed:8102379}. 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: 0.330

Intolerance Scores

• loftool: 0.144
• rvis_EVS: -2.64
• rvis_percentile_EVS: 0.78

Haploinsufficiency Scores

• pHI: 0.313
• hipred: Y
• hipred_score: 0.793
• ghis: 0.557

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.853

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Sptb
• 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); hematopoietic 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); liver/biliary system phenotype; renal/urinary system phenotype; immune system 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: sptb
• Affected structure: nucleate erythrocyte
• Phenotype tag: abnormal
• Phenotype quality: teardrop-shaped

Gene ontology

• Biological process: MAPK cascade;endoplasmic reticulum to Golgi vesicle-mediated transport;cytoskeleton organization;axon guidance;actin filament capping
• Cellular component: Golgi apparatus;cytosol;spectrin;spectrin-associated cytoskeleton;actin cytoskeleton;intrinsic component of the cytoplasmic side of the plasma membrane;protein-containing complex
• Molecular function: actin binding;Ras guanyl-nucleotide exchange factor activity;structural constituent of cytoskeleton;protein binding;ankyrin binding;actin filament binding