SPTB

protein-coding

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

Gene summary

This locus encodes a member of the spectrin gene family. Spectrin proteins, along with ankyrin, play a role in cell membrane organization and stability. The protein encoded by this locus functions in stability of erythrocyte membranes, and mutations in this gene have been associated with spherocytosis type 2, hereditary elliptocytosis, and neonatal hemolytic anemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

MANE transcript

NM_001355436.2

Inheritance

AD, AR

ClinVar variants

P:603U:693B:286

Top phenotype

Spherocytosis, type 2; Ellipsocytosis 3

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr14:64,746,283-64,879,907

External References & Databases

Ensembl (ENSG00000070182)

Transcript & Mutation Effects

hg38 • Region Span ~133.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary spherocytosis type 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0000913

Submitter: PanelApp Australia

elliptocytosis 3STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0054780

Submitter: PanelApp Australia

elliptocytosis 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054780

Submitter: PanelApp Australia

elliptocytosis 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0054780

Submitter: Labcorp Genetics (formerly Invitae)

hereditary spherocytosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019350

Submitter: Orphanet

hereditary elliptocytosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0017319

Submitter: Orphanet

hereditary spherocytosis type 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0000913

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Spherocytosis, type 2; Ellipsocytosis 3AD/AR

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Some individuals may have severe, transfusion-requiring anemia, and splenectomy may also be beneficial

Refs: 4426130; 7229027; 7119110; 7104494; 4052329; 3276733; 2807277; 2346784; 2070088; 1391962; 8102379; 8226774; 7883966; 8675627; 8844207; 9075575; 9005995; 9163587; 9414314; 9450796; 9609518; 9887280; 11703334; 19538529

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPTB variants in ClinVar

18 Conditions Cataloged

not providedTotal: 1279

Inborn genetic diseasesTotal: 327

SPTB-related disorderTotal: 175

Hereditary spherocytosis type 2Total: 160

not specifiedTotal: 155

Elliptocytosis 3Total: 43

Hereditary spherocytosisTotal: 6

Rare anaemiaTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001355436.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	15 clinvar	199 clinvar	7 clinvar	222
missense	5 clinvar	16 clinvar	674 clinvar	80 clinvar		775
nonsense	92 clinvar	125 clinvar				217
start loss		2 clinvar				2
frameshift	104 clinvar	177 clinvar				281
splice donor/acceptor (+/-2bp)	16 clinvar	65 clinvar	4 clinvar			85
Total	217	386	693	279	7	1582

Highest pathogenic variant AF is 0.00020326336

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001355436.2	RefSeq	NP_001342365.1	35	MANE Select
ENST00000644917.1	Ensembl	ENSP00000495909.1	35	MANE Select
NM_001024858.4	RefSeq	NP_001020029.1	35	Standard
NM_001355437.2	RefSeq	NP_001342366.1	31	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sptb	Danio rerio	Structure: nucleate erythrocyte Quality: teardrop-shaped abnormal

Gene / Model

Organism

Observed Phenotype

sptb

Danio rerio

Structure: nucleate erythrocyte

Quality: teardrop-shaped

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
Signal Transduction
Vesicle-mediated transport
Membrane Trafficking
Post-translational protein modification

Biological Process

MAPK cascade
endoplasmic reticulum to Golgi vesicle-mediated transport
cytoskeleton organization
axon guidance
actin filament capping

Molecular Function

actin binding
Ras guanyl-nucleotide exchange factor activity
structural constituent of cytoskeleton
protein binding
ankyrin binding

Cellular Component

Golgi apparatus
cytosol
spectrin
spectrin-associated cytoskeleton
actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389722
Coding exons: 35
Length: 133600
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125748
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.751	1278	1.36e+3	0.943	0.0000939	15320
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0015	0.0015	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.330

Intolerance Scores

LoFtool: 0.144
RVIS EVS: -2.64
RVIS percentile EVS: 0.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.853

Gene Damage Prediction

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