SPTA1

spectrin alpha, erythrocytic 1, the group of EF-hand domain containing|Spectrins

Basic information

Region (hg38): 1:158610704-158686715

Links

ENSG00000163554 ∙ NCBI:6708 ∙ OMIM:182860 ∙ HGNC:11272 ∙ Uniprot:P02549 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spherocytosis, type 3; Pyropoikilocytosis , hereditary; Ellipsocytosis 2	AD/AR	Hematologic	Individuals have been described with severe hemolytic anemia, which has been treated by interventions such as frequent transfusions and splenectomy	Hematologic	1191563; 7070419; 2987946; 3785322; 3597773; 2567189; 2794061; 1541680; 8226774; 8941647; 16150946; 21251457

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPTA1 gene.

• not_provided (1017 variants)
• not_specified (436 variants)
• Elliptocytosis_2 (256 variants)
• Hereditary_spherocytosis_type_3 (250 variants)
• Pyropoikilocytosis,_hereditary (242 variants)
• SPTA1-related_disorder (56 variants)
• Elliptocytosis (8 variants)
• Spherocytosis,_Recessive (8 variants)
• Familial_hemolytic_anemia (4 variants)
• Hereditary_spherocytosis (2 variants)
• Hemolytic_anemia (2 variants)
• See_cases (2 variants)
• Spherocytosis (2 variants)
• Hereditary_spherocytosis_type_2 (1 variants)
• Anemia (1 variants)
• Autosomal_recessive_SPTA1-related_disorders (1 variants)
• Prenatal_anemia (1 variants)
• Inborn_genetic_diseases (1 variants)
• Lysinuric_protein_intolerance (1 variants)
• Juvenile_polyposis/hereditary_hemorrhagic_telangiectasia_syndrome (1 variants)
• Abnormality_of_blood_and_blood-forming_tissues (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPTA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003126.4. 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		2	30	97	18	147
missense	3	22	714	137	7	883
nonsense	34	56	3			93
start loss			2			2
frameshift	17	41	2			60
splice donor/acceptor (+/-2bp)	5	39	2			46
Total	59	160	753	234	25

Highest pathogenic variant AF is 0.006348737

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPTA1	protein_coding	protein_coding	ENST00000368147	52	75993

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		124691	0	109	124800	0.000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.25	1456	1.23e+3	1.18	0.0000709	16002
Missense in Polyphen		569	482.03	1.1804		6693
Synonymous	-2.89	540	461	1.17	0.0000242	4375
Loss of Function	6.75	57	145	0.394	0.00000844	1685

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00103	0.00103
Ashkenazi Jewish	0.000596	0.000596
East Asian	0.000223	0.000222
Finnish	0.000186	0.000186
European (Non-Finnish)	0.000434	0.000433
Middle Eastern	0.000223	0.000222
South Asian	0.000523	0.000523
Other	0.000331	0.000330

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 2 (EL2) [MIM:130600]: A Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape. {ECO:0000269|PubMed:1541680, ECO:0000269|PubMed:1638030, ECO:0000269|PubMed:1679439, ECO:0000269|PubMed:1878597, ECO:0000269|PubMed:2384601, ECO:0000269|PubMed:2568861, ECO:0000269|PubMed:2568862, ECO:0000269|PubMed:2794061, ECO:0000269|PubMed:7772539, ECO:0000269|PubMed:8018926, ECO:0000269|PubMed:8193371, ECO:0000269|PubMed:8364215}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hereditary pyropoikilocytosis (HPP) [MIM:266140]: Autosomal recessive hematologic disorder characterized by hemolytic anemia, microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells. {ECO:0000269|PubMed:1878597}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spherocytosis 3 (SPH3) [MIM:270970]: Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH3 is characterized by severe hemolytic anemia. Inheritance is autosomal recessive. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Apoptosis - Homo sapiens (human);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: 0.0869

Intolerance Scores

• loftool: 0.806
• rvis_EVS: 4.85
• rvis_percentile_EVS: 99.79

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.579

Gene Damage Prediction

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

Gene ontology

• Biological process: MAPK cascade;lymphocyte homeostasis;porphyrin-containing compound biosynthetic process;endoplasmic reticulum to Golgi vesicle-mediated transport;plasma membrane organization;actin filament organization;axon guidance;regulation of cell shape;hemopoiesis;positive regulation of protein binding;positive regulation of T cell proliferation;actin filament capping
• Cellular component: cytosol;spectrin;spectrin-associated cytoskeleton;actin cytoskeleton;axon;intrinsic component of the cytoplasmic side of the plasma membrane;cuticular plate
• Molecular function: Ras guanyl-nucleotide exchange factor activity;structural constituent of cytoskeleton;calcium ion binding;protein binding;protein heterodimerization activity;actin filament binding