SPTAN1

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

Basic information

Region (hg38): 9:128552558-128633662

Links

ENSG00000197694 ∙ NCBI:6709 ∙ OMIM:182810 ∙ HGNC:11273 ∙ Uniprot:Q13813 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 5 (Definitive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 5 (Definitive), mode of inheritance: AD
• West syndrome (Supportive), mode of inheritance: AD
• developmental and epileptic encephalopathy, 5 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy, 5 (Strong), mode of inheritance: AD
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 5; Developmental delay with or without epilepsy; Neuronopathy, distal hereditary motor, 11, autosomal dominant; Spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia	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	Neurologic	18469812; 18065176; 20493457; 22258530; 29050398; 31332438; 33206935; 33578420; 35150594; 36331550
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPTAN1 gene.

• Early infantile epileptic encephalopathy with suppression bursts (20 variants)
• Developmental and epileptic encephalopathy, 5 (6 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPTAN1 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			10	581	19	610
missense	3	22	808	117	15	965
nonsense	10	8	12			30
start loss						0
frameshift	13	3	7			23
inframe indel	3	13	9			25
splice donor/acceptor (+/-2bp)		8	2		1	11
splice region			70	115	11	196
non coding			19	416	111	546
Total	29	54	867	1114	146

Variants in SPTAN1

This is a list of pathogenic ClinVar variants found in the SPTAN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-128552633-G-GGCTCCTCGGTCCTTCAGC		not specified	Likely benign (Mar 15, 2016)
9-128552666-C-G		not specified	Likely benign (Sep 24, 2012)
9-128552680-T-C		not specified	Likely benign (Jan 28, 2016)
9-128552687-C-G		not specified	Likely benign (Mar 08, 2017)
9-128552696-G-A		not specified	Likely benign (Jan 06, 2016)
9-128552713-G-A		not specified	Likely benign (Jun 20, 2016)
9-128552752-C-G			Likely benign (Feb 08, 2022)
9-128566720-C-T			Benign (Mar 03, 2015)
9-128566746-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Apr 16, 2022)
9-128566761-A-T		Inborn genetic diseases	Uncertain significance (Jun 30, 2016)
9-128566777-G-C		Developmental and epileptic encephalopathy, 5	Uncertain significance (-)
9-128566785-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Mar 10, 2022)
9-128566787-A-G		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Jan 14, 2021)
9-128566795-C-A		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Nov 23, 2022)
9-128566795-C-T		Early infantile epileptic encephalopathy with suppression bursts • SPTAN1-related disorder • Spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia	Conflicting classifications of pathogenicity (Aug 29, 2024)
9-128566796-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Dec 02, 2023)
9-128566797-G-A		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Dec 11, 2023)
9-128566797-G-GC		Early infantile epileptic encephalopathy with suppression bursts	Pathogenic (May 16, 2023)
9-128566809-A-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Dec 17, 2022)
9-128566813-C-T		Developmental and epileptic encephalopathy, 5 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 22, 2023)
9-128566814-G-A		Developmental and epileptic encephalopathy, 5 • Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (Feb 11, 2022)
9-128566822-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Jun 17, 2022)
9-128566823-G-A		Inborn genetic diseases • Early infantile epileptic encephalopathy with suppression bursts	Conflicting classifications of pathogenicity (Feb 11, 2022)
9-128566824-C-T		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Mar 30, 2020)
9-128566829-A-G		Early infantile epileptic encephalopathy with suppression bursts	Likely benign (Sep 14, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPTAN1	protein_coding	protein_coding	ENST00000372739	56	81076

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.37e-18	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.52	802	1.38e+3	0.582	0.0000917	16469
Missense in Polyphen		230	520.81	0.44162		6284
Synonymous	-1.25	574	537	1.07	0.0000352	4517
Loss of Function	10.5	8	143	0.0559	0.00000783	1644

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000232	0.000232
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000969	0.0000967
Middle Eastern	0.000272	0.000272
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.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 5 (EIEE5) [MIM:613477]: A disorder characterized by seizures associated with hypsarrhythmia, profound mental retardation with lack of visual attention and speech development, as well as spastic quadriplegia. {ECO:0000269|PubMed:20493457, ECO:0000269|PubMed:27864847}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Apoptosis - Homo sapiens (human);Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Developmental Biology;Neutrophil degranulation;Signal Transduction;Vesicle-mediated transport;ucalpain and friends in cell spread;induction of apoptosis through dr3 and dr4/5 death receptors;hiv-1 nef: negative effector of fas and tnf;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Caspase-mediated cleavage of cytoskeletal proteins;Apoptotic cleavage of cellular proteins;Innate Immune System;Immune System;Apoptotic execution phase;Apoptosis;Programmed Cell Death;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;Caspase Cascade in Apoptosis (Consensus)

Recessive Scores

• pRec: 0.391

Intolerance Scores

• loftool: 0.116
• rvis_EVS: -3.53
• rvis_percentile_EVS: 0.31

Haploinsufficiency Scores

• pHI: 0.603
• hipred: Y
• hipred_score: 0.736
• ghis: 0.659

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.930

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sptan1
• Phenotype: craniofacial phenotype; cellular phenotype; growth/size/body region 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); embryo 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); normal 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)

Zebrafish Information Network

• Gene name: sptan1
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: lethal (sensu genetics)

Gene ontology

• Biological process: MAPK cascade;endoplasmic reticulum to Golgi vesicle-mediated transport;cytoskeleton organization;axon guidance;neutrophil degranulation;actin filament capping
• Cellular component: extracellular region;cytosol;spectrin;microtubule cytoskeleton;membrane;specific granule lumen;intracellular membrane-bounded organelle;extracellular exosome;extracellular vesicle;tertiary granule lumen
• Molecular function: actin binding;Ras guanyl-nucleotide exchange factor activity;structural constituent of cytoskeleton;calcium ion binding;protein binding;calmodulin binding;cadherin binding