SPTBN4

spectrin beta, non-erythrocytic 4, the group of Spectrins|Pleckstrin homology domain containing

Basic information

Region (hg38): 19:40466240-40576464

Links

ENSG00000160460 ∙ NCBI:57731 ∙ OMIM:606214 ∙ HGNC:14896 ∙ Uniprot:Q9H254 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with hypotonia, neuropathy, and deafness (Strong), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, neuropathy, and deafness (Definitive), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, neuropathy, and deafness (Strong), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, neuropathy, and deafness (Strong), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, neuropathy, and deafness (Definitive), 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	AR	Hematologic	Individuals with Spherocytosis, Pyropoikilocytosis, and Ellipsocytosis have been described with severe hemolytic anemia, which has been treated by interventions such as frequent transfusions and splenectomy	Audiologic/Otolaryngologic; Craniofacial; Hematologic; Musculoskeletal; Neurologic	1191563; 7070419; 2987946; 3785322; 3597773; 2567189; 2794061; 1541680; 8226774; 8941647; 16150946; 21251457; 28540413

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPTBN4 gene.

• Neurodevelopmental disorder with hypotonia, neuropathy, and deafness (7 variants)
• not provided (3 variants)
• Inborn genetic diseases (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPTBN4 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				65	9	74
missense		1	211	10	8	230
nonsense	5	3	1			9
start loss						0
frameshift	6	5				11
inframe indel			1	2		3
splice donor/acceptor (+/-2bp)	1	1	1			3
splice region				8	2	10
non coding			1	3	34	38
Total	12	10	215	80	51

Variants in SPTBN4

This is a list of pathogenic ClinVar variants found in the SPTBN4 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-40472546-G-A			Benign (May 16, 2021)
19-40472632-T-C		Inborn genetic diseases	Uncertain significance (Apr 07, 2022)
19-40472663-G-A		SPTBN4-related disorder	Likely benign (May 07, 2019)
19-40472683-C-T		Inborn genetic diseases	Likely benign (Sep 09, 2021)
19-40472685-G-A		Neurodevelopmental disorder with hypotonia, neuropathy, and deafness	Uncertain significance (Aug 13, 2021)
19-40472692-G-A			Uncertain significance (Dec 30, 2023)
19-40472704-C-T		Inborn genetic diseases	Uncertain significance (Jan 25, 2022)
19-40472709-C-G		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
19-40472721-C-T		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
19-40472733-G-A		Neurodevelopmental disorder with hypotonia, neuropathy, and deafness	Benign (Jul 15, 2021)
19-40472736-G-T		Inborn genetic diseases	Uncertain significance (Mar 11, 2024)
19-40472737-C-T		SPTBN4-related disorder	Likely benign (Jul 01, 2024)
19-40472749-C-T		Inborn genetic diseases	Uncertain significance (Apr 01, 2021)
19-40472779-A-G		Inborn genetic diseases	Uncertain significance (Sep 22, 2021)
19-40472781-G-A			Uncertain significance (Jun 16, 2022)
19-40472853-C-T			Benign (May 15, 2021)
19-40472962-C-A			Benign (May 15, 2021)
19-40487509-C-T			Benign (May 16, 2021)
19-40487742-A-G		Inborn genetic diseases	Uncertain significance (Jul 31, 2023)
19-40487752-C-T		SPTBN4-related disorder	Likely benign (Nov 16, 2019)
19-40487839-G-A		SPTBN4-related disorder	Likely benign (Feb 01, 2023)
19-40489864-T-A			Benign (May 17, 2021)
19-40490101-G-A		SPTBN4-related disorder	Benign/Likely benign (Jun 07, 2019)
19-40490153-C-T		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
19-40490208-T-G		Neurodevelopmental disorder with hypotonia, neuropathy, and deafness	Uncertain significance (Feb 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPTBN4	protein_coding	protein_coding	ENST00000352632	35	110223

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	9.97e-9	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.93	958	1.37e+3	0.701	0.0000859	16172
Missense in Polyphen		292	450.17	0.64864		5177
Synonymous	2.79	508	595	0.854	0.0000376	5320
Loss of Function	8.48	13	108	0.120	0.00000511	1255

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000584	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000715	0.0000703
Middle Eastern	0.0000584	0.0000544
South Asian	0.000231	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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: 0.152

Intolerance Scores

• loftool: 0.365
• rvis_EVS: -1.82
• rvis_percentile_EVS: 2.13

Haploinsufficiency Scores

• pHI: 0.161
• ghis: 0.680

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.836

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sptbn4
• Phenotype: growth/size/body region phenotype; muscle phenotype; vision/eye 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; 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)

Gene ontology

• Biological process: MAPK cascade;regulation of sodium ion transport;endoplasmic reticulum to Golgi vesicle-mediated transport;cytoskeletal anchoring at plasma membrane;axonogenesis;axon guidance;sensory perception of sound;adult walking behavior;fertilization;negative regulation of heart rate;vesicle-mediated transport;transmission of nerve impulse;central nervous system projection neuron axonogenesis;regulation of peptidyl-serine phosphorylation;positive regulation of multicellular organism growth;clustering of voltage-gated sodium channels;actin filament capping;cardiac conduction;protein localization to plasma membrane
• Cellular component: cytoplasm;cytosol;plasma membrane;adherens junction;spectrin;intercalated disc;membrane;nuclear matrix;PML body;node of Ranvier;paranode region of axon;neuronal cell body;axon initial segment;axon hillock;extracellular exosome;cell body fiber
• Molecular function: actin binding;Ras guanyl-nucleotide exchange factor activity;structural constituent of cytoskeleton;protein binding;phospholipid binding;phosphatase binding;ankyrin binding;spectrin binding