DST

dystonin, the group of Plakins|EF-hand domain containing

Basic information

Region (hg38): 6:56457986-56954830

Previous symbols: [ "BPAG1" ]

Links

ENSG00000151914 ∙ NCBI:667 ∙ OMIM:113810 ∙ HGNC:1090 ∙ Uniprot:Q03001 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (Strong), mode of inheritance: AR
• hereditary sensory and autonomic neuropathy type 6 (Moderate), mode of inheritance: AR
• epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (Moderate), mode of inheritance: AR
• epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (Strong), mode of inheritance: AR
• hereditary sensory and autonomic neuropathy type 6 (Supportive), mode of inheritance: AR
• epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (Supportive), mode of inheritance: AR
• hereditary sensory and autonomic neuropathy type 6 (Limited), mode of inheritance: AR
• epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (Strong), mode of inheritance: AR
• hereditary sensory and autonomic neuropathy type 6 (Strong), mode of inheritance: AR
• hereditary sensory and autonomic neuropathy type 6 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermolysis bullosa simplex 3, localized or generalized intermediate, with bp230 deficiency; Neuropathy, hereditary sensory and autonomic, type VI	AR	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	Dermatologic; Neurologic	20164846; 22113475; 22522446

ClinVar

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

• Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (1471 variants)
• Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6 (1460 variants)
• not provided (572 variants)
• Inborn genetic diseases (497 variants)
• Hereditary sensory and autonomic neuropathy type 6 (131 variants)
• not specified (26 variants)
• Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (17 variants)
• Charcot-Marie-Tooth disease (2 variants)
• Distal spinal muscular atrophy (1 variants)
• DST-related condition (1 variants)
• Global developmental delay;Congenital contracture;Hypotonia;Cardiomyopathy (1 variants)
• Moyamoya angiopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DST 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			72	649	32	753
missense		1	1858	52	17	1928
nonsense	44	6	10			60
start loss						0
frameshift	42	1	9			52
inframe indel			15			15
splice donor/acceptor (+/-2bp)		20	5			25
splice region			77	52	5	134
non coding			64	277	161	502
Total	86	28	2033	978	210

Highest pathogenic variant AF is 0.0000985

Variants in DST

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

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

Position	Type	Phenotype	Significance	ClinVar
6-56458752-G-T			Likely benign (Mar 28, 2021)
6-56459023-GT-G		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Uncertain significance (Mar 09, 2020)
6-56459025-C-T		Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6	Uncertain significance (Aug 26, 2021)
6-56459027-A-C		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Uncertain significance (Sep 01, 2021)
6-56459029-T-C		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Likely benign (Dec 05, 2022)
6-56459030-T-C		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency • Inborn genetic diseases	Uncertain significance (Aug 21, 2022)
6-56459033-CT-GG		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Uncertain significance (Aug 03, 2022)
6-56459036-G-T		Inborn genetic diseases	Uncertain significance (Aug 19, 2021)
6-56459037-C-G		Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6	Uncertain significance (Dec 09, 2021)
6-56459047-C-T		Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6	Likely benign (May 21, 2019)
6-56459056-C-T		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency • DST-related disorder	Likely benign (Jan 30, 2024)
6-56459057-G-A		Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6 • Inborn genetic diseases	Uncertain significance (May 08, 2023)
6-56459060-G-A		Hereditary sensory and autonomic neuropathy type 6	Likely pathogenic (Oct 08, 2018)
6-56459077-C-T		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Likely benign (Dec 29, 2022)
6-56459101-T-C		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Likely benign (Jun 13, 2022)
6-56459102-C-T		Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6 • Inborn genetic diseases	Uncertain significance (Aug 24, 2021)
6-56459109-T-A		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Uncertain significance (Jan 29, 2022)
6-56459114-C-G		Inborn genetic diseases • Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6	Conflicting classifications of pathogenicity (Aug 08, 2023)
6-56459128-G-C		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Likely benign (Mar 04, 2023)
6-56459141-T-G		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Uncertain significance (Aug 21, 2021)
6-56459151-C-T		Inborn genetic diseases • Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6	Uncertain significance (Dec 06, 2022)
6-56459152-G-A		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Likely benign (May 04, 2023)
6-56459156-T-A		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Uncertain significance (Feb 08, 2022)
6-56459158-G-T		Hereditary sensory and autonomic neuropathy type 6;Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Likely benign (Dec 06, 2023)
6-56459198-C-T		Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency;Hereditary sensory and autonomic neuropathy type 6 • Inborn genetic diseases	Uncertain significance (Apr 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DST	protein_coding	protein_coding	ENST00000244364	84	496642

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.61e-18	125601	0	147	125748	0.000585

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.22	2223	2.54e+3	0.876	0.000132	34119
Missense in Polyphen		874	1127.8	0.77496		15377
Synonymous	0.430	912	929	0.982	0.0000483	9351
Loss of Function	13.3	38	277	0.137	0.0000146	3460

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000913	0.000912
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000894	0.000816
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000750	0.000739
Middle Eastern	0.000894	0.000816
South Asian	0.000500	0.000457
Other	0.000348	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cytoskeletal linker protein. Acts as an integrator of intermediate filaments, actin and microtubule cytoskeleton networks. Required for anchoring either intermediate filaments to the actin cytoskeleton in neural and muscle cells or keratin- containing intermediate filaments to hemidesmosomes in epithelial cells. The proteins may self-aggregate to form filaments or a two- dimensional mesh. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Mediates docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport through its interaction with TMEM108 and DCTN1 (By similarity). {ECO:0000250|UniProtKB:Q91ZU6}.; FUNCTION: Isoform 6: required for bundling actin filaments around the nucleus. {ECO:0000250, ECO:0000269|PubMed:10428034, ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692}.
• Disease: DISEASE: Neuropathy, hereditary sensory and autonomic, 6 (HSAN6) [MIM:614653]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN6 is a severe autosomal recessive disorder characterized by neonatal hypotonia, respiratory and feeding difficulties, lack of psychomotor development, and autonomic abnormalities including labile cardiovascular function, lack of corneal reflexes leading to corneal scarring, areflexia, and absent axonal flare response after intradermal histamine injection. {ECO:0000269|PubMed:22522446}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa simplex, autosomal recessive 2 (EBSB2) [MIM:615425]: A form of epidermolysis bullosa, a dermatologic disorder characterized by localized blistering on the dorsal, lateral and plantar surfaces of the feet. EBSB2 is characterized by trauma-induced blistering mainly occurring on the feet and ankles. Ultrastructural analysis of skin biopsy shows abnormal hemidesmosomes with poorly formed inner plaques. {ECO:0000269|PubMed:20164846, ECO:0000269|PubMed:22113475}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Assembly of collagen fibrils and other multimeric structures;Alpha6Beta4Integrin;Collagen formation;Extracellular matrix organization;Validated transcriptional targets of TAp63 isoforms;Type I hemidesmosome assembly;Cell junction organization;Cell-Cell communication (Consensus)

Recessive Scores

• pRec: 0.407

Intolerance Scores

• loftool: 0.554
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.71

Haploinsufficiency Scores

• pHI: 0.876
• hipred: Y
• hipred_score: 0.706
• ghis: 0.533

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.644

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dst
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail 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); renal/urinary system phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; growth/size/body region phenotype; hematopoietic system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); 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); craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; taste/olfaction phenotype

Gene ontology

• Biological process: cytoskeleton organization;cell adhesion;integrin-mediated signaling pathway;retrograde axonal transport;response to wounding;maintenance of cell polarity;cytoplasmic microtubule organization;hemidesmosome assembly;wound healing;intermediate filament cytoskeleton organization;cell motility
• Cellular component: basement membrane;nucleus;nuclear envelope;cytoplasm;endoplasmic reticulum membrane;cytosol;intermediate filament;focal adhesion;cell cortex;basal plasma membrane;microtubule cytoskeleton;membrane;integral component of membrane;Z disc;hemidesmosome;cell leading edge;cytoplasmic vesicle;H zone;microtubule plus-end;axon cytoplasm
• Molecular function: actin binding;integrin binding;structural molecule activity;calcium ion binding;protein binding;microtubule binding;protein C-terminus binding;microtubule plus-end binding