DST

Summary

DST (dystonin, HGNC:1090) is a protein-coding gene on chromosome 6p12.1, encoding Dystonin (Q03001). Cytoskeletal linker protein.

This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been reported that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration.

Source: NCBI Gene 667 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary sensory and autonomic neuropathy type 6 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 4,078 total — 152 pathogenic, 43 likely-pathogenic
• Phenotypes (HPO): 46
• MANE Select transcript: NM_001374736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1090
Approved symbol	DST
Name	dystonin
Location	6p12.1
Locus type	gene with protein product
Status	Approved
Aliases	BP240, KIAA0728, FLJ21489, FLJ13425, FLJ32235, FLJ30627, CATX-15, BPA, MACF2
Ensembl gene	ENSG00000151914
Ensembl biotype	protein_coding
OMIM	113810
Entrez	667

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 20 protein_coding, 18 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000244364, ENST00000312431, ENST00000340834, ENST00000361203, ENST00000370765, ENST00000370788, ENST00000421834, ENST00000439203, ENST00000449297, ENST00000459869, ENST00000466429, ENST00000482156, ENST00000487754, ENST00000492944, ENST00000517840, ENST00000517937, ENST00000518398, ENST00000518464, ENST00000518828, ENST00000518935, ENST00000520144, ENST00000520645, ENST00000521104, ENST00000521821, ENST00000522360, ENST00000522538, ENST00000523292, ENST00000523597, ENST00000523817, ENST00000523943, ENST00000523967, ENST00000524186, ENST00000524216, ENST00000524302, ENST00000650917, ENST00000651289, ENST00000651457, ENST00000651790, ENST00000651941, ENST00000652573, ENST00000680361

RefSeq mRNA: 11 — MANE Select: NM_001374736 NM_001144769, NM_001144770, NM_001374722, NM_001374729, NM_001374730, NM_001374734, NM_001374736, NM_001386100, NM_001723, NM_015548, NM_183380

CCDS: CCDS47443, CCDS4959, CCDS75474, CCDS93934, CCDS93935, CCDS93936

Canonical transcript exons

ENST00000680361 — 104 exons

Exon	Start	End
ENSE00000850627	56953785	56953819
ENSE00000974197	56900421	56900621
ENSE00001453610	56601443	56601676
ENSE00001453611	56602882	56603031
ENSE00001453612	56603205	56603420
ENSE00001453613	56603564	56603713
ENSE00001453630	56464685	56464756
ENSE00001592060	56632854	56633037
ENSE00001594996	56610427	56610562
ENSE00001599274	56624530	56624628
ENSE00001611579	56634462	56634616
ENSE00001624657	56573679	56573887
ENSE00001628996	56600069	56600221
ENSE00001636006	56639259	56639363
ENSE00001640044	56627999	56628161
ENSE00001646607	56578814	56578937
ENSE00001649490	56598476	56598709
ENSE00001653482	56629250	56629443
ENSE00001672022	56611508	56611596
ENSE00001675459	56597740	56598006
ENSE00001696517	56614356	56614484
ENSE00001703382	56634801	56634953
ENSE00001704487	56592182	56592358
ENSE00001708717	56636557	56636652
ENSE00001724347	56627204	56627287
ENSE00001727319	56635589	56635714
ENSE00001746628	56631211	56631389
ENSE00001755934	56625157	56625264
ENSE00001757312	56634132	56634258
ENSE00001765990	56630245	56630383
ENSE00001770312	56593663	56594193
ENSE00001792799	56631883	56632040
ENSE00003461087	56511197	56511400
ENSE00003463404	56572747	56573064
ENSE00003466006	56701888	56701965
ENSE00003466112	56527493	56527734
ENSE00003468037	56463565	56463764
ENSE00003468112	56536779	56536940
ENSE00003469284	56517198	56517305
ENSE00003470051	56735228	56735289
ENSE00003470427	56463046	56463156
ENSE00003484587	56497856	56498053
ENSE00003495131	56489490	56489609
ENSE00003497555	56699653	56699745
ENSE00003501586	56494010	56494180
ENSE00003512138	56650926	56651032
ENSE00003516263	56641947	56642101
ENSE00003526107	56642410	56642503
ENSE00003526275	56497379	56497507
ENSE00003529695	56517501	56517620
ENSE00003530219	56639696	56639773
ENSE00003549566	56651132	56651244
ENSE00003549648	56503997	56504098
ENSE00003557234	56501520	56501693
ENSE00003559629	56526361	56526567
ENSE00003565544	56572100	56572266
ENSE00003570047	56466078	56466195
ENSE00003571721	56515450	56515668
ENSE00003578872	56704280	56704369
ENSE00003581309	56535122	56535292
ENSE00003592554	56639450	56639611
ENSE00003598361	56509642	56509873
ENSE00003601509	56487104	56487273
ENSE00003606329	56645866	56645993
ENSE00003612009	56557319	56557518
ENSE00003617600	56506667	56506789
ENSE00003621970	56670641	56670807
ENSE00003624940	56648570	56648689
ENSE00003633741	56460131	56460254
ENSE00003635440	56851397	56851604
ENSE00003638122	56501080	56501235
ENSE00003645466	56528841	56528925
ENSE00003657636	56529448	56529774
ENSE00003669033	56508529	56508755
ENSE00003671680	56529974	56530133
ENSE00003672958	56639929	56640057
ENSE00003674374	56477345	56477488
ENSE00003674399	56506443	56506544
ENSE00003688580	56646087	56646182
ENSE00003690948	56640143	56640605
ENSE00003694353	56532344	56532510
ENSE00003711498	56472059	56472222
ENSE00003713885	56560294	56560423
ENSE00003715168	56468982	56468999
ENSE00003722080	56568469	56568595
ENSE00003724117	56569856	56570012
ENSE00003726475	56485312	56485471
ENSE00003729350	56482050	56482178
ENSE00003730029	56473873	56474002
ENSE00003733457	56482683	56482877
ENSE00003734926	56562138	56562200
ENSE00003736046	56469883	56469957
ENSE00003736613	56492227	56492433
ENSE00003736715	56471106	56471268
ENSE00003736836	56476149	56476337
ENSE00003738814	56492934	56493089
ENSE00003739323	56552184	56553655
ENSE00003746970	56561308	56561549
ENSE00003751488	56470128	56470282
ENSE00003752674	56555345	56555840
ENSE00003790862	56603837	56609344
ENSE00003914664	56703648	56703746
ENSE00003915380	56954407	56954830
ENSE00003993001	56457996	56459267

Expression profiles

Bgee: expression breadth ubiquitous, 305 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.6397 / max 3310.3946, expressed in 1755 samples.

FANTOM5 promoters (51 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74126	16.3211	312
74162	11.2721	1100
74173	10.0881	1272
74153	8.1108	1283
74076	4.7079	1111
74137	3.4330	577
74156	2.2344	979
74163	1.8226	134
74175	1.7336	713
74171	1.5353	609

Top tissues by expression

305 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.58	gold quality
calcaneal tendon	UBERON:0003701	99.54	gold quality
medial globus pallidus	UBERON:0002477	99.46	gold quality
globus pallidus	UBERON:0001875	99.42	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.38	gold quality
inferior olivary complex	UBERON:0002127	99.38	gold quality
substantia nigra pars compacta	UBERON:0001965	99.33	gold quality
lateral globus pallidus	UBERON:0002476	99.26	gold quality
subthalamic nucleus	UBERON:0001906	99.19	gold quality
inferior vagus X ganglion	UBERON:0005363	99.19	gold quality
tendon	UBERON:0000043	99.17	gold quality
upper leg skin	UBERON:0004262	99.17	gold quality
body of uterus	UBERON:0009853	99.17	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.10	gold quality
mucosa of stomach	UBERON:0001199	99.04	gold quality
skin of hip	UBERON:0001554	99.01	gold quality
medulla oblongata	UBERON:0001896	99.01	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.97	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.95	gold quality
trigeminal ganglion	UBERON:0001675	98.93	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.93	gold quality
superior vestibular nucleus	UBERON:0007227	98.93	gold quality
blood vessel layer	UBERON:0004797	98.92	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.92	gold quality
skin of abdomen	UBERON:0001416	98.86	gold quality
dorsal root ganglion	UBERON:0000044	98.85	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.83	gold quality
left uterine tube	UBERON:0001303	98.82	gold quality
lower esophagus	UBERON:0013473	98.82	gold quality
right lung	UBERON:0002167	98.80	gold quality

Single-cell (SCXA)

Detected in 24 experiment(s), a significant marker in 23.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	4842.18
E-ANND-2	yes	4758.24
E-MTAB-10855	yes	4718.50
E-MTAB-10885	yes	3643.71
E-GEOD-137537	yes	1939.14
E-MTAB-7316	yes	1759.05
E-MTAB-8142	yes	1669.80
E-CURD-114	yes	1271.61
E-HCAD-38	yes	1054.67
E-HCAD-1	yes	350.66
E-GEOD-135922	yes	35.54
E-CURD-119	yes	28.04
E-HCAD-35	yes	23.60
E-HCAD-11	yes	23.43
E-GEOD-125970	yes	23.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EN1, FOXO3, GLI2, GLI3, HOXA5, HOXC8, IRF1, IRF2, TFAP2A

miRNA regulators (miRDB)

34 targeting DST, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-509-3P	98.12	67.25	612
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-708-3P	97.50	68.67	1082
HSA-MIR-4714-5P	97.04	67.76	955

Literature-anchored findings (GeneRIF, showing 35)

• keratinocyte responsive element 3 functions as a position-, copy number-, and orientation-dependent cis-element contributing to tissue-specific regulation of the 230-kDa bullous pemphigoid antigen gene. (PMID:12542537)
• Bpag1 is not strictly a cytoplasmic/membrane protein but that it can also localize to the nucleus (PMID:14576348)
• Additional autoantibodies against a 230-kDa protein and against a 190-kDa protein comigrating with bullous pemphigoid antigen 1 (BP230) and periplakin, respectively, were present in all the patients’ sera. (PMID:14705806)
• IFN-gamma-IRF system is involved in BPAG1 gene regulation in type-1 helper T-cell inflammatory skin conditions, such as psoriasis vulgaris (PMID:15560761)
• antibodies against BP230 can elicit the clinical and immunopathological features of Bullous pemphigoid in neonatal mice (PMID:15725571)
• findings demonstrated that disruption of the IFN-stimulated responsive element sequences, but not the IFNgamma activation site, markedly suppressed the BPAG1 basal promoter activity and resulted in attenuated IFNgamma response in keratinocytes (PMID:16512878)
• We report the crystal structure of a stable fragment from BPAG1, residues 226-448, defined by limited proteolysis of the whole plakin domain. The plakin domains has two pairs of spectrin repeats interrupted by a putative Src-Homology 3 (SH3) domain. (PMID:17161423)
• IgE autoantibodies to BP180 and BP230 are detected at high frequencies in bullous pemphigoid. (PMID:17920818)
• Vitamin D(3) inhibits expression of bullous pemphigoid antigen 1 through post-transcriptional mechanism without new protein synthesis. (PMID:18207369)
• BPAG1e is required for efficient regulation of keratinocyte polarity and migration by determining the activation of Rac1. (PMID:19403692)
• BPAG1-b was detectable in vitro and in vivo as a high molecular mass protein in striated and heart muscle cells, co-localizing with alpha-actinin-2 and partially with the cytolinker plectin as well as with the intermediate filament protein desmin. (PMID:19932097)
• A homozygous nonsense mutation within the dystonin gene coding for the coiled-coil domain of the epithelial isoform of BPAG1 underlies a new subtype of autosomal recessive epidermolysis bullosa simplex. (PMID:20164846)
• Bullous pemphigoid antigen 1 (BPAG1) was identified as a melanoma antigen recognized by its auto-antibody. (PMID:20479946)
• There is a significantly enhanced ratio between the dynorphin A immunoreactive area and the whole area of the entopeduncular nucleus in genetically dystonic hamsters compared to controls. (PMID:21638337)
• in motile cells Col XVII recruits BPAG1e to alpha6beta4 integrin and is necessary for activation of signaling pathways, motile behavior, and lamellipodial stability. (PMID:21642434)
• This is the first report of a defect in the neuronal isoform of dystonin in humans. (PMID:22522446)
• Mutations of the EF-hands of BPAG1n4 abolish calcium-dependent microtubule plus end dynamics. (PMID:22995871)
• study identifies dystonin, a cytoskeleton cross-linker involved in microtubule-based transport, as a binding partner of the HSV-1 protein pUL37, implicated in capsid transport; study provides insight into cellular requirements for HSV-1 capsid transport and identifies dystonin as a nonmotor protein part of transport machinery (PMID:23269794)
• Authors conclude that, during entry of herpes simplex virus 1, dystonin has a specific role in plus-ended transport of capsids from the centrosome to the nucleus. (PMID:23903849)
• A key role for BPAG1-e in regulating keratinocyte adhesion and migration and suggest a requirement for this protein in controlling functional switching between integrin types in epithelial cells. (PMID:24025550)
• Two of the six genes (LAMA3 and DST) validated by quantitative RT-PCR for tumor-specific alternative splicing events (PMID:24675808)
• Circulating anti-BP230 autoantibodies are not correlated with severity of genital lichen sclerosis or itching. (PMID:24676719)
• Results identify four families with autosomal recessive EBS from Kuwait in whom the skin fragility is caused by recurrent nonsense mutation in DST-4. (PMID:25059916)
• dystonin and bullous pemphigoid antigen 1 are encoded by the same gene but are different proteins with different diseases [review] (PMID:26479498)
• A report on 2 novel heterozygous mutations in the dystonin (DST) gene from a family with hereditary sensory and autonomic neuropathy type VI. Induced-pluripotent stem cells findings suggest that the dystonin defect might alter proper development of the peripheral nerves (PMID:28468842)
• novel biallelic mutations in the DST gene encoding dystonin, a large cytolinker protein of the plakin family, in an adult form of Hereditary sensory and autonomic neuropathies type VI, are reported. (PMID:30371979)
• Our finding suggests that DST alteration may involve in the mechanism of diabetic dementia (PMID:30963337)
• Disruption of BP230 (BPAG1e)-integrin beta-4 (beta4) binding prevents recruitment of BP230 to hemidesmosomes in keratinocytes. (PMID:31006587)
• FLG and DST support melanoma cell growth in vitro and in vivo. Growth effects of JUP were only evident in vivo, and may be mediated, in part, by enhancing angiogenesis. In addition, growth-promoting effects of FLG and DST in vitro suggest that these genes may also support melanoma cell proliferation through angiogenesis-independent pathways. (PMID:31425296)
• Epidermolysis bullosa simplex due to bi-allelic DST mutations: Case series and review of the literature. (PMID:33471381)
• Age related gene DST represents an independent prognostic factor for MYCN non-amplified neuroblastoma. (PMID:34116676)
• Pathogenic DST sequence variants result in either epidermolysis bullosa simplex (EBS) or hereditary sensory and autonomic neuropathy type 6 (HSAN-VI). (PMID:35276021)
• What’s new in the pathogeneses and triggering factors of bullous pemphigoid. (PMID:36412277)
• DST variants are responsible for neurogenic arthrogryposis multiplex congenita enlarging the spectrum of type VI hereditary sensory autonomic neuropathy. (PMID:37431644)
• The DST gene in neurobiology. (PMID:38465459)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000098631
danio_rerio	DST	ENSDARG00000101858
danio_rerio	si:ch211-165e15.1	ENSDARG00000102406
danio_rerio		ENSDARG00000115956
mus_musculus	Dst	ENSMUSG00000026131
rattus_norvegicus	Dst	ENSRNOG00000012207

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), FLNB (ENSG00000136068), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Dystonin — Q03001 (reviewed: Q03001)

Alternative names: 230 kDa bullous pemphigoid antigen, 230/240 kDa bullous pemphigoid antigen, Bullous pemphigoid antigen 1, Dystonia musculorum protein, Hemidesmosomal plaque protein

All UniProt accessions (17): Q03001, A0A0U1RQJ2, A0A494C073, A0A494C1D7, A0A494C1U5, A0A7P0T890, E7ERX3, E7ETB9, E9PHM6, F6QMI7, F8W9J4, H0YAT7, H0YBX0, H0YC65, H0YC82, Q5T0V7, Q6P0N6

UniProt curated annotations — full annotation on UniProt →

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. Plays a structural role in the assembly of hemidesmosomes of epithelial cells; anchors keratin-containing intermediate filaments to the inner plaque of hemidesmosomes. Required for the regulation of keratinocyte polarity and motility; mediates integrin ITGB4 regulation of RAC1 activity. Required for bundling actin filaments around the nucleus. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport.

Subunit / interactions. Homodimer. Isoform 1 interacts (via N-terminus) with PLEC (via N-terminus). Interacts with the neuronal intermediate filament protein, PRPH. Interacts with DES. Interacts with SYNE3. Isoform 1 and isoform 6 can homodimerize (via N-terminus). Isoform 1 interacts (via N-terminus) with ACTN2. Isoform 1 interacts (via N-terminus) with PLEC (via N-terminus). Isoform 3 interacts (via N-terminus) with COL17A1 (via cytoplasmic region). Isoform 3 interacts (via N-terminus) with ITGB4 isoform beta-4a (via cytoplasmic region). Isoform 3 interacts (via N-terminus) with ERBIN (via C-terminus). Isoform 3 associates (via C-terminal) with KRT5-KRT14 (via rod region) intermediate filaments of keratins. Interacts with MAPRE1; probably required for targeting to the growing microtubule plus ends. Interacts with TMIGD2. Isoform 9 interacts with TMEM108.

Subcellular location. Cytoplasm. Cytoskeleton. Stress fiber. Cell projection. Axon Cytoplasm. Myofibril. Sarcomere. Z line. H zone Cytoplasm. Cytoskeleton Cytoplasm. Cell junction. Hemidesmosome Nucleus. Nucleus envelope. Membrane. Endoplasmic reticulum membrane. Stress fiber Cytoplasm. Axon. Membrane Cytoplasm. Cell cortex. Cell membrane.

Tissue specificity. Isoform 1 is expressed in myoblasts (at protein level). Isoform 3 is expressed in the skin. Isoform 6 is expressed in the brain. Highly expressed in skeletal muscle and cultured keratinocytes.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry. Epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (EBS3) [MIM:615425] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. EBS3 is an autosomal recessive disorder characterized by skin blistering mainly occurring on the feet and ankles. Ultrastructural analysis of skin biopsy shows abnormal hemidesmosomes with poorly formed inner plaques. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Its association with epidermal and simple keratins is dependent on the tertiary structure induced by heterodimerization of these intermediate filaments proteins and most likely involves recognition sites located in the rod domain of these keratins. The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.

Miscellaneous. Incomplete sequence. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Incomplete sequence. Transmembrane protein (helical transmembrane domain from amino acid 18 to 38). Incomplete sequence. Probably myristoylated on Gly-2. Probably S-palmitoylated on Cys-5 and Cys-7.

Isoforms (9)

UniProt ID	Names	Canonical?
Q03001-7	1, BPAG1-b	yes
Q03001-8	2, BPAG1eA, Dystonin-1, eA
Q03001-3	3, BPAG1e, eBPAG1
Q03001-9	4, BPAG1eA, eB
Q03001-10	5
Q03001-11	6, BPAG1n1, BPAG1n2, Dystonin-2
Q03001-12	7, BPAG1n3
Q03001-13	8
Q03001-14	9, BPAG1-a, BAPG1n4

RefSeq proteins (11): NP_001138241, NP_001138242, NP_001361651, NP_001361658, NP_001361659, NP_001361663, NP_001361665, NP_001373029, NP_001714, NP_056363, NP_899236 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001101	Plectin_repeat	Repeat
IPR001452	SH3_domain	Domain
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001715	CH_dom	Domain
IPR002017	Spectrin_repeat	Repeat
IPR002048	EF_hand_dom	Domain
IPR003108	GAR_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018159	Spectrin/alpha-actinin	Repeat
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR035915	Plakin_repeat_sf	Homologous_superfamily
IPR036534	GAR_dom_sf	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily
IPR041573	Desmoplakin_Spectrin-like	Domain
IPR041615	Desmoplakin_SH3	Domain
IPR043197	Plakin	Family
IPR049538	PCN-like_spectrin-like_rpt	Repeat

Pfam: PF00307, PF00435, PF00681, PF02187, PF13499, PF17902, PF18373, PF21019, PF21020, PF21097

UniProt features (140 total): repeat 37, sequence conflict 22, splice variant 19, modified residue 14, compositionally biased region 10, binding site 10, region of interest 8, domain 6, mutagenesis site 6, sequence variant 4, short sequence motif 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3GJO	X-RAY DIFFRACTION	2.5
7OLG	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for Q03001 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (10): 7210; 7212; 7214; 7216; 7221; 7246; 7248; 7250; 7252; 7257

Post-translational modifications (15): 1565, 135, 184, 236, 237, 1382, 2229, 2919, 3968, 4749, 7432, 7510, 7513, 7525, 5470

Mutagenesis-validated functional residues (6):

Position	Phenotype
7548	loss of interaction with mapre1 and association with microtubule growing ends.
7550	loss of association with microtubule growing ends.
7552	loss of interaction with mapre1 and association with the growing microtubule plus ends; when associated with n-7553.
7553	loss of interaction with mapre1 and association with the growing microtubule plus ends; when associated with n-7552.
7557	loss of interaction with mapre1 and association with the growing microtubule plus ends.
7558	loss of interaction with mapre1 and association with the growing microtubule plus ends.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-446107	Type I hemidesmosome assembly
R-HSA-9013420	RHOU GTPase cycle
R-HSA-9013424	RHOV GTPase cycle
R-HSA-9696264	RND3 GTPase cycle
R-HSA-9696270	RND2 GTPase cycle
R-HSA-9696273	RND1 GTPase cycle
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures

MSigDB gene sets: 498 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_AXO_DENDRITIC_TRANSPORT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, JAEGER_METASTASIS_DN, GCANCTGNY_MYOD_Q6, ATACCTC_MIR202, AREB6_03, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, FOXO4_01, TOMLINS_PROSTATE_CANCER_DN

GO Biological Process (11): microtubule cytoskeleton organization (GO:0000226), cytoskeleton organization (GO:0007010), cell adhesion (GO:0007155), integrin-mediated signaling pathway (GO:0007229), retrograde axonal transport (GO:0008090), response to wounding (GO:0009611), maintenance of cell polarity (GO:0030011), hemidesmosome assembly (GO:0031581), wound healing (GO:0042060), intermediate filament cytoskeleton organization (GO:0045104), cell motility (GO:0048870)

GO Molecular Function (9): actin binding (GO:0003779), integrin binding (GO:0005178), structural molecule activity (GO:0005198), calcium ion binding (GO:0005509), microtubule binding (GO:0008017), protein homodimerization activity (GO:0042803), microtubule plus-end binding (GO:0051010), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (33): stress fiber (GO:0001725), basement membrane (GO:0005604), nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), intermediate filament (GO:0005882), focal adhesion (GO:0005925), cell cortex (GO:0005938), basal plasma membrane (GO:0009925), actin cytoskeleton (GO:0015629), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), Z disc (GO:0030018), hemidesmosome (GO:0030056), axon (GO:0030424), cell leading edge (GO:0031252), cytoplasmic vesicle (GO:0031410), H zone (GO:0031673), microtubule plus-end (GO:0035371), intermediate filament cytoskeleton (GO:0045111), axon cytoplasm (GO:1904115), endoplasmic reticulum (GO:0005783), cytoskeleton (GO:0005856), microtubule (GO:0005874), plasma membrane (GO:0005886), cell projection (GO:0042995), organelle (GO:0043226), anchoring junction (GO:0070161), cell periphery (GO:0071944), polymeric cytoskeletal fiber (GO:0099513)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	5
Cell junction organization	1
Collagen formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoplasm	3
cytoskeleton organization	2
cellular process	2
cell-substrate junction	2
cytoskeleton	2
microtubule-based process	1
organelle organization	1
cell surface receptor signaling pathway	1
axonal transport	1
axon cytoplasm	1
response to stress	1
establishment or maintenance of cell polarity	1
cell-substrate junction assembly	1
response to wounding	1
tissue regeneration	1
intermediate filament-based process	1
cytoskeletal protein binding	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
molecular_function	1
metal ion binding	1
tubulin binding	1
identical protein binding	1
protein dimerization activity	1
microtubule binding	1
binding	1
cation binding	1
actomyosin	1
contractile actin filament bundle	1
extracellular matrix	1
intracellular membrane-bounded organelle	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear lumen	1
intracellular anatomical structure	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1

Protein interactions and networks

STRING

1456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DST	COL17A1	Q9UMD9	999
DST	PLEC	Q15149	988
DST	CD151	P48509	983
DST	ITGB4	P16144	973
DST	DSG3	P32926	863
DST	DSG1	Q02413	833
DST	ERBIN	Q96RT1	784
DST	DSP	P15924	755
DST	EVPL	Q92817	744
DST	PPL	O60437	707
DST	TMEM108	Q6UXF1	695
DST	LAMA3	Q16787	675
DST	ITGA6	P23229	656
DST	CALM1	P02593	643
DST	A0A590UK56	A0A590UK56	640

IntAct

194 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
BMI1	CBX4	psi-mi:“MI:0914”(association)	0.900
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
MAPRE1	DST	psi-mi:“MI:0915”(physical association)	0.840
DST	MAPRE1	psi-mi:“MI:0407”(direct interaction)	0.840
MAPRE1	DST	psi-mi:“MI:0914”(association)	0.840
VSX1	USP12	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GPC6	GPC4	psi-mi:“MI:0914”(association)	0.710
Mapre1	DST	psi-mi:“MI:0407”(direct interaction)	0.700
DST	Mapre1	psi-mi:“MI:0915”(physical association)	0.700
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
COPS7B	ZZEF1	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
MOB1B	PPP6C	psi-mi:“MI:2364”(proximity)	0.480
OPTN	DST	psi-mi:“MI:2364”(proximity)	0.450
DST	APPL1	psi-mi:“MI:2364”(proximity)	0.450
GSK3B	SEC16A	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (359): DST (Affinity Capture-MS), DST (Affinity Capture-MS), DST (Affinity Capture-MS), DST (Affinity Capture-MS), DST (Affinity Capture-MS), DST (Affinity Capture-RNA), MAPRE1 (Protein-peptide), MAPRE1 (Reconstituted Complex), EB1A (Reconstituted Complex), mal3 (Reconstituted Complex), DST (Proximity Label-MS), DST (Proximity Label-MS), DST (Proximity Label-MS), DST (Affinity Capture-MS), DST (Affinity Capture-MS)

ESM2 similar proteins: A0A3B6UES5, A0A3G2LGI8, D3ZHV2, G8JYB2, O46037, O60437, P0CE94, P0CE95, P11533, P12003, P18206, P19826, P26039, P26231, P26234, P30427, P33338, P35220, P35221, P54939, P85972, P90947, Q02328, Q03001, Q04615, Q15149, Q17162, Q3MHM6, Q54K81, Q54MH2, Q59I72, Q64727, Q6ZWR6, Q71LX4, Q8MSU4, Q91ZU6, Q95XZ0, Q9ERE8, Q9H1K6, Q9MBF8

Diamond homologs: A0A1L8H8C0, A0A1L8HFX9, D3ZHV2, D3ZUE1, O43903, O94854, P11862, Q03001, Q3UWW6, Q5SSG4, Q69ZZ9, Q86XJ1, Q8JZP9, Q8NHY3, Q91ZU6, Q99501, Q9QXZ0, Q9UPN3, Q9W3Y4, A5D7D1, D3ZEN0, D3ZHA0, D3ZQL6, E1BBG2, F1MF74, F1RA39, F6QZ15, G3MWR8, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O94851, O97592, P05094

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
IRF1	“down-regulates quantity by repression”	DST	“transcriptional regulation”
IRF2	“down-regulates quantity by repression”	DST	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 199 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	36.5×	1e-07
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	32.2×	2e-07
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	32.2×	2e-07
Activation of BH3-only proteins	7	23.8×	1e-06
Signaling by Hippo	6	22.4×	1e-05
RHO GTPases activate PKNs	8	17.4×	1e-06
Intrinsic Pathway for Apoptosis	7	14.0×	3e-05
Downstream signal transduction	5	13.0×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	6	14.6×	8e-04
cell surface receptor protein tyrosine kinase signaling pathway	10	10.0×	3e-05
positive regulation of neuron projection development	11	8.7×	3e-05
protein autophosphorylation	10	8.4×	1e-04
axonogenesis	8	7.4×	2e-03
intracellular protein localization	10	6.0×	1e-03
protein phosphorylation	15	5.9×	3e-05
protein localization to plasma membrane	9	5.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

4078 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	152
Likely pathogenic	43
Uncertain significance	2303
Likely benign	1213
Benign	222

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072927	NM_001374736.1(DST):c.4083_4086dup (p.Val1363Ter)	Pathogenic
1073401	NM_001374736.1(DST):c.16780C>T (p.Arg5594Ter)	Pathogenic
1074277	NM_001723.7(DST):c.4477del (p.Ala1493fs)	Pathogenic
1074760	NM_001374736.1(DST):c.3015C>A (p.Cys1005Ter)	Pathogenic
1320273	NM_001374736.1(DST):c.10_19dup (p.Leu7fs)	Pathogenic
1320274	NM_001374736.1(DST):c.22720G>T (p.Glu7574Ter)	Pathogenic
1322785	NM_001723.7(DST):c.6387dup (p.Asn2130Ter)	Pathogenic
1322786	NM_001723.7(DST):c.3565del (p.Ala1189fs)	Pathogenic
1339419	NM_001723.7(DST):c.7097dup (p.Tyr2366Ter)	Pathogenic
1339420	NM_001723.7(DST):c.7429del (p.Leu2477fs)	Pathogenic
1359095	NM_001374736.1(DST):c.15360del (p.Gly5121fs)	Pathogenic
1379301	NM_001723.7(DST):c.5854C>T (p.Gln1952Ter)	Pathogenic
1381303	NM_001374736.1(DST):c.21862C>T (p.Gln7288Ter)	Pathogenic
1393103	NM_001723.7(DST):c.5357del (p.Asn1786fs)	Pathogenic
1396176	NM_001374736.1(DST):c.4669_4670del (p.Ser1557fs)	Pathogenic
1407009	NM_001374736.1(DST):c.16435C>T (p.Arg5479Ter)	Pathogenic
1414183	NM_001723.7(DST):c.5949_5950del (p.Lys1984fs)	Pathogenic
1426055	NM_001374736.1(DST):c.4854_4855dup (p.Thr1619fs)	Pathogenic
1451280	NM_001374736.1(DST):c.18439C>T (p.Gln6147Ter)	Pathogenic
1452005	NM_001374736.1(DST):c.13707_13708insTAATATAAATAGAATAAAATAT (p.Thr4570Ter)	Pathogenic
1452921	NM_001374736.1(DST):c.20254G>T (p.Glu6752Ter)	Pathogenic
1453209	NM_001374736.1(DST):c.21985C>T (p.Arg7329Ter)	Pathogenic
1454212	NM_001723.7(DST):c.5086C>T (p.Arg1696Ter)	Pathogenic
1454492	NM_001374736.1(DST):c.4016del (p.Asn1339fs)	Pathogenic
1454567	NM_001374736.1(DST):c.18061C>T (p.Arg6021Ter)	Pathogenic
1455496	NM_001374736.1(DST):c.4792C>T (p.Arg1598Ter)	Pathogenic
1456005	NM_001374736.1(DST):c.16174C>T (p.Arg5392Ter)	Pathogenic
1459548	NM_001723.7(DST):c.3383del (p.Ala1128fs)	Pathogenic
1687490	NM_001374736.1(DST):c.364C>T (p.Arg122Ter)	Pathogenic
1693464	NM_001374736.1(DST):c.616C>T (p.Arg206Trp)	Pathogenic

SpliceAI

14427 predictions. Top by Δscore:

Variant	Effect	Δscore
6:56460252:TCCC:T	acceptor_loss	1.0000
6:56460253:CC:C	acceptor_gain	1.0000
6:56460254:CC:C	acceptor_gain	1.0000
6:56460254:CCTG:C	acceptor_loss	1.0000
6:56460255:C:CG	acceptor_loss	1.0000
6:56460256:T:A	acceptor_loss	1.0000
6:56460267:A:T	acceptor_gain	1.0000
6:56463770:T:TC	acceptor_gain	1.0000
6:56463772:A:AC	acceptor_gain	1.0000
6:56463775:C:CT	acceptor_gain	1.0000
6:56463777:C:CT	acceptor_gain	1.0000
6:56463779:C:CT	acceptor_gain	1.0000
6:56463782:A:T	acceptor_gain	1.0000
6:56463784:CAA:C	acceptor_gain	1.0000
6:56463785:A:T	acceptor_gain	1.0000
6:56463786:A:AC	acceptor_gain	1.0000
6:56463786:A:C	acceptor_gain	1.0000
6:56463789:C:CT	acceptor_gain	1.0000
6:56463791:C:CT	acceptor_gain	1.0000
6:56463793:C:CT	acceptor_gain	1.0000
6:56463794:A:T	acceptor_gain	1.0000
6:56466076:ACC:A	donor_gain	1.0000
6:56466077:CCC:C	donor_gain	1.0000
6:56466110:T:C	donor_gain	1.0000
6:56466202:A:T	acceptor_gain	1.0000
6:56470123:AGTAC:A	donor_loss	1.0000
6:56470124:GTA:G	donor_loss	1.0000
6:56470125:TA:T	donor_loss	1.0000
6:56470126:ACCTC:A	donor_loss	1.0000
6:56470127:C:A	donor_loss	1.0000

AlphaMissense

51945 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002422 (6:56918872 T>C,G), RS1000004141 (6:56754431 T>A,C), RS1000008275 (6:56872121 A>G), RS1000008561 (6:56664243 T>G), RS1000040279 (6:56754982 G>A), RS1000042778 (6:56472714 T>A,G), RS1000051795 (6:56788909 T>C), RS1000054629 (6:56613599 C>T), RS1000068793 (6:56710281 C>A), RS1000080586 (6:56519029 A>G), RS1000086029 (6:56925040 A>G), RS1000088055 (6:56695869 A>C,G,T), RS1000094704 (6:56630061 A>G), RS1000102595 (6:56854048 C>T), RS1000111215 (6:56648977 T>C)

Disease associations

OMIM: gene MIM:113810 | disease phenotypes: MIM:614653, MIM:615425, MIM:118220

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary sensory and autonomic neuropathy type 6	Strong	Autosomal recessive
epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary sensory and autonomic neuropathy type 6	Definitive	AR

Mondo (10): hereditary sensory and autonomic neuropathy type 6 (MONDO:0013839), epidermolysis bullosa simplex 3, localized or generalized intermediate, with BP230 deficiency (MONDO:0014180), multiple sclerosis (MONDO:0005301), cardiomyopathy (MONDO:0004994), congenital contractures (MONDO:0022823), Charcot-Marie-Tooth disease (MONDO:0015626), distal hereditary motor neuropathy (MONDO:0018894), esophageal atresia (MONDO:0001044), pyloric stenosis (MONDO:0001561), autism spectrum disorder (MONDO:0005258)

Orphanet (8): Hereditary sensory and autonomic neuropathy type 6 (Orphanet:314381), Epidermolysis bullosa simplex due to BP230 deficiency (Orphanet:412181), Rare cardiomyopathy (Orphanet:167848), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Distal hereditary motor neuropathy (Orphanet:53739), Moyamoya angiopathy (Orphanet:477768), NON RARE IN EUROPE: Multiple sclerosis (Orphanet:802), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000331	Short chin
HP:0000369	Low-set ears
HP:0000522	Alacrima
HP:0000559	Corneal scarring
HP:0000573	Retinal hemorrhage
HP:0000763	Sensory neuropathy
HP:0000822	Hypertension
HP:0000972	Palmoplantar hyperkeratosis
HP:0000975	Hyperhidrosis
HP:0001075	Atrophic scars
HP:0001188	Hand clenching
HP:0001252	Hypotonia
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001319	Neonatal hypotonia
HP:0001371	Flexion contracture
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001623	Breech presentation
HP:0001629	Ventricular septal defect
HP:0001649	Tachycardia
HP:0001662	Bradycardia
HP:0001762	Talipes equinovarus
HP:0001810	Dystrophic toenail
HP:0001945	Fever
HP:0002020	Gastroesophageal reflux
HP:0002033	Poor suck

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST002541_23	Menarche (age at onset)	8.000000e-12
GCST003025_8	Attention function in attention deficit hyperactive disorder	2.000000e-06
GCST003134_8	Cerebrospinal fluid clusterin levels	3.000000e-06
GCST003427_45	Alzheimer disease and age of onset	2.000000e-07
GCST003518_100	Daytime sleep phenotypes	5.000000e-06
GCST004746_12	Small cell lung carcinoma	8.000000e-06
GCST006979_293	Heel bone mineral density	8.000000e-14
GCST010273_8	Gout (normal type)	4.000000e-07
GCST90000025_55	Appendicular lean mass	6.000000e-11
GCST90002397_468	Mean spheric corpuscular volume	2.000000e-14
GCST90002403_165	Red blood cell count	3.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche
EFO:0007636	attention function measurement
EFO:0004847	age at onset
EFO:0007828	daytime rest measurement
EFO:0009270	heel bone mineral density
EFO:0004980	appendicular lean mass
EFO:0004305	erythrocyte count

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D017219	Gastric Outlet Obstruction	C06.405.748.340
D009103	Multiple Sclerosis	C10.114.375.500; C10.314.350.500; C20.111.258.250.500
D011707	Pyloric Stenosis	C06.405.748.340.690

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

107 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation, increases expression	6
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation, increases expression	5
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases methylation	4
trichostatin A	affects cotreatment, decreases expression	3
Tetrachlorodibenzodioxin	increases expression, affects cotreatment, decreases expression	3
Aflatoxin B1	decreases methylation, increases expression, increases methylation	3
sodium arsenite	decreases expression, increases abundance	2
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	2
bisphenol S	affects expression, affects cotreatment, decreases expression	2
Fulvestrant	decreases methylation, increases expression, increases methylation, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Acrolein	decreases expression, increases abundance, affects cotreatment	2
Cisplatin	affects cotreatment, affects expression, affects response to substance	2
Folic Acid	affects cotreatment, increases expression, decreases expression	2
Formaldehyde	decreases expression	2
Indomethacin	decreases expression, affects cotreatment	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
Tretinoin	decreases expression	2
Cyclosporine	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	decreases expression, affects cotreatment	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment	1
decabromobiphenyl ether	decreases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00037102	PHASE4	COMPLETED	Combination Therapy With Avonex and BiMonthly High Dose Intravenous Methotrexate in Multiple Sclerosis
NCT00037115	PHASE4	WITHDRAWN	Induction Therapy With a Single High Dose Bolus of Intravenous Methotrexate With Leucovorin Rescue, Prior to Initiation of AVONEX® Treatment, in Patients Presenting With a First Acute Demyelinating Event.
NCT00146068	PHASE4	COMPLETED	EARLY IFNB-1a and Simvastatin Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
NCT00151294	PHASE4	TERMINATED	The Efficacy and Safety of Escitalopram for Depression in Multiple Sclerosis
NCT00176592	PHASE4	COMPLETED	Phase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI
NCT00179478	PHASE4	COMPLETED	Long Term Study of Avonex Therapy Following a First Attack of Multiple Sclerosis
NCT00220922	PHASE4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Using Alcohol Wipes Prior to Daily Injections of Copaxone®.
NCT00239993	PHASE4	COMPLETED	A Study to Evaluate the Impact of Using Warm Compress Prior to Daily Injections of Copaxone®
NCT00240006	PHASE4	COMPLETED	A Study Comparing Shared Solutions® Plus MS Center Support Versus Shared Solutions® Alone
NCT00240032	PHASE4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Taking an Antihistamine (Zyrtec®) or Placebo Prior to Daily Injections of Copaxone®.
NCT00246324	PHASE4	COMPLETED	Safety and Efficacy Study of Doxycycline in Combination With Interferon-B-1a to Treat Multiple Sclerosis
NCT00267319	PHASE4	COMPLETED	FOCUS Fatigue Outcome in Copaxone USers
NCT00381264	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Multiple Sclerosis
NCT00414453	PHASE4	TERMINATED	Trial of Analgesia With Lidocaine or Extended-release Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis
NCT00423527	PHASE4	COMPLETED	Levetiracetam in Central Pain in Multiple Sclerosis(MS)
NCT00480181	PHASE4	COMPLETED	Efficacy and Safety Evaluation of Nabilone as Adjunctive Therapy to Gabapentin for the Management of Neuropathic Pain in Multiple Sclerosis
NCT00492765	PHASE4	COMPLETED	Simvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
NCT00493077	PHASE4	COMPLETED	Safety of Avonex Treatment in Multiple Sclerosis Patients With Neutralizing Antibodies to Interferon Beta Therapy
NCT00536120	PHASE4	COMPLETED	The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis
NCT00629642	PHASE4	COMPLETED	Clinical Study of Solifenacin Succinate in Patients With Bladder Symptoms Due to Spinal Cord Injury or Multiple Sclerosis
NCT00638027	PHASE4	COMPLETED	Memantine for Spasticity in MS Patients
NCT00744679	PHASE4	COMPLETED	A Pharmacokinetic (PK) Study of Natalizumab (Tysabri) at Steady State
NCT00752778	PHASE4	TERMINATED	Magnetic Resonance Imaging (MRI) Follow-up of Macrophagic Infiltration in MS Patients Treated With Tysabri
NCT00753792	PHASE4	COMPLETED	Oral Corticotherapy in Megadoses to Treat Multiple Sclerosis During Relapse
NCT00854750	PHASE4	TERMINATED	Modeling and Treating the Pathophysiology of Demyelination in Multiple Sclerosis
NCT00881205	PHASE4	TERMINATED	Rivastigmine in Multiple Sclerosis Patients With Cognitive Impairment
NCT00910598	PHASE4	UNKNOWN	Optical Coherence Tomography: Glatiramer in Clinically Isolated Syndrome or Early Relapsing Remitting Multiple Sclerosis (MS)
NCT00913666	PHASE4	COMPLETED	Pharmacodynamic Study to Better Understand the Therapeutic Response and Immunomodulatory Effects of Avonex in Multiple Sclerosis (MS) Patients and Healthy Volunteers
NCT00915460	PHASE4	COMPLETED	Open-Label Safety Extension Study of Avonex
NCT00942214	PHASE4	COMPLETED	Biomarkers and Response to Natalizumab for Multiple Sclerosis Treatment
NCT00988988	PHASE4	WITHDRAWN	The Effects of Ethyl-Alpha-Guanido-Methyl Ethanoate on Skin Reactions From Glatiramer Acetate Injections
NCT01005095	PHASE4	TERMINATED	The Effects of Interferon Beta Combined With Vitamin D on Relapsing Remitting Multiple Sclerosis Patients
NCT01034579	PHASE4	COMPLETED	The REbif® vs Glatiramer Acetate in Relapsing Multiple Sclerosis Pharmacogenetics Trial
NCT01085318	PHASE4	COMPLETED	Rebif Advanced Magnetic Resonance Imaging (MRI) and Immunology Pilot Trial
NCT01236534	PHASE4	COMPLETED	Lubiprostone in Patients With Multiple Sclerosis Associated Constipation
NCT01333501	PHASE4	COMPLETED	Fingolimod Versus Interferon Beta 1b in Cognitive Symptoms
NCT01339676	PHASE4	UNKNOWN	Colecalciferol as an Add-on Treatment to Interferon-beta-1b for Treatment of Multiple Sclerosis (MS)
NCT01356940	PHASE4	COMPLETED	A Placebo Controlled Trial of Dalfampridine ER for Ambulatory Activity in People With Multiple Sclerosis
NCT01395316	PHASE4	COMPLETED	Alemtuzumab on Surrogate Markers of Disease Activity and Repair Using Advanced MRI Measures in Subjects With Relapsing Remitting Multiple Sclerosis
NCT01411514	PHASE4	TERMINATED	Oral Prednisone Taper Versus Placebo for the Treatment of Acute Relapses in Multiple Sclerosis