DMD

Summary

DMD (dystrophin, HGNC:2928) is a protein-coding gene on chromosome Xp21.2-p21.1, encoding Dystrophin (P11532). Anchors the extracellular matrix to the cytoskeleton via F-actin. It is haploinsufficient (ClinGen: sufficient evidence).

This gene spans a genomic range of greater than 2 Mb and encodes a large protein containing an N-terminal actin-binding domain and multiple spectrin repeats. The encoded protein forms a component of the dystrophin-glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extracellular matrix. Deletions, duplications, and point mutations at this gene locus may cause Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), or cardiomyopathy. Alternative promoter usage and alternative splicing result in numerous distinct transcript variants and protein isoforms for this gene.

Source: NCBI Gene 1756 — RefSeq curated summary.

At a glance

• Gene–disease (curated): progressive muscular dystrophy (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 11
• Clinical variants (ClinVar): 11,716 total — 2661 pathogenic, 614 likely-pathogenic
• Phenotypes (HPO): 80
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004006

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2928
Approved symbol	DMD
Name	dystrophin
Location	Xp21.2-p21.1
Locus type	gene with protein product
Status	Approved
Aliases	BMD, DXS142, DXS164, DXS206, DXS230, DXS239, DXS268, DXS269, DXS270, DXS272
Ensembl gene	ENSG00000198947
Ensembl biotype	protein_coding
OMIM	300377
Entrez	1756

Gene structure

Transcript identifiers

Ensembl transcripts: 91 — 38 protein_coding, 35 retained_intron, 14 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay

ENST00000288447, ENST00000343523, ENST00000357033, ENST00000358062, ENST00000359836, ENST00000361471, ENST00000378677, ENST00000378680, ENST00000378702, ENST00000378705, ENST00000378707, ENST00000378723, ENST00000420596, ENST00000447523, ENST00000448370, ENST00000463609, ENST00000471779, ENST00000472266, ENST00000472681, ENST00000474231, ENST00000475732, ENST00000480751, ENST00000481143, ENST00000488902, ENST00000493412, ENST00000541735, ENST00000619831, ENST00000620040, ENST00000634285, ENST00000634315, ENST00000679437, ENST00000679482, ENST00000679641, ENST00000679669, ENST00000679706, ENST00000679850, ENST00000680162, ENST00000680216, ENST00000680355, ENST00000680557, ENST00000680701, ENST00000680768, ENST00000680961, ENST00000681026, ENST00000681153, ENST00000681334, ENST00000681646, ENST00000681654, ENST00000681839, ENST00000681870, ENST00000681989, ENST00000682071, ENST00000682135, ENST00000682183, ENST00000682207, ENST00000682238, ENST00000682307, ENST00000682322, ENST00000682437, ENST00000682439, ENST00000682584, ENST00000682600, ENST00000682746, ENST00000682769, ENST00000682870, ENST00000682899, ENST00000682924, ENST00000683117, ENST00000683309, ENST00000683450, ENST00000683503, ENST00000683509, ENST00000683658, ENST00000683675, ENST00000683709, ENST00000683851, ENST00000683957, ENST00000683985, ENST00000683995, ENST00000684056, ENST00000684072, ENST00000684103, ENST00000684130, ENST00000684165, ENST00000684237, ENST00000684247, ENST00000684292, ENST00000684342, ENST00000684350, ENST00000684357, ENST00000684660

RefSeq mRNA: 17 — MANE Select: NM_004006 NM_000109, NM_004006, NM_004009, NM_004010, NM_004011, NM_004012, NM_004013, NM_004014, NM_004015, NM_004016, NM_004017, NM_004018, NM_004019, NM_004020, NM_004021, NM_004022, NM_004023

CCDS: CCDS14229, CCDS14230, CCDS14231, CCDS14232, CCDS14233, CCDS14234, CCDS48091, CCDS55394, CCDS55395, CCDS94585, CCDS94586

Canonical transcript exons

ENST00000357033 — 79 exons

Exon	Start	End
ENSE00000978409	32365020	32365199
ENSE00001034039	31178669	31178805
ENSE00001034045	31182738	31182904
ENSE00001034085	31146291	31146414
ENSE00001157370	32364582	32364710
ENSE00001158874	31134102	31134194
ENSE00001158887	31147275	31147518
ENSE00001158895	31169443	31169601
ENSE00001158901	31172348	31172413
ENSE00001158905	31173539	31173604
ENSE00001158912	31177932	31177970
ENSE00001158937	31203961	31204118
ENSE00001158943	31206582	31206667
ENSE00001158950	31209498	31209699
ENSE00001213199	31657990	31658144
ENSE00001213215	31729631	31729748
ENSE00001258577	31679375	31679586
ENSE00001258641	31627673	31627862
ENSE00001259171	31444481	31444627
ENSE00001259193	31478106	31478374
ENSE00001434585	32411752	32411913
ENSE00001434823	32565702	32565881
ENSE00001434995	32697870	32697998
ENSE00001434999	32438241	32438390
ENSE00001435146	32441180	32441314
ENSE00001435151	32484919	32485099
ENSE00001435180	32468498	32468710
ENSE00001435218	32389501	32389674
ENSE00001435573	32390071	32390181
ENSE00001435581	32644964	32645152
ENSE00001435583	32472164	32472309
ENSE00001435605	32545159	32545334
ENSE00001435687	32644132	32644313
ENSE00001435796	32614303	32614453
ENSE00001435906	32463439	32463594
ENSE00001435954	32380510	32380680
ENSE00001436039	32386310	32386465
ENSE00001436107	31126642	31126673
ENSE00001436267	32518008	32518131
ENSE00001436271	32464586	32464699
ENSE00001436342	32809493	32809611
ENSE00001436506	32699112	32699293
ENSE00001436512	32491277	32491518
ENSE00001436545	32448456	32448638
ENSE00001436655	32501755	32501842
ENSE00001436731	32454662	32454832
ENSE00001436736	32595757	32595876
ENSE00001479014	32573530	32573637
ENSE00001640206	32844783	32844860
ENSE00001685282	32823295	32823387
ENSE00001789498	32816468	32816640
ENSE00001899141	33211282	33211549
ENSE00003463064	33020139	33020200
ENSE00003500236	31507281	31507453
ENSE00003554036	31223047	31223121
ENSE00003569118	31180370	31180481
ENSE00003592729	31836718	31836819
ENSE00003620850	31260955	31261016
ENSE00003637702	31348556	31348634
ENSE00003639303	31819975	31820083
ENSE00003639921	32573745	32573846
ENSE00003669069	31496788	31496944
ENSE00003669071	31773960	31774192
ENSE00003675980	31478983	31479103
ENSE00003687899	31875188	31875373
ENSE00003691097	32849728	32849820
ENSE00003693649	31323598	31323658
ENSE00003901420	31119222	31121930
ENSE00003988219	32216916	32217063
ENSE00003988220	31929596	31929745
ENSE00003988221	32310082	32310276
ENSE00003988222	32348406	32348528
ENSE00003988223	31932080	31932227
ENSE00003988224	32345943	32346080
ENSE00003988225	32362788	32362958
ENSE00003988226	32342100	32342282
ENSE00003988227	32287529	32287701
ENSE00003988228	31968339	31968514
ENSE00003988229	32343134	32343286

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.0455 / max 746.3879, expressed in 1383 samples.

FANTOM5 promoters (42 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198804	8.2198	1190
198850	3.0035	393
198848	2.1553	393
198810	1.5761	218
198849	1.0252	266
198852	0.5213	110
198799	0.3646	91
198803	0.2888	164
198847	0.2371	91
198802	0.1912	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trigeminal ganglion	UBERON:0001675	98.90	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.70	gold quality
dorsal root ganglion	UBERON:0000044	98.12	gold quality
seminal vesicle	UBERON:0000998	97.61	gold quality
sural nerve	UBERON:0015488	97.47	gold quality
biceps brachii	UBERON:0001507	97.46	gold quality
vastus lateralis	UBERON:0001379	97.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.29	gold quality
blood vessel layer	UBERON:0004797	97.19	gold quality
quadriceps femoris	UBERON:0001377	96.94	gold quality
endothelial cell	CL:0000115	96.73	gold quality
saphenous vein	UBERON:0007318	96.67	gold quality
body of tongue	UBERON:0011876	96.58	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.49	gold quality
left ventricle myocardium	UBERON:0006566	96.48	gold quality
skeletal muscle tissue	UBERON:0001134	96.45	gold quality
cauda epididymis	UBERON:0004360	96.42	gold quality
myocardium	UBERON:0002349	96.28	gold quality
tibial nerve	UBERON:0001323	96.25	gold quality
tibialis anterior	UBERON:0001385	96.21	gold quality
heart right ventricle	UBERON:0002080	96.17	gold quality
colonic epithelium	UBERON:0000397	95.89	gold quality
vena cava	UBERON:0004087	95.86	gold quality
muscle tissue	UBERON:0002385	95.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.51	gold quality
skeletal muscle organ	UBERON:0014892	95.39	gold quality
muscle organ	UBERON:0001630	95.38	gold quality
secondary oocyte	CL:0000655	95.31	gold quality
deltoid	UBERON:0001476	95.20	gold quality
choroid plexus epithelium	UBERON:0003911	95.11	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	8285.36
E-GEOD-75140	yes	1559.00
E-MTAB-7316	yes	968.52
E-GEOD-124472	yes	291.21
E-GEOD-135922	yes	24.19
E-GEOD-137537	yes	19.67
E-CURD-119	yes	9.53
E-MTAB-11268	no	9617.53
E-GEOD-109979	no	269.32
E-GEOD-70580	no	57.17
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HR, MYOD1, SP1, SP3, SRF, TFAP2A, YY1

miRNA regulators (miRDB)

171 targeting DMD, 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-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-8068	99.98	73.85	2376
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The absence of skeletal muscle degeneration associated with loss of dystrophin function was shown to be due to increased expression of brain (B) and cerebellar Purkinje (CP) isoforms of the gene exclusively in the skeletal muscle of XLDC patients. (PMID:11726549)
• SSCA and heteroduplex analysis showed a nucleotide change in exon 17 of patients with Duchenne and Becker muscular dystrophies. (PMID:11795488)
• Accumulation of repeated elements could account for intron expansion in the evolution of the gene. (PMID:11861579)
• precise function of dystrophin is unknown, but the lack of protein causes membrane destabilization and the activation of multiple pathophysiological processes, many of which converge on alterations in intracellular calcium handling. (PMID:11917091)
• The MCK1350 promoter allows for sustained dystrophin expression after AdV-mediated gene transfer to skeletal muscle of newborn mdx mice, which may have implications for the use of muscle-specific promoters for gene therapy of Duchenne muscular dystrophy. (PMID:11922612)
• Novel deletion at the M and P promoters of the human dystrophin gene associated with a Duchenne muscular dystrophy. (PMID:12031623)
• The dystrophin gene is alternatively spliced throughout its coding sequence. (PMID:12062429)
• 3’-untranslated region is conserved and so may represent a significant target for pathogenic mutations (PMID:12107815)
• the dystrophin rod domain is not merely a spacer but likely contributes an important mechanical role to overall dystrophin function (PMID:12140183)
• We have identified antisense oligoribonucleotides with which the skipping of 11 other Duchenne muscular dystrophy exons could be induced in cultured human muscle cells. May restore the reading frame in a series of patients with different mutations. (PMID:12206800)
• missense mutations and other less severe mutations of the dystrophin gene predispose to the common form of sporadic dilated cardiomyopathy (PMID:12359139)
• Dp71Delta(110) is a component of the platelet membrane cytoskeleton, is involved in cytoskeletal reorganization and/or signaling, and plays a role in thrombin-mediated platelet adhesion (PMID:12370193)
• tumor cells express Dp71f as part of lamellipodia and focal complex proteins, and possibly connected via distroglycan complexes to integrin complexes (PMID:12389738)
• Since Dp71 lacks the actin binding domain, it cannot form the essential linkage between the dystrophin associated proteins complex and the cytoskeleton. (PMID:12398834)
• The tryptophan residues of this protein interact with membrane phospholipids. (PMID:12480947)
• Two alternative exons can result from activation of the cryptic splice acceptor site deep within intron 2 of the dystrophin gene in a patient with as yet asymptomatic dystrophinopathy (PMID:12522557)
• No association with either sequence or structure elements involved in known illegitimate recombination mechanisms was identified. (PMID:12596052)
• Trans-acting factors may cause splicing misregulation in Becker muscular dystrophy skeletal muscles. (PMID:12606026)
• A method is provided for rapid direct sequence analysis of the dystrophin gene. (PMID:12632325)
• DNA mutational analysis in sporadic deletional Duchenne muscular dystrophy (DMD) cases (PMID:12754415)
• characterization of two deep intronic mutations in the Duchenne muscular dystrophy (DMD) gene of two unrelated Becker muscular dystrophy (BMD) patients, causing the aberrant inclusion of a pseudoexon in the mature transcripts (PMID:12754707)
• Patients with double deletion mutations within the dystrophin gene have a milder phenotype than patients harboring single deletions at either major or minor hot spots of the gene. (PMID:12757471)
• Parental attitudes regarding newborn screening of DMD were compiled and evaluated. (PMID:12833401)
• Intronic breakpoint regions in two patients with Duchenne muscular dystrophy carrying the in frame isolated deletion of dystrophin exon 5, representing a known example of “exception to the frame rule” dystrophin mutation. (PMID:12920092)
• 86 haplotypes of dystrophin in 1,343 chromosomes from around the world (PMID:14513410)
• It was found that all of breakpoints were located in repeat sequences and the repeat sequences formed the single-strand hairpin which could make the introns instable and result in exon deletion. (PMID:14556187)
• Nitric oxide synthase (NOS) mRNA was significantly decreased by about 35% in neurons treated with brain-specific dystrophin antisense, whereas inducible NOS expression was not affected. (PMID:14559354)
• Review discusses current understanding of the genotype-phenotype relation for mutations in the dystrophin gene and their implications for gene functions. (PMID:14636778)
• deviation of more than 30% from the reading frame hypothesis in Duchenne muscular dystrophy patients (47/147). (PMID:14652441)
• In 72 Duchenne and Becker Muscular Dystrophies (DMD/BMD) patients without gross gene defect, we encountered four unrelated cases with additional out-of-frame sequences precisely intercalated between two intact exons of the mature muscle dystrophin mRNA (PMID:14659407)
• predicted the translational reading frame for all the deletions in Egyptian dystrophin males, and the frameshift rule was confirmed positively ranging for 50 to 67% of the cases (PMID:15528988)
• Mutation rates of the dystrophin gene were studied in Duchenne muscular dystrophy patients. (PMID:15643612)
• Deletion of exons and rearrangements may apply to female carrier analysis in musscular dystsrophy. (PMID:15655674)
• Results indicate that 7% of dystrophinopathy patients do not have coding region mutations, suggesting that intronic mutations are not uncommon. (PMID:15723292)
• A novel cryptic exon was identified in the 3’ region of intron 2 of the dystrophin gene. (PMID:16133659)
• Disruption of DMD and the absence of ACSL4 in a patient are responsible for neuromuscular disease and cognitive impairment. (PMID:16276108)
• These data reposition dystrophin as a signaling protein and connect an important cellular complex required for the structural integrity of muscle to the pathways that modulate muscle size. (PMID:16286242)
• similar to muscular dystrophy, DGC dysfunction plays a critical role in cancer-induced wasting (PMID:16286249)
• 30 muscle biopsies of patients with Duchenne muscular dystrophy (DMD) showed all or majority of muscle fibers deficient for dystrophin and positive for utrophin. (PMID:16295426)
• Dystrophin mutations were identified in 67% of Duchenne muscular dystrophy patients. (PMID:16331671)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dmd	ENSDARG00000008487
mus_musculus	Dmd	ENSMUSG00000045103
rattus_norvegicus	Dmd	ENSRNOG00000046366

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), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Dystrophin — P11532 (reviewed: P11532)

All UniProt accessions (39): P11532, A0A087WTU7, A0A087WV90, A0A0B4J1W6, A0A0C4DH61, A0A0S2Z3B2, A0A0S2Z3B5, A0A0S2Z3J7, A0A5H1ZRP7, A0A5H1ZRP8, A0A5H1ZRP9, A0A5H1ZRQ1, A0A5H1ZRQ8, A0A5H1ZRR9, A0A7P0T8I2, A0A7P0TA90, A0A7P0TAD9, A0A7P0TAM6, A0A7P0TAW7, A0A7P0TAX0, A0A7P0TB71, A0A7P0TBK1, A0A7P0Z447, A0A7P0Z4M9, A0A7P0Z4P7, A0A7P0Z4Q6, A0A804HIY5, A0A804HJY0, A0A804HKR4, A0A804HKY9, A0A804HKZ5, A0A804HL39, B4DSV7, H0Y304, H0Y3E8, H0Y864, Q14172, Q14174, Q4G0X0

UniProt curated annotations — full annotation on UniProt →

Function. Anchors the extracellular matrix to the cytoskeleton via F-actin. Ligand for dystroglycan. Component of the dystrophin-associated glycoprotein complex which accumulates at the neuromuscular junction (NMJ) and at a variety of synapses in the peripheral and central nervous systems and has a structural function in stabilizing the sarcolemma. Also implicated in signaling events and synaptic transmission.

Subunit / interactions. Interacts with SYNM. Interacts with the syntrophins SNTA1, SNTB1, SNTB2, SNTG1 and SNTG2. Interacts with KRT19. Component of the dystrophin-associated glycoprotein complex which is composed of three subcomplexes: a cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane dystroglycan complex, and the sarcoglycan-sarcospan complex. Interacts with DAG1 (betaDAG1) with DMD; the interaction is inhibited by phosphorylation on the PPXY motif of DAG1. Interacts with CMYA5. Directly interacts with ANK2 and ANK3; these interactions do not interfere with betaDAG1-binding and are necessary for proper localization in muscle cells. Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1. Interacts with DTNB. Interacts with PGM5; the interaction is direct. Interacts with NOS1; localizes NOS1 to sarcolemma in muscle cells.

Subcellular location. Cell membrane. Sarcolemma. Cytoplasm. Cytoskeleton. Postsynaptic cell membrane.

Tissue specificity. Expressed in muscle fibers accumulating in the costameres of myoplasm at the sarcolemma. Expressed in brain, muscle, kidney, lung and testis. Most tissues contain transcripts of multiple isoforms. Isoform 15: Only isoform to be detected in heart and liver and is also expressed in brain, testis and hepatoma cells.

Disease relevance. Duchenne muscular dystrophy (DMD) [MIM:310200] Most common form of muscular dystrophy; a sex-linked recessive disorder. It typically presents in boys aged 3 to 7 year as proximal muscle weakness causing waddling gait, toe-walking, lordosis, frequent falls, and difficulty in standing up and climbing up stairs. The pelvic girdle is affected first, then the shoulder girdle. Progression is steady and most patients are confined to a wheelchair by age of 10 or 12. Flexion contractures and scoliosis ultimately occur. About 50% of patients have a lower IQ than their genetic expectations would suggest. There is no treatment. The disease is caused by variants affecting the gene represented in this entry. Becker muscular dystrophy (BMD) [MIM:300376] A neuromuscular disorder characterized by dystrophin deficiency. It appears between the age of 5 and 15 years with a proximal motor deficiency of variable progression. Heart involvement can be the initial sign. Becker muscular dystrophy has a more benign course than Duchenne muscular dystrophy. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, 3B (CMD3B) [MIM:302045] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. CMD3B is an X-linked disorder. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. The DMD gene is the largest known gene in humans. It is 2.4 million base-pairs in size, comprises 79 exons and takes over 16 hours to be transcribed and cotranscriptionally spliced. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative splicing of isoform 4. Produced by alternative promoter usage. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 6. Produced by alternative splicing of isoform 6. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative splicing of isoform 12. Produced by alternative splicing of isoform 12. Produced by alternative splicing of isoform 12. Produced by alternative splicing of isoform 12. Produced by alternative splicing of isoform 12.

Isoforms (17)

UniProt ID	Names	Canonical?
P11532-1	1, Dystrophin-4, Dp427m	yes
P11532-4	2, Dystrophin-3, Dp427c
P11532-11	3, Dp427p
P11532-2	4, Dystrophin-1, Dp260-1
P11532-3	5, Dystrophin-2, Dp260-2
P11532-12	6, Dp140
P11532-13	7, Dp140c
P11532-14	8, Dp140b
P11532-15	9, Dp140ab
P11532-16	10, Dp140bc
P11532-17	11, Dp116
P11532-7	12, Dp71
P11532-8	13, Dp71a
P11532-6	14, Dp71b
P11532-5	15, Dp71ab
P11532-9	16, Dp60, Dp71delta110
P11532-18	17, Dp40

RefSeq proteins (17): NP_000100, NP_003997, NP_004000, NP_004001, NP_004002, NP_004003, NP_004004, NP_004005, NP_004006, NP_004007, NP_004008, NP_004009, NP_004010, NP_004011, NP_004012, NP_004013, NP_004014 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000433	Znf_ZZ	Domain
IPR001202	WW_dom	Domain
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001715	CH_dom	Domain
IPR002017	Spectrin_repeat	Repeat
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR015153	EF-hand_dom_typ1	Domain
IPR015154	EF-hand_dom_typ2	Domain
IPR018159	Spectrin/alpha-actinin	Repeat
IPR035436	Dystrophin/utrophin	Family
IPR036020	WW_dom_sf	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily
IPR043145	Znf_ZZ_sf	Homologous_superfamily
IPR050774	KCMF1/Dystrophin	Family

Pfam: PF00307, PF00397, PF00435, PF00569, PF09068, PF09069

UniProt features (175 total): sequence variant 50, helix 32, repeat 24, modified residue 18, splice variant 14, strand 10, region of interest 7, turn 5, sequence conflict 4, binding site 4, domain 3, compositionally biased region 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9D58	X-RAY DIFFRACTION	1.94
1EG3	X-RAY DIFFRACTION	2
1EG4	X-RAY DIFFRACTION	2
9EC1	X-RAY DIFFRACTION	2.14
3UUN	X-RAY DIFFRACTION	2.3
1DXX	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

No AlphaFold model available for P11532 — 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 (4): 3313; 3316; 3337; 3340

Post-translational modifications (18): 340, 344, 348, 616, 629, 340, 344, 348, 519, 3483, 3490, 3500, 3612, 3613, 3617, 3623, 3624, 3666

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-390522	Striated Muscle Contraction
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)

MSigDB gene sets: 0 (showing top):

GO Biological Process (29): regulation of heart rate (GO:0002027), muscle organ development (GO:0007517), skeletal muscle tissue development (GO:0007519), intracellular protein localization (GO:0008104), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion (GO:0010881), positive regulation of neuron projection development (GO:0010976), regulation of skeletal muscle contraction by regulation of release of sequestered calcium ion (GO:0014809), regulation of skeletal muscle contraction (GO:0014819), maintenance of blood-brain barrier (GO:0035633), response to muscle stretch (GO:0035994), peptide biosynthetic process (GO:0043043), motile cilium assembly (GO:0044458), positive regulation of neuron differentiation (GO:0045666), muscle cell cellular homeostasis (GO:0046716), neuron development (GO:0048666), muscle cell development (GO:0055001), cardiac muscle contraction (GO:0060048), protein-containing complex assembly (GO:0065003), cardiac muscle cell action potential (GO:0086001), regulation of muscle system process (GO:0090257), regulation of cellular response to growth factor stimulus (GO:0090287), synaptic signaling (GO:0099536), regulation of sodium ion transmembrane transport (GO:1902305), regulation of calcium ion transmembrane transport (GO:1903169), carbohydrate metabolic process (GO:0005975), muscle contraction (GO:0006936), cytoskeleton organization (GO:0007010), regulation of system process (GO:0044057)

GO Molecular Function (11): dystroglycan binding (GO:0002162), actin binding (GO:0003779), structural constituent of cytoskeleton (GO:0005200), zinc ion binding (GO:0008270), structural constituent of muscle (GO:0008307), myosin binding (GO:0017022), vinculin binding (GO:0017166), nitric-oxide synthase binding (GO:0050998), protein binding (GO:0005515), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds (GO:0016810), metal ion binding (GO:0046872)

GO Cellular Component (25): nucleus (GO:0005634), cytosol (GO:0005829), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell surface (GO:0009986), dystrophin-associated glycoprotein complex (GO:0016010), syntrophin complex (GO:0016013), Z disc (GO:0030018), cell-substrate junction (GO:0030055), filopodium (GO:0030175), filopodium membrane (GO:0031527), protein-containing complex (GO:0032991), sarcolemma (GO:0042383), costamere (GO:0043034), neuron projection terminus (GO:0044306), membrane raft (GO:0045121), synapse (GO:0045202), postsynaptic membrane (GO:0045211), cytoplasm (GO:0005737), actin cytoskeleton (GO:0015629), membrane (GO:0016020), lateral plasma membrane (GO:0016328), myofibril (GO:0030016), organelle (GO:0043226), postsynapse (GO:0098794)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Extracellular matrix organization	1
Muscle contraction	1
Non-integrin membrane-ECM interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cytoskeletal protein binding	3
regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	2
neuron differentiation	2
cell development	2
structural molecule activity	2
cytoskeleton	2
plasma membrane protein complex	2
regulation of heart contraction	1
regulation of biological quality	1
animal organ development	1
muscle structure development	1
striated muscle tissue development	1
skeletal muscle organ development	1
macromolecule localization	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of release of sequestered calcium ion into cytosol	1
regulation of cardiac muscle contraction by calcium ion signaling	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
regulation of skeletal muscle contraction by calcium ion signaling	1
skeletal muscle contraction	1
regulation of striated muscle contraction	1
tissue homeostasis	1
response to mechanical stimulus	1
peptide metabolic process	1
biosynthetic process	1
cilium assembly	1
positive regulation of cell differentiation	1
regulation of neuron differentiation	1
cellular homeostasis	1
muscle cell differentiation	1
striated muscle contraction	1
heart contraction	1
cellular component assembly	1
protein-containing complex organization	1
action potential	1
protein binding	1
cytoskeleton organization	1

Protein interactions and networks

STRING

2170 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMD	DAG1	Q14118	999
DMD	SSPN	Q14714	996
DMD	SGCA	Q16586	982
DMD	UTRN	P46939	972
DMD	SNTA1	Q13424	966
DMD	SGCG	Q13326	965
DMD	SGCD	Q92629	965
DMD	DYSF	O75923	959
DMD	LAMA2	P24043	957
DMD	SNTB1	Q13884	956
DMD	DTNA	Q9Y4J8	936
DMD	VCL	P18206	933
DMD	SNTG1	Q9NSN8	932
DMD	SGCB	Q16585	923
DMD	AGRN	O00468	912

IntAct

131 interactions, top by confidence:

A	B	Type	Score
DMD	DTNB	psi-mi:“MI:0915”(physical association)	0.890
DTNB	DMD	psi-mi:“MI:0915”(physical association)	0.890
DTNB	DMD	psi-mi:“MI:0914”(association)	0.890
DMD	DTNB	psi-mi:“MI:0914”(association)	0.890
CTNNAL1	DMD	psi-mi:“MI:0915”(physical association)	0.880
DMD	CTNNAL1	psi-mi:“MI:0915”(physical association)	0.880
CTNNAL1	DMD	psi-mi:“MI:0914”(association)	0.880
SNTB1	DMD	psi-mi:“MI:0915”(physical association)	0.840
DMD	SNTB1	psi-mi:“MI:0915”(physical association)	0.840
DMD	HAUS1	psi-mi:“MI:0915”(physical association)	0.800
HAUS1	DMD	psi-mi:“MI:0915”(physical association)	0.800
DMD	SNTA1	psi-mi:“MI:0915”(physical association)	0.800
DMD	DTNA	psi-mi:“MI:0915”(physical association)	0.760
DTNA	DMD	psi-mi:“MI:0407”(direct interaction)	0.760
SNTB2	DMD	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
E6	CASK	psi-mi:“MI:0915”(physical association)	0.660
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590

BioGRID (178): DTNB (Two-hybrid), CTNNAL1 (Two-hybrid), HAUS1 (Two-hybrid), DMD (Affinity Capture-MS), DMD (Co-fractionation), DMD (Far Western), DMD (Affinity Capture-MS), DMD (Affinity Capture-MS), DMD (Affinity Capture-MS), DMD (Affinity Capture-MS), DMD (Affinity Capture-MS), DMD (Affinity Capture-MS), DMD (Affinity Capture-MS), DMD (Affinity Capture-MS), DMD (Two-hybrid)

ESM2 similar proteins: A0A3B6UES5, A0A3G2LGI8, F4HXZ1, G5EES6, O14134, O43150, O46037, O74749, O97592, P05095, P0CE94, P0CE95, P11532, P11533, P12003, P18206, P19826, P26039, P26234, P27619, P30427, P33338, P39055, P54939, P85972, P90947, Q02328, Q03001, Q04615, Q0WNJ6, Q17162, Q2QYW2, Q54K81, Q54MH2, Q5GN48, Q64727, Q71LX4, Q7SIG6, Q7XPJ0, Q8LPK4

Diamond homologs: A2CI97, A2CI98, A2CJ06, G3V7L1, O97592, P11530, P11531, P11532, P11533, P46939, Q05AA6, Q0KI50, Q13474, Q5GN48, Q7YU29, Q8NEG5, Q9EPA0, Q9TW65, Q9VDW3, Q9VDW6, Q9Y4J8, O60941, O70585, P84060, Q4U2R1, Q9D2N4, Q9VUX2, A5D7D1, D3ZEN0, D3ZHA0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, F1RA39, F6QZ15, G3MWR8, L7UZ85, M9MRD1, O13728

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
DMD	“form complex”	DGC	binding
ANK2	“up-regulates quantity”	DMD	relocalization
ANK3	“up-regulates quantity”	DMD	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 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
Formation of the dystrophin-glycoprotein complex (DGC)	8	35.3×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

11716 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2661
Likely pathogenic	614
Uncertain significance	3462
Likely benign	3204
Benign	479

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012902	GRCh37/hg19 Xp21.1(chrX:32235033-32235180)x4	Pathogenic
1050819	NC_000023.10:g.(32430031_32456357)_(32563452_32583818)del	Pathogenic
1062575	NC_000023.10:g.(?32613864)(32841514_?)dup	Pathogenic
1065130	NC_000023.10:g.(31697704_31747747)_(31747866_31792076)del	Pathogenic
1066543	NM_004006.3(DMD):c.961-2A>G	Pathogenic
1068606	NC_000023.10:g.(?_31462588)_31697713dup	Pathogenic
1068684	NM_004006.3(DMD):c.1402_1406del (p.Glu468fs)	Pathogenic
1069170	NC_000023.10:g.(?_31139940)_33229483del	Pathogenic
1069343	NC_000023.10:g.(?31279052)(31279153_?)del	Pathogenic
1069344	NC_000023.10:g.(?_32732288)_32834581del	Pathogenic
1069345	NC_000023.10:g.(?32305637)(33357392_?)del	Pathogenic
1069390	NM_004006.3(DMD):c.3426C>A (p.Cys1142Ter)	Pathogenic
1069564	NC_000023.10:g.(?32328179)(32536268_?)del	Pathogenic
1069565	NC_000023.10:g.(?32380895)(32519969_?)del	Pathogenic
1069566	NC_000023.10:g.(?32827600)(33038327_?)del	Pathogenic
1069567	NC_000023.10:g.(?32583809)(33038327_?)del	Pathogenic
1069568	NC_000023.10:g.(?32456338)(32509655_?)del	Pathogenic
1069569	NC_000023.10:g.(?32328189)(32503226_?)del	Pathogenic
1069570	NC_000023.10:g.(?32479316)(32490436_?)del	Pathogenic
1069704	NM_004006.3(DMD):c.418del (p.Leu140fs)	Pathogenic
1069818	NM_004006.3(DMD):c.1383dup (p.Asp462Ter)	Pathogenic
1069847	NC_000023.10:g.(?32429859)(32862987_?)del	Pathogenic
1069848	NC_000023.10:g.(?32305636)(32361413_?)del	Pathogenic
1069895	NM_004006.3(DMD):c.5404C>T (p.Gln1802Ter)	Pathogenic
1069896	NM_004006.3(DMD):c.4777G>T (p.Glu1593Ter)	Pathogenic
1069989	NM_004006.3(DMD):c.8853_8865del (p.Gln2952fs)	Pathogenic
1070053	NM_004006.3(DMD):c.3511G>T (p.Glu1171Ter)	Pathogenic
1070054	NM_004006.3(DMD):c.2994T>A (p.Tyr998Ter)	Pathogenic
1070271	NC_000023.10:g.(?31164402)(31697709_?)del	Pathogenic
1070272	NC_000023.10:g.(?31697482)(31792319_?)del	Pathogenic

SpliceAI

7041 predictions. Top by Δscore:

Variant	Effect	Δscore
X:31146284:CACTT:C	donor_loss	1.0000
X:31146285:ACTT:A	donor_loss	1.0000
X:31146286:CTTA:C	donor_loss	1.0000
X:31146287:TTA:T	donor_loss	1.0000
X:31146288:TA:T	donor_loss	1.0000
X:31146289:A:AC	donor_gain	1.0000
X:31146289:AC:A	donor_gain	1.0000
X:31146289:ACCCA:A	donor_loss	1.0000
X:31146290:C:CC	donor_gain	1.0000
X:31146290:CC:C	donor_gain	1.0000
X:31146425:C:CT	acceptor_gain	1.0000
X:31147273:A:AC	donor_gain	1.0000
X:31147274:C:CC	donor_gain	1.0000
X:31147274:CTTG:C	donor_gain	1.0000
X:31147294:AG:A	donor_gain	1.0000
X:31147295:G:C	donor_gain	1.0000
X:31147304:A:C	donor_gain	1.0000
X:31147333:T:TA	donor_gain	1.0000
X:31147346:T:TA	donor_gain	1.0000
X:31147530:A:T	acceptor_gain	1.0000
X:31169597:CATCT:C	acceptor_gain	1.0000
X:31169600:CT:C	acceptor_gain	1.0000
X:31172339:GATAC:G	donor_loss	1.0000
X:31172340:ATAC:A	donor_loss	1.0000
X:31172341:TACT:T	donor_loss	1.0000
X:31172342:AC:A	donor_loss	1.0000
X:31172343:CTTA:C	donor_loss	1.0000
X:31172344:T:TC	donor_loss	1.0000
X:31172345:T:TG	donor_loss	1.0000
X:31172346:A:AC	donor_gain	1.0000

AlphaMissense

24447 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:31147294:A:G	L3593P	1.000
X:31147303:A:G	L3590S	1.000
X:31147315:A:G	L3586P	1.000
X:31147327:T:G	H3582P	1.000
X:31147336:A:G	L3579P	1.000
X:31147345:A:G	M3576T	1.000
X:31147348:C:A	R3575M	1.000
X:31147357:A:G	L3572P	1.000
X:31147365:T:A	K3569N	1.000
X:31147365:T:G	K3569N	1.000
X:31147366:T:A	K3569I	1.000
X:31147378:A:G	L3565P	1.000
X:31147388:C:G	A3562P	1.000
X:31147513:A:G	L3520P	1.000
X:31169458:A:G	L3513P	1.000
X:31172411:A:G	L3444P	1.000
X:31173545:G:T	A3441D	1.000
X:31178708:A:G	L3395P	1.000
X:31178715:C:G	G3393R	1.000
X:31178753:A:G	F3380S	1.000
X:31178755:T:A	K3379N	1.000
X:31178755:T:G	K3379N	1.000
X:31178757:T:C	K3379E	1.000
X:31178758:G:C	N3378K	1.000
X:31178758:G:T	N3378K	1.000
X:31178761:T:A	K3377N	1.000
X:31178761:T:G	K3377N	1.000
X:31178763:T:C	K3377E	1.000
X:31178765:A:G	L3376P	1.000
X:31178774:G:T	A3373D	1.000

dbSNP variants (sampled 300 via entrez): RS1000004757 (X:32037749 A>G), RS1000004941 (X:31951819 T>C,G), RS1000007688 (X:32303104 T>C), RS1000008352 (X:33226674 T>C), RS1000009087 (X:33300961 A>G), RS1000009323 (X:32821392 G>T), RS1000011193 (X:32717685 T>A), RS1000011261 (X:32764750 T>G), RS1000012703 (X:31703013 C>T), RS1000013351 (X:32948742 G>A), RS1000016028 (X:31282378 C>A,T), RS1000016589 (X:32514428 G>T), RS1000018548 (X:32949034 C>A), RS1000019266 (X:31876760 A>G), RS1000019944 (X:32956319 T>G)

Disease associations

OMIM: gene MIM:300377 | disease phenotypes: MIM:300376, MIM:310200, MIM:302045, MIM:181500, MIM:100800, MIM:192600, MIM:115200, MIM:115210, MIM:300018, MIM:300200, MIM:619681, MIM:169300, MIM:601144, MIM:115080, MIM:108800, MIM:209850, MIM:114500

GenCC curated gene-disease

Disease	Classification	Inheritance
Becker muscular dystrophy	Definitive	X-linked
dilated cardiomyopathy 3B	Definitive	X-linked
Duchenne muscular dystrophy	Definitive	X-linked
Duchenne and Becker muscular dystrophy	Definitive	X-linked
progressive muscular dystrophy	Strong	X-linked
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers	Supportive	X-linked
non-syndromic X-linked intellectual disability	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
progressive muscular dystrophy	Definitive	XL

Mondo (41): cardiomyopathy (MONDO:0004994), Becker muscular dystrophy (MONDO:0010311), Duchenne muscular dystrophy (MONDO:0010679), dilated cardiomyopathy 3B (MONDO:0010542), neuromuscular disease caused by qualitative or quantitative defects of dystrophin (MONDO:0016147), progressive muscular dystrophy (MONDO:0016106), intellectual disability (MONDO:0001071), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), dilated cardiomyopathy (MONDO:0005021), muscular dystrophy (MONDO:0020121), schizophrenia (MONDO:0005090), achondroplasia (MONDO:0007037), familial hypertrophic cardiomyopathy (MONDO:0024573), familial dilated cardiomyopathy (MONDO:0016333), familial restrictive cardiomyopathy (MONDO:0016340)

Orphanet (28): Rare cardiomyopathy (Orphanet:167848), Becker muscular dystrophy (Orphanet:98895), Duchenne muscular dystrophy (Orphanet:98896), Familial isolated dilated cardiomyopathy (Orphanet:154), Qualitative or quantitative defects of dystrophin (Orphanet:207085), Progressive muscular dystrophy (Orphanet:206644), Duchenne and Becker muscular dystrophy (Orphanet:262), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Dilated cardiomyopathy (Orphanet:217604), Muscular dystrophy (Orphanet:98473), Achondroplasia (Orphanet:15), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Familial dilated cardiomyopathy (Orphanet:217607), Familial restrictive cardiomyopathy (Orphanet:217635), X-linked adrenal hypoplasia congenita (Orphanet:95702)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000407	Sensorineural hearing impairment
HP:0000750	Delayed speech and language development
HP:0000969	Edema
HP:0001252	Hypotonia
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001288	Gait disturbance
HP:0001324	Muscle weakness
HP:0001328	Specific learning disability
HP:0001371	Flexion contracture
HP:0001417	X-linked inheritance
HP:0001419	X-linked recessive inheritance
HP:0001435	Abnormality of the shoulder girdle musculature
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001712	Left ventricular hypertrophy
HP:0001727	Thromboembolic stroke
HP:0001763	Pes planus
HP:0001771	Achilles tendon contracture
HP:0002091	Restrictive ventilatory defect
HP:0002093	Respiratory insufficiency
HP:0002194	Delayed gross motor development
HP:0002380	Fasciculations
HP:0002505	Loss of ambulation
HP:0002515	Waddling gait
HP:0002527	Falls
HP:0002540	Inability to walk

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001308_20	Response to anti-depressant treatment in major depressive disorder	2.000000e-06
GCST002202_3	Anxiety in major depressive disorder	4.000000e-06
GCST003124_19	Mild influenza (H1N1) infection	5.000000e-14
GCST003125_11	Influenza A (H1N1) infection	4.000000e-11
GCST004034_1	Temporomandibular joint disorder	4.000000e-08
GCST004862_125	Itch intensity from mosquito bite adjusted by bite size	5.000000e-06
GCST004904_10	Body mass index	1.000000e-08
GCST008151_30	Waist circumference	4.000000e-06
GCST008160_75	Waist circumference	4.000000e-06
GCST009139_1	Ankle-brachial index	7.000000e-08
GCST012304_6	Major depressive disorder	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006321	antidepressant-induced dizziness
EFO:1001488	influenza A (H1N1)
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004340	body mass index
EFO:0003912	ankle brachial index

MeSH disease descriptors (25)

Descriptor	Name	Tree numbers
D000130	Achondroplasia	C05.116.099.343.110; C05.116.099.708.017; C16.320.240.500
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D001321	Autistic Disorder	F03.625.164.113.500
D001763	Blepharoptosis	C11.338.204
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D002313	Cardiomyopathy, Restrictive	C14.280.238.160
D005094	Exophthalmos	C11.675.349
D005660	Funnel Chest	C05.116.099.386; C05.660.386; C16.131.621.386
D006333	Heart Failure	C14.280.434
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
D020388	Muscular Dystrophy, Duchenne	C05.651.534.500.300; C10.668.491.175.500.300; C16.320.322.562; C16.320.577.300
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C570377	Benign Pseudohypertrophic Muscular Dystrophy (supp.)
C580047	Dmd-Associated Dilated Cardiomyopathy (supp.)
C535601	Dosage-sensitive sex reversal (supp.)
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5498504 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression	5
viltolarsen	affects splicing, increases expression	3
sodium arsenite	increases abundance, increases expression, affects binding, increases reaction, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Doxorubicin	decreases expression	3
golodirsen	affects splicing	2
arsenite	affects binding, decreases reaction, increases methylation	2
Daunorubicin	decreases expression	2
Etoposide	affects response to substance, decreases expression	2
Gentamicins	increases expression	2
Mitoxantrone	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
eteplirsen	affects splicing	1
geldanamycin	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects methylation, affects cotreatment	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	increases abundance, increases expression	1
tobacco tar	decreases expression	1
periodate-oxidized adenosine	affects expression	1
cupric chloride	increases expression	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
dinophysistoxin 1	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1

Cellosaurus cell lines

189 cell lines: 112 induced pluripotent stem cell, 33 transformed cell line, 31 finite cell line, 8 embryonic stem cell, 4 cancer cell line, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1Q66	HPS0317	Induced pluripotent stem cell	Female
CVCL_1Q67	HPS0322	Induced pluripotent stem cell	Female
CVCL_5M71	GM02298	Finite cell line	Male
CVCL_5M72	GM02339	Finite cell line	Male
CVCL_5M82	GM03429	Finite cell line	Male
CVCL_5M84	GM03604	Finite cell line	Male
CVCL_5M85	GM03782	Transformed cell line	Male
CVCL_5M86	GM03783	Finite cell line	Male
CVCL_5M87	GM03929	Transformed cell line	Male
CVCL_5M89	GM04099	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00819845	PHASE4	UNKNOWN	Ramipril Versus Carvedilol in Duchenne and Becker Patients
NCT01070511	PHASE4	COMPLETED	Tadalafil in Becker Muscular Dystrophy
NCT05704088	PHASE4	COMPLETED	SGLT2 Inhibitors Between Reno Protective Effects and Impact on Bone and Mineral Disease Among Lupus Nephritis Patients
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT01422200	PHASE4	COMPLETED	Flu Vaccine Study in Neuromuscular Patients 2011
NCT01999075	PHASE4	COMPLETED	Stacking Exercises Aid the Decline in FVC and Sick Time
NCT04687020	PHASE4	ACTIVE_NOT_RECRUITING	Long-term Use of Viltolarsen in Boys With Duchenne Muscular Dystrophy in Clinical Practice (VILT-502)
NCT04708314	PHASE4	TERMINATED	An Open-Label Study of Golodirsen in Non-Ambulant Patients With Duchenne Muscular Dystrophy
NCT05412394	PHASE4	RECRUITING	Once Weekly Infant Corticosteroid Trial for DMD
NCT06713135	PHASE4	ACTIVE_NOT_RECRUITING	A Study on Safety and Effectiveness of Long-term Treatment With Vamorolone in Boys With Duchenne Muscular Dystrophy
NCT07542314	PHASE4	NOT_YET_RECRUITING	Study to Evaluate the Safety and Effectiveness of ELEVIDYS in Participants With Duchenne Muscular Dystrophy Treated in a Post-Marketing Setting
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT01557400	PHASE3	COMPLETED	Study of Ataluren for Previously Treated Participants With Nonsense Mutation Duchenne/Becker Muscular Dystrophy (nmDBMD) in Europe, Israel, Australia, and Canada
NCT05457530	PHASE3	WITHDRAWN	Doravirine and Weight Gain in Antiretroviral Naive
NCT00004646	PHASE3	COMPLETED	Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy
NCT00110669	PHASE3	COMPLETED	High-dose Prednisone in Duchenne Muscular Dystrophy
NCT00308113	PHASE3	TERMINATED	CoQ10 and Prednisone in Non-Ambulatory DMD
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT01247207	PHASE3	COMPLETED	Study of Ataluren in Previously Treated Participants With Nonsense Mutation Dystrophinopathy (nmDBMD)
NCT01603407	PHASE3	COMPLETED	Finding the Optimum Regimen for Duchenne Muscular Dystrophy
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02255552	PHASE3	COMPLETED	Study of Eteplirsen in DMD Patients
NCT02354352	PHASE3	COMPLETED	Therapeutic Potential for Aldosterone Inhibition in Duchenne Muscular Dystrophy