DTNA

Summary

DTNA (dystrobrevin alpha, HGNC:3057) is a protein-coding gene on chromosome 18q12.1, encoding Dystrobrevin alpha (Q9Y4J8). May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.

The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene.

Source: NCBI Gene 1837 — RefSeq curated summary.

At a glance

• Gene–disease (curated): muscular dystrophy (Strong, GenCC) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 755 total — 1 pathogenic
• Phenotypes (HPO): 35
• MANE Select transcript: NM_001386795

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3057
Approved symbol	DTNA
Name	dystrobrevin alpha
Location	18q12.1
Locus type	gene with protein product
Status	Approved
Aliases	D18S892E, DTN, DTN-1, DTN-2, DTN-3, DRP3
Ensembl gene	ENSG00000134769
Ensembl biotype	protein_coding
OMIM	601239
Entrez	1837

Gene structure

Transcript identifiers

Ensembl transcripts: 87 — 76 protein_coding, 4 protein_coding_CDS_not_defined, 4 nonsense_mediated_decay, 3 retained_intron

ENST00000269192, ENST00000283365, ENST00000315456, ENST00000348997, ENST00000399113, ENST00000399121, ENST00000444659, ENST00000554864, ENST00000556414, ENST00000585446, ENST00000587723, ENST00000588125, ENST00000588506, ENST00000588684, ENST00000588771, ENST00000588949, ENST00000590412, ENST00000590598, ENST00000590727, ENST00000590831, ENST00000591182, ENST00000591816, ENST00000592114, ENST00000592449, ENST00000595022, ENST00000596745, ENST00000597599, ENST00000597674, ENST00000598142, ENST00000598334, ENST00000598774, ENST00000599844, ENST00000601125, ENST00000601632, ENST00000679372, ENST00000679678, ENST00000679731, ENST00000679796, ENST00000679936, ENST00000680346, ENST00000680366, ENST00000680767, ENST00000680822, ENST00000681065, ENST00000681241, ENST00000681274, ENST00000681470, ENST00000681759, ENST00000682129, ENST00000682406, ENST00000682483, ENST00000682581, ENST00000682923, ENST00000683092, ENST00000683370, ENST00000683379, ENST00000683705, ENST00000683876, ENST00000684228, ENST00000684266, ENST00000684359, ENST00000684377, ENST00000684560, ENST00000684610, ENST00000684734, ENST00000854467, ENST00000854468, ENST00000854469, ENST00000854470, ENST00000854471, ENST00000854472, ENST00000854473, ENST00000854474, ENST00000854475, ENST00000854476, ENST00000854477, ENST00000854478, ENST00000854479, ENST00000854480, ENST00000854481, ENST00000913593, ENST00000970103, ENST00000970104, ENST00000970105, ENST00000970106, ENST00000970107, ENST00000970108

RefSeq mRNA: 44 — MANE Select: NM_001386795 NM_001128175, NM_001198938, NM_001198939, NM_001198940, NM_001198941, NM_001198942, NM_001198943, NM_001198944, NM_001198945, NM_001386753, NM_001386754, NM_001386755, NM_001386756, NM_001386757, NM_001386758, NM_001386759, NM_001386760, NM_001386761, NM_001386762, NM_001386763, NM_001386764, NM_001386765, NM_001386766, NM_001386767, NM_001386768, NM_001386769, NM_001386770, NM_001386771, NM_001386772, NM_001386773, NM_001386774, NM_001386775, NM_001386776, NM_001386777, NM_001386788, NM_001386795, NM_001390, NM_001391, NM_001392, NM_032975, NM_032978, NM_032979, NM_032980, NM_032981

CCDS: CCDS11908, CCDS11909, CCDS42426, CCDS45848, CCDS56060, CCDS56061, CCDS56062, CCDS56063, CCDS59309, CCDS59310, CCDS59311, CCDS59312, CCDS59313, CCDS59314, CCDS92448, CCDS92449, CCDS92450

Canonical transcript exons

ENST00000444659 — 23 exons

Exon	Start	End
ENSE00001536479	34887766	34891844
ENSE00002781873	34875239	34875398
ENSE00002858198	34863966	34864062
ENSE00002940946	34858285	34858398
ENSE00003081797	34877719	34877808
ENSE00003098612	34884728	34884776
ENSE00003122243	34879551	34879719
ENSE00003149460	34882069	34882201
ENSE00003498348	34838745	34838837
ENSE00003502503	34818164	34818330
ENSE00003508158	34827593	34827676
ENSE00003532886	34829400	34829489
ENSE00003580649	34851831	34851928
ENSE00003581099	34806219	34806304
ENSE00003607725	34838094	34838171
ENSE00003612417	34755976	34756043
ENSE00003612904	34811959	34812113
ENSE00003623963	34820791	34820915
ENSE00003637903	34765961	34766041
ENSE00003671884	34848296	34848383
ENSE00003675278	34815909	34816014
ENSE00003679313	34794037	34794250
ENSE00003915984	34710298	34710445

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.4732 / max 2930.8043, expressed in 1454 samples.

FANTOM5 promoters (24 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169898	13.4824	806
169886	9.4713	1098
169904	3.6855	101
169905	2.8968	88
169895	2.4666	339
169906	1.1762	79
169887	1.0220	326
169899	0.9218	197
169890	0.8780	249
169903	0.8699	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
medial globus pallidus	UBERON:0002477	99.50	gold quality
globus pallidus	UBERON:0001875	99.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.27	gold quality
lateral globus pallidus	UBERON:0002476	99.10	gold quality
nucleus accumbens	UBERON:0001882	98.93	gold quality
spinal cord	UBERON:0002240	98.86	gold quality
amygdala	UBERON:0001876	98.82	gold quality
superior vestibular nucleus	UBERON:0007227	98.74	gold quality
caudate nucleus	UBERON:0001873	98.55	gold quality
right frontal lobe	UBERON:0002810	98.49	gold quality
corpus callosum	UBERON:0002336	98.47	gold quality
putamen	UBERON:0001874	98.39	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.39	gold quality
Ammon’s horn	UBERON:0001954	98.26	gold quality
inferior vagus X ganglion	UBERON:0005363	98.21	gold quality
substantia nigra pars compacta	UBERON:0001965	98.18	gold quality
temporal lobe	UBERON:0001871	98.17	gold quality
ventral tegmental area	UBERON:0002691	98.16	gold quality
subthalamic nucleus	UBERON:0001906	98.15	gold quality
hypothalamus	UBERON:0001898	98.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.07	gold quality
cerebellar hemisphere	UBERON:0002245	97.98	gold quality
cerebellar cortex	UBERON:0002129	97.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.89	gold quality
cingulate cortex	UBERON:0003027	97.77	gold quality
anterior cingulate cortex	UBERON:0009835	97.76	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.70	gold quality
primary visual cortex	UBERON:0002436	97.69	gold quality
substantia nigra	UBERON:0002038	97.58	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	4699.77
E-GEOD-180759	yes	4054.08
E-HCAD-30	yes	2634.74
E-HCAD-25	yes	2003.22
E-GEOD-84465	yes	30.76
E-ANND-3	yes	8.93
E-GEOD-83139	yes	3.80
E-ENAD-27	no	3.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

186 targeting DTNA, 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-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977

Literature-anchored findings (GeneRIF, showing 19)

• During a cycle of regeneration in tibialis anterior muscle following myonecrosis, alpha-dystrobrevin reaches 50% of the protein level on day 28 by 6.6 days, regenerating more slowly than dystrophin. (PMID:12416719)
• alpha-dystrobrevin and its splice isoforms have a role in signal transduction in myeloid cells during induction of granulocytic differentiation and/or at the commitment stage of differentiation or phagocytic cells (PMID:12475945)
• Transgenic expression of either isoform of alpha-dystrobrevin prevented muscle fiber degeneration in knockout mice; however, only alphaDB1 corrected defects at neuromuscular and musculotendinous junctions. (PMID:12604589)
• patients with deficiency of beta2-syntrophin and alpha-dystrobrevin presented with severe congenital weakness and died in the first year, and patients with deficiency of alpha-DNT had congenital muscular dystrophy with complete external ophthalmoplegia. (PMID:12899872)
• findings suggest that a-dystrobrevin specifically is associated with the tight junctions during their reorganization (PMID:15834686)
• Results confirm that dystrophin is required for anchorage of the syntrophin-dystrobrevin subcomplex and suggest that expression of the syntrophin-dystrobrevin complex may be independently regulated through neuromuscular transmission. (PMID:15835271)
• Dystrobrevin mRNA including exons 11A and 12 was increased in both skeletal and cardiac muscle of DM1 patients. The aberrantly spliced alpha-dystrobrevin isoform was localized to the sarcolemma. (PMID:18299519)
• Fundamental functional differences between the alpha-dystrobrevins of mice and humans raises questions about the use of the mouse as a model animal for Duchenne muscular dystrophy. (PMID:19961569)
• Results suggest that alpha-dystrobrevin isoforms play a central role in cytoskeleton reorganization via their multiple interactions with actin and actin-associating proteins. (PMID:20111909)
• Data show that alpha-dystrobrevin-1 recruits alpha-catulin, which supersensitizes alpha(1D)-AR functional responses by recruiting effector molecules to the signalosome. (PMID:21115837)
• apoptosis-induction in HL-60 cells involves not only classical markers of apoptosis but also a network alpha-DB-associated proteins at the cell membrane, the cytoplasm and nucleus, affecting key cellular transport processes and cellular structure. (PMID:22507200)
• Ordered disorder of the astrocytic dystrophin-associated protein complex in the norm and pathology. (PMID:24014171)
• our findings suggest that novel mutations in FAM136A and DTNA genes are probably causal variants in FMD. (PMID:25305078)
• we show for the first time localization of alpha-DB2 in nucleoli and Cajal bodies and provide evidence that a-DB2 is involved in the structure of nucleoli and might modulate nucleolar functions (PMID:25959029)
• Report left ventricular non-compaction associated with Barth Syndrome due to triple mutations in TAZ, DTNA, and SDHA genes in multiple members of one family. (PMID:29508483)
• DTNA promotes HBV-induced hepatocellular carcinoma progression by activating STAT3 and regulating TGFbeta1 and P53 signaling. (PMID:32619495)
• Oncogenic microRNA-301b regulates tumor repressor dystrobrevin alpha to facilitate cell growth, invasion and migration in esophageal cancer. (PMID:32737801)
• Whole-exome sequencing reveals a rare missense variant in DTNA in an Iranian pedigree with early-onset atrial fibrillation. (PMID:35148685)
• Variants in DTNA cause a mild, dominantly inherited muscular dystrophy. (PMID:36799992)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dtna	ENSDARG00000031015
mus_musculus	Dtna	ENSMUSG00000024302
rattus_norvegicus	Dtna	ENSRNOG00000016671
drosophila_melanogaster	Dyb	FBGN0033739
caenorhabditis_elegans	dyb-1	WBGENE00001115

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), 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), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Dystrobrevin alpha — Q9Y4J8 (reviewed: Q9Y4J8)

Alternative names: Alpha-dystrobrevin, Dystrophin-related protein 3

All UniProt accessions (27): A0A7P0T818, A0A7P0T8G2, A0A7P0T8J4, A0A7P0T8Y5, A0A7P0T9L1, A0A7P0TAN3, A0A7P0TAU5, A0A7P0TBG1, A0A7P0TBH9, Q9Y4J8, A0A7P0Z4D7, A0A804HHT6, A0A804HHU2, A0A804HII3, A0A804HII4, A0A804HJU0, A0A804HKS8, A0A804HKZ4, A0A804HLB1, K7EIV1, K7EJ84, K7EMN1, K7ENJ7, K7ERZ2, K7ESB2, M0QZ28, M0R021

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.

Subunit / interactions. Interacts with dystrophin, utrophin and the syntrophins SNTA1, SNTB1, SNTB2, SNTG1 and SNTG2. Interacts with MAGEE1. Binds dystrobrevin binding protein 1. Interacts with CTNNAL1. The interaction is required for correct localization of both CTNNAL1 and DTNA. Does not interact with dystrophin. Does not interact with dystrophin.

Subcellular location. Cytoplasm. Synapse. Cell membrane.

Tissue specificity. Highly expressed in brain, skeletal and cardiac muscles, and expressed at lower levels in lung, liver and pancreas. Isoform 2 is not expressed in cardiac muscle. Isoform 7 and isoform 8 are only expressed in muscle.

Post-translational modifications. Phosphorylation of DTN-1 on tyrosine kinase substrate domain present in the C-terminus.

Disease relevance. Left ventricular non-compaction 1 (LVNC1) [MIM:604169] A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. LVNC1 is an autosomal dominant condition. The disease is caused by variants affecting the gene represented in this entry. Myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2 (MMCKR2) [MIM:620971] An autosomal dominant muscular disorder characterized by myalgia, muscle cramps and exercise intolerance with variable ages of onset, and persistent elevations of serum creatine kinase levels. Muscle biopsy shows mixed myopathic and dystrophic findings, characterized by fiber size variability, internalized nuclei, and slightly increased extracellular connective tissue and inflammation. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The coiled coil domain mediates the interaction with dystrophin, alpha-catulin and utrophin.

Similarity. Belongs to the dystrophin family. Dystrobrevin subfamily.

Isoforms (17)

UniProt ID	Names	Canonical?
Q9Y4J8-1	1, DTN-1	yes
Q9Y4J8-2	2, Dystrobrevin-alpha
Q9Y4J8-3	3, DTN-2
Q9Y4J8-4	4, Dystrobrevin-beta
Q9Y4J8-5	5, Dystrobrevin-gamma
Q9Y4J8-6	6, Dystrobrevin-epsilon
Q9Y4J8-7	7, DTN-3, Alpha-dystrobrevin-3, Dystrobrevin-delta
Q9Y4J8-8	8, Dystrobrevin-zeta
Q9Y4J8-9	9
Q9Y4J8-10	10
Q9Y4J8-11	11
Q9Y4J8-12	12
Q9Y4J8-13	13
Q9Y4J8-14	14
Q9Y4J8-15	15
Q9Y4J8-16	16
Q9Y4J8-17	17

RefSeq proteins (44): NP_001121647, NP_001185867, NP_001185868, NP_001185869, NP_001185870, NP_001185871, NP_001185872, NP_001185873, NP_001185874, NP_001373682, NP_001373683, NP_001373684, NP_001373685, NP_001373686, NP_001373687, NP_001373688, NP_001373689, NP_001373690, NP_001373691, NP_001373692, NP_001373693, NP_001373694, NP_001373695, NP_001373696, NP_001373697, NP_001373698, NP_001373699, NP_001373700, NP_001373701, NP_001373702, NP_001373703, NP_001373704, NP_001373705, NP_001373706, NP_001373717, NP_001373724, NP_001381, NP_001382, NP_001383, NP_116757, NP_116760, NP_116761, NP_116762, NP_116763 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000433	Znf_ZZ	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR015153	EF-hand_dom_typ1	Domain
IPR015154	EF-hand_dom_typ2	Domain
IPR017432	Distrobrevin	Family
IPR043145	Znf_ZZ_sf	Homologous_superfamily
IPR050774	KCMF1/Dystrophin	Family

Pfam: PF00569, PF09068, PF09069

UniProt features (49 total): splice variant 14, sequence conflict 9, binding site 8, sequence variant 5, strand 4, region of interest 3, chain 1, zinc finger region 1, modified residue 1, helix 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2E5R	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4J8-F1	69.98	0.35

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 (8): 261; 267; 270; 280; 284; 243; 246; 258

Post-translational modifications (1): 662

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)

MSigDB gene sets: 396 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GCM_MAP4K4, AP1_01, LEE_NEURAL_CREST_STEM_CELL_DN, FREAC2_01, YAGI_AML_WITH_INV_16_TRANSLOCATION, RORA1_01, MORF_BRCA1, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, MORF_ATRX, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GCAAGGA_MIR502, MORF_ESR1, FOXO1_01

GO Biological Process (5): striated muscle contraction (GO:0006941), signal transduction (GO:0007165), chemical synaptic transmission (GO:0007268), neuromuscular synaptic transmission (GO:0007274), synaptic signaling (GO:0099536)

GO Molecular Function (4): zinc ion binding (GO:0008270), PDZ domain binding (GO:0030165), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (12): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell junction (GO:0030054), axon (GO:0030424), extrinsic component of cytoplasmic side of plasma membrane (GO:0031234), protein-containing complex (GO:0032991), sarcolemma (GO:0042383), intermediate filament cytoskeleton (GO:0045111), synapse (GO:0045202), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Non-integrin membrane-ECM interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
muscle contraction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
anterograde trans-synaptic signaling	1
chemical synaptic transmission	1
cell-cell signaling	1
synapse	1
transition metal ion binding	1
protein domain specific binding	1
binding	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
neuron projection	1
cytoplasmic side of plasma membrane	1
extrinsic component of plasma membrane	1
cellular_component	1
plasma membrane	1
cytoskeleton	1
cell junction	1

Protein interactions and networks

STRING

1468 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DTNA	SSPN	Q14714	990
DTNA	SYNC	Q9H7C4	987
DTNA	DAG1	Q14118	975
DTNA	SNTA1	Q13424	946
DTNA	DMD	P11532	936
DTNA	SNTB2	Q13425	904
DTNA	SGCA	Q16586	902
DTNA	SGCD	Q92629	869
DTNA	SYNM	O15061	858
DTNA	SNTB1	Q13884	846
DTNA	PLEC	Q15149	841
DTNA	SNTG2	Q9NY99	797
DTNA	SNTG1	Q9NSN8	766
DTNA	TAFAZZIN	Q16635	753
DTNA	SGCG	Q13326	738

IntAct

99 interactions, top by confidence:

A	B	Type	Score
DMD	DTNB	psi-mi:“MI:0914”(association)	0.890
CTNNAL1	DMD	psi-mi:“MI:0914”(association)	0.880
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
SCRIB	ADRA1D	psi-mi:“MI:0914”(association)	0.820
ADRA1D	UTRN	psi-mi:“MI:0915”(physical association)	0.770
DMD	DTNA	psi-mi:“MI:0915”(physical association)	0.760
DTNA	DMD	psi-mi:“MI:0407”(direct interaction)	0.760
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
ADRA1D	CTNNAL1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SNTB2	CASK	psi-mi:“MI:0914”(association)	0.670
CTNNAL1	DTNA	psi-mi:“MI:0915”(physical association)	0.620
DTNA	CTNNAL1	psi-mi:“MI:0403”(colocalization)	0.620
ADRA1D	LIN7A	psi-mi:“MI:0914”(association)	0.590
DTNA	UTRN	psi-mi:“MI:0407”(direct interaction)	0.590
SLC16A3	CASK	psi-mi:“MI:0914”(association)	0.590
UTRN	DTNA	psi-mi:“MI:0407”(direct interaction)	0.590
SNTG2	DTNB	psi-mi:“MI:0914”(association)	0.550
Sync	DTNA	psi-mi:“MI:0403”(colocalization)	0.540
Sync	DTNA	psi-mi:“MI:0915”(physical association)	0.540
DTNA	Sync	psi-mi:“MI:0915”(physical association)	0.540
ADRA1D	DMD	psi-mi:“MI:0914”(association)	0.530

BioGRID (171): DTNA (Affinity Capture-MS), DTNA (Affinity Capture-MS), DTNA (Affinity Capture-MS), NMT1 (Affinity Capture-MS), POTEI (Affinity Capture-MS), SAR1A (Affinity Capture-MS), DTNA (Affinity Capture-MS), DTNA (Far Western), DRP2 (Far Western), DMD (Far Western), UTRN (Far Western), DTNA (Two-hybrid), DMD (Two-hybrid), DTNA (Proximity Label-MS), DTNA (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVV1, A0M8S0, A0M8T1, A0M8U1, A3KN28, A4D7R9, A9JRA0, B1AZA5, E9Q2Z6, P01134, P48030, Q00PJ0, Q07DV5, Q07DW9, Q07DX8, Q07DY8, Q07E08, Q07E45, Q09YH4, Q09YI5, Q09YJ7, Q09YK8, Q09YN2, Q108U3, Q1RLU8, Q2IBA8, Q2IBD0, Q2IBE0, Q2IBE8, Q2PG42, Q2QL86, Q2QLA6, Q2QLB7, Q2QLD7, Q2QLE8, Q2QLG2, Q3KRC4, Q3SXP7, Q5T292, Q68FW3

Diamond homologs: A2CI97, A2CI98, A2CJ06, G3V7L1, O97592, P11530, P11531, P11532, P11533, P46939, Q05AA6, Q0KI50, Q13474, Q5GN48, Q7YU29, Q8NEG5, Q9EPA0, Q9TW65, Q9VDW3, Q9VDW6, Q9Y4J8, O70585, P84060, Q9D2N4, Q9P792, O60941, Q4U2R1, Q9VUX2, Q9Y048, O08623, O95714, P14199, P34664, Q13501, Q24629, Q5RBA5, Q64337, Q6GNY1, Q804S5, Q80SY4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DTNA	“form complex”	DGC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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)	7	34.3×	7e-07
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	9.2×	1e-02
PIP3 activates AKT signaling	7	7.4×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
protein autophosphorylation	6	10.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	350
Likely benign	260
Benign	90

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3363146	NM_001386795.1(DTNA):c.1666G>A (p.Glu556Lys)	Pathogenic

SpliceAI

3988 predictions. Top by Δscore:

Variant	Effect	Δscore
18:34765956:ACTAG:A	acceptor_gain	1.0000
18:34766040:TT:T	donor_gain	1.0000
18:34766042:G:GG	donor_gain	1.0000
18:34792631:A:G	acceptor_gain	1.0000
18:34794036:G:GA	acceptor_gain	1.0000
18:34794246:GATCC:G	donor_gain	1.0000
18:34794251:G:GG	donor_gain	1.0000
18:34811958:GAT:G	acceptor_gain	1.0000
18:34812109:AACAG:A	donor_loss	1.0000
18:34812111:CAGG:C	donor_loss	1.0000
18:34812112:AGGT:A	donor_loss	1.0000
18:34812113:GGTAG:G	donor_loss	1.0000
18:34812114:G:T	donor_loss	1.0000
18:34812115:T:A	donor_loss	1.0000
18:34814030:A:T	donor_gain	1.0000
18:34820785:TTCCA:T	acceptor_loss	1.0000
18:34820786:TCCA:T	acceptor_loss	1.0000
18:34820787:CCAG:C	acceptor_loss	1.0000
18:34820788:CAG:C	acceptor_loss	1.0000
18:34820789:A:AG	acceptor_gain	1.0000
18:34820789:AGAAA:A	acceptor_loss	1.0000
18:34820790:G:A	acceptor_loss	1.0000
18:34820790:G:GG	acceptor_gain	1.0000
18:34820790:GA:G	acceptor_gain	1.0000
18:34820911:ATCGT:A	donor_gain	1.0000
18:34820912:TCGT:T	donor_gain	1.0000
18:34820913:CGTG:C	donor_loss	1.0000
18:34820914:GT:G	donor_gain	1.0000
18:34820914:GTGT:G	donor_loss	1.0000
18:34820915:TG:T	donor_loss	1.0000

AlphaMissense

5093 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:34765996:T:G	Y35D	1.000
18:34766000:G:C	R36T	1.000
18:34766000:G:T	R36I	1.000
18:34766024:T:A	V44D	1.000
18:34794054:T:A	W56R	1.000
18:34794054:T:C	W56R	1.000
18:34812022:T:C	L171P	1.000
18:34815975:T:A	W224R	1.000
18:34815975:T:C	W224R	1.000
18:34818181:T:C	C243R	1.000
18:34818183:T:G	C243W	1.000
18:34818211:G:A	G253R	1.000
18:34818211:G:C	G253R	1.000
18:34818212:G:A	G253E	1.000
18:34818226:T:C	C258R	1.000
18:34818228:C:G	C258W	1.000
18:34818253:T:C	C267R	1.000
18:34818255:T:G	C267W	1.000
18:34818262:T:C	C270R	1.000
18:34818264:C:G	C270W	1.000
18:34818265:T:C	F271L	1.000
18:34818267:C:A	F271L	1.000
18:34818267:C:G	F271L	1.000
18:34818268:T:A	W272R	1.000
18:34818268:T:C	W272R	1.000
18:34818270:G:C	W272C	1.000
18:34818270:G:T	W272C	1.000
18:34848337:T:C	L436P	1.000
18:34848340:T:A	I437N	1.000
18:34851901:T:C	L475P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002274 (18:34851255 C>T), RS1000013565 (18:34607307 A>G,T), RS1000019702 (18:34492841 T>C), RS1000019780 (18:34690747 T>C), RS1000022664 (18:34752770 C>CTAAT), RS1000023028 (18:34651110 C>T), RS1000052540 (18:34806499 A>G), RS1000053436 (18:34764090 C>G), RS1000055316 (18:34659791 G>A,C), RS1000062447 (18:34568058 A>G,T), RS1000068498 (18:34646414 A>G), RS1000071295 (18:34534207 G>A,C), RS1000081767 (18:34561933 C>G), RS1000086358 (18:34736315 A>G), RS1000090287 (18:34676732 G>A,T)

Disease associations

OMIM: gene MIM:601239 | disease phenotypes: MIM:604169, MIM:156000, MIM:192600, MIM:613881, MIM:620971, MIM:620138

GenCC curated gene-disease

Disease	Classification	Inheritance
muscular dystrophy	Strong	Autosomal dominant
Meniere disease	Limited	Autosomal dominant
left ventricular noncompaction 1	Limited	Autosomal dominant
congenital heart disease	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
dilated cardiomyopathy	Limited	AD
congenital heart disease	Disputed	AD

Mondo (14): left ventricular noncompaction 1 (MONDO:0011403), Meniere disease (MONDO:0007972), dilated cardiomyopathy (MONDO:0005021), familial hypertrophic cardiomyopathy (MONDO:0024573), dilated cardiomyopathy 1HH (MONDO:0013479), hypertrophic cardiomyopathy (MONDO:0005045), congenital heart disease (MONDO:0005453), myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2 (MONDO:0975830), myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis (MONDO:0979249), cardiomyopathy (MONDO:0004994), cardiac rhythm disease (MONDO:0007263), systolic heart failure (MONDO:0006993), ventricular tachycardia (MONDO:0005477), muscular dystrophy (MONDO:0020121)

Orphanet (8): Left ventricular noncompaction (Orphanet:54260), Dilated cardiomyopathy (Orphanet:217604), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Familial isolated dilated cardiomyopathy (Orphanet:154), Rare hypertrophic cardiomyopathy (Orphanet:217569), Rare cardiomyopathy (Orphanet:167848), NON RARE IN EUROPE: Menière disease (Orphanet:45360), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

35 total (30 of 35 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000729	Autistic behavior
HP:0001324	Muscle weakness
HP:0001328	Specific learning disability
HP:0001629	Ventricular septal defect
HP:0001635	Congestive heart failure
HP:0001643	Patent ductus arteriosus
HP:0001645	Sudden cardiac death
HP:0001653	Mitral regurgitation
HP:0001712	Left ventricular hypertrophy
HP:0001962	Palpitations
HP:0003201	Rhabdomyolysis
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003326	Myalgia
HP:0003546	Exercise intolerance
HP:0003557	Increased variability in muscle fiber diameter
HP:0003577	Congenital onset
HP:0003581	Adult onset
HP:0003687	Centrally nucleated skeletal muscle fibers
HP:0003803	Type 1 muscle fiber predominance
HP:0004308	Ventricular arrhythmia
HP:0004383	Hypoplastic left ventricle
HP:0005110	Atrial fibrillation
HP:0007018	Attention deficit hyperactivity disorder
HP:0011462	Young adult onset
HP:0011664	Left ventricular noncompaction cardiomyopathy
HP:0011705	First degree atrioventricular block
HP:0012548	Fatty replacement of skeletal muscle
HP:0012817	Noncompaction cardiomyopathy
HP:0030682	Left ventricular noncompaction

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002829_19	Urate levels in overweight individuals	8.000000e-06
GCST005173_56	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	9.000000e-06
GCST010320_9	PR interval	3.000000e-11
GCST010321_62	PR interval	7.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004723	coronary artery calcification
EFO:0004462	PR interval

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
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
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D054143	Heart Failure, Systolic	C14.280.434.676
D008575	Meniere Disease	C09.218.568.217.500
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	8
methylmercuric chloride	increases expression	2
bisphenol A	increases methylation, increases expression, affects methylation, affects cotreatment	2
mercuric bromide	increases expression, affects cotreatment	2
Vorinostat	affects expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Cyclosporine	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
uranyl acetate	increases expression	1
methylselenic acid	increases expression	1
trichostatin A	increases expression	1
tobacco tar	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	affects methylation	1
pentabromodiphenyl ether	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Ethanol	increases expression	1
Caffeine	increases phosphorylation	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B5H2	GENYOi007-A	Induced pluripotent stem cell	Female
CVCL_E7TW	FMD patient III.4 LCL	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy