SGCD

Summary

SGCD (sarcoglycan delta, HGNC:10807) is a protein-coding gene on chromosome 5q33.2-q33.3, encoding Delta-sarcoglycan (Q92629). Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.

The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene.

Source: NCBI Gene 6444 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 25
• Clinical variants (ClinVar): 839 total — 32 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 38
• MANE Select transcript: NM_000337

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10807
Approved symbol	SGCD
Name	sarcoglycan delta
Location	5q33.2-q33.3
Locus type	gene with protein product
Status	Approved
Aliases	DAGD, LGMD2F, CMD1L
Ensembl gene	ENSG00000170624
Ensembl biotype	protein_coding
OMIM	601411
Entrez	6444

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000337851, ENST00000435422, ENST00000517913, ENST00000524347, ENST00000959782, ENST00000959783, ENST00000959784, ENST00000959785, ENST00000959786, ENST00000959787

RefSeq mRNA: 3 — MANE Select: NM_000337 NM_000337, NM_001128209, NM_172244

CCDS: CCDS47325, CCDS47326, CCDS47327

Canonical transcript exons

ENST00000337851 — 9 exons

Exon	Start	End
ENSE00001133336	156757581	156757704
ENSE00001133342	156647464	156647536
ENSE00001133349	156594932	156595051
ENSE00001133355	156589231	156589318
ENSE00001357879	156759217	156767788
ENSE00001357905	156327164	156327232
ENSE00002322170	156329534	156329579
ENSE00003542291	156508601	156508702
ENSE00003757279	156344489	156344677

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 96.24.

FANTOM5 (CAGE): breadth broad, TPM avg 7.0787 / max 243.7578, expressed in 742 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59775	2.9653	564
59774	2.2491	601
59771	1.0396	383
59773	0.3709	197
59770	0.1443	92
59772	0.1143	46
59769	0.1044	70
59768	0.0907	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	96.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.97	gold quality
heart right ventricle	UBERON:0002080	95.06	gold quality
myocardium	UBERON:0002349	94.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.81	gold quality
vastus lateralis	UBERON:0001379	93.72	gold quality
biceps brachii	UBERON:0001507	93.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.21	gold quality
quadriceps femoris	UBERON:0001377	92.84	gold quality
skeletal muscle tissue	UBERON:0001134	92.16	gold quality
deltoid	UBERON:0001476	91.76	gold quality
muscle tissue	UBERON:0002385	91.59	gold quality
saphenous vein	UBERON:0007318	91.37	gold quality
gluteal muscle	UBERON:0002000	91.21	gold quality
tibialis anterior	UBERON:0001385	90.61	gold quality
muscle organ	UBERON:0001630	89.83	gold quality
cardiac ventricle	UBERON:0002082	89.46	gold quality
buccal mucosa cell	CL:0002336	89.42	gold quality
heart left ventricle	UBERON:0002084	89.33	gold quality
triceps brachii	UBERON:0001509	89.28	silver quality
body of tongue	UBERON:0011876	88.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.96	gold quality
cardiac atrium	UBERON:0002081	88.89	gold quality
heart	UBERON:0000948	88.60	gold quality
muscle of leg	UBERON:0001383	88.55	gold quality
diaphragm	UBERON:0001103	88.42	gold quality
right atrium auricular region	UBERON:0006631	88.25	gold quality
gastrocnemius	UBERON:0001388	88.06	gold quality
tibial artery	UBERON:0007610	87.28	gold quality
popliteal artery	UBERON:0002250	87.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	50.75
E-HCAD-25	yes	7.71
E-ANND-3	yes	6.38
E-MTAB-11268	no	1932.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

339 targeting SGCD, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 9)

• These data suggest that formation of the beta-delta-core may promote the export and deposition of sarcoglycan subcomplexes at the plasma membrane, and therefore identifies a mechanism for sarcoglycan transport. (PMID:17036316)
• The 5’-UTR G to C polymorphism on delta-sarcoglycan gene was associated with coronary spasm in Japanese patients with hypertrophic cardiomyopathy. (PMID:17652892)
• The limb-girdle muscular dystrophy patients with delta-sarcoglycan deficient LGMD2F do not enable an accurate prediction of the genotype. (PMID:18996010)
• Finding questions the pathological relevance of sequence variant of the delta-sarcoglycan gene for causing familial autosomal-dominant dilated cardiomyopathy. (PMID:19259135)
• Genetic variation at the delta-sarcoglycan locus elevates heritable sympathetic nerve activity in human twin pairs (PMID:23786442)
• CC genotype of the delta-sarcoglycan gene polymorphism rs13170573 is associated with obstructive sleep apnea in the Chinese population (PMID:25474115)
• haplotype -_G composed of c.-100~-110 and A848G confers higher susceptibility to dilated cardiomyopathy in the Mongoloid population. (PMID:26720722)
• Dilated cardiomyopathy mutations in delta-sarcoglycan can exert a dominant negative effect on dystrophin-glycoprotein complex function leading to myocardial mechanical instability that may underlie the pathogenesis of delta-sarcoglycan-associated DCM. (PMID:26968544)
• Study identified 2 non-synonymous missense mutations: c.C652T, p.R218W in ACVRL1, c.C717G, p.D239E in SGCD in Chinese population with total anomalous pulmonary venous return. (PMID:28412737)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgcd	ENSDARG00000098573
mus_musculus	Sgcd	ENSMUSG00000020354
rattus_norvegicus	Sgcd	ENSRNOG00000002372
drosophila_melanogaster	Scgdelta	FBGN0025391
caenorhabditis_elegans		WBGENE00004790

Paralogs (2): SGCG (ENSG00000102683), SGCZ (ENSG00000185053)

Protein

Protein identifiers

Delta-sarcoglycan — Q92629 (reviewed: Q92629)

Alternative names: 35 kDa dystrophin-associated glycoprotein

All UniProt accessions (2): Q92629, E5RI34

UniProt curated annotations — full annotation on UniProt →

Function. Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.

Subunit / interactions. Interacts with FLNC and DAG1. Cross-link to form 2 major subcomplexes: one consisting of SGCB, SGCD and SGCG and the other consisting of SGCB and SGCD. The association between SGCB and SGCG is particularly strong while SGCA is loosely associated with the other sarcoglycans.

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

Tissue specificity. Most strongly expressed in skeletal and cardiac muscle. Also detected in smooth muscle. Weak expression in brain and lung.

Post-translational modifications. Glycosylated. Disulfide bonds are present.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal recessive 6 (LGMDR6) [MIM:601287] An autosomal recessive degenerative myopathy initially affecting the proximal limb girdle musculature. Muscle from patients shows a complete loss of delta-sarcoglycan as well as of the others components of the sarcoglycan complex. The disease is caused by variants affecting the gene represented in this entry. Cardiomyopathy, dilated, 1L (CMD1L) [MIM:606685] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the sarcoglycan beta/delta/gamma/zeta family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q92629-1	1	yes
Q92629-2	2
Q92629-3	3

RefSeq proteins (3): NP_000328, NP_001121681, NP_758447 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006875	Sarcoglycan	Family
IPR039972	Sarcoglycan_gamma/delta/zeta	Family

Pfam: PF04790

UniProt features (15 total): splice variant 3, sequence variant 3, glycosylation site 3, topological domain 2, disulfide bond 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92629-F1	81.43	0.27

Functional residue map

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

Disulfide bonds (2): 263–288, 265–281

Glycosylation sites (3): 60, 108, 284

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)
R-HSA-1474244	Extracellular matrix organization
R-HSA-3000171	Non-integrin membrane-ECM interactions

MSigDB gene sets: 311 (showing top): MODULE_97, AAGCAAT_MIR137, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CORONARY_VASCULATURE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GCAAGGA_MIR502, MODULE_182, AAAYRNCTG_UNKNOWN, MORF_RAD51L3, BROWNE_HCMV_INFECTION_48HR_DN, TCF4_Q5, KEGG_VIRAL_MYOCARDITIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (11): muscle organ development (GO:0007517), calcium-mediated signaling (GO:0019722), protein-containing complex localization (GO:0031503), cardiac muscle tissue development (GO:0048738), cardiac muscle cell development (GO:0055013), calcium ion homeostasis (GO:0055074), heart contraction (GO:0060047), coronary vasculature morphogenesis (GO:0060977), cardiac muscle cell contraction (GO:0086003), heart process (GO:0003015), cardiac muscle contraction (GO:0060048)

GO Molecular Function (0):

GO Cellular Component (11): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), dystrophin-associated glycoprotein complex (GO:0016010), sarcoglycan complex (GO:0016012), sarcoplasmic reticulum (GO:0016529), sarcolemma (GO:0042383), cytoplasm (GO:0005737), dystroglycan complex (GO:0016011), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane protein complex	3
cellular anatomical structure	2
animal organ development	1
muscle structure development	1
intracellular signaling cassette	1
macromolecule localization	1
heart development	1
striated muscle tissue development	1
striated muscle cell development	1
cardiac cell development	1
cardiac muscle cell differentiation	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
heart process	1
blood circulation	1
blood vessel morphogenesis	1
coronary vasculature development	1
cardiac muscle contraction	1
actin-mediated cell contraction	1
circulatory system process	1
striated muscle contraction	1
heart contraction	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
membrane	1
cell periphery	1
glycoprotein complex	1
dystroglycan complex	1
endoplasmic reticulum	1
sarcoplasm	1
plasma membrane	1
intracellular anatomical structure	1
dystrophin-associated glycoprotein complex	1

Protein interactions and networks

STRING

1062 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGCD	SGCA	Q16586	999
SGCD	DAG1	Q14118	993
SGCD	SSPN	Q14714	990
SGCD	SGCB	Q16585	972
SGCD	DMD	P11532	965
SGCD	SGCG	Q13326	949
SGCD	FLNC	Q14315	946
SGCD	SGCE	O43556	941
SGCD	SNTA1	Q13424	887
SGCD	SNTB1	Q13884	880
SGCD	DTNA	Q9Y4J8	869
SGCD	UTRN	P46939	823
SGCD	LMNA	P02545	815
SGCD	DYSF	O75923	813
SGCD	TCAP	O15273	798

IntAct

15 interactions, top by confidence:

A	B	Type	Score
FLNC	SGCD	psi-mi:“MI:0915”(physical association)	0.590
FLNC	SGCD	psi-mi:“MI:0407”(direct interaction)	0.590
SGCD	FLNC	psi-mi:“MI:0915”(physical association)	0.590
SGCD		psi-mi:“MI:0915”(physical association)	0.550
SGCD	ADA	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
DAG1	AGRN	psi-mi:“MI:0914”(association)	0.350
DAG1	SGCE	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SGCD	FAM241A	psi-mi:“MI:0914”(association)	0.350
SGCD	SERPINA3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): SGCB (Affinity Capture-MS), C4orf32 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), C10orf35 (Affinity Capture-MS), C4orf32 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), ACP2 (Affinity Capture-MS), C10orf35 (Affinity Capture-MS), SGCD (Affinity Capture-MS), SGCD (Affinity Capture-MS), SGCD (Proximity Label-MS), FLNC (Two-hybrid), SGCD (Proximity Label-MS), SERPINA3 (Two-hybrid), SGCD (Affinity Capture-MS)

ESM2 similar proteins: A0M8S0, A0M8T1, A0M8U1, A4D7R9, A6QP70, A9JRA0, P11029, P13666, P82347, P82349, P97281, Q00PJ0, Q07DV5, Q07DW9, Q07DX8, Q07DY8, Q07E08, Q07E45, Q09YH4, Q09YI5, Q09YJ7, Q09YK8, Q09YN2, Q108U3, Q13085, Q16585, Q28635, Q2IBA8, Q2IBD0, Q2IBE0, Q2IBE8, Q2PG42, Q2QL86, Q2QLA6, Q2QLB7, Q2QLD7, Q2QLE8, Q2QLG2, Q5R660, Q5R8N4

Diamond homologs: O08597, P82347, P82348, P97281, Q0VCU7, Q13326, Q8BX51, Q8SQ72, Q92629, Q96LD1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SGCD	“form complex”	DGC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	26
Uncertain significance	351
Likely benign	282
Benign	62

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068999	NC_000005.9:g.(?155935601)(156074556_?)del	Pathogenic
1180701	NM_000337.6(SGCD):c.568G>T (p.Glu190Ter)	Pathogenic
1394105	NM_000337.6(SGCD):c.466G>T (p.Glu156Ter)	Pathogenic
1451957	NM_000337.6(SGCD):c.97C>T (p.Arg33Ter)	Pathogenic
1677453	NM_000337.6(SGCD):c.289C>T (p.Arg97Ter)	Pathogenic
1977494	NM_000337.6(SGCD):c.90G>A (p.Trp30Ter)	Pathogenic
2422916	NC_000005.9:g.(?156074454)(156074566_?)del	Pathogenic
2422917	NC_000005.9:g.(?156184572)(156184735_?)del	Pathogenic
2422918	NC_000005.9:g.(?155756587)(156074566_?)del	Pathogenic
2422920	NC_000005.9:g.(?155756587)(156184735_?)del	Pathogenic
2713565	NM_000337.6(SGCD):c.248_249del (p.Asp82_Ser83insTer)	Pathogenic
2741520	NM_000337.6(SGCD):c.133_172dup (p.Lys58fs)	Pathogenic
2760849	NM_000337.6(SGCD):c.414dup (p.Phe139fs)	Pathogenic
2816447	NM_000337.6(SGCD):c.654_655del (p.Glu218fs)	Pathogenic
2835886	NM_000337.6(SGCD):c.540_541del (p.Thr180_Pro181insTer)	Pathogenic
285158	NM_000337.6(SGCD):c.65dup (p.Tyr23fs)	Pathogenic
286720	NM_000337.6(SGCD):c.443T>A (p.Leu148Ter)	Pathogenic
3013440	NM_000337.6(SGCD):c.481_485dup (p.Arg163fs)	Pathogenic
3338340	NM_000337.6(SGCD):c.382+1G>A	Pathogenic
3641138	NM_000337.6(SGCD):c.258dup (p.Gln87fs)	Pathogenic
3669608	NM_000337.6(SGCD):c.172A>T (p.Lys58Ter)	Pathogenic
4081797	NM_000337.6(SGCD):c.506del (p.Ala169fs)	Pathogenic
411697	NM_000337.6(SGCD):c.74_77dup (p.Ile27fs)	Pathogenic
4740008	NM_000337.6(SGCD):c.491T>G (p.Leu164Ter)	Pathogenic
584277	NC_000005.10:g.(?156757561)(156759410_?)del	Pathogenic
8171	NM_000337.6(SGCD):c.657del (p.Thr220fs)	Pathogenic
8172	NM_000337.6(SGCD):c.493C>T (p.Arg165Ter)	Pathogenic
8173	NM_000337.6(SGCD):c.89G>A (p.Trp30Ter)	Pathogenic
8177	NM_000337.6(SGCD):c.391G>C (p.Ala131Pro)	Pathogenic
831480	NC_000005.10:g.(?156329567)(156344687_?)del	Pathogenic

SpliceAI

1420 predictions. Top by Δscore:

Variant	Effect	Δscore
5:156344482:A:AG	acceptor_gain	1.0000
5:156344485:TCAG:T	acceptor_loss	1.0000
5:156344486:CA:C	acceptor_loss	1.0000
5:156344487:A:AG	acceptor_gain	1.0000
5:156344487:A:T	acceptor_loss	1.0000
5:156344488:G:GG	acceptor_gain	1.0000
5:156344673:CAATT:C	donor_gain	1.0000
5:156344675:ATT:A	donor_gain	1.0000
5:156344676:TT:T	donor_gain	1.0000
5:156344678:G:GG	donor_gain	1.0000
5:156508588:T:TA	acceptor_gain	1.0000
5:156508594:A:AG	acceptor_gain	1.0000
5:156508595:T:G	acceptor_gain	1.0000
5:156508595:TTTCA:T	acceptor_loss	1.0000
5:156508596:TTCA:T	acceptor_loss	1.0000
5:156508597:TCAG:T	acceptor_loss	1.0000
5:156508598:CAGG:C	acceptor_loss	1.0000
5:156508599:A:AG	acceptor_gain	1.0000
5:156508599:AG:A	acceptor_gain	1.0000
5:156508599:AGGAT:A	acceptor_gain	1.0000
5:156508600:G:GC	acceptor_gain	1.0000
5:156508600:G:T	acceptor_loss	1.0000
5:156508600:GG:G	acceptor_gain	1.0000
5:156508600:GGAT:G	acceptor_gain	1.0000
5:156508600:GGATG:G	acceptor_gain	1.0000
5:156508698:GACCA:G	donor_gain	1.0000
5:156508699:ACCA:A	donor_gain	1.0000
5:156508699:ACCAG:A	donor_loss	1.0000
5:156508700:CCA:C	donor_gain	1.0000
5:156508701:CA:C	donor_gain	1.0000

AlphaMissense

1872 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:156344632:C:A	N48K	0.999
5:156344632:C:G	N48K	0.999
5:156344670:T:C	F61S	0.999
5:156508617:T:C	L69P	0.999
5:156594998:T:C	F149S	0.999
5:156647509:T:A	V182D	0.999
5:156757588:T:C	S194P	0.999
5:156757598:G:C	R197P	0.999
5:156757604:T:C	L199P	0.999
5:156759307:T:C	C263R	0.999
5:156759308:G:A	C263Y	0.999
5:156759309:C:G	C263W	0.999
5:156759315:C:G	C265W	0.999
5:156759361:T:A	C281S	0.999
5:156759362:G:C	C281S	0.999
5:156344573:T:A	W29R	0.998
5:156344573:T:C	W29R	0.998
5:156344575:G:C	W29C	0.998
5:156344575:G:T	W29C	0.998
5:156344581:A:C	K31N	0.998
5:156344581:A:T	K31N	0.998
5:156344589:T:C	L34P	0.998
5:156344610:T:C	L41P	0.998
5:156344648:T:A	W54R	0.998
5:156344648:T:C	W54R	0.998
5:156344655:T:C	L56P	0.998
5:156508661:T:C	F84L	0.998
5:156508662:T:C	F84S	0.998
5:156508662:T:G	F84C	0.998
5:156508663:C:A	F84L	0.998

dbSNP variants (sampled 300 via entrez): RS1000003802 (5:156012241 C>G), RS1000003815 (5:156177090 C>T), RS1000011281 (5:156262449 G>A), RS1000015495 (5:156684309 A>G), RS1000017877 (5:155769018 T>C), RS1000017928 (5:156098226 A>G), RS1000020104 (5:156013843 T>C), RS1000020755 (5:156655224 C>A,T), RS1000021778 (5:156534530 G>A), RS1000029597 (5:156443410 G>A), RS1000030270 (5:156483611 A>T), RS1000031172 (5:156701855 C>A), RS1000034200 (5:156273676 C>T), RS1000040809 (5:155731788 G>T), RS1000049079 (5:156289596 A>C,G,T)

Disease associations

OMIM: gene MIM:601411 | disease phenotypes: MIM:601287, MIM:606685, MIM:115200, MIM:253600, MIM:192600, MIM:236600

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type 2F	Definitive	Autosomal recessive
autosomal recessive limb-girdle muscular dystrophy	Strong	Autosomal recessive
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
dilated cardiomyopathy 1L	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy	Definitive	AR
dilated cardiomyopathy 1L	Limited	AD

Mondo (13): autosomal recessive limb-girdle muscular dystrophy type 2F (MONDO:0011028), dilated cardiomyopathy 1L (MONDO:0011702), cardiomyopathy (MONDO:0004994), qualitative or quantitative defects of delta-sarcoglycan (MONDO:0016144), neuromuscular disease (MONDO:0019056), dilated cardiomyopathy (MONDO:0005021), dilated cardiomyopathy 1A (MONDO:0007269), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), muscular dystrophy (MONDO:0020121), hypertrophic cardiomyopathy 1 (MONDO:0008647), congenital hydrocephalus (MONDO:0016349), familial dilated cardiomyopathy (MONDO:0016333), (MONDO:0015470)

Orphanet (11): Delta-sarcoglycan-related limb-girdle muscular dystrophy R6 (Orphanet:219), Familial isolated dilated cardiomyopathy (Orphanet:154), Rare cardiomyopathy (Orphanet:167848), Qualitative or quantitative defects of delta-sarcoglycan (Orphanet:207070), Neuromuscular disease (Orphanet:68381), Dilated cardiomyopathy (Orphanet:217604), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Muscular dystrophy (Orphanet:98473), Congenital hydrocephalus (Orphanet:2185), Familial dilated cardiomyopathy (Orphanet:217607)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000969	Edema
HP:0001288	Gait disturbance
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001714	Ventricular hypertrophy
HP:0001727	Thromboembolic stroke
HP:0002362	Shuffling gait
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003391	Gowers sign
HP:0003457	EMG abnormality
HP:0003551	Difficulty climbing stairs
HP:0003560	Muscular dystrophy
HP:0003593	Infantile onset
HP:0003621	Juvenile onset
HP:0003691	Scapular winging
HP:0003701	Proximal muscle weakness
HP:0006673	Reduced systolic function
HP:0007126	Proximal amyotrophy
HP:0008948	Proximal upper limb amyotrophy
HP:0008956	Proximal lower limb amyotrophy
HP:0008981	Calf muscle hypertrophy
HP:0009055	Generalized limb muscle atrophy
HP:0010628	Facial palsy
HP:0011462	Young adult onset

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000267_5	Multiple sclerosis (age of onset)	7.000000e-06
GCST000327_5	Anthropometric traits	6.000000e-06
GCST000327_6	Anthropometric traits	4.000000e-06
GCST001762_717	Obesity-related traits	9.000000e-06
GCST002724_23	Airway responsiveness in chronic obstructive pulmonary disease	3.000000e-06
GCST002724_4	Airway responsiveness in chronic obstructive pulmonary disease	6.000000e-06
GCST002724_8	Airway responsiveness in chronic obstructive pulmonary disease	2.000000e-06
GCST002789_1	Egg allergy	1.000000e-06
GCST002976_6	HIV-1 viral setpoint	8.000000e-06
GCST003518_84	Daytime sleep phenotypes	1.000000e-06
GCST003830_35	Response to bronchodilator in chronic obstructive pulmonary disease (change in FEV1)	5.000000e-08
GCST006138_15	Resting-state electroencephalogram vigilance	8.000000e-06
GCST007269_259	Pulse pressure	2.000000e-09
GCST008476_25	Emphysema annual change measurement in smokers (percent low attenuation area)	4.000000e-06
GCST008674_15	Glycemic traits (pleiotropy)	5.000000e-08
GCST009256_4	Superior temporal sulcus banks volume	3.000000e-06
GCST010396_195	Gut microbiota (bacterial taxa, hurdle binary method)	3.000000e-06
GCST010500_2	T-Cell Immunoglobulin and Mucin domain 1 levels	7.000000e-10
GCST010500_3	T-Cell Immunoglobulin and Mucin domain 1 levels	3.000000e-09
GCST010575_2	Evening vs. morning chronotype (sMEQ score)	2.000000e-06
GCST011362_2	Mental health related quality of life	3.000000e-07
GCST011703_72	Smoking initiation	2.000000e-09
GCST011769_14	Schizophrenia	3.000000e-08
GCST012490_532	Femur bone mineral density x serum urate levels interaction	3.000000e-09
GCST90000050_38	Age at first birth	2.000000e-09

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004302	anthropometric measurement
EFO:0004730	hormone measurement
EFO:0006897	airway responsiveness measurement
EFO:0007018	egg allergy measurement
EFO:0006319	HIV viral set point measurement
EFO:0007828	daytime rest measurement
EFO:0005921	FEV change measurement
EFO:0004357	electroencephalogram measurement
EFO:0005763	pulse pressure measurement
EFO:0007626	emphysema imaging measurement
EFO:0004469	HOMA-B
EFO:0007874	gut microbiome measurement
EFO:0010812	T-cell immunoglobulin and mucin domain 1 measurement
EFO:0008328	chronotype measurement
EFO:0011014	health-related quality of life measurement
EFO:0005670	smoking initiation
EFO:0004531	urate measurement
EFO:0009101	age at first birth measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D009136	Muscular Dystrophies	C05.651.534.500; C10.668.491.175.500; C16.320.577
D009468	Neuromuscular Diseases	C10.668
C564679	Cardiomyopathy, Dilated, 1l (supp.)
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)
C535896	Limb-girdle muscular dystrophy type 2F (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Doxorubicin	decreases expression	2
Nickel	decreases expression	2
Aflatoxin B1	decreases methylation	2
trichostatin A	decreases expression	1
cinnamaldehyde	increases expression	1
butyraldehyde	decreases expression	1
pentabromodiphenyl ether	increases expression	1
entinostat	decreases expression	1
clothianidin	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Acetaminophen	increases expression	1
Cadmium	increases expression	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Haloperidol	affects cotreatment, increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Tretinoin	increases expression	1
Triclosan	increases expression	1
Valproic Acid	decreases methylation	1
Zinc	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
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
NCT00170183	PHASE3	COMPLETED	Brain Natriuretic Peptide (BNP) to Preserve Renal Function in Hospitalized Patients With Heart Failure
NCT00270387	PHASE3	COMPLETED	A Study of Short-Term Outcomes and Economic Impact For Patients With Worsening Congestive Heart Failure When Natrecor (Nesiritide) is Added to Standard-Care Therapy, Compared to Administration of Placebo With Standard-Care Therapy
NCT00321295	PHASE3	COMPLETED	Biventricular Pacing In Patients With Left Ventricular Dysfunction After Cardiovascular Surgery
NCT00483197	PHASE3	UNKNOWN	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Pivotal Trial
NCT00490321	PHASE3	UNKNOWN	VentrAssistTM LVAD for the Treatment of Advanced Heart Failure - Destination Therapy
NCT00626028	PHASE3	COMPLETED	Comparison of Inhaled Nitric Oxide and Oxygen in Participants Reactivity During Acute Pulmonary Vasodilator Testing
NCT01013714	PHASE3	UNKNOWN	Cardiac Sympathetic Denervation for Prevention of Ventricular Tachyarrhythmias
NCT01217827	PHASE3	COMPLETED	Implantable Cardioverter-Defibrillator Use in the VA System
NCT01648634	PHASE3	COMPLETED	Nebivolol for the Prevention of Left Ventricular Systolic Dysfunction in Patients With Duchenne Muscular Dystrophy
NCT02924285	PHASE3	COMPLETED	Catheter Ablation Versus Amiodarone for Therapy of Premature Ventricular Contractions in Patients With Structural Heart Disease
NCT03860935	PHASE3	COMPLETED	Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy
NCT04166331	PHASE3	COMPLETED	Adjunctive DobutAmine in sePtic Cardiomyopathy With Tissue Hypoperfusion
NCT05175066	PHASE3	COMPLETED	Bisoprolol Administration to Prevent Anthracycline-induced Cardiotoxicity
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT06158698	PHASE3	RECRUITING	CMP-MYTHiC Trial and Registry - CardioMyoPathy With MYocarditis THerapy With Colchicine
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06846086	PHASE3	RECRUITING	Cardioprotective Effects of Melatonin in Patients With Cardiomyopathy
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT00185250	PHASE2	COMPLETED	Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy
NCT00490347	PHASE2	COMPLETED	VentrAssistTM LVAD as a Bridge to Cardiac Transplantation - Feasibility Trial
NCT00694161	PHASE2	COMPLETED	The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy