SGCA

Summary

SGCA (sarcoglycan alpha, HGNC:10805) is a protein-coding gene on chromosome 17q21.33, encoding Alpha-sarcoglycan (Q16586). 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.

This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6442 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 850 total — 55 pathogenic, 95 likely-pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_000023

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10805
Approved symbol	SGCA
Name	sarcoglycan alpha
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	SCARMD1, LGMD2D, adhalin, DMDA2, A2
Ensembl gene	ENSG00000108823
Ensembl biotype	protein_coding
OMIM	600119
Entrez	6442

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 21 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000262018, ENST00000344627, ENST00000502555, ENST00000504073, ENST00000505964, ENST00000508382, ENST00000511303, ENST00000512526, ENST00000513821, ENST00000513942, ENST00000514934, ENST00000682109, ENST00000683226, ENST00000683294, ENST00000683544, ENST00000895791, ENST00000895792, ENST00000895793, ENST00000895794, ENST00000895795, ENST00000895796, ENST00000895797, ENST00000895798, ENST00000952403, ENST00000952404, ENST00000952405, ENST00000952406, ENST00000952407, ENST00000952408, ENST00000952409, ENST00000952410, ENST00000952411

RefSeq mRNA: 2 — MANE Select: NM_000023 NM_000023, NM_001135697

CCDS: CCDS32679, CCDS45729

Canonical transcript exons

ENST00000262018 — 10 exons

Exon	Start	End
ENSE00001018428	50170143	50170351
ENSE00001018435	50167582	50167736
ENSE00001157873	50169092	50169254
ENSE00001506421	50166005	50166077
ENSE00003495581	50167947	50168019
ENSE00003549815	50170640	50170666
ENSE00003584701	50168374	50168572
ENSE00003654707	50175257	50175449
ENSE00003662321	50167368	50167487
ENSE00003689905	50175712	50175928

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 99.19.

FANTOM5 (CAGE): breadth broad, TPM avg 7.9851 / max 686.2811, expressed in 541 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161587	7.7815	468
161589	0.1360	72
161588	0.0677	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	99.19	gold quality
gastrocnemius	UBERON:0001388	99.02	gold quality
apex of heart	UBERON:0002098	98.87	gold quality
right coronary artery	UBERON:0001625	98.71	gold quality
ascending aorta	UBERON:0001496	98.59	gold quality
thoracic aorta	UBERON:0001515	98.57	gold quality
popliteal artery	UBERON:0002250	98.35	gold quality
tibial artery	UBERON:0007610	98.34	gold quality
descending thoracic aorta	UBERON:0002345	98.31	gold quality
aorta	UBERON:0000947	98.28	gold quality
muscle of leg	UBERON:0001383	98.15	gold quality
right atrium auricular region	UBERON:0006631	98.05	gold quality
mucosa of stomach	UBERON:0001199	97.87	gold quality
muscle organ	UBERON:0001630	97.60	gold quality
left coronary artery	UBERON:0001626	97.58	gold quality
heart left ventricle	UBERON:0002084	97.45	gold quality
triceps brachii	UBERON:0001509	97.29	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.10	gold quality
cardiac ventricle	UBERON:0002082	97.08	gold quality
lower esophagus	UBERON:0013473	97.06	gold quality
vastus lateralis	UBERON:0001379	96.92	gold quality
cardiac atrium	UBERON:0002081	96.62	gold quality
coronary artery	UBERON:0001621	96.53	gold quality
gluteal muscle	UBERON:0002000	96.48	silver quality
quadriceps femoris	UBERON:0001377	96.47	gold quality
heart	UBERON:0000948	95.91	gold quality
skeletal muscle tissue	UBERON:0001134	95.69	gold quality
biceps brachii	UBERON:0001507	95.65	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.46	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-5	yes	535.48
E-GEOD-124858	no	4.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL2, CLOCK, DIDO1, FOS, GATA4, ID2, MEF2C, MYOCD, MYOD1, MYOG, NFIC, NKX2-5, SMAD3, SMARCD3, SOX9, TBP, THRB, TP53

miRNA regulators (miRDB)

20 targeting SGCA, 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-23B-5P	99.98	66.07	587
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-3138	98.41	67.53	744
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-4778-5P	97.96	68.06	1634
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-1227-3P	97.36	66.94	834

Literature-anchored findings (GeneRIF, showing 20)

• Two adult brothers with a mild form of LGMD2D, compound heterozygous for two missense mutations of the SGCA gene (Arg77Cys, Val247Met), presented with respiratory insufficiency while they were still ambulatory. (PMID:15298081)
• Biglycan is a ligand for two members of the sarcoglycan complex and regulates their expression at discrete developmental ages. (PMID:16883602)
• identified a negative regulatory element in the alpha-SG distal promoter including two conserved E-boxes (E1 and E2), which interact with MyoD (PMID:18078839)
• The limb-girdle muscular dystrophy patients with alpha-sarcoglycan deficient LGMD2D do not enable an accurate prediction of the genotype. (PMID:18996010)
• Absence of members of the dystrophin-associated glycoprotein complex constitutes a permissive environment for spontaneous development of embryonal rhabdomyosarcoma associated with mutation of p53 and mutation or altered splicing of Mdm2. (PMID:20019182)
• Long-term, sustainable gene expression of alpha-sarcoglycan was observed following gene transfer mediated by AAV. (PMID:21031578)
• Peptide sequences in alpha-DG are substrates for protein-O-mannose N-acetylglucosaminyltransferase 1 (POMGnT1), demonstrated when a library of mannopeptides is generated which corresponds to sequences of the mucin-like stem region of alpha-DG. (PMID:21361872)
• Reduced expression of laminin-binding glycans on alpha-DG may contribute to formation of highly infiltrative behavior of prostate carcinoma cells. (PMID:21656825)
• This study reported recessive founder LGMD2D for the Magdalen Islands, an archipelago settled in the XIXth century, largely by Acadian immigrants. (PMID:21856579)
• E-cadherin,alpha-dystroglycan and beta-dystroglycan levels were decreased in the oesophageal primary tumour samples, despite the presence of normal levels of dystroglycan mRNA. (PMID:21884196)
• DNA analysis demonstrated homozygosity for a point mutation (574C>T) in the alpha-sarcoglycan gene. (PMID:22303798)
• 2 members of a Spanish family with muscular dystrophy had a new missense mutation c409G>A, p.Glu137Lys in exon 5 of the alpha-sarcoglycan gene, as well as a paternal c739G>A, p.Val24Met mutation inexon 6. (PMID:23703062)
• Results show that HRD1 and RFP2 contributes are required for the disposal of V247M alpha-sarcoglycan mutant. (PMID:24565866)
• B4GAT1 is involved in the initiation of the LARGE-dependent repeating disaccharide that is necessary for extracellular matrix protein binding to O-mannosylated alpha-dystroglycan. (PMID:25279697)
• Pathogenic mutations were found in SGCA from Egyptian families with limb-girdle muscular dystrophy. (PMID:26934379)
• The results suggest that the carrier rate of c.101G>T in SGCA may be high in Taiwan, especially in the aboriginal population regardless of the tribes. (PMID:26944168)
• IN TMD patients, a locus near the sarcoglycan alpha ( SGCA), rs4794106, was suggestive in the discovery analysis ( P = 2.6 x 10(6)) and replicated (i.e., 1-tailed P = 0.016) in the Brazilian cohort. (PMID:28081371)
• This study showed three Sarcoglycanopathies caused by mutations in SGCA genes. (PMID:30218921)
• Base editing repairs an SGCA mutation in human primary muscle stem cells. (PMID:33848270)
• Exome sequencing revealed variants in SGCA and SIL1 genes underlying limb girdle muscular dystrophy and Marinesco-Sjogren syndrome patients. (PMID:39060875)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgca	ENSDARG00000074156
mus_musculus	Sgca	ENSMUSG00000001508
rattus_norvegicus	Sgca	ENSRNOG00000003998
drosophila_melanogaster	Scgalpha	FBGN0032013
caenorhabditis_elegans		WBGENE00019227

Paralogs (1): SGCE (ENSG00000127990)

Protein

Protein identifiers

Alpha-sarcoglycan — Q16586 (reviewed: Q16586)

Alternative names: 50 kDa dystrophin-associated glycoprotein, Adhalin, Dystroglycan-2

All UniProt accessions (10): Q16586, A0A0S2Z4P8, A0A0S2Z4Q1, A0A804HKR7, A0A804HKZ6, D6R9S3, D6RAA4, E9PCT8, H0Y8T1, H0YAB9

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 the syntrophin SNTA1. 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 muscle. Also expressed in cardiac muscle and, at much lower levels, in lung. In the fetus, most abundant in cardiac muscle and, at lower levels, in lung. Also detected in liver and kidney. Not expressed in brain.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal recessive 3 (LGMDR3) [MIM:608099] An autosomal recessive degenerative myopathy characterized by progressive muscle wasting from early childhood with loss of independent ambulation by teenage years. Muscle biopsy shows necrosis, decreased immunostaining for alpha sarcoglycan, and adhalin deficiency. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the sarcoglycan alpha/epsilon family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16586-1	SGCA-1	yes
Q16586-2	SGCA-2

RefSeq proteins (2): NP_000014, NP_001129169 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006644	Cadg	Domain
IPR008908	Sarcoglycan_alpha/epsilon	Family
IPR015919	Cadherin-like_sf	Homologous_superfamily
IPR048346	Sarcoglycan_N	Domain
IPR048347	Sarcoglycan_C	Domain

Pfam: PF05510, PF20989

UniProt features (39 total): sequence variant 30, topological domain 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16586-F1	80.15	0.47

Functional residue map

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

Post-translational modifications (1): 377

Glycosylation sites (2): 174, 246

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: 163 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GNF2_MYL3, KEGG_VIRAL_MYOCARDITIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MUSCLE_CONTRACTION, GOBP_MUSCLE_SYSTEM_PROCESS, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOCC_CELL_CELL_JUNCTION, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, KEGG_ARRHYTHMOGENIC_RIGHT_VENTRICULAR_CARDIOMYOPATHY_ARVC, GOCC_GLYCOPROTEIN_COMPLEX, GOCC_SYNAPSE, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ANCHORING_JUNCTION

GO Biological Process (2): muscle contraction (GO:0006936), muscle organ development (GO:0007517)

GO Molecular Function (2): calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (12): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), dystrophin-associated glycoprotein complex (GO:0016010), sarcoglycan complex (GO:0016012), sarcolemma (GO:0042383), membrane raft (GO:0045121), 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
muscle system process	1
animal organ development	1
muscle structure development	1
metal ion binding	1
binding	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
anchoring junction	1
glycoprotein complex	1
dystroglycan complex	1
plasma membrane	1
membrane microdomain	1
intracellular anatomical structure	1
dystrophin-associated glycoprotein complex	1

Protein interactions and networks

STRING

976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGCA	SGCG	Q13326	999
SGCA	SGCD	Q92629	999
SGCA	SGCB	Q16585	998
SGCA	DAG1	Q14118	997
SGCA	SSPN	Q14714	991
SGCA	DMD	P11532	982
SGCA	DYSF	O75923	905
SGCA	LAMA2	P24043	905
SGCA	DTNA	Q9Y4J8	902
SGCA	UTRN	P46939	889
SGCA	SNTA1	Q13424	880
SGCA	SNTB1	Q13884	879
SGCA	FKRP	Q9H9S5	868
SGCA	ANO5	Q75V66	829
SGCA	POMT1	Q9Y6A1	779

IntAct

36 interactions, top by confidence:

A	B	Type	Score
SGCA	SGTA	psi-mi:“MI:0915”(physical association)	0.900
SGTA	SGCA	psi-mi:“MI:0915”(physical association)	0.900
SGCA	SGTB	psi-mi:“MI:0915”(physical association)	0.560
SERPINH1	SGCA	psi-mi:“MI:0915”(physical association)	0.560
RAD23A	SGCA	psi-mi:“MI:0915”(physical association)	0.560
	SGCA	psi-mi:“MI:0915”(physical association)	0.560
SGCA	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
SGCA	GPR180	psi-mi:“MI:0914”(association)	0.530
SGCA	ACP2	psi-mi:“MI:0914”(association)	0.350
SGCA	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SGCA	SGTA	psi-mi:“MI:0915”(physical association)	0.000
SGCA	SGTB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (120): SGTA (Two-hybrid), DAD1 (Affinity Capture-MS), LEMD3 (Affinity Capture-MS), PTPRU (Affinity Capture-MS), MED23 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), LEMD2 (Affinity Capture-MS), SLC25A17 (Affinity Capture-MS), GPR180 (Affinity Capture-MS), ACP2 (Affinity Capture-MS), SGTA (Two-hybrid), SGTA (Two-hybrid), LEMD3 (Affinity Capture-MS), ACP2 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5PJB7, A0A1L8HX76, A6QR40, O08764, O60294, O95382, P10938, P70218, P97452, Q12851, Q14137, Q15334, Q16586, Q28686, Q32P44, Q3TJ91, Q499N3, Q499U2, Q4KLI9, Q561R2, Q562C2, Q5RBH8, Q5RCX2, Q61161, Q6AY79, Q6F5E8, Q6P1M3, Q6V7V2, Q7SZE3, Q7TMC8, Q80Y17, Q8BYZ7, Q8C3I8, Q8C6B2, Q8CHW4, Q8K4K5, Q8MKF0, Q8N0W3, Q8VC03, Q91WI7

Diamond homologs: O43556, O70258, P82350, Q16586, Q28686, Q29S03, Q4R5B1, Q5RAP2, Q64255, Q6YAT4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SGCA	“form complex”	DGC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	55
Likely pathogenic	95
Uncertain significance	233
Likely benign	320
Benign	31

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1052453	NM_000023.4(SGCA):c.203G>A (p.Gly68Glu)	Pathogenic
1068550	NM_000023.4(SGCA):c.402C>A (p.Tyr134Ter)	Pathogenic
1068994	NC_000017.10:g.(?_48243138)_48245027del	Pathogenic
1175917	NM_000023.4(SGCA):c.864_870del (p.Asp289fs)	Pathogenic
1180729	NM_000023.4(SGCA):c.320_330del (p.Ala107fs)	Pathogenic
1379390	NM_000023.4(SGCA):c.862del (p.Val288fs)	Pathogenic
1399916	NM_000023.4(SGCA):c.238C>T (p.Gln80Ter)	Pathogenic
1453713	NM_000023.4(SGCA):c.105del (p.Phe36fs)	Pathogenic
1453960	NM_000023.4(SGCA):c.828C>A (p.Cys276Ter)	Pathogenic
1454362	NC_000017.10:g.(?48243138)(48245027_?)del	Pathogenic
1459870	NC_000017.10:g.(?48243336)(48253303_?)del	Pathogenic
191294	NM_000023.4(SGCA):c.981_982dup (p.Asp328fs)	Pathogenic
1936207	NM_000023.4(SGCA):c.488del (p.Gly163fs)	Pathogenic
1967847	NM_000023.4(SGCA):c.218C>G (p.Pro73Arg)	Pathogenic
2007370	NM_000023.4(SGCA):c.250dup (p.His84fs)	Pathogenic
2029637	NM_000023.4(SGCA):c.225del (p.Trp75fs)	Pathogenic
2422148	NC_000017.10:g.(?48243336)(48246625_?)del	Pathogenic
2690698	NM_000023.4(SGCA):c.558_559del (p.Leu187fs)	Pathogenic
280105	NM_000023.4(SGCA):c.530del (p.Ser177fs)	Pathogenic
2821596	NM_000023.4(SGCA):c.29_33del (p.Leu10fs)	Pathogenic
2842791	NM_000023.4(SGCA):c.618_619del (p.Ser207fs)	Pathogenic
284945	NM_000023.4(SGCA):c.402C>G (p.Tyr134Ter)	Pathogenic
288637	NM_000023.4(SGCA):c.770del (p.Pro257fs)	Pathogenic
290641	NM_000023.4(SGCA):c.161del (p.Val54fs)	Pathogenic
3240442	NM_000023.4(SGCA):c.385+1G>T	Pathogenic
3384024	NM_000023.4(SGCA):c.920del (p.Leu307fs)	Pathogenic
3582315	NM_000023.4(SGCA):c.834_837del (p.Thr279fs)	Pathogenic
3685857	NM_000023.4(SGCA):c.550del (p.Arg184fs)	Pathogenic
370116	NM_000023.4(SGCA):c.488dup (p.Leu164fs)	Pathogenic
370642	NM_000023.4(SGCA):c.313-2A>G	Pathogenic

SpliceAI

1918 predictions. Top by Δscore:

Variant	Effect	Δscore
17:50167580:A:AG	acceptor_gain	1.0000
17:50167581:G:GG	acceptor_gain	1.0000
17:50167581:GCT:G	acceptor_gain	1.0000
17:50167942:CCCA:C	acceptor_loss	1.0000
17:50167943:CCA:C	acceptor_loss	1.0000
17:50167944:CA:C	acceptor_loss	1.0000
17:50167945:A:AC	acceptor_loss	1.0000
17:50167945:A:AG	acceptor_gain	1.0000
17:50167946:G:GG	acceptor_gain	1.0000
17:50168015:AGAAG:A	donor_loss	1.0000
17:50168016:GAAG:G	donor_gain	1.0000
17:50168020:G:C	donor_loss	1.0000
17:50168372:A:AG	acceptor_gain	1.0000
17:50168373:G:GG	acceptor_gain	1.0000
17:50168568:GAAGG:G	donor_gain	1.0000
17:50168571:GG:G	donor_gain	1.0000
17:50168572:GG:G	donor_gain	1.0000
17:50170665:GA:G	donor_gain	1.0000
17:50170667:G:GG	donor_gain	1.0000
17:50170678:A:T	donor_gain	1.0000
17:50175255:A:AG	acceptor_gain	1.0000
17:50175256:G:GC	acceptor_gain	1.0000
17:50175256:GC:G	acceptor_gain	1.0000
17:50175256:GCA:G	acceptor_gain	1.0000
17:50167354:T:TA	acceptor_gain	0.9900
17:50167355:G:A	acceptor_gain	0.9900
17:50167484:GTCG:G	donor_gain	0.9900
17:50167570:C:CA	acceptor_gain	0.9900
17:50167577:A:AG	acceptor_gain	0.9900
17:50167579:CA:C	acceptor_loss	0.9900

AlphaMissense

2482 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:50167647:T:A	W75R	0.995
17:50167647:T:C	W75R	0.995
17:50169239:G:C	W244C	0.995
17:50169239:G:T	W244C	0.995
17:50167649:G:C	W75C	0.993
17:50167649:G:T	W75C	0.993
17:50169237:T:A	W244R	0.989
17:50169237:T:C	W244R	0.989
17:50168401:T:C	F138S	0.988
17:50169171:T:A	C222S	0.986
17:50169172:G:C	C222S	0.986
17:50169240:T:A	C245S	0.986
17:50169241:G:C	C245S	0.986
17:50169100:T:A	I198N	0.985
17:50168483:G:C	W165C	0.984
17:50168483:G:T	W165C	0.984
17:50167651:T:A	L76H	0.983
17:50167732:T:A	I103N	0.983
17:50167696:G:A	G91D	0.981
17:50169241:G:A	C245Y	0.981
17:50170285:C:G	P297R	0.980
17:50167651:T:C	L76P	0.979
17:50168394:G:C	A136P	0.979
17:50169124:T:G	F206C	0.979
17:50167690:T:A	L89H	0.978
17:50169123:T:C	F206L	0.978
17:50169125:T:A	F206L	0.978
17:50169125:T:G	F206L	0.978
17:50169241:G:T	C245F	0.978
17:50168458:T:C	F157S	0.977

dbSNP variants (sampled 300 via entrez): RS1000084672 (17:50174040 T>C), RS1000194400 (17:50175493 T>A,G), RS1000827324 (17:50167423 T>G), RS1001754498 (17:50168811 C>T), RS1001862771 (17:50173378 T>C), RS1002158074 (17:50172431 C>T), RS1002437554 (17:50166680 A>C,G,T), RS1002485317 (17:50171256 C>A,T), RS1002487574 (17:50166387 C>A), RS1002709084 (17:50165609 G>A), RS1003079710 (17:50176398 A>T), RS1003100139 (17:50171715 G>A), RS1003172840 (17:50165333 A>G,T), RS1003821613 (17:50175009 C>T), RS1003864772 (17:50173060 G>A,T)

Disease associations

OMIM: gene MIM:600119 | disease phenotypes: MIM:608099, MIM:253600

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type 2D	Definitive	Autosomal recessive
autosomal recessive limb-girdle muscular dystrophy	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy	Definitive	AR

Mondo (9): autosomal recessive limb-girdle muscular dystrophy type 2D (MONDO:0011968), sarcoglycanopathy (MONDO:0016140), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), cardiomyopathy (MONDO:0004994), muscular dystrophy (MONDO:0020121), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), qualitative or quantitative defects of alpha-sarcoglycan (MONDO:0016141), hypertrophic cardiomyopathy (MONDO:0005045), limb-girdle muscular dystrophy (MONDO:0016971)

Orphanet (9): Alpha-sarcoglycan-related limb-girdle muscular dystrophy R3 (Orphanet:62), Qualitative or quantitative defects of sarcoglycan (Orphanet:207052), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Rare cardiomyopathy (Orphanet:167848), Muscular dystrophy (Orphanet:98473), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Qualitative or quantitative defects of alpha-sarcoglycan (Orphanet:207060), Rare hypertrophic cardiomyopathy (Orphanet:217569), Limb-girdle muscular dystrophy (Orphanet:263)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001371	Flexion contracture
HP:0001635	Congestive heart failure
HP:0001638	Cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001771	Achilles tendon contracture
HP:0002317	Unsteady gait
HP:0002359	Frequent falls
HP:0002515	Waddling gait
HP:0002650	Scoliosis
HP:0002943	Thoracic scoliosis
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003307	Hyperlordosis
HP:0003325	Limb-girdle muscle weakness
HP:0003391	Gowers sign
HP:0003458	EMG: myopathic abnormalities
HP:0003551	Difficulty climbing stairs
HP:0003557	Increased variability in muscle fiber diameter
HP:0003560	Muscular dystrophy
HP:0003621	Juvenile onset
HP:0003676	Progressive
HP:0003691	Scapular winging
HP:0003701	Proximal muscle weakness
HP:0003707	Calf muscle pseudohypertrophy
HP:0003713	Muscle fiber necrosis
HP:0003797	Limb-girdle muscle atrophy
HP:0006466	Ankle flexion contracture
HP:0006467	Limited shoulder movement
HP:0006785	Limb-girdle muscular dystrophy
HP:0008981	Calf muscle hypertrophy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004034_2	Temporomandibular joint disorder	3.000000e-06
GCST006979_825	Heel bone mineral density	3.000000e-10
GCST009724_70	Vertical cup-disc ratio (multi-trait analysis)	4.000000e-12
GCST90013442_31	Keratoconus	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0006939	cup-to-disc ratio measurement

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D009202	Cardiomyopathies	C14.280.238
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
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
D058088	Sarcoglycanopathies	C05.651.534.500.280.500; C08.618.923; C10.668.491.175.500.149.500; C14.280.238.812; C16.320.577.280.500
C538640	Limb-girdle muscular dystrophy autosomal recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
perfluorobutanesulfonic acid	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benztropine	decreases expression	1
Carmustine	decreases expression	1
Silicon Dioxide	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_9S57	UCLi005-A	Induced pluripotent stem cell	Male
CVCL_D8A4	Ubigene A-549 SGCA KO	Cancer cell line	Male

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