SGCB

Summary

SGCB (sarcoglycan beta, HGNC:10806) is a protein-coding gene on chromosome 4q12, encoding Beta-sarcoglycan (Q16585). 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 member of the sarcoglycan family. Sarcoglycans are transmembrane components in the dystrophin-glycoprotein complex which help stabilize the muscle fiber membranes and link the muscle cytoskeleton to the extracellular matrix. Mutations in this gene have been associated with limb-girdle muscular dystrophy.

Source: NCBI Gene 6443 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 578 total — 50 pathogenic, 47 likely-pathogenic
• Phenotypes (HPO): 24
• MANE Select transcript: NM_000232

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10806
Approved symbol	SGCB
Name	sarcoglycan beta
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	SGC, A3b
Ensembl gene	ENSG00000163069
Ensembl biotype	protein_coding
OMIM	600900
Entrez	6443

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 nonsense_mediated_decay

ENST00000381431, ENST00000506357, ENST00000514133, ENST00000899666, ENST00000912466

RefSeq mRNA: 1 — MANE Select: NM_000232 NM_000232

CCDS: CCDS3488

Canonical transcript exons

ENST00000381431 — 6 exons

Exon	Start	End
ENSE00001071313	52028730	52028921
ENSE00001071318	52027968	52028099
ENSE00001071319	52033431	52033640
ENSE00001304151	52020706	52024160
ENSE00001910281	52038227	52038299
ENSE00003635513	52029678	52029863

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 98.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.0417 / max 265.9175, expressed in 1556 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52100	12.0417	1556

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	98.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.35	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.32	gold quality
biceps brachii	UBERON:0001507	98.13	gold quality
heart right ventricle	UBERON:0002080	96.95	gold quality
ganglionic eminence	UBERON:0004023	96.46	gold quality
medial globus pallidus	UBERON:0002477	96.28	gold quality
trigeminal ganglion	UBERON:0001675	96.17	gold quality
ventricular zone	UBERON:0003053	96.09	gold quality
sperm	CL:0000019	96.03	gold quality
globus pallidus	UBERON:0001875	96.03	gold quality
skeletal muscle tissue	UBERON:0001134	95.62	gold quality
tibia	UBERON:0000979	95.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.45	gold quality
muscle of leg	UBERON:0001383	95.12	gold quality
gastrocnemius	UBERON:0001388	95.00	gold quality
lateral globus pallidus	UBERON:0002476	94.97	gold quality
vena cava	UBERON:0004087	94.90	gold quality
deltoid	UBERON:0001476	94.85	gold quality
subthalamic nucleus	UBERON:0001906	94.79	gold quality
saphenous vein	UBERON:0007318	94.78	gold quality
muscle organ	UBERON:0001630	94.68	gold quality
dorsal root ganglion	UBERON:0000044	94.49	gold quality
stromal cell of endometrium	CL:0002255	94.42	gold quality
tendon	UBERON:0000043	94.38	gold quality
triceps brachii	UBERON:0001509	94.36	gold quality
cortical plate	UBERON:0005343	94.29	gold quality
muscle tissue	UBERON:0002385	94.24	gold quality
thoracic aorta	UBERON:0001515	94.22	gold quality
descending thoracic aorta	UBERON:0002345	94.18	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.67
E-MTAB-6678	yes	4.13
E-MTAB-6386	no	212.30
E-CURD-112	no	3.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

190 targeting SGCB, 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-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587

Literature-anchored findings (GeneRIF, showing 10)

• Defective assembly of sarcoglycan complex in patients with beta-sarcoglycan gene mutations (PMID:12060343)
• beta-sarcoglycan and SPATA18 may have a role in limb-girdle muscular dystrophy type 2E (PMID:16088906)
• While the quantity of beta-sarcoglycan was nearly normal in the limb girdle muscular dystrophy (LGMD)2E carrier, the levels of dysferlin protein were reduced to 50% of controls in the carriers of LGMD2B. (PMID:16934466)
• 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 limb-girdle muscular dystrophy patients with beta-sarcoglycan deficient LGMD2E do not enable an accurate prediction of the genotype. (PMID:18996010)
• Clinical severity of limb-girdle muscular dystrophy type 2Emay be predicted by SGCB gene mutation and sarcoglycan protein expression. (PMID:25862795)
• This study demonstrated that LGMD2E is the most common type of sarcoglycanopathies in the Iranian population. (PMID:28687063)
• Clinical, genetic profile and disease progression of sarcoglycanopathies in a large cohort from India: high prevalence of SGCB c.544A > C. (PMID:35416532)
• Comprehensive functional characterization of SGCB coding variants predicts pathogenicity in limb-girdle muscular dystrophy type R4/2E. (PMID:37317968)
• Identification of a shared, common haplotype segregating with an SGCB c.544 T > G mutation in Indian patients affected with sarcoglycanopathy. (PMID:37699968)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgcb	ENSDARG00000052341
mus_musculus	Sgcb	ENSMUSG00000029156
rattus_norvegicus	Sgcb	ENSRNOG00000002135
drosophila_melanogaster	Scgbeta	FBGN0038042
caenorhabditis_elegans		WBGENE00019277

Protein

Protein identifiers

Beta-sarcoglycan — Q16585 (reviewed: Q16585)

Alternative names: 43 kDa dystrophin-associated glycoprotein, A3b

All UniProt accessions (4): Q16585, H0Y8J3, H0YA15, Q5U0N0

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. 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. Highest expression in heart and skeletal muscle. Low expression in brain, kidney, placenta, pancreas and lung. High expression in fetal brain. Also found in fetal lung, kidney and liver.

Post-translational modifications. Disulfide bonds are present.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal recessive 4 (LGMDR4) [MIM:604286] An autosomal recessive degenerative myopathy characterized by pelvic and shoulder muscle wasting, onset usually in childhood and variable progression rate. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q16585-1	1	yes
Q16585-2	2

RefSeq proteins (1): NP_000223* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006875	Sarcoglycan	Family
IPR027659	Sgcb	Family

Pfam: PF04790

UniProt features (26 total): sequence variant 14, glycosylation site 3, topological domain 2, disulfide bond 2, chain 1, splice variant 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16585-F1	76.67	0.13

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): 290–307, 288–314

Glycosylation sites (3): 158, 211, 258

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: 315 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_MUSCLE_TISSUE_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, KYNG_DNA_DAMAGE_DN, GOBP_VASCULAR_ASSOCIATED_SMOOTH_MUSCLE_CELL_DIFFERENTIATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, DOANE_BREAST_CANCER_CLASSES_DN, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOLDRATH_ANTIGEN_RESPONSE, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_2_UP

GO Biological Process (8): muscle organ development (GO:0007517), response to glucose (GO:0009749), gene expression (GO:0010467), glucose homeostasis (GO:0042593), glucose import in response to insulin stimulus (GO:0044381), cardiac muscle cell development (GO:0055013), vascular associated smooth muscle cell development (GO:0097084), muscle cell development (GO:0055001)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (10): 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), 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
response to hexose	1
macromolecule biosynthetic process	1
carbohydrate homeostasis	1
cellular response to insulin stimulus	1
D-glucose import across plasma membrane	1
striated muscle cell development	1
cardiac cell development	1
cardiac muscle cell differentiation	1
vascular associated smooth muscle cell differentiation	1
muscle cell development	1
muscle cell differentiation	1
cell development	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
glycoprotein complex	1
dystroglycan complex	1
plasma membrane	1
intracellular anatomical structure	1
dystrophin-associated glycoprotein complex	1

Protein interactions and networks

STRING

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGCB	SGCA	Q16586	998
SGCB	SGCD	Q92629	972
SGCB	SGCE	O43556	928
SGCB	DMD	P11532	923
SGCB	SGCG	Q13326	914
SGCB	DAG1	Q14118	901
SGCB	FKRP	Q9H9S5	866
SGCB	UTRN	P46939	840
SGCB	DYSF	O75923	832
SGCB	ANO5	Q75V66	825
SGCB	CAPN3	P20807	819
SGCB	SNTB1	Q13884	790
SGCB	SSPN	Q14714	787
SGCB	SPATA18	Q8TC71	786
SGCB	POMT2	Q9UKY4	785
SGCB	POMT1	Q9Y6A1	785

IntAct

158 interactions, top by confidence:

A	B	Type	Score
TCTN2	CLGN	psi-mi:“MI:0914”(association)	0.780
SGCZ	SGCB	psi-mi:“MI:0915”(physical association)	0.670
PMP22	SGCB	psi-mi:“MI:0915”(physical association)	0.560
MAL	SGCB	psi-mi:“MI:0915”(physical association)	0.560
SGCB	MGST2	psi-mi:“MI:0915”(physical association)	0.560
TMEM11	SGCB	psi-mi:“MI:0915”(physical association)	0.560
SGCB	BRICD5	psi-mi:“MI:0915”(physical association)	0.560
SGCB	SMIM3	psi-mi:“MI:0915”(physical association)	0.560
APOL3	SGCB	psi-mi:“MI:0915”(physical association)	0.560
TNF	SGCB	psi-mi:“MI:0915”(physical association)	0.560
ADAM33	SGCB	psi-mi:“MI:0915”(physical association)	0.560
SGCB	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
SGCB	SLC52A1	psi-mi:“MI:0915”(physical association)	0.560
EHHADH	SGCB	psi-mi:“MI:0915”(physical association)	0.560
SGCB	CMTM5	psi-mi:“MI:0915”(physical association)	0.560
PTTG1IP	SGCB	psi-mi:“MI:0915”(physical association)	0.560
SGCB	NINJ1	psi-mi:“MI:0915”(physical association)	0.560
TSPAN17	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
LINGO1	LGALS8	psi-mi:“MI:0914”(association)	0.530
NCEH1	CLGN	psi-mi:“MI:0914”(association)	0.530
DCT	CANX	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
SPCS3	ENTPD6	psi-mi:“MI:0914”(association)	0.530

BioGRID (107): SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Affinity Capture-MS), SGCB (Two-hybrid), SGCB (Two-hybrid), SGCB (Two-hybrid), SGCB (Two-hybrid), SGCB (Two-hybrid)

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: A6QP70, P82349, Q16585, Q28635, Q5R9U1, Q60538

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SGCB	“form complex”	DGC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 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
Neurotransmitter receptors and postsynaptic signal transmission	9	8.7×	2e-04
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	8	6.7×	2e-03
Transmission across Chemical Synapses	8	5.9×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
acetylcholine receptor signaling pathway	6	26.8×	4e-05
positive regulation of T cell mediated cytotoxicity	6	21.9×	9e-05
membrane depolarization	5	18.2×	1e-03
monoatomic ion transmembrane transport	9	13.4×	2e-05
immune response	13	4.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	50
Likely pathogenic	47
Uncertain significance	211
Likely benign	189
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074218	NM_000232.5(SGCB):c.255dup (p.Ile86fs)	Pathogenic
1076257	NM_000232.5(SGCB):c.261G>A (p.Trp87Ter)	Pathogenic
1180815	NM_000232.5(SGCB):c.185del (p.Gly62fs)	Pathogenic
1215280	NM_000232.5(SGCB):c.-18_8dup (p.Ala6fs)	Pathogenic
1301699	NM_000232.5(SGCB):c.622-1G>C	Pathogenic
1364546	NM_000232.5(SGCB):c.579dup (p.Gly194fs)	Pathogenic
1414584	NM_000232.5(SGCB):c.85dup (p.Arg29fs)	Pathogenic
1451523	NM_000232.5(SGCB):c.539dup (p.Ser181fs)	Pathogenic
1451596	NM_000232.5(SGCB):c.735_736del (p.Asn246fs)	Pathogenic
1454994	NM_000232.5(SGCB):c.373dup (p.Ser125fs)	Pathogenic
1458791	NC_000004.11:g.(?52890123)(52904425_?)del	Pathogenic
1686178	NM_000232.5(SGCB):c.243+2T>C	Pathogenic
1947827	NM_000232.5(SGCB):c.37del (p.Ser13fs)	Pathogenic
2000921	NM_000232.5(SGCB):c.583dup (p.Val195fs)	Pathogenic
2025299	NM_000232.5(SGCB):c.708_709insTTTTCATTATGGGC (p.Lys237fs)	Pathogenic
2129011	NM_000232.5(SGCB):c.494del (p.Asp165fs)	Pathogenic
2133941	NM_000232.5(SGCB):c.661_662insGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGGTCNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAGTTG (p.Val220_Asp221insGlyProGlyAlaValAlaHisAlaCysAsnProSerThrLeuGlyGlyArgGlyGlyArgIleThrArgSerXaaXaaXaaLysLysLysLysLysLysLysLysVal)	Pathogenic
2422615	NC_000004.11:g.(?52894124)(52896039_?)del	Pathogenic
2422616	NC_000004.11:g.(?52899577)(52899826_?)del	Pathogenic
2444452	NM_000232.5:c.74_283del	Pathogenic
2678683	NM_000232.5(SGCB):c.36_37delinsG (p.Ser13fs)	Pathogenic
2695058	NM_000232.5(SGCB):c.622-1G>T	Pathogenic
2712374	NM_000232.5(SGCB):c.543_547del (p.Ser181fs)	Pathogenic
2752736	NM_000232.5(SGCB):c.460_482del (p.Ser154fs)	Pathogenic
283057	NM_000232.5(SGCB):c.572del (p.Leu191fs)	Pathogenic
2835264	NM_000232.5(SGCB):c.558_568del (p.His187fs)	Pathogenic
2966468	NM_000232.5(SGCB):c.433del (p.Val145fs)	Pathogenic
3069174	NM_000232.5(SGCB):c.683G>A (p.Gly228Glu)	Pathogenic
3246667	NC_000004.11:g.(?52894876)(52895107_?)del	Pathogenic
3381206	NM_000232.5(SGCB):c.34-150_243+150del	Pathogenic

SpliceAI

980 predictions. Top by Δscore:

Variant	Effect	Δscore
4:52027959:AATAC:A	donor_loss	1.0000
4:52027960:ATAC:A	donor_loss	1.0000
4:52027961:TAC:T	donor_loss	1.0000
4:52027962:ACTC:A	donor_loss	1.0000
4:52027963:CT:C	donor_loss	1.0000
4:52027964:TCA:T	donor_loss	1.0000
4:52027965:C:CC	donor_loss	1.0000
4:52027966:A:AC	donor_gain	1.0000
4:52027966:ACCG:A	donor_gain	1.0000
4:52027967:C:CC	donor_gain	1.0000
4:52027967:C:CT	donor_loss	1.0000
4:52027967:CCG:C	donor_gain	1.0000
4:52027967:CCGC:C	donor_gain	1.0000
4:52027983:A:AC	donor_gain	1.0000
4:52028918:CAAT:C	acceptor_gain	1.0000
4:52028922:C:CC	acceptor_gain	1.0000
4:52029671:AACTT:A	donor_loss	1.0000
4:52029672:ACTTA:A	donor_loss	1.0000
4:52029673:CTT:C	donor_loss	1.0000
4:52029674:TTAC:T	donor_loss	1.0000
4:52029675:TA:T	donor_loss	1.0000
4:52029676:A:AC	donor_gain	1.0000
4:52029676:A:AT	donor_loss	1.0000
4:52029676:ACAGG:A	donor_gain	1.0000
4:52029677:C:CA	donor_gain	1.0000
4:52029677:CA:C	donor_gain	1.0000
4:52029677:CAG:C	donor_gain	1.0000
4:52029677:CAGG:C	donor_gain	1.0000
4:52029677:CAGGC:C	donor_gain	1.0000
4:52029757:C:CA	donor_gain	1.0000

AlphaMissense

2143 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:52024050:G:C	C288W	0.998
4:52028091:G:C	S210R	0.998
4:52028091:G:T	S210R	0.998
4:52028093:T:G	S210R	0.998
4:52029778:A:G	F110S	0.998
4:52029781:C:G	R109P	0.998
4:52024051:C:G	C288S	0.997
4:52024052:A:T	C288S	0.997
4:52028015:C:G	G236R	0.997
4:52028039:C:G	G228R	0.997
4:52028039:C:T	G228R	0.997
4:52028074:A:G	L216S	0.997
4:52029784:A:G	L108P	0.997
4:52023994:C:G	C307S	0.996
4:52023995:A:T	C307S	0.996
4:52024051:C:T	C288Y	0.996
4:52024052:A:G	C288R	0.996
4:52028038:C:T	G228E	0.996
4:52028098:A:T	I208N	0.996
4:52028812:A:G	F180S	0.996
4:52028893:A:G	L153P	0.996
4:52029697:A:T	I137N	0.996
4:52033437:A:C	N79K	0.996
4:52033437:A:T	N79K	0.996
4:52023995:A:G	C307R	0.995
4:52028041:C:G	R227P	0.995
4:52028092:C:A	S210I	0.995
4:52028098:A:C	I208S	0.995
4:52028752:A:T	V200D	0.995
4:52028758:A:G	L198S	0.995

dbSNP variants (sampled 300 via entrez): RS1000000127 (4:52034000 C>A), RS1000013570 (4:52039198 A>C), RS1000176683 (4:52027216 T>C), RS1000264668 (4:52032621 G>C), RS1000289681 (4:52027574 A>T), RS1000519936 (4:52034203 G>A), RS1000941286 (4:52038928 T>G), RS1001016213 (4:52026119 G>C), RS1001072864 (4:52026588 A>G), RS1001173778 (4:52034411 T>C,G), RS1001299587 (4:52027747 C>G), RS1001308557 (4:52031683 AT>A,ATT), RS1001400815 (4:52032198 A>G), RS1001412178 (4:52028229 T>C,G), RS1001687382 (4:52034661 A>G)

Disease associations

OMIM: gene MIM:600900 | disease phenotypes: MIM:604286, MIM:253600

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type 2E	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 (7): autosomal recessive limb-girdle muscular dystrophy type 2E (MONDO:0011423), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), sialidosis (MONDO:0017734), qualitative or quantitative defects of beta-sarcoglycan (MONDO:0016142), dilated cardiomyopathy (MONDO:0005021), hypertrophic cardiomyopathy (MONDO:0005045), limb-girdle muscular dystrophy (MONDO:0016971)

Orphanet (7): Beta-sarcoglycan-related limb-girdle muscular dystrophy R4 (Orphanet:119), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Sialidosis (Orphanet:309294), Qualitative or quantitative defects of beta-sarcoglycan (Orphanet:207063), Dilated cardiomyopathy (Orphanet:217604), Rare hypertrophic cardiomyopathy (Orphanet:217569), Limb-girdle muscular dystrophy (Orphanet:263)

HPO phenotypes

24 total (25 of 24 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000750	Delayed speech and language development
HP:0001288	Gait disturbance
HP:0001638	Cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0002058	Myopathic facies
HP:0002136	Broad-based gait
HP:0002505	Loss of ambulation
HP:0002515	Waddling gait
HP:0002913	Myoglobinuria
HP:0003198	Myopathy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003325	Limb-girdle muscle weakness
HP:0003391	Gowers sign
HP:0003557	Increased variability in muscle fiber diameter
HP:0003560	Muscular dystrophy
HP:0003621	Juvenile onset
HP:0003691	Scapular winging
HP:0003707	Calf muscle pseudohypertrophy
HP:0003724	Shoulder girdle muscle atrophy
HP:0003749	Pelvic girdle muscle weakness
HP:0007126	Proximal amyotrophy
HP:0008981	Calf muscle hypertrophy
HP:0008988	Pelvic girdle muscle atrophy
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008473_30	Visceral fat	9.000000e-06

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
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
D049288	Muscular Dystrophies, Limb-Girdle	C05.651.534.500.280; C10.668.491.175.500.149; C16.320.577.280
C535435	Beta-sarcoglycanopathy (supp.)
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

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
methylmercuric chloride	decreases expression, increases expression	3
trichostatin A	affects cotreatment, decreases expression	3
Benzo(a)pyrene	increases expression, increases methylation	3
Cocaine	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
thifluzamide	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Lead	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Rotenone	increases expression	1
Tretinoin	decreases expression	1
Crack Cocaine	increases expression	1
Paclitaxel	affects response to substance	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

6 cell lines: 3 induced pluripotent stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9AA	JUCTCi017-A	Induced pluripotent stem cell	Female
CVCL_A9AB	JUCTCi017-B	Induced pluripotent stem cell	Female
CVCL_A9AC	JUCTCi017-C	Induced pluripotent stem cell	Female
CVCL_E2JX	HAP1 SGCB (-) 2	Cancer cell line	Male
CVCL_E2JY	HAP1 SGCB (-) 3	Cancer cell line	Male
CVCL_XS70	HAP1 SGCB (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
NCT00317967	PHASE3	COMPLETED	Study to Determine if Atorvastatin Reduces Size and Stiffness of Muscle in the Left Ventricle of the Heart
NCT00698074	PHASE3	UNKNOWN	Diastolic Ventricular Interaction and the Effects of Biventricular Pacing in Hypertrophic Cardiomyopathy
NCT00821353	PHASE3	COMPLETED	Antiarrhythmic Therapy Versus Catheter Ablation for Atrial Fibrillation in Hypertrophic Cardiomyopathy
NCT02431221	PHASE3	WITHDRAWN	Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
NCT03470545	PHASE3	COMPLETED	Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT05174416	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mavacamten in Chinese Adults With Symptomatic Obstructive HCM
NCT05182658	PHASE3	ACTIVE_NOT_RECRUITING	Empagliflozin in Hypertrophic Cardiomyopathy
NCT05186818	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM
NCT05767346	PHASE3	COMPLETED	Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Metoprolol Succinate in Adults With Symptomatic oHCM
NCT06116968	PHASE3	COMPLETED	An Open-Label Study of Aficamten for Chinese Patients With Symptomatic oHCM
NCT06873828	PHASE3	NOT_YET_RECRUITING	Evaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter MonitoringEvaluation of the Efficacy and Safety of Wearable ECG (AT-Patch) in Patients With Hypertrophic Cardiomyopathy Requiring 48-Hour Holter Monitoring
NCT07021976	PHASE3	RECRUITING	A Phase III Trial of HRS-1893 in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT07023341	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Learn More About How Well Aficamten Works in Japanese Participants With Symptomatic Obstructive Hypertrophic Cardiomyopathy
NCT07202897	PHASE3	NOT_YET_RECRUITING	LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.
NCT00629018	PHASE2	COMPLETED	Safety and Efficacy Study of Stem Cell Transplantation to Treat Dilated Cardiomyopathy
NCT00629096	PHASE2	COMPLETED	Intracoronary Infusion of Autologous Bone Marrow Cells for Treatment of Idiopathic Dilated Cardiomyopathy