SGCG

Summary

SGCG (sarcoglycan gamma, HGNC:10809) is a protein-coding gene on chromosome 13q12.12, encoding Gamma-sarcoglycan (Q13326). 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 gamma-sarcoglycan, one of several sarcolemmal transmembrane glycoproteins that interact with dystrophin. The dystrophin-glycoprotein complex (DGC) spans the sarcolemma and is comprised of dystrophin, syntrophin, alpha- and beta-dystroglycans and sarcoglycans. The DGC provides a structural link between the subsarcolemmal cytoskeleton and the extracellular matrix of muscle cells. Defects in the encoded protein can lead to early onset autosomal recessive muscular dystrophy, in particular limb-girdle muscular dystrophy, type 2C (LGMD2C).

Source: NCBI Gene 6445 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive limb-girdle muscular dystrophy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 15
• Clinical variants (ClinVar): 687 total — 55 pathogenic, 46 likely-pathogenic
• Phenotypes (HPO): 42
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_000231

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10809
Approved symbol	SGCG
Name	sarcoglycan gamma
Location	13q12.12
Locus type	gene with protein product
Status	Approved
Aliases	SCARMD2, DAGA4, SCG3, DMDA, TYPE, A4, MGC130048
Ensembl gene	ENSG00000102683
Ensembl biotype	protein_coding
OMIM	608896
Entrez	6445

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000218867, ENST00000876364, ENST00000876365, ENST00000876366, ENST00000876367, ENST00000942466, ENST00000942467, ENST00000942468, ENST00000942469, ENST00000942470, ENST00000942471

RefSeq mRNA: 4 — MANE Select: NM_000231 NM_000231, NM_001378244, NM_001378245, NM_001378246

CCDS: CCDS9299

Canonical transcript exons

ENST00000218867 — 8 exons

Exon	Start	End
ENSE00000876423	23234611	23234712
ENSE00000876424	23250630	23250717
ENSE00000906497	23279359	23279478
ENSE00000906498	23295415	23295487
ENSE00000906499	23320637	23320760
ENSE00001093703	23324368	23325162
ENSE00001093706	23180979	23181075
ENSE00003621118	23203695	23203889

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 98.90.

FANTOM5 (CAGE): breadth broad, TPM avg 2.5656 / max 152.4122, expressed in 456 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134392	0.8299	267
134395	0.7090	113
134393	0.3044	47
134394	0.2711	67
134391	0.2216	110
134385	0.0700	29
134390	0.0698	32
134386	0.0621	30
134389	0.0113	3
134387	0.0111	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.90	gold quality
gluteal muscle	UBERON:0002000	98.66	gold quality
triceps brachii	UBERON:0001509	98.47	gold quality
biceps brachii	UBERON:0001507	98.42	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.41	gold quality
left ventricle myocardium	UBERON:0006566	98.39	gold quality
diaphragm	UBERON:0001103	98.36	gold quality
vastus lateralis	UBERON:0001379	98.34	gold quality
quadriceps femoris	UBERON:0001377	98.03	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.99	gold quality
myocardium	UBERON:0002349	97.85	gold quality
heart right ventricle	UBERON:0002080	97.41	gold quality
skeletal muscle tissue	UBERON:0001134	96.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.49	gold quality
apex of heart	UBERON:0002098	96.25	gold quality
body of tongue	UBERON:0011876	95.94	gold quality
heart left ventricle	UBERON:0002084	95.88	gold quality
cardiac ventricle	UBERON:0002082	95.87	gold quality
deltoid	UBERON:0001476	95.69	gold quality
cardiac atrium	UBERON:0002081	94.31	gold quality
right atrium auricular region	UBERON:0006631	94.06	gold quality
muscle organ	UBERON:0001630	93.83	gold quality
gastrocnemius	UBERON:0001388	93.40	gold quality
muscle tissue	UBERON:0002385	93.38	gold quality
muscle of leg	UBERON:0001383	92.33	gold quality
heart	UBERON:0000948	91.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.82	gold quality
tibialis anterior	UBERON:0001385	90.52	silver quality
tongue	UBERON:0001723	85.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.81	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IKZF1, MYOD1

miRNA regulators (miRDB)

41 targeting SGCG, 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-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-655-5P	98.74	65.93	888

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 18)

• Clinical, histologic, and immunohistochemical characteristics of three children with limb-girdle muscular dystrophy type 2C. Two novel mutations in the gamma-sarcoglycan gene were present. We found phenotypic differences in two brothers. (PMID:15087111)
• two unrelated patients of Puerto Rican descent who have identical previously undescribed homozygous E263K (G787A) missense mutations on exon 8, and a white North American child with del521T on one allele and a deletion of exon 6 on the other allele. (PMID:16832103)
• Biglycan is a ligand for two members of the sarcoglycan complex and regulates their expression at discrete developmental ages. (PMID:16883602)
• The limb-girdle muscular dystrophy patients with gamma-sarcoglycan deficient LGMD2C do not enable an accurate prediction of the genotype. (PMID:18996010)
• This study, the first mutational analysis of Indian patients with sarcoglycanopathies suggests gamma SG mutations were the most common and the most prevalent mutation in the gamma SG gene was 525del.T. (PMID:19770540)
• four Greek Gypsy patients with limb girdle muscular dystrophy type 2C carried the same homozygous C283Y mutation in the gamma-sarcoglycan gene (PMID:20345928)
• The relative incidence of LGMD2C among Japanese Duchenne muscular dystrophy-like patients can be calculated as 1 in 161 patients suspected to have Duchenne muscular dystrophy. (PMID:20350330)
• The C allele of the c.-94C>G polymorphism in delta-sarcoglycan is a risk factor for HCM, which is increased by the Amerindian component and can play an important role in the etiology and progression of disease in Mexican patients (PMID:22524166)
• Data suggest that an SNP in an intron of SGCG (rs9552911) is associated with type 2 diabetes [Genome-Wide Association Study in Sikh populations in India & Meta-Analysis] (PMID:23300278)
• A report of two siblings with severe childhood onset limb-girdle muscular dystrophy type 2C supports the theory that the mutation G787A in the SGCG gene is a founder mutation. (PMID:24534832)
• Molecular epidemiologic methods were used to calculate the frequency of heterozygotes for this SGCG mutation in Moroccan newborns and to estimate the prevalence of LGMD2C in the Moroccan population. (PMID:24552312)
• These results position archvillin as a mechanically sensitive component of the dystrophin complex and demonstrate that signaling defects caused by loss of gamma-SG occur both at the sarcolemma and in the nucleus. (PMID:25605665)
• FADH2-dependent monooxygenase (SgcE6 and SgcC) that catalyzes the hydroxylation of a PCP-tethered substrate (PMID:27560143)
• This study showed that fifteen families were shown to carry SGCG variants in patient with early onset severe muscular dystrophy. (PMID:27759885)
• Expression, purification, and structural analysis of the full-length human integral membrane protein gamma-sarcoglycan. (PMID:31682967)
• SGCG rs679482 Associates With Weight Loss Success in Response to an Intensively Supervised Outpatient Program. (PMID:32527767)
• Homozygous Inversion on Chromosome 13 Involving SGCG Detected by Short Read Whole Genome Sequencing in a Patient Suffering from Limb-Girdle Muscular Dystrophy. (PMID:36292638)
• Disruption of MAM integrity in mutant FUS oligodendroglial progenitors from hiPSCs. (PMID:38170217)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgcg	ENSDARG00000038107
mus_musculus	Sgcg	ENSMUSG00000035296
rattus_norvegicus	Sgcg	ENSRNOG00000014603
drosophila_melanogaster	Scgdelta	FBGN0025391
caenorhabditis_elegans		WBGENE00004790

Paralogs (2): SGCD (ENSG00000170624), SGCZ (ENSG00000185053)

Protein

Protein identifiers

Gamma-sarcoglycan — Q13326 (reviewed: Q13326)

Alternative names: 35 kDa dystrophin-associated glycoprotein

All UniProt accessions (1): Q13326

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. Interacts with FLNC.

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

Tissue specificity. Expressed in skeletal and heart muscle.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal recessive 5 (LGMDR5) [MIM:253700] An autosomal recessive degenerative myopathy characterized by rapidly progressive muscle wasting from early childhood with loss of independent ambulation around age 12 years, dystrophic pattern on muscle biopsy, absence of gamma-sarcoglycan and normal dystrophin immunostaining. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (4): NP_000222, NP_001365173, NP_001365174, NP_001365175 (=MANE)

Domains & families (InterPro)

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

Pfam: PF04790

UniProt features (13 total): sequence variant 6, topological domain 2, disulfide bond 2, chain 1, transmembrane region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13326-F1	80.24	0.22

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): 265–290, 267–283

Glycosylation sites (1): 110

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: 352 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, WWTAAGGC_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, MODULE_329, CAGCTG_AP4_Q5, FOXD3_01, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, MARTINEZ_RB1_TARGETS_UP, TCF4_Q5, KEGG_VIRAL_MYOCARDITIS, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (4): muscle organ development (GO:0007517), gene expression (GO:0010467), cardiac muscle tissue development (GO:0048738), heart contraction (GO:0060047)

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

GO Cellular Component (8): endoplasmic reticulum membrane (GO:0005789), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), 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	2
cellular anatomical structure	2
animal organ development	1
muscle structure development	1
macromolecule biosynthetic process	1
heart development	1
striated muscle tissue development	1
heart process	1
blood circulation	1
binding	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
dystroglycan complex	1
plasma membrane	1
intracellular anatomical structure	1
dystrophin-associated glycoprotein complex	1

Protein interactions and networks

STRING

866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGCG	SGCA	Q16586	999
SGCG	DAG1	Q14118	990
SGCG	SSPN	Q14714	975
SGCG	DMD	P11532	965
SGCG	SGCD	Q92629	949
SGCG	SGCB	Q16585	914
SGCG	BGN	P13247	897
SGCG	FLNC	Q14315	893
SGCG	FKRP	Q9H9S5	867
SGCG	DYSF	O75923	864
SGCG	CAPN3	P20807	852
SGCG	SNTB1	Q13884	848
SGCG	SNTA1	Q13424	825
SGCG	ANO5	Q75V66	810
SGCG	UTRN	P46939	806

IntAct

31 interactions, top by confidence:

A	B	Type	Score
FLNC	SGCG	psi-mi:“MI:0915”(physical association)	0.590
SGCG	FLNC	psi-mi:“MI:0407”(direct interaction)	0.590
CLDN5	SGCG	psi-mi:“MI:0915”(physical association)	0.560
SGCG	SPACA1	psi-mi:“MI:0915”(physical association)	0.560
SGCG	ACO1	psi-mi:“MI:2364”(proximity)	0.450
DNAJB6	SGCG	psi-mi:“MI:2364”(proximity)	0.450
DYSF	SGCG	psi-mi:“MI:2364”(proximity)	0.450
PTPN11	SGCG	psi-mi:“MI:2364”(proximity)	0.270
SGCG	CLDN5	psi-mi:“MI:0915”(physical association)	0.000
SGCG	SPACA1	psi-mi:“MI:0915”(physical association)	0.000
ACO1	SGCG	psi-mi:“MI:0915”(physical association)	0.000
CCT6A	SGCG	psi-mi:“MI:0915”(physical association)	0.000
DNAJB6	SGCG	psi-mi:“MI:0915”(physical association)	0.000
SGCG	DYSF	psi-mi:“MI:0915”(physical association)	0.000
ENO1	SGCG	psi-mi:“MI:0915”(physical association)	0.000
ENO3	SGCG	psi-mi:“MI:0915”(physical association)	0.000
SGCG	HSPA1A	psi-mi:“MI:0915”(physical association)	0.000
MYBPC1	SGCG	psi-mi:“MI:0915”(physical association)	0.000
SGCG	MYBPC2	psi-mi:“MI:0915”(physical association)	0.000
MYBPC2	SGCG	psi-mi:“MI:0915”(physical association)	0.000
MYL11	SGCG	psi-mi:“MI:0915”(physical association)	0.000
PSAP	SGCG	psi-mi:“MI:0915”(physical association)	0.000
PYGM	SGCG	psi-mi:“MI:0915”(physical association)	0.000
SUCLG2	SGCG	psi-mi:“MI:0915”(physical association)	0.000
SGCG	TTN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): SPACA1 (Two-hybrid), CLDN5 (Two-hybrid), FLNC (Two-hybrid), CCT6A (Two-hybrid), DNAJB6 (Two-hybrid), DYSF (Two-hybrid), ENO1 (Two-hybrid), HSPA1B (Two-hybrid), MYBPC1 (Two-hybrid), MYBPC2 (Two-hybrid), PSAP (Two-hybrid), SUCLG2 (Two-hybrid), TTN (Two-hybrid), MYLPF (Two-hybrid), ENO3 (Two-hybrid)

ESM2 similar proteins: A0A140LIJ0, A2A863, A2VE04, A4IH88, A6QQ07, L7VG99, O02668, O08597, P08587, P16144, P19827, P40935, P43251, P79263, P82348, P97278, Q01841, Q059Y8, Q0VCM5, Q0VCU7, Q13326, Q14624, Q3SZL5, Q3T052, Q5FWI3, Q5R7K6, Q5T197, Q5XI31, Q5ZL00, Q61702, Q64632, Q6DDG2, Q6INU7, Q6NRB9, Q6PD26, Q6ZNA5, Q8BG22, Q8BH86, Q8BX51, Q8BXJ9

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SGCG	“form complex”	DGC	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	55
Likely pathogenic	46
Uncertain significance	257
Likely benign	209
Benign	51

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070855	NC_000013.10:g.(?23898497)(23898690_?)del	Pathogenic
1071940	NM_000231.3(SGCG):c.673_674insTATTCTTTTTCTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGACGGGGTTTCACCGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGTCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCC (p.Asp225delinsValPhePhePhePhePhePhePhePhePheXaaXaaXaaXaaAspGlyValSerProCysTer)	Pathogenic
1073532	NM_000231.3(SGCG):c.699_702del (p.Met234fs)	Pathogenic
1074004	NM_000231.3(SGCG):c.298-1G>A	Pathogenic
1173091	NM_000231.3(SGCG):c.128T>A (p.Leu43Ter)	Pathogenic
1323589	NM_000231.3(SGCG):c.526G>T (p.Glu176Ter)	Pathogenic
1323590	NM_000231.3(SGCG):c.177dup (p.Val60fs)	Pathogenic
1366500	NM_000231.3(SGCG):c.174_175insTTTTTTTTTTTTTTTTTTNNNNNNNNNNTTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCACAATTTGGATTCTT (p.Lys59delinsPhePhePhePhePhePheXaaXaaXaaXaaValSerGlnAspGlyLeuAspLeuLeuThrSerTer)	Pathogenic
1383126	NM_000231.3(SGCG):c.524_527del (p.Phe175fs)	Pathogenic
1391542	NM_000231.3(SGCG):c.533del (p.His177_Ser178insTer)	Pathogenic
1397202	NM_000231.3(SGCG):c.87T>A (p.Tyr29Ter)	Pathogenic
1452070	NM_000231.3(SGCG):c.648_649insC (p.Lys217fs)	Pathogenic
1455016	NM_000231.3(SGCG):c.775_776del (p.Gln259fs)	Pathogenic
1455914	NM_000231.3(SGCG):c.549dup (p.Val184fs)	Pathogenic
1459731	NC_000013.10:g.(?23755215)(23853627_?)del	Pathogenic
1459732	NC_000013.10:g.(?23824749)(23853637_?)del	Pathogenic
1459762	NM_000231.3(SGCG):c.105T>A (p.Cys35Ter)	Pathogenic
1460232	NC_000013.10:g.(?23808730)(23808871_?)del	Pathogenic
1698497	NC_000013.10:g.(23869627_23894775)_(23894900_23898506)del	Pathogenic
189243	NM_000231.3(SGCG):c.525del (p.Phe175fs)	Pathogenic
198699	NM_000231.3(SGCG):c.735dup (p.Lys246fs)	Pathogenic
2008	NM_000231.3(SGCG):c.87dup (p.Gly30fs)	Pathogenic
2009	NM_000231.3(SGCG):c.787G>A (p.Glu263Lys)	Pathogenic
208611	NM_000231.3(SGCG):c.195+4_195+7del	Pathogenic
2579222	GRCh38/hg38 13q12.12(chr13:23320540-23320858)x0	Pathogenic
2678708	NM_000231.3(SGCG):c.582dup (p.Glu195fs)	Pathogenic
2740381	NM_000231.3(SGCG):c.528_534del (p.His177fs)	Pathogenic
2763459	NM_000231.3(SGCG):c.735del (p.Lys246fs)	Pathogenic
2818710	NM_000231.3(SGCG):c.82del (p.Ile28fs)	Pathogenic
2822772	NM_000231.3(SGCG):c.89del (p.Gly30fs)	Pathogenic

SpliceAI

3249 predictions. Top by Δscore:

Variant	Effect	Δscore
13:23203674:C:A	acceptor_gain	1.0000
13:23203676:T:TA	acceptor_gain	1.0000
13:23203681:A:AG	acceptor_gain	1.0000
13:23203682:C:G	acceptor_gain	1.0000
13:23203683:A:AG	acceptor_gain	1.0000
13:23203683:ACTCC:A	acceptor_gain	1.0000
13:23234608:CA:C	acceptor_loss	1.0000
13:23234609:A:AC	acceptor_loss	1.0000
13:23234708:GAGTG:G	donor_gain	1.0000
13:23234710:GTG:G	donor_gain	1.0000
13:23250714:GTCG:G	donor_gain	1.0000
13:23279353:CTTCA:C	acceptor_loss	1.0000
13:23279354:TTCA:T	acceptor_loss	1.0000
13:23279356:CAGG:C	acceptor_loss	1.0000
13:23279357:A:AG	acceptor_gain	1.0000
13:23279357:AGGTC:A	acceptor_loss	1.0000
13:23279358:G:GA	acceptor_gain	1.0000
13:23279358:G:GT	acceptor_loss	1.0000
13:23279358:GGT:G	acceptor_gain	1.0000
13:23279442:G:GT	donor_gain	1.0000
13:23279475:ACTG:A	donor_gain	1.0000
13:23279477:TGG:T	donor_loss	1.0000
13:23279479:G:GG	donor_gain	1.0000
13:23279479:GTA:G	donor_loss	1.0000
13:23279480:T:G	donor_loss	1.0000
13:23295411:TTA:T	acceptor_loss	1.0000
13:23295412:TAGG:T	acceptor_loss	1.0000
13:23295413:A:AG	acceptor_gain	1.0000
13:23295413:A:G	acceptor_loss	1.0000
13:23295413:AG:A	acceptor_gain	1.0000

AlphaMissense

1894 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:23234699:T:A	I95K	0.961
13:23234671:T:C	F86L	0.960
13:23234673:T:A	F86L	0.960
13:23234673:T:G	F86L	0.960
13:23203844:T:A	N50K	0.952
13:23203844:T:G	N50K	0.952
13:23234699:T:G	I95R	0.949
13:23203790:A:C	R32S	0.948
13:23203790:A:T	R32S	0.948
13:23295460:T:A	V184D	0.941
13:23203793:G:C	K33N	0.940
13:23203793:G:T	K33N	0.940
13:23234672:T:C	F86S	0.940
13:23279425:T:C	F151S	0.938
13:23320660:T:C	L201P	0.929
13:23250651:T:C	S107P	0.927
13:23203787:G:C	W31C	0.924
13:23203787:G:T	W31C	0.924
13:23203860:T:A	W56R	0.923
13:23203860:T:C	W56R	0.923
13:23250679:G:C	R116P	0.917
13:23320639:T:C	L194S	0.914
13:23203785:T:A	W31R	0.912
13:23203785:T:C	W31R	0.912
13:23234699:T:C	I95T	0.911
13:23203881:T:C	F63L	0.908
13:23203883:T:A	F63L	0.908
13:23203883:T:G	F63L	0.908
13:23250664:T:A	V111E	0.906
13:23203789:G:C	R32T	0.905

dbSNP variants (sampled 300 via entrez): RS1000011362 (13:23174218 C>G), RS1000035628 (13:23166472 GC>G), RS1000039303 (13:23223333 C>T), RS1000057694 (13:23250478 T>G), RS1000057936 (13:23217694 G>C), RS1000068252 (13:23185580 A>G), RS1000074654 (13:23168740 A>C,G), RS1000108142 (13:23250715 T>A,C), RS1000129446 (13:23315675 C>T), RS1000139271 (13:23240839 C>T), RS1000143277 (13:23205535 A>T), RS1000147615 (13:23168942 A>G), RS1000159724 (13:23279860 T>C), RS1000160576 (13:23315486 A>G,T), RS1000169646 (13:23277934 A>G,T)

Disease associations

OMIM: gene MIM:608896 | disease phenotypes: MIM:253700, MIM:253600, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive limb-girdle muscular dystrophy type 2C	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 (5): autosomal recessive limb-girdle muscular dystrophy type 2C (MONDO:0009677), autosomal recessive limb-girdle muscular dystrophy (MONDO:0015152), sarcoglycanopathy (MONDO:0016140), schizophrenia (MONDO:0005090), dilated cardiomyopathy (MONDO:0005021)

Orphanet (5): Gamma-sarcoglycan-related limb-girdle muscular dystrophy R5 (Orphanet:353), Autosomal recessive limb-girdle muscular dystrophy (Orphanet:102015), Qualitative or quantitative defects of sarcoglycan (Orphanet:207052), Dilated cardiomyopathy (Orphanet:217604), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

42 total (30 of 42 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000276	Long face
HP:0001371	Flexion contracture
HP:0001667	Right ventricular hypertrophy
HP:0001771	Achilles tendon contracture
HP:0002090	Pneumonia
HP:0002091	Restrictive ventilatory defect
HP:0002136	Broad-based gait
HP:0002359	Frequent falls
HP:0002505	Loss of ambulation
HP:0002515	Waddling gait
HP:0002650	Scoliosis
HP:0002938	Lumbar hyperlordosis
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003307	Hyperlordosis
HP:0003391	Gowers sign
HP:0003458	EMG: myopathic abnormalities
HP:0003484	Upper limb muscle weakness
HP:0003551	Difficulty climbing stairs
HP:0003555	Muscle fiber splitting
HP:0003557	Increased variability in muscle fiber diameter
HP:0003560	Muscular dystrophy
HP:0003621	Juvenile onset
HP:0003678	Rapidly progressive
HP:0003691	Scapular winging
HP:0003707	Calf muscle pseudohypertrophy
HP:0003713	Muscle fiber necrosis
HP:0003722	Neck flexor weakness

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST000576_2	Asthma	2.000000e-06
GCST001135_4	Bipolar disorder	9.000000e-06
GCST001806_18	Corneal structure	4.000000e-09
GCST001809_2	Type 2 diabetes	2.000000e-08
GCST002219_1	Triglycerides	3.000000e-128
GCST003831_7	Asthma	7.000000e-06
GCST005316_542	Intelligence (MTAG)	1.000000e-08
GCST005667_31	Central corneal thickness	1.000000e-09
GCST006414_17	Atrial fibrillation	3.000000e-09
GCST006585_2011	Blood protein levels	4.000000e-58
GCST008173_4	Alanine aminotransferase levels	9.000000e-06
GCST008446_1	Number of alcoholic drinks required to feel an effect (first five times drinking)	6.000000e-08
GCST012303_9	Recurrent major depressive disorder x sex interaction	1.000000e-05
GCST90002396_633	Mean reticulocyte volume	1.000000e-10
GCST90011899_8	Aspartate aminotransferase levels	6.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004530	triglyceride measurement
EFO:0004337	intelligence
EFO:0005213	central corneal thickness
EFO:0008343	sex interaction measurement
EFO:0010701	mean reticulocyte volume
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
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.)
C535900	Limb-girdle muscular dystrophy, type 2C (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	6
Estradiol	affects cotreatment, increases expression, decreases expression	3
sodium arsenite	affects methylation, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
Doxorubicin	decreases expression	2
terbufos	increases methylation	1
tetrabromobisphenol A	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
hydroquinone	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Fonofos	increases methylation	1
Nickel	decreases expression	1
Parathion	increases methylation	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, increases expression, decreases expression	1
Triclosan	decreases expression	1
Aflatoxin B1	increases methylation	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety