SGCZ

Summary

SGCZ (sarcoglycan zeta, HGNC:14075) is a protein-coding gene on chromosome 8p22, encoding Zeta-sarcoglycan (Q96LD1). Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.

The zeta-sarcoglycan gene measures over 465 kb and localizes to 8p22. This protein is part of the sarcoglycan complex, a group of 6 proteins. The sarcoglycans are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a carboxyl-terminal cluster with several conserved cysteine residues. The sarcoglycan complex is part of the dystrophin-associated glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extra-cellular matrix.

Source: NCBI Gene 137868 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_139167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14075
Approved symbol	SGCZ
Name	sarcoglycan zeta
Location	8p22
Locus type	gene with protein product
Status	Approved
Aliases	ZSG1
Ensembl gene	ENSG00000185053
Ensembl biotype	protein_coding
OMIM	608113
Entrez	137868

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000382080, ENST00000421524

RefSeq mRNA: 4 — MANE Select: NM_139167 NM_001322879, NM_001322880, NM_001322881, NM_139167

CCDS: CCDS5992

Canonical transcript exons

ENST00000382080 — 8 exons

Exon	Start	End
ENSE00001297458	14324103	14324204
ENSE00001299798	14102376	14102499
ENSE00001308436	14164580	14164702
ENSE00001314298	14554732	14554926
ENSE00001321357	14108163	14108235
ENSE00001330841	14237592	14237679
ENSE00001490843	14084845	14090637
ENSE00001490883	15237585	15238431

Expression profiles

Bgee: expression breadth broad, 70 present calls, max score 75.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5162 / max 57.2208, expressed in 135 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91955	0.2844	109
91954	0.1259	67
91956	0.1058	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.48	gold quality
oocyte	CL:0000023	68.59	silver quality
secondary oocyte	CL:0000655	62.83	silver quality
islet of Langerhans	UBERON:0000006	59.29	gold quality
prefrontal cortex	UBERON:0000451	57.26	gold quality
cortical plate	UBERON:0005343	55.30	gold quality
stromal cell of endometrium	CL:0002255	53.87	silver quality
ganglionic eminence	UBERON:0004023	53.38	gold quality
cerebellar cortex	UBERON:0002129	50.52	silver quality
adrenal tissue	UBERON:0018303	50.51	gold quality
cerebellar hemisphere	UBERON:0002245	50.29	silver quality
cerebellum	UBERON:0002037	49.85	silver quality
frontal cortex	UBERON:0001870	49.84	gold quality
nucleus accumbens	UBERON:0001882	49.60	gold quality
left ovary	UBERON:0002119	49.51	gold quality
colonic epithelium	UBERON:0000397	49.37	gold quality
neocortex	UBERON:0001950	49.37	gold quality
corpus callosum	UBERON:0002336	49.17	gold quality
right hemisphere of cerebellum	UBERON:0014890	49.00	silver quality
ovary	UBERON:0000992	48.85	gold quality
right ovary	UBERON:0002118	48.67	gold quality
anterior cingulate cortex	UBERON:0009835	48.61	gold quality
hypothalamus	UBERON:0001898	48.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	48.21	gold quality
amygdala	UBERON:0001876	48.17	gold quality
tendon of biceps brachii	UBERON:0008188	46.73	gold quality
primary visual cortex	UBERON:0002436	46.64	gold quality
cerebral cortex	UBERON:0000956	46.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	46.16	gold quality
brain	UBERON:0000955	45.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	4554.14
E-HCAD-25	yes	3040.37
E-ANND-3	yes	4.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR5A1

miRNA regulators (miRDB)

238 targeting SGCZ, 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-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
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-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084

Literature-anchored findings (GeneRIF, showing 2)

• three CNVs associated with BMI, obesity, and other obesity-related traits after adjusting for multiple testing. These CNVs overlap the PARK2, GYPA, and SGCZ genes (PMID:22836685)
• No pathogenic SGCZ mutations were identified (PMID:24792710)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	SGCZ	ENSDARG00000106258
mus_musculus	Sgcz	ENSMUSG00000039539
rattus_norvegicus	Sgcz	ENSRNOG00000057716
drosophila_melanogaster	Scgdelta	FBGN0025391
caenorhabditis_elegans		WBGENE00004790

Paralogs (2): SGCG (ENSG00000102683), SGCD (ENSG00000170624)

Protein

Protein identifiers

Zeta-sarcoglycan — Q96LD1 (reviewed: Q96LD1)

Alternative names: ZSG1

All UniProt accessions (2): Q96LD1, Q08AT0

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. May play a role in the maintenance of striated muscle membrane stability.

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

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q96LD1-1	1	yes
Q96LD1-2	2

RefSeq proteins (4): NP_001309808, NP_001309809, NP_001309810, NP_631906* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF04790

UniProt features (8 total): topological domain 2, glycosylation site 2, chain 1, transmembrane region 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LD1-F1	80.59	0.26

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 (1): 273–289

Glycosylation sites (2): 62, 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: 110 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CELL_SIGNALING, MAYBURD_RESPONSE_TO_L663536_UP, GTGCCTT_MIR506, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, AAAGGGA_MIR204_MIR211, TGANTCA_AP1_C, GOBP_SYNAPTIC_SIGNALING, DOUGLAS_BMI1_TARGETS_DN, GOBP_HEART_PROCESS, GOBP_MUSCLE_CELL_CELLULAR_HOMEOSTASIS, GOBP_MEMBRANE_ORGANIZATION, GOBP_MUSCLE_CELL_DEVELOPMENT, AGCATTA_MIR155

GO Biological Process (5): muscle cell cellular homeostasis (GO:0046716), cardiac muscle tissue development (GO:0048738), muscle cell development (GO:0055001), heart contraction (GO:0060047), membrane organization (GO:0061024)

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

GO Cellular Component (8): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), cytoskeleton (GO:0005856), plasma membrane (GO:0005886), sarcoglycan complex (GO:0016012), sarcolemma (GO:0042383), cytoplasm (GO:0005737), 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
cellular anatomical structure	2
cellular homeostasis	1
heart development	1
striated muscle tissue development	1
muscle cell differentiation	1
cell development	1
heart process	1
blood circulation	1
cellular component organization	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
dystroglycan complex	1
plasma membrane protein complex	1
plasma membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

682 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGCZ	SGCE	O43556	830
SGCZ	DSG1	Q02413	775
SGCZ	SSPN	Q14714	720
SGCZ	SGCA	Q16586	652
SGCZ	GOLGA6L7	A0A1B0GV03	507
SGCZ	XYLB	O75191	505
SGCZ	NRXN1	Q9ULB1	470
SGCZ	PIGT	Q969N2	445
SGCZ	REEP3	Q6NUK4	443
SGCZ	ZNF584	Q8IVC4	438
SGCZ	OR5J2	Q8NH18	435
SGCZ	FBXL17	Q9UF56	433
SGCZ	TUSC3	Q13454	418
SGCZ	SKAP1	Q86WV1	400
SGCZ	SGCD	Q92629	396
SGCZ	AFF3	P51826	396

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SGCZ	HARS1	psi-mi:“MI:0914”(association)	0.350
SGCZ	ATP5PD	psi-mi:“MI:0914”(association)	0.350

BioGRID (50): SGCB (Affinity Capture-MS), HARS (Affinity Capture-MS), REEP5 (Affinity Capture-MS), GK (Affinity Capture-MS), ACACA (Affinity Capture-MS), GNPTAB (Affinity Capture-MS), RANGRF (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), C4orf32 (Affinity Capture-MS), SP3 (Affinity Capture-MS), RTN4 (Affinity Capture-MS), DAGLB (Affinity Capture-MS), RANGRF (Affinity Capture-MS), SP3 (Affinity Capture-MS), C4orf32 (Affinity Capture-MS)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4477 predictions. Top by Δscore:

Variant	Effect	Δscore
8:14090790:T:A	donor_gain	1.0000
8:14102371:CTCA:C	donor_loss	1.0000
8:14102372:TCAC:T	donor_loss	1.0000
8:14102373:CACCT:C	donor_loss	1.0000
8:14102374:ACCTC:A	donor_gain	1.0000
8:14102375:C:CA	donor_loss	1.0000
8:14102375:CCTCC:C	donor_gain	1.0000
8:14102495:CAAGC:C	acceptor_gain	1.0000
8:14102496:AAGC:A	acceptor_gain	1.0000
8:14102497:AGC:A	acceptor_gain	1.0000
8:14102498:GC:G	acceptor_gain	1.0000
8:14102499:CC:C	acceptor_gain	1.0000
8:14102500:C:CA	acceptor_loss	1.0000
8:14102500:C:CC	acceptor_gain	1.0000
8:14102501:T:G	acceptor_loss	1.0000
8:14237688:CA:C	acceptor_gain	1.0000
8:14237689:A:AC	acceptor_gain	1.0000
8:14237689:A:C	acceptor_gain	1.0000
8:14237691:G:GC	acceptor_gain	1.0000
8:14320702:A:C	donor_gain	1.0000
8:14437417:CATAT:C	acceptor_gain	1.0000
8:14554922:GTCAT:G	acceptor_gain	1.0000
8:14554923:TCAT:T	acceptor_gain	1.0000
8:14554924:CAT:C	acceptor_gain	1.0000
8:14554924:CATC:C	acceptor_gain	1.0000
8:14554925:AT:A	acceptor_gain	1.0000
8:14554926:TC:T	acceptor_loss	1.0000
8:14554927:C:CA	acceptor_loss	1.0000
8:14554927:C:CC	acceptor_gain	1.0000
8:14090635:TAT:T	acceptor_gain	0.9900

AlphaMissense

2016 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000460 (8:14239090 T>C,G), RS1000000840 (8:14674807 A>C,G), RS1000006810 (8:15016226 C>T), RS1000009404 (8:14992833 C>T), RS1000010640 (8:14189616 G>T), RS1000013291 (8:14333075 T>C,G), RS1000022583 (8:14842254 C>T), RS1000023484 (8:14781579 C>G), RS1000028598 (8:14494343 G>A,T), RS1000029537 (8:15201969 G>A), RS1000031158 (8:14759272 G>A), RS1000034164 (8:14209046 A>T), RS1000037892 (8:14303975 C>A,T), RS1000038496 (8:14932727 A>C,T), RS1000039622 (8:14150331 T>C)

Disease associations

OMIM: gene MIM:608113 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000693_7	Platelet aggregation	5.000000e-06
GCST001762_660	Obesity-related traits	5.000000e-07
GCST001762_911	Obesity-related traits	2.000000e-06
GCST001972_1	Methamphetamine dependence	4.000000e-06
GCST002783_155	Body mass index	8.000000e-07
GCST002783_208	Body mass index	4.000000e-07
GCST002783_561	Body mass index	5.000000e-06
GCST003805_4	Diastolic blood pressure response to hydrochlorothiazide in hypertension	8.000000e-07
GCST004746_18	Small cell lung carcinoma	3.000000e-06
GCST005316_78	Intelligence (MTAG)	4.000000e-09
GCST005652_7	Cleft lip with or without cleft palate (maternal periconceptional vitamin use interaction)	3.000000e-06
GCST005959_33	Waist-to-hip ratio adjusted for BMI x sex interaction	4.000000e-07
GCST005962_41	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	6.000000e-06
GCST006269_1081	General cognitive ability	3.000000e-11
GCST006269_1120	General cognitive ability	5.000000e-10
GCST006466_3	Endometrial cancer (Non-endometrioid histology)	2.000000e-07
GCST006940_167	Neurociticism	4.000000e-09
GCST007643_4	Gemcitabine-induced early high-grade neutropenia in pancreatic cancer	5.000000e-06
GCST007666_5	Depressive symptom improvement	7.000000e-07
GCST008163_35	Height	5.000000e-06
GCST008992_1	Joint damage in rheumatoid arthritis	9.000000e-07
GCST008993_14	Joint damage in rheumatoid arthritis	4.000000e-06
GCST010242_180	HDL cholesterol levels	4.000000e-08
GCST010988_287	Adult body size	4.000000e-10
GCST012489_68	Heel bone mineral density x serum urate levels interaction	2.000000e-09
GCST90011894_9	Retinitis pigmentosa	9.000000e-06
GCST90026413_1	Severe insulin-deficient type 2 diabetes	4.000000e-06

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0004520	ICAM-1 measurement
EFO:0004340	body mass index
EFO:0006945	diastolic blood pressure change measurement
EFO:0004337	intelligence
EFO:0003959	cleft lip
EFO:0009116	vitamin supplement exposure measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008343	sex interaction measurement
EFO:0008007	age at assessment
EFO:0007660	neuroticism measurement
EFO:0007006	depressive symptom measurement
EFO:0005413	joint damage measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

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	increases expression, increases methylation, affects methylation, decreases methylation	3
Aflatoxin B1	affects methylation, decreases methylation	2
bisphenol F	increases methylation	1
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, affects methylation, increases methylation	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	decreases methylation	1
Fulvestrant	affects methylation, decreases methylation, affects cotreatment	1
Arsenic	affects methylation	1
Methamphetamine	affects response to substance	1
Methapyrilene	affects methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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