SDC1

Summary

SDC1 (syndecan 1, HGNC:10658) is a protein-coding gene on chromosome 2p24.1, encoding Syndecan-1 (P18827). Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix.

The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.

Source: NCBI Gene 6382 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 53 total
• Druggable target: yes
• MANE Select transcript: NM_002997

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10658
Approved symbol	SDC1
Name	syndecan 1
Location	2p24.1
Locus type	gene with protein product
Status	Approved
Aliases	CD138, syndecan, SYND1
Ensembl gene	ENSG00000115884
Ensembl biotype	protein_coding
OMIM	186355
Entrez	6382

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000254351, ENST00000381150, ENST00000403076, ENST00000429035, ENST00000447124, ENST00000482879, ENST00000852541, ENST00000852542, ENST00000917369, ENST00000970834

RefSeq mRNA: 2 — MANE Select: NM_002997 NM_001006946, NM_002997

CCDS: CCDS1697

Canonical transcript exons

ENST00000254351 — 5 exons

Exon	Start	End
ENSE00000714726	20203087	20203222
ENSE00000999271	20224802	20225130
ENSE00001145388	20203813	20204291
ENSE00001872920	20200797	20202935
ENSE00003627470	20205343	20205424

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 99.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.4616 / max 1208.8518, expressed in 1425 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
27111	13.5092	907
27112	12.8857	1206
27113	9.4882	1189
27110	1.9072	671
27116	1.8666	792
27115	1.3551	728
27114	1.0123	542
27119	0.2336	121
27118	0.0911	40
27117	0.0872	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.38	gold quality
skin of abdomen	UBERON:0001416	99.05	gold quality
pharyngeal mucosa	UBERON:0000355	98.89	gold quality
right lobe of liver	UBERON:0001114	98.82	gold quality
esophagus mucosa	UBERON:0002469	98.72	gold quality
esophagus squamous epithelium	UBERON:0006920	98.72	gold quality
zone of skin	UBERON:0000014	98.64	gold quality
skin of leg	UBERON:0001511	98.64	gold quality
gingiva	UBERON:0001828	98.64	gold quality
upper arm skin	UBERON:0004263	98.56	gold quality
upper leg skin	UBERON:0004262	98.52	gold quality
squamous epithelium	UBERON:0006914	98.52	gold quality
gingival epithelium	UBERON:0001949	98.48	gold quality
mammalian vulva	UBERON:0000997	98.43	gold quality
hair follicle	UBERON:0002073	98.37	gold quality
penis	UBERON:0000989	98.17	gold quality
liver	UBERON:0002107	98.16	gold quality
cervix epithelium	UBERON:0004801	97.99	gold quality
epithelium of esophagus	UBERON:0001976	97.95	gold quality
nipple	UBERON:0002030	97.87	gold quality
nasal cavity epithelium	UBERON:0005384	97.87	gold quality
oral cavity	UBERON:0000167	97.74	gold quality
cervix squamous epithelium	UBERON:0006922	97.57	gold quality
tongue squamous epithelium	UBERON:0006919	97.29	gold quality
skin of hip	UBERON:0001554	97.22	gold quality
palpebral conjunctiva	UBERON:0001812	96.99	gold quality
mucosa of urinary bladder	UBERON:0001259	96.86	gold quality
ileal mucosa	UBERON:0000331	96.78	gold quality
adult mammalian kidney	UBERON:0000082	96.76	gold quality
mucosa of transverse colon	UBERON:0004991	96.48	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	309.80
E-HCAD-1	yes	250.15
E-CURD-88	yes	184.05
E-CURD-114	yes	66.23
E-HCAD-4	yes	45.42
E-CURD-122	yes	39.52
E-CURD-46	yes	37.62
E-MTAB-8410	yes	31.03
E-MTAB-5061	yes	27.72
E-HCAD-11	yes	25.92
E-HCAD-10	yes	15.78
E-MTAB-10553	yes	9.74
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHE41, GLI2, HIF1A, MITF, MSX1, MYOG, NFKB1, NFKB, NR1H4, PAX5, PPARA, PPARG, PRDM1, RELA, RUNX2, WT1, XBP1

miRNA regulators (miRDB)

118 targeting SDC1, 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-4776-3P	100.00	68.73	1340
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-659-3P	99.85	70.69	1620

Literature-anchored findings (GeneRIF, showing 40)

• The loss of syndecan-1 expression evident in acantholytic conditions (PMID:11168765)
• mediates hepatocyte growth factor binding and promotes Met signaling in multiple myeloma (PMID:11830493)
• Serum levels of soluble syndecan-1 correlated with tumor mass in patients with multiple myeloma. (PMID:11877089)
• Soluble syndecan-1 promotes growth and dissemination of transplanted human myeloma tumors in vivo in SCID mice implanted with human bones. (PMID:12091355)
• review of structure, function, cell and tissue distribution (PMID:12144130)
• regulation of expression in isoform specific manner by farnesoid X receptor (PMID:12660231)
• Cells adherent via syndecan-1 do not spread, but can be induced to spread by Mn(2+), suggesting that activation of a beta(1) or beta(3) integrin partner is required. (PMID:12749851)
• TNF-alpha and IL-1beta are capable of down-regulating syndecan-1 expression (PMID:12824007)
• High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype (PMID:12879463)
• shedding of syndecan-1 promoted by MT1-MMP through the preferential cleavage of Gly245-Leu246 peptide bond stimulates cell migration (PMID:12904296)
• The increased stromal syndecan-1 expression, coupled with its loss from the surface of carcinoma cells, may contribute to tumor cell invasion and the development of metastases (PMID:12920224)
• results demonstrate that the laminin alpha3 LG4/5 modules within unprocessed laminin-5 permit its cell binding activity through heparan and chondroitin sulfate chains of syndecan-1 (PMID:12947106)
• the extracellular domain mediates an interaction that is necessary for dynamic cytoskeletal rearrangements whereas an interaction of the transmembrane domain is required for the initial spreading response (PMID:12975379)
• results demonstrate that cell-surface syndecan-1 is a degradative target of heparanase (HPSE-1), and syndecan-1 regulates HPSE-1 biological activity (PMID:14630925)
• serves as a primary human papillomavirus receptor protein in natural HPV11 infection of keratinocytes. (PMID:14645569)
• MT4-MMP and the proteoglycan form of syndecan-1 have roles in ADAMTS-4 activation on the cell surface (PMID:14701864)
• Growth-promoting loop exists between breast cancer cells and their stroma that depends on the activity of glycanated Sdc1. (PMID:14744776)
• Consistent with a possible biochemical role for syndecan-1 in prostate cancer progression and metastasis, syndecan-1 expression correlated with serologic recurrence in Gleason sum 7 prostate cancer and was highly expressed in soft-tissue metastases. (PMID:14972511)
• in hyperinflammatory lesions, ephrinB2 was predominantly expressed in macrophage-like cells and EphB4 in small venules; syntenin and syndecan-1 were up-regulated in EphB4-positive endothelial cells after stimulation with preclustered ephrinB2 (PMID:15126321)
• syndecan-1 and glypican-1 have roles in progression of ovarian cancer (PMID:15297422)
• Altered matrix-dependent signaling due to increased levels of cell surface syndecan-1 may lead to epithelial cell invasion during early stages of tumorigenesis. (PMID:15383330)
• Concomitant expression of syndecan-1 in both epithelium and stroma may be a predictor of unfavourable prognosis in breast cancer, and in contrast with previous studies, loss of epithelial syndecan-1 was associated with a more favourable prognosis (PMID:15459490)
• syndecan-1 is likely to be a critical regulator of many cellular behaviors that depend on activated alpha(v)beta(3) integrins (PMID:15479743)
• constitutive shedding corresponding to the basal level of soluble syndecan-1 ectodomain was significantly increased when cells were stimulated with P. gingivalis lipopolysaccharide (PMID:15648090)
• osteoprotegerin affects monocyte mi-gration and protein kinase C and phosphatidylinositol 3-kinase/Akt activation via syndecan-1. (PMID:15728209)
• syndecan-1 has a role in progression of invasive breast carcinomas through the remodeling of breast cancer tissue via interaction with other extracellular matrix components (PMID:15743035)
• Expression of paxillin and syndecan-1 in hepatocellular carcinoma(HCC) may affect its invasive and metastatic ability. May be converse correlation between expression of paxillin and syndecan-1 protein in HCC. (PMID:15770719)
• Stromal syndecan-1 expression is an independent prognostic marker in pancreatic cancer, whereas epithelial syndecan-1 expression predicts better prognosis only in resectable disease. (PMID:15886501)
• Loss of syndecan-1 plays a role in the growth of G-type cancers of differentiated type gastric cancers at an early stage (PMID:15902740)
• Low epithelial syndecan-1 expression was associated with a higher histological grade and a more advanced clinical stage of the colorectal cancer (PMID:16020957)
• Malignant glioma cells express all types of syndecans. NF-kappaB participates in the upregulation of the syndecan-1 expression at the transcriptional level, and increased expression of syndecan-1 could associate with thrombospondin-1. (PMID:16132527)
• stromal fibroblast-derived Sdc1 stimulates breast carcinoma growth and angiogenesis in vivo (PMID:16247452)
• shed syndecan-1 or MMP7-syndecan-1 complexes may have roles in tumor progression (PMID:16286510)
• Syndecan-1 and syndecan-4 may have roles in progression of breast carcinoma (PMID:16636895)
• The ectodomain of the syndecan-1 core protein contains an active site that assembles into a complex with the alphavbeta5 integrin and regulates alphavbeta5 integrin activity. (PMID:16720645)
• Certain immunomarkers like syndecan-1, kappa and lambda light chains and IgA heavy chain could be of much help in identifying early stage immunoproliferative small intestinal disease (IPSID). (PMID:16773719)
• CD138 may have a role in progression of nodal diffuse large B cell lymphoma (PMID:16778379)
• syndecan-1 may have a role in progression of B-cell chronic lymphocytic leukemia (PMID:16840194)
• increase of Syndecan-1 in all tissue compartments and a redistribution from epithelium to stroma may be a characteristic feature for dense breast tissue (PMID:16857657)
• syndecan-1 shedding may modulate the pathogenesis of specific microbes (PMID:16884912)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sdc1	ENSMUSG00000020592
rattus_norvegicus	Sdc1	ENSRNOG00000059947
drosophila_melanogaster	Sdc	FBGN0010415
caenorhabditis_elegans		WBGENE00004749

Paralogs (3): SDC4 (ENSG00000124145), SDC3 (ENSG00000162512), SDC2 (ENSG00000169439)

Protein

Protein identifiers

Syndecan-1 — P18827 (reviewed: P18827)

All UniProt accessions (4): P18827, E9PHH3, F8WCX9, H7C1K4

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface proteoglycan that contains both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix. Regulates exosome biogenesis in concert with SDCBP and PDCD6IP. Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway.

Subunit / interactions. Interacts with CDCP1. Interacts (via C-terminus) with TIAM1 (via PDZ domain). Interacts with MDK.

Subcellular location. Membrane. Secreted. Extracellular exosome.

Tissue specificity. Detected in placenta (at protein level). Detected in fibroblasts (at protein level).

Post-translational modifications. Shedding is enhanced by a number of factors such as heparanase, thrombin or EGF. Also by stress and wound healing. PMA-mediated shedding is inhibited by TIMP3.

Similarity. Belongs to the syndecan proteoglycan family.

RefSeq proteins (2): NP_001006947, NP_002988* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001050	Syndecan	Family
IPR003585	Neurexin-like	Domain
IPR027789	Syndecan/Neurexin_dom	Domain
IPR030479	Syndecan_CS	Conserved_site

Pfam: PF01034

UniProt features (26 total): glycosylation site 6, compositionally biased region 5, region of interest 3, topological domain 2, sequence variant 2, sequence conflict 2, signal peptide 1, chain 1, site 1, modified residue 1, strand 1, transmembrane region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4GVC	X-RAY DIFFRACTION	1.54
4GVD	X-RAY DIFFRACTION	1.85
6EJE	X-RAY DIFFRACTION	2.43

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18827-F1	55.44	0.05

Functional residue map

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

Catalytic / active sites (1): 242–243 (cleavage)

Post-translational modifications (1): 285

Glycosylation sites (6): 37, 43, 45, 47, 206, 216

Function

Pathways and Gene Ontology

Reactome pathways

44 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022928	HS-GAG biosynthesis
R-HSA-2024096	HS-GAG degradation
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-3000170	Syndecan interactions
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3656237	Defective EXT2 causes exostoses 2
R-HSA-3656253	Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-449836	Other interleukin signaling
R-HSA-9694614	Attachment and Entry
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9833110	RSV-host interactions
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918485	Dengue Virus Attachment and Entry
R-HSA-109582	Hemostasis
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1430728	Metabolism
R-HSA-1474244	Extracellular matrix organization
R-HSA-1630316	Glycosaminoglycan metabolism
R-HSA-1638091	Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-1793185	Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction

MSigDB gene sets: 387 (showing top): MODULE_52, WWTAAGGC_UNKNOWN, GOBP_VESICLE_LOCALIZATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, JAEGER_METASTASIS_DN, GOBP_VESICLE_ORGANIZATION, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOCC_CELL_SURFACE, MCBRYAN_TERMINAL_END_BUD_UP, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (7): receptor-mediated endocytosis (GO:0006898), cell migration (GO:0016477), myoblast development (GO:0048627), striated muscle cell development (GO:0055002), canonical Wnt signaling pathway (GO:0060070), positive regulation of exosomal secretion (GO:1903543), positive regulation of extracellular exosome assembly (GO:1903553)

GO Molecular Function (3): cargo receptor activity (GO:0038024), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (8): Golgi lumen (GO:0005796), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	5
Heparan sulfate/heparin (HS-GAG) metabolism	2
Coagulation pathway	2
Respiratory Syncytial Virus Infection Pathway	2
Dengue Virus Infection	2
Glycosaminoglycan metabolism	1
Hemostasis	1
Non-integrin membrane-ECM interactions	1
Signaling by Interleukins	1
Early SARS-CoV-2 Infection Events	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
endocytosis	1
cell motility	1
myoblast differentiation	1
cell development	1
striated muscle cell differentiation	1
muscle cell development	1
Wnt signaling pathway	1
positive regulation of cellular component biogenesis	1
positive regulation of exocytosis	1
regulation of exosomal secretion	1
exosomal secretion	1
extracellular exosome assembly	1
positive regulation of organelle assembly	1
regulation of extracellular exosome assembly	1
molecular_function	1
vesicle-mediated transport	1
molecular adaptor activity	1
protein binding	1
binding	1
Golgi apparatus	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
lysosome	1
vacuolar lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

3212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDC1	SDCBP	O00560	996
SDC1	FN1	P02751	992
SDC1	RBBP5	Q15291	989
SDC1	WDR82	Q6UXN9	989
SDC1	ASH2L	Q9UBL3	989
SDC1	FGF2	P09038	988
SDC1	WDR5	P61964	987
SDC1	GPC1	P35052	962
SDC1	HSPG2	P98160	944
SDC1	CD44	P16070	927
SDC1	SDCBP2	Q9H190	922
SDC1	HMGB1	P09429	921
SDC1	THBS1	P07996	891
SDC1	BGN	P13247	884
SDC1	CD38	P28907	882
SDC1	SETD1A	O15047	882

IntAct

66 interactions, top by confidence:

A	B	Type	Score
SDC1	SDC1	psi-mi:“MI:0407”(direct interaction)	0.670
TIAM1	SDC1	psi-mi:“MI:0407”(direct interaction)	0.650
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
TULP3	GGPS1	psi-mi:“MI:0914”(association)	0.640
SDC2	SDC1	psi-mi:“MI:0407”(direct interaction)	0.590
SDC1	SDC2	psi-mi:“MI:0407”(direct interaction)	0.590
APP	SDC1	psi-mi:“MI:0915”(physical association)	0.560
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
HADHA	GPC4	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
FAM20B	SDC1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
SDC1	SDC3	psi-mi:“MI:0407”(direct interaction)	0.440
TNFRSF21	SDC1	psi-mi:“MI:0407”(direct interaction)	0.440
PDCD6IP	SDCBP	psi-mi:“MI:0403”(colocalization)	0.440
LAMA3	SDC1	psi-mi:“MI:0915”(physical association)	0.400
PCOLCE	SDC1	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (109): SDC1 (Reconstituted Complex), SDC1 (Reconstituted Complex), EP300 (Affinity Capture-Western), SDC1 (Affinity Capture-Western), FARP1 (Affinity Capture-MS), DHRS2 (Affinity Capture-MS), GMEB2 (Affinity Capture-MS), FGF2 (Affinity Capture-MS), PRDM10 (Affinity Capture-MS), CYHR1 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), CSNK1G3 (Affinity Capture-MS), OCLN (Affinity Capture-MS), HMGCS1 (Affinity Capture-MS), CCNY (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8Y7Y5, A1KXC4, A6QLF8, J3KML8, O00592, O35188, O55145, O57604, P06484, P07141, P13838, P14220, P15702, P16150, P18827, P20934, P26260, P34740, P47951, P59647, P78423, P97808, Q08DZ5, Q1ECS6, Q28270, Q28645, Q29RT9, Q3MIW9, Q3TNW5, Q52S86, Q58Y74, Q5RAF8, Q62170, Q64314, Q6MG22, Q6P9X9, Q6UWI2, Q6UXF1, Q86YL7, Q8BHE4

Diamond homologs: O35988, O75056, P18827, P18828, P26260, P26261, P31431, P33671, P34740, P34741, P34900, P34901, P43407, P47951, P49414, P49415, P49416, Q08DZ5, Q1AGV6, Q1AGV7, Q58DD4, Q5RAT9, Q64519, Q6GR51, Q8HZJ6, P50605

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 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
Glycosaminoglycan-protein linkage region biosynthesis	5	38.6×	4e-05
Regulation of clotting cascade	5	22.9×	1e-04
EPH-Ephrin signaling	5	16.2×	4e-04
PIP3 activates AKT signaling	6	7.9×	2e-03
Dengue Virus-Host Interactions	6	5.4×	1e-02
Infectious disease	8	3.9×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	5
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1332 predictions. Top by Δscore:

Variant	Effect	Δscore
2:20202933:CCC:C	acceptor_gain	1.0000
2:20202934:CCC:C	acceptor_gain	1.0000
2:20203082:CTCA:C	donor_loss	1.0000
2:20203085:A:AC	donor_gain	1.0000
2:20203085:ACCT:A	donor_gain	1.0000
2:20203085:ACCTC:A	donor_gain	1.0000
2:20203086:C:CC	donor_gain	1.0000
2:20203086:CCT:C	donor_gain	1.0000
2:20203086:CCTC:C	donor_gain	1.0000
2:20203086:CCTCC:C	donor_gain	1.0000
2:20203102:T:A	donor_gain	1.0000
2:20203218:AAGTC:A	acceptor_gain	1.0000
2:20203219:AGTC:A	acceptor_gain	1.0000
2:20203220:GTC:G	acceptor_gain	1.0000
2:20203221:TC:T	acceptor_gain	1.0000
2:20203222:CC:C	acceptor_gain	1.0000
2:20203223:C:CC	acceptor_gain	1.0000
2:20203225:G:C	acceptor_gain	1.0000
2:20203234:C:CT	acceptor_gain	1.0000
2:20203808:CTCA:C	donor_loss	1.0000
2:20203811:A:AC	donor_gain	1.0000
2:20203811:ACCT:A	donor_loss	1.0000
2:20203812:C:CC	donor_gain	1.0000
2:20203812:CCTG:C	donor_gain	1.0000
2:20205420:ATTTG:A	acceptor_gain	1.0000
2:20205421:TTTG:T	acceptor_gain	1.0000
2:20205422:TTG:T	acceptor_gain	1.0000
2:20205423:TG:T	acceptor_gain	1.0000
2:20205423:TGC:T	acceptor_loss	1.0000
2:20205425:C:CA	acceptor_loss	1.0000

AlphaMissense

1974 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:20202775:G:C	F308L	0.999
2:20202775:G:T	F308L	0.999
2:20202777:A:G	F308L	0.999
2:20202776:A:C	F308C	0.996
2:20202894:A:G	C269R	0.996
2:20202911:C:T	G263E	0.996
2:20202926:G:T	A258D	0.996
2:20202899:G:T	A267D	0.995
2:20202912:C:G	G263R	0.995
2:20202912:C:T	G263R	0.995
2:20202923:C:T	G259E	0.995
2:20202920:C:T	G260D	0.994
2:20202929:A:T	I257N	0.994
2:20202770:G:T	A310D	0.993
2:20202844:G:C	S285R	0.993
2:20202844:G:T	S285R	0.993
2:20202846:T:G	S285R	0.993
2:20202869:C:G	R277P	0.993
2:20202921:C:G	G260R	0.992
2:20202866:A:G	M278T	0.991
2:20202924:C:G	G259R	0.990
2:20202924:C:T	G259R	0.990
2:20202776:A:G	F308S	0.989
2:20202836:A:G	L288S	0.989
2:20202843:A:G	Y286H	0.989
2:20202855:C:G	D282H	0.989
2:20202856:C:A	K281N	0.989
2:20202856:C:G	K281N	0.989
2:20202842:T:C	Y286C	0.988
2:20202854:T:G	D282A	0.988

dbSNP variants (sampled 300 via entrez): RS1000022786 (2:20200915 C>T), RS1000024390 (2:20207701 G>A), RS1000269171 (2:20210140 C>T), RS1000615386 (2:20202159 G>A,C), RS1000686843 (2:20203256 G>A), RS1000701658 (2:20209985 C>CA), RS1000740219 (2:20204924 C>A,G), RS1000774287 (2:20220351 C>G,T), RS1000799381 (2:20225019 G>C,T), RS1000830420 (2:20224778 C>A,T), RS1000990569 (2:20200525 A>G), RS1001100856 (2:20207744 G>A), RS1001380192 (2:20212924 C>G), RS1001508599 (2:20227422 G>C), RS1001559561 (2:20212844 G>C)

Disease associations

OMIM: gene MIM:186355 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): long QT syndrome (MONDO:0002442)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST002337_72	Amyotrophic lateral sclerosis (sporadic)	3.000000e-06
GCST002719_7	Seasonality	8.000000e-06
GCST004904_124	Body mass index	2.000000e-08
GCST008466_14	Alanine aminotransferase levels in non-alcoholic fatty liver disease	5.000000e-06
GCST010241_176	Apolipoprotein A1 levels	3.000000e-32
GCST010242_429	HDL cholesterol levels	2.000000e-21
GCST010244_262	Triglyceride levels	2.000000e-20
GCST010245_159	LDL cholesterol levels	4.000000e-17
GCST90020028_422	Hip circumference adjusted for BMI	1.000000e-10
GCST90020028_423	Hip circumference adjusted for BMI	1.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006876	seasonality measurement
EFO:0004340	body mass index
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712898 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.04	Kd	906.2	nM	CHEMBL5653589
5.97	ED50	1070	nM	CHEMBL5653589
5.82	Kd	1503	nM	CHEMBL3752910
5.75	ED50	1774	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149356: Binding affinity to human SDC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.9062	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149356: Binding affinity to human SDC1 incubated for 45 mins by Kinobead based pull down assay	kd	1.5031	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Acetaminophen	decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, affects methylation	3
Aflatoxin B1	affects expression, decreases expression, increases expression	3
N-((2-(hydroxyaminocarbonyl)methyl)-4-methylpentanoyl)-3-(2’-naphthyl)alanylalanine, 2-aminoethylamide	affects cotreatment, decreases reaction, increases secretion, decreases secretion	2
Arsenic Trioxide	decreases expression, decreases response to substance	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Colforsin	decreases reaction, increases abundance, increases expression	2
Methyl Methanesulfonate	increases expression, decreases expression	2
Progesterone	decreases expression	2
Smoke	decreases expression	2
Tetradecanoylphorbol Acetate	increases cleavage, decreases expression, decreases reaction, increases secretion, affects localization	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	affects methylation, decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, decreases reaction, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
lead acetate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression, affects localization	1
afimoxifene	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
rutecarpine	decreases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone	decreases reaction, increases activity, increases reaction, decreases activity, decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652398	Binding	Binding affinity to human SDC1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

5 cell lines: 3 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9RC	Ubigene HEK293 SDC1 KO	Transformed cell line	Female
CVCL_RY72	293_hSyn1	Transformed cell line	Female
CVCL_TK24	HAP1 SDC1 (-) 1	Cancer cell line	Male
CVCL_UE21	293T human CD138	Transformed cell line	Female
CVCL_XS51	HAP1 SDC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea