SDC2

Summary

SDC2 (syndecan 2, HGNC:10659) is a protein-coding gene on chromosome 8q22.1, encoding Syndecan-2 (P34741). Cell surface proteoglycan which regulates dendritic arbor morphogenesis.

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-2 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-2 expression has been detected in several different tumor types.

Source: NCBI Gene 6383 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10659
Approved symbol	SDC2
Name	syndecan 2
Location	8q22.1
Locus type	gene with protein product
Status	Approved
Aliases	fibroglycan, SYND2, CD362
Ensembl gene	ENSG00000169439
Ensembl biotype	protein_coding
OMIM	142460
Entrez	6383

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000302190, ENST00000518385, ENST00000519587, ENST00000519914, ENST00000520233, ENST00000521590, ENST00000522911, ENST00000523877, ENST00000862192, ENST00000862193, ENST00000932834

RefSeq mRNA: 1 — MANE Select: NM_002998 NM_002998

CCDS: CCDS6272

Canonical transcript exons

ENST00000302190 — 5 exons

Exon	Start	End
ENSE00001154724	96608335	96608470
ENSE00001154730	96602395	96602528
ENSE00001156732	96609385	96611790
ENSE00002108661	96493813	96494331
ENSE00003635882	96593480	96593591

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.3369 / max 1236.1429, expressed in 1563 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89838	36.0728	1539
89836	6.5781	1179
89837	2.3602	997
89844	0.1658	83
89845	0.1600	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.63	gold quality
calcaneal tendon	UBERON:0003701	99.40	gold quality
synovial joint	UBERON:0002217	99.25	gold quality
pigmented layer of retina	UBERON:0001782	98.86	gold quality
retina	UBERON:0000966	98.83	gold quality
left lobe of thyroid gland	UBERON:0001120	98.74	gold quality
thyroid gland	UBERON:0002046	98.74	gold quality
right coronary artery	UBERON:0001625	98.64	gold quality
right lobe of thyroid gland	UBERON:0001119	98.58	gold quality
popliteal artery	UBERON:0002250	98.52	gold quality
tibial artery	UBERON:0007610	98.51	gold quality
artery	UBERON:0001637	98.40	gold quality
descending thoracic aorta	UBERON:0002345	98.34	gold quality
saphenous vein	UBERON:0007318	98.32	gold quality
aorta	UBERON:0000947	98.31	gold quality
thoracic aorta	UBERON:0001515	98.05	gold quality
left ovary	UBERON:0002119	98.05	gold quality
ascending aorta	UBERON:0001496	98.02	gold quality
blood vessel layer	UBERON:0004797	98.01	gold quality
vena cava	UBERON:0004087	97.95	gold quality
stromal cell of endometrium	CL:0002255	97.91	gold quality
periodontal ligament	UBERON:0008266	97.88	gold quality
right ovary	UBERON:0002118	97.85	gold quality
liver	UBERON:0002107	97.78	gold quality
left coronary artery	UBERON:0001626	97.69	gold quality
coronary artery	UBERON:0001621	97.65	gold quality
tendon	UBERON:0000043	97.63	gold quality
decidua	UBERON:0002450	97.63	gold quality
ovary	UBERON:0000992	97.61	gold quality
mucosa of stomach	UBERON:0001199	97.59	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	883.02
E-GEOD-81383	yes	486.31
E-MTAB-10018	yes	150.10
E-MTAB-6701	yes	114.99
E-MTAB-8410	yes	63.63
E-HCAD-10	yes	56.46
E-GEOD-135922	yes	50.35
E-HCAD-11	yes	47.12
E-MTAB-8142	yes	34.84
E-HCAD-1	yes	33.93
E-MTAB-5061	yes	25.51
E-MTAB-10287	yes	18.87
E-CURD-112	yes	16.66
E-GEOD-81608	yes	13.97
E-GEOD-93593	yes	13.82

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOXO3, HNF4A, RUNX2

miRNA regulators (miRDB)

256 targeting SDC2, 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-9-5P	100.00	72.28	2361
HSA-MIR-98-3P	100.00	74.08	3907
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-4776-3P	100.00	68.73	1340
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588

Literature-anchored findings (GeneRIF, showing 40)

• Identification of integrin alpha(M)beta(2) as an adhesion receptor on human peripheral blood monocytes for Cyr61 and connective tissue growth factor: immediate-early gene products expressed in atherosclerotic lesions.(integrin alpha(M)beta(2)) (PMID:12036876)
• role in mediating adhesion and proliferation of colon carcinoma cells (PMID:12055189)
• Ezrin N-terminal domain binds to the syndecan-2 cytoplasmic domain with an estimated K(D) of 0.71 microM and without the requirement of other proteins (PMID:12860416)
• Mechanisms for the regulation of HSPG have been studied. (PMID:12860968)
• Interleukin-8 binds to syndecan-2 on vascular endothelial cells. (PMID:14527339)
• the HSPG T allele is a risk factor for the development of severe diabetic nephropathy in type 2 diabetic patients (PMID:14674716)
• Syndecan-2 induces osteoblastic cell apoptosis through the JNK/Bax apoptotic pathway and the cytoplasmic domain of syndecan-2 is required for this action. (PMID:15936998)
• the transmembrane domains are sufficient for inducing dimerization and transmembrane domain-induced oligomerization is crucial for syndecan-2 and syndecan-4 functions (PMID:16253987)
• PKCdelta acts as a pro-survival kinase and that SYND2 inhibits the anti-apoptotic action of PKCdelta in osteoblast. (PMID:16440330)
• molecular complex most likely to obstruct RACK1 for functional attachment at syndecan-2, as revealed in cells transfected with oncogenic ras (PMID:16997272)
• HSPGs are expressed on the membrane of myeloid leukemic cell lineages. (PMID:17035092)
• heparanase-1 expression and heparan sulphate proteoglycan degradation are induced by estradiol in human endometrium (PMID:17261577)
• these data suggested that both HSPG and CD81 are important for HCV entry. (PMID:17457918)
• HSPG modulation of BMP signaling in myositis ossificans cells is reported. (PMID:17516498)
• syndecan-2 acts as a suppressor for MMP-2 activation, causing suppression of metastasis (PMID:17623663)
• There are pronounced tubulointerstitial HSPG alterations in primary kidney disease, which may affect the inflammatory response. (PMID:18032547)
• syndecan TMD homodimerization and heterodimerization can be mediated by GxxxG motifs and modulated by sequence context (PMID:18093920)
• This study provides evidence for the up-regulation of syndecan-2 and -4 in human primary CD4 T cells during in vitro activation and suggest an inhibitory role for these syndecans in CD4 T cells. (PMID:18342939)
• pleiotrophin (PTN) and syndecan-2 and -3 as direct binding partners of Y-P30. (PMID:18599487)
• A pivotal role of this heparan sulphate proteoglycan in the formation of new blood vessels. (PMID:19073173)
• HSPGs and HSPG-dependent signaling are affected in both central and peripheral chondrosarcomas. (PMID:19179614)
• SDC2 and CYR61 expression affect the severity of cancer, and the survival of patients with esophageal squamous cell carcinoma (ESCC). (PMID:19288017)
• estradiol affects the expression of syndecan-2, but not of syndecan-4, through ERalpha (PMID:19383343)
• changes in the pattern expression of syndecan-1 and -2 indicate that both molecules may be involved in the epithelial-mesenchymal transition (EMT) and tumor progression of prostate cancer. (PMID:19450993)
• Syndecan-2 plays a crucial role in the migratory potential of melanoma cells. (PMID:19641225)
• Study results supported the potential role of SDC2 in prostatic carcinogenesis and cancer progression. (PMID:19786981)
• Data report that the bFGF, FGFR1/2 and syndecan 1-4 expressions are altered in bladder tumours. (PMID:19822079)
• these results suggest that syndecan-2 regulates cell migration of colon carcinoma cells through Tiam1-dependent Rac activation in colon cancer cells. (PMID:19962968)
• syndecan’s interactions with both CASK and neurofibromin are dependent on syndecan homodimerization. (PMID:20006588)
• Results support a potential role for syndecan-2 in pancreatic carcinogenesis and cancer progression. Expression of syndecan-2 might serve as a prognostic marker. (PMID:20683009)
• RGD-independent cell adhesion via a tissue transglutaminase 2-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 and {alpha}5{beta}1 integrin co-signaling. (PMID:20929862)
• syndecan-2 and syndecan-4 regulate the compensatory effect of TG-FN on osteoblast cell adhesion and actin cytoskeletal formation in the presence of RGD peptides. (PMID:21036168)
• These results demonstrate that syndecan-1 and syndecan-2 gene silencing by RNA interference reduces HSV-1 entry, plaque formation and facilitates cell survival. (PMID:21148276)
• The findings demonstrate that LRP1 and HSPG function in a cooperative manner to mediate cellular Abeta uptake and define a major pathway through which Abeta gains entry to neuronal cells. (PMID:21289173)
• syndecan-2 was expressed preferentially in basal cells in benign tissue. In prostate cancer samples, syndecan 2 was expressed in granular-cytoplasmic localisation. (PMID:21317913)
• HIV-1 p17 matrix protein interacts with heparan sulfate side chain of CD44v3, syndecan-2, and syndecan-4 proteoglycans expressed on human activated CD4+ T cells affecting tumor necrosis factor alpha and interleukin 2 production. (PMID:21482826)
• the cytoplasmic domain of syndecan-2 regulates colon cancer cell migration via interaction with syntenin-1. (PMID:21569759)
• Here the protein tyrosine phosphatase receptor CD148 is shown to be a key intermediary in cell adhesion to syndecan-2 extracellular domain, with downstream beta1 integrin-mediated adhesion and cytoskeletal organization. (PMID:21813734)
• a specific glycochain is a receptor for dengue virus strain DEN2 16681 (PMID:22170634)
• the data suggest that MMP-7 directly mediates shedding of syndecan-2 from colon cancer cells. (PMID:22227189)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sdc2	ENSDARG00000002731
mus_musculus	Sdc2	ENSMUSG00000022261
rattus_norvegicus	Sdc2	ENSRNOG00000004936
drosophila_melanogaster	Sdc	FBGN0010415
caenorhabditis_elegans		WBGENE00004749

Paralogs (3): SDC1 (ENSG00000115884), SDC4 (ENSG00000124145), SDC3 (ENSG00000162512)

Protein

Protein identifiers

Syndecan-2 — P34741 (reviewed: P34741)

Alternative names: Fibroglycan, Heparan sulfate proteoglycan core protein

All UniProt accessions (5): E5RHU3, E5RJB8, E7ESK6, E9PBI9, P34741

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface proteoglycan which regulates dendritic arbor morphogenesis.

Subunit / interactions. Interacts (via cytoplasmic domain) with SARM1. Forms a complex with SDCBP and PDCD6IP.

Subcellular location. Membrane.

Post-translational modifications. O-glycosylated with core 1 or possibly core 8 glycans. Contains heparan sulfate. Also contains chondroitin sulfate.

Similarity. Belongs to the syndecan proteoglycan family.

RefSeq proteins (1): NP_002989* (*=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 (21 total): glycosylation site 4, region of interest 3, modified residue 2, sequence variant 2, topological domain 2, compositionally biased region 2, signal peptide 1, chain 1, site 1, sequence conflict 1, helix 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6ITH	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P34741-F1	60.79	0.08

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): 142–143 (cleavage of ectodomain)

Post-translational modifications (2): 115, 187

Glycosylation sites (4): 41, 55, 57, 101

Function

Pathways and Gene Ontology

Reactome pathways

49 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-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-8957275	Post-translational protein phosphorylation
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-1266738	Developmental Biology
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-1793185	Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 379 (showing top): PID_SHP2_PATHWAY, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_DENDRITE_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, TSENG_IRS1_TARGETS_UP, TTTGTAG_MIR520D, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, CLASPER_LYMPHATIC_VESSELS_DURING_METASTASIS_DN, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_DN, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, BROWNE_HCMV_INFECTION_48HR_DN, AGTCTTA_MIR499

GO Biological Process (5): cell migration (GO:0016477), dendrite morphogenesis (GO:0048813), regulation of dendrite morphogenesis (GO:0048814), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (3): PDZ domain binding (GO:0030165), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): endoplasmic reticulum lumen (GO:0005788), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular matrix (GO:0031012), lysosomal lumen (GO:0043202), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-14 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
Glycosaminoglycan metabolism	1
Hemostasis	1
Non-integrin membrane-ECM interactions	1
Metabolism of proteins	1
EPH-Ephrin signaling	1
Post-translational protein modification	1
Early SARS-CoV-2 Infection Events	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular organelle lumen	2
cellular anatomical structure	2
cell motility	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
regulation of anatomical structure morphogenesis	1
dendrite morphogenesis	1
regulation of dendrite development	1
system development	1
cellular developmental process	1
protein domain specific binding	1
protein binding	1
binding	1
endoplasmic reticulum	1
Golgi apparatus	1
membrane	1
cell periphery	1
external encapsulating structure	1
lysosome	1
vacuolar lumen	1

Protein interactions and networks

STRING

1282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDC2	TRAPPC4	Q9Y296	912
SDC2	GPC1	P35052	875
SDC2	SDCBP	O00560	843
SDC2	CASK	O14936	789
SDC2	PTPRJ	Q12913	789
SDC2	EZR	P15311	722
SDC2	HSPG2	P98160	667
SDC2	CD44	P16070	648
SDC2	GPC3	P51654	632
SDC2	SFRP2	Q96HF1	630
SDC2	GPC4	O75487	622
SDC2	GPC2	Q8N158	601
SDC2	GRPR	P30550	593
SDC2	PRIMA1	Q86XR5	552
SDC2	GPC6	Q9Y625	550

IntAct

245 interactions, top by confidence:

A	B	Type	Score
SDC4	SDC2	psi-mi:“MI:0407”(direct interaction)	0.690
SDC2	SDC4	psi-mi:“MI:0407”(direct interaction)	0.690
CASK	SDC2	psi-mi:“MI:0915”(physical association)	0.670
CASK	SDC2	psi-mi:“MI:0407”(direct interaction)	0.670
SDC2	SDC2	psi-mi:“MI:0407”(direct interaction)	0.660
SDC2	SDC2	psi-mi:“MI:0915”(physical association)	0.660
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
SDC2	PDPK1	psi-mi:“MI:0914”(association)	0.640
AMPD2	SDC2	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
SDC2	ASPH	psi-mi:“MI:0915”(physical association)	0.560
SDC2	DMWD	psi-mi:“MI:0915”(physical association)	0.560
GPR37	SDC2	psi-mi:“MI:0915”(physical association)	0.560
SDC2	GRN	psi-mi:“MI:0915”(physical association)	0.560
SDC2	PIK3R1	psi-mi:“MI:0915”(physical association)	0.560
SDC2	NBL1	psi-mi:“MI:0915”(physical association)	0.560
SDC2	TOM1	psi-mi:“MI:0915”(physical association)	0.560
SDC2		psi-mi:“MI:0915”(physical association)	0.560
SYNCRIP	SDC2	psi-mi:“MI:0915”(physical association)	0.560
SDC2	MAPK8IP2	psi-mi:“MI:0915”(physical association)	0.560
SDC2	ESRP1	psi-mi:“MI:0915”(physical association)	0.560
SDC2	WFS1	psi-mi:“MI:0915”(physical association)	0.560
SDC2	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
SDC2	RNF11	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (225): SDC2 (Reconstituted Complex), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Affinity Capture-MS), SDC2 (Two-hybrid), DHRS2 (Affinity Capture-MS)

ESM2 similar proteins: A1A4K1, B1H3G4, E9PV24, O35988, O61704, O75167, O93383, P14209, P14599, P15514, P24338, P31431, P31955, P34741, P34900, P34901, P43322, P43407, P49414, P49416, P50605, P55808, P58239, Q02297, Q0VFF9, Q1RMT9, Q27913, Q56A20, Q58DD4, Q5RAT9, Q5RCS3, Q5RE35, Q5REP3, Q5XG99, Q6DBW9, Q6GR51, Q6PKG0, Q6ZQ58, Q7SXB3, Q7TMJ8

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

6 interactions.

A	Effect	B	Mechanism
PRKCA	unknown	SDC2	phosphorylation
PRKCB	unknown	SDC2	phosphorylation
PRKCG	unknown	SDC2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 147 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
Attachment and Entry	7	41.7×	1e-07
Defective B4GALT7 causes EDS, progeroid type	6	33.9×	1e-06
Defective B3GAT3 causes JDSSDHD	6	33.9×	1e-06
Defective B3GALT6 causes EDSP2 and SEMDJL1	6	33.9×	1e-06
Trafficking of GluR2-containing AMPA receptors	5	33.3×	1e-05
HS-GAG degradation	6	29.5×	2e-06
Respiratory syncytial virus (RSV) attachment and entry	6	29.5×	2e-06
Initiation of coagulation cascade	6	28.3×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to synapse	5	28.2×	4e-04
receptor clustering	5	22.9×	8e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	6	21.9×	3e-04
establishment or maintenance of epithelial cell apical/basal polarity	5	21.4×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	27
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
815145	GRCh37/hg19 8q22.1(chr8:96646399-98973327)x3	Likely pathogenic

SpliceAI

1909 predictions. Top by Δscore:

Variant	Effect	Δscore
8:96593475:CTCAG:C	acceptor_gain	1.0000
8:96593476:TCAG:T	acceptor_gain	1.0000
8:96593477:CAG:C	acceptor_gain	1.0000
8:96593478:A:AG	acceptor_gain	1.0000
8:96593478:AGA:A	acceptor_gain	1.0000
8:96593479:G:GG	acceptor_gain	1.0000
8:96593479:GA:G	acceptor_gain	1.0000
8:96593479:GAG:G	acceptor_gain	1.0000
8:96593479:GAGA:G	acceptor_gain	1.0000
8:96593589:CGGGT:C	donor_loss	1.0000
8:96593590:GG:G	donor_gain	1.0000
8:96593591:GG:G	donor_gain	1.0000
8:96593592:G:GG	donor_gain	1.0000
8:96593593:T:A	donor_loss	1.0000
8:96602393:A:AG	acceptor_gain	1.0000
8:96602394:G:GC	acceptor_gain	1.0000
8:96602394:GGA:G	acceptor_gain	1.0000
8:96602526:AAGG:A	donor_loss	1.0000
8:96602529:G:GG	donor_gain	1.0000
8:96608320:T:TA	acceptor_gain	1.0000
8:96608328:A:AG	acceptor_gain	1.0000
8:96608329:T:G	acceptor_gain	1.0000
8:96608330:A:AG	acceptor_gain	1.0000
8:96608331:C:G	acceptor_gain	1.0000
8:96608331:CCAG:C	acceptor_loss	1.0000
8:96608333:A:AG	acceptor_gain	1.0000
8:96608333:A:C	acceptor_loss	1.0000
8:96608334:G:GC	acceptor_gain	1.0000
8:96608334:GT:G	acceptor_gain	1.0000
8:96608334:GTC:G	acceptor_gain	1.0000

AlphaMissense

1296 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:96609409:G:A	G156D	0.999
8:96609537:T:C	F199L	0.999
8:96609539:T:A	F199L	0.999
8:96609539:T:G	F199L	0.999
8:96609394:C:A	A151D	0.998
8:96609397:G:A	G152D	0.998
8:96609399:G:A	G153R	0.998
8:96609399:G:C	G153R	0.998
8:96609408:G:C	G156R	0.998
8:96609421:C:A	A160E	0.998
8:96609461:G:C	K173N	0.998
8:96609461:G:T	K173N	0.998
8:96609538:T:G	F199C	0.998
8:96609400:G:A	G153E	0.997
8:96609471:G:A	G177R	0.997
8:96609471:G:C	G177R	0.997
8:96609474:A:C	S178R	0.997
8:96609476:C:A	S178R	0.997
8:96609476:C:G	S178R	0.997
8:96609477:T:C	Y179H	0.997
8:96609538:T:C	F199S	0.997
8:96609388:T:A	V149D	0.996
8:96609396:G:C	G152R	0.996
8:96609430:T:C	L163P	0.996
8:96609451:G:C	R170P	0.996
8:96609454:T:C	M171T	0.996
8:96609458:A:C	R172S	0.996
8:96609458:A:T	R172S	0.996
8:96609465:G:C	D175H	0.996
8:96609472:G:A	G177E	0.996

dbSNP variants (sampled 300 via entrez): RS1000009555 (8:96550168 T>C), RS1000011844 (8:96566716 T>A), RS1000061744 (8:96603907 A>G,T), RS1000065250 (8:96598023 T>G), RS1000073990 (8:96565988 C>T), RS1000137535 (8:96541032 C>T), RS1000201641 (8:96520647 A>AT), RS1000221132 (8:96598963 A>G), RS1000231868 (8:96560481 T>C), RS1000247081 (8:96507991 G>A,T), RS1000325166 (8:96546904 C>T), RS1000326627 (8:96547647 G>A,C), RS1000402251 (8:96526331 C>G), RS1000426071 (8:96553090 T>C), RS1000442752 (8:96595014 G>A)

Disease associations

OMIM: gene MIM:142460 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002963_8	Post-traumatic stress disorder	6.000000e-06
GCST010002_309	Refractive error	4.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4888448 (PROTEIN COMPLEX), CHEMBL6066914 (SINGLE PROTEIN)

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

ChEMBL bioactivities

13 potent at pChembl≥5 of 34 total, top 13 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.40	IC50	400	nM	CHEMBL5439384
6.09	IC50	820	nM	CHEMBL5414896
5.82	IC50	1500	nM	CHEMBL5400712
5.40	IC50	4000	nM	CHEMBL5421218
5.38	IC50	4200	nM	CHEMBL5417771
5.28	IC50	5200	nM	CHEMBL5409717
5.28	IC50	5300	nM	CHEMBL5407115
5.20	IC50	6300	nM	CHEMBL5440871
5.13	IC50	7400	nM	CHEMBL4849179
5.11	IC50	7700	nM	CHEMBL5431937
5.06	IC50	8800	nM	CHEMBL5400307
5.00	IC50	1e+04	nM	CHEMBL5434947
5.00	IC50	9900	nM	CHEMBL5412078

PubChem BioAssay actives

13 with measured affinity, of 88 total; 13 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
(2S)-2-[[(2S)-3-[4-(5-acetyl-2-fluorophenyl)phenyl]-2-(6-bromo-3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	0.4000	uM
(2S)-2-[[(2S)-3-[4-(4-acetamidophenyl)phenyl]-2-(6-bromo-3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	0.8200	uM
(2S)-2-[[(2S)-2-(6-bromo-3-oxo-1H-isoindol-2-yl)-3-[4-[2-fluoro-5-(hydroxymethyl)phenyl]phenyl]propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	1.5000	uM
(2S)-2-[[(2S)-3-[4-(4-oxochromen-6-yl)phenyl]-2-(3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	4.0000	uM
(2S)-2-[[(2S)-3-[4-(5-acetyl-2-fluorophenyl)phenyl]-2-(3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	4.2000	uM
(2S)-2-[[(2S)-2-(6-bromo-3-oxo-1H-isoindol-2-yl)-3-naphthalen-2-ylpropanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	5.2000	uM
(2S)-2-[[(2S)-3-[4-[2-fluoro-5-(hydroxymethyl)phenyl]phenyl]-2-(3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	5.3000	uM
(2S)-2-[[(2S)-3-[4-(2-methyl-3-oxo-1H-isoindol-5-yl)phenyl]-2-(3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	6.3000	uM
(2S)-3-methyl-2-[3-[4-(4-methylsulfonyloxyphenyl)phenyl]sulfanylpropanoylamino]butanoic acid	1772478: Inhibition of recombinant human full-length GST-tagged syntenin-1/Syndecan-2 complex interaction expressed in Escherichia coli ER2566 measured after 16 hrs by HTRF assay	ic50	7.4000	uM
(2S)-2-[[(2S)-3-[4-(4-acetamidophenyl)phenyl]-2-(3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	7.7000	uM
(2S)-2-[[(2S)-3-[4-(5-cyano-2-fluorophenyl)phenyl]-2-(3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	8.8000	uM
(2S)-2-[[(2S)-3-[4-(2-fluorophenyl)phenyl]-2-(3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	9.9000	uM
(2S)-2-[[(2S)-3-[4-(2-fluoro-5-methoxyphenyl)phenyl]-2-(3-oxo-1H-isoindol-2-yl)propanoyl]amino]propanoic acid	2029350: Inhibition of full length N-terminal GST-tagged human syntenin-1 expressed in Escherichia coli ER2566/syndecan2 (unknown origin) interaction incubated for 16 hrs by HTRF assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects cotreatment, decreases expression, increases expression	5
Arsenic Trioxide	decreases expression	4
Cyclosporine	decreases expression, affects cotreatment	4
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	affects splicing, decreases expression, affects cotreatment, increases abundance, increases expression	3
nickel sulfate	increases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
bisphenol A	affects expression, decreases expression	2
entinostat	affects cotreatment, decreases expression	2
Acetaminophen	affects cotreatment, increases expression, decreases expression	2
Arsenic	decreases ubiquitination, affects cotreatment, decreases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	decreases expression	2
Particulate Matter	increases abundance, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
perfluorotetradecanoic acid	increases expression	1
methylmercuric chloride	increases expression	1
methylselenic acid	increases expression	1
sulforaphane	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
perfluorobutyric acid	decreases expression	1
diallyl trisulfide	decreases expression	1
nefazodone	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
bisphenol B	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4831858	Binding	Inhibition of recombinant human full-length GST-tagged syntenin-1/Syndecan-2 complex interaction expressed in Escherichia coli ER2566 at 400 uM measured after 16 hrs by HTRF assay	Fragment-based drug design targeting syntenin PDZ2 domain involved in exosomal release and tumour spread. — Eur J Med Chem

Cellosaurus cell lines

6 cell lines: 4 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_RY62	293_hEcad/hSyn2	Transformed cell line	Female
CVCL_RY63	293_hSyn2	Transformed cell line	Female
CVCL_TK25	HAP1 SDC2 (-) 1	Cancer cell line	Male
CVCL_TK26	HAP1 SDC2 (-) 2	Cancer cell line	Male
CVCL_TK27	HAP1 SDC2 (-) 3	Cancer cell line	Male
CVCL_TK28	HAP1 SDC2 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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