DCN

Summary

DCN (decorin, HGNC:2705) is a protein-coding gene on chromosome 12q21.33, encoding Decorin (P07585). May affect the rate of fibrils formation.

This gene encodes a member of the small leucine-rich proteoglycan family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. This protein plays a role in collagen fibril assembly. Binding of this protein to multiple cell surface receptors mediates its role in tumor suppression, including a stimulatory effect on autophagy and inflammation and an inhibitory effect on angiogenesis and tumorigenesis. This gene and the related gene biglycan are thought to be the result of a gene duplication. Mutations in this gene are associated with congenital stromal corneal dystrophy in human patients.

Source: NCBI Gene 1634 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital stromal corneal dystrophy (Definitive, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 102 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_001920

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2705
Approved symbol	DCN
Name	decorin
Location	12q21.33
Locus type	gene with protein product
Status	Approved
Aliases	DSPG2, SLRR1B
Ensembl gene	ENSG00000011465
Ensembl biotype	protein_coding
OMIM	125255
Entrez	1634

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 33 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000052754, ENST00000393155, ENST00000420120, ENST00000425043, ENST00000441303, ENST00000456569, ENST00000546370, ENST00000546391, ENST00000546745, ENST00000547568, ENST00000547937, ENST00000548218, ENST00000548768, ENST00000549513, ENST00000550099, ENST00000550563, ENST00000550758, ENST00000551354, ENST00000552145, ENST00000552962, ENST00000880701, ENST00000880702, ENST00000880703, ENST00000880704, ENST00000880705, ENST00000880706, ENST00000880707, ENST00000880708, ENST00000880709, ENST00000880710, ENST00000970668, ENST00000970669, ENST00000970670, ENST00000970671, ENST00000970672

RefSeq mRNA: 6 — MANE Select: NM_001920 NM_001920, NM_133503, NM_133504, NM_133505, NM_133506, NM_133507

CCDS: CCDS44951, CCDS9039, CCDS9040, CCDS9041, CCDS9042

Canonical transcript exons

ENST00000052754 — 8 exons

Exon	Start	End
ENSE00000431371	91157075	91157188
ENSE00000752998	91153096	91153189
ENSE00000843482	91151654	91151792
ENSE00000843485	91164605	91164717
ENSE00001151433	91178342	91178585
ENSE00002339799	91182655	91182817
ENSE00002386376	91140484	91146252
ENSE00003789264	91158296	91158509

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 224.2491 / max 8074.4836, expressed in 961 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132582	98.6481	935
132577	70.3534	752
132578	29.6241	709
132576	15.2375	554
132580	5.1058	582
132581	2.3049	459
132571	1.0639	351
132559	0.8837	286
132558	0.4134	170
132573	0.2201	105

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	99.99	gold quality
calcaneal tendon	UBERON:0003701	99.99	gold quality
synovial joint	UBERON:0002217	99.98	gold quality
vena cava	UBERON:0004087	99.98	gold quality
gall bladder	UBERON:0002110	99.93	gold quality
tendon of biceps brachii	UBERON:0008188	99.93	gold quality
skin of hip	UBERON:0001554	99.92	gold quality
pericardium	UBERON:0002407	99.92	gold quality
cauda epididymis	UBERON:0004360	99.92	gold quality
stromal cell of endometrium	CL:0002255	99.91	gold quality
tendon	UBERON:0000043	99.91	gold quality
mucosa of stomach	UBERON:0001199	99.90	gold quality
right coronary artery	UBERON:0001625	99.90	gold quality
left uterine tube	UBERON:0001303	99.87	gold quality
mammary duct	UBERON:0001765	99.87	gold quality
right atrium auricular region	UBERON:0006631	99.86	gold quality
nerve	UBERON:0001021	99.85	gold quality
tibial nerve	UBERON:0001323	99.85	gold quality
right ovary	UBERON:0002118	99.85	gold quality
left ovary	UBERON:0002119	99.85	gold quality
upper leg skin	UBERON:0004262	99.84	gold quality
endocervix	UBERON:0000458	99.83	gold quality
superficial temporal artery	UBERON:0001614	99.83	gold quality
coronary artery	UBERON:0001621	99.83	gold quality
dorsal root ganglion	UBERON:0000044	99.82	gold quality
urethra	UBERON:0000057	99.82	gold quality
left coronary artery	UBERON:0001626	99.82	gold quality
nipple	UBERON:0002030	99.82	gold quality
peritoneum	UBERON:0002358	99.82	gold quality
caput epididymis	UBERON:0004358	99.82	gold quality

Single-cell (SCXA)

Detected in 61 experiment(s), a significant marker in 57.

Experiment	Marker?	Max mean expression
E-HCAD-23	yes	38608.77
E-MTAB-6678	yes	18967.23
E-MTAB-6653	yes	17941.34
E-MTAB-8410	yes	17148.70
E-HCAD-1	yes	16438.01
E-GEOD-130148	yes	15597.07
E-MTAB-8142	yes	15451.93
E-MTAB-6701	yes	15336.58
E-MTAB-8322	yes	14607.25
E-HCAD-15	yes	14056.74
E-HCAD-36	yes	13620.55
E-CURD-126	yes	12075.44
E-CURD-88	yes	11252.13
E-GEOD-84465	yes	11003.22
E-GEOD-75688	yes	10853.74

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
FBN1	Activation

Upstream regulators (CollecTRI, top): AP1, FOSL1, FOXD1, FOXO1, JUN, JUNB, KLF5, NR1H4, SKIL, SLC2A10, SPI1, SPIB, STAT5A, USF1, VDR, ZFPM2, ZHX2

miRNA regulators (miRDB)

132 targeting DCN, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798

Literature-anchored findings (GeneRIF, showing 40)

• decorin can disrupt glucose and TGFbeta/Smad-dependent transcription in mesangial cells through a mechanism that involves an increase in Ca(2+) signalling, the activation of Ca(2+)/calmodulin-dependent protein kinase II and phosphorylation of Smad2 (PMID:11879191)
• has a GAG chain and affinity to collagen (PMID:11979972)
• binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope (PMID:12105206)
• decorin supports adhesion and activation of human platelets (PMID:12176891)
• The 179 allele variant of the Decorin gene is related to a slower progression of diabetic nephropathy in type 1 diabetic patients with albuminuria and receiving antihypertensive therapy (PMID:12187087)
• the glycosaminoglycan chains in decorin are chondroitin, chondroitin 4-sulfate or chondroitin 6-sulfate (PMID:12372409)
• carbohydrate recognition domains of SP-D interact with the dermatan sulfate moiety of decorin via lectin activity and the core protein of decorin binds the collagen-like region of SP-D (PMID:12730206)
• might play a pivotal role in tissue remodeling by acting on the balance between extracellular matrix synthesis and degradation (PMID:12853035)
• Decorin expressed in oral cancer may have lost its ability to inhibit TGF-beta signaling and activate epidermal growth factor receptor signaling pathways because of aberrant nuclear localization. (PMID:14633702)
• decorin is a monomer in solution and is a monovalent ligand for various extracellular matrix proteins, growth factors, and cell surface receptors (PMID:14660661)
• Continuous infusion of recombinant human decorin into acute stab injuries of adult rat spinal cord results in major reduction in astrogliosis, macrophage accumulation and deposition of chondroitin sulfate proteoglycans within spinal cord scar tissue. (PMID:15016081)
• IL-10 and IL-6 induce decorin mRNA transcription, but additional signals from the extracellular matrix are necessary for its translation. (PMID:15016829)
• Clones derived from a fibrotic patient secreted 3-fold greater amounts of decorin than those from a control subject; furthermore, there was a negative correlation between proliferation and synthesis of decorin (PMID:15147736)
• decorin secreted by MRC-5 cells is a dermatan sulfate proteoglycan; glycosaminoglycans from the purified protein were treated with chondroitinases and the resulting disaccharides were analyzed (PMID:15147741)
• dynamically increased expression of decorin in the choriodecidual membrane during parturition may be a part of the uterine preparation for labor (PMID:15209389)
• decorin not only can regulate collagen fibril formation but that it also can act as an intermediary between type I and type VI collagen (PMID:15291816)
• Malignant cells can actively influence the composition of the extracellular matrix through TGFbeta1 and other soluble factors. (PMID:15336555)
• investigates the complex composed of one decorin core protein and one collagen molecule in order to obtain their binding force and binding stiffness (PMID:15652541)
• Subsequent sequencing of candidate genes revealed a frameshift mutation in the DCN gene (c.967delT) that encodes for decorin, predicting a C-terminal truncation of the decorin protein (PMID:15671264)
• 505 transcripts are differentially expressed in the thyroid carcinoma cell lines. (PMID:15785240)
• a novel collagen binding domain in decorin acts cooperatively with leucine-rich repeat 4 to mask the alpha2beta1 integrin-binding site on collagen, an important sequence for the phagocytosis of collagen fibrils (PMID:15811857)
• decorin peptides from the leucine-rich repeat 5 region inhibit angiogenesis (PMID:15923192)
• decorin is not required for cell survival (PMID:15949467)
• Decorin causes EGFR internalization via caveolae (PMID:15994311)
• decorin secretion regulation has several components, including appropriate substitution with N-linked oligosaccharides and factors involved in glycosaminoglycan synthesis (PMID:16258169)
• beta ig-h3 can differentially modulate the aggregation of collagen VI with biglycan and decorin (PMID:16434404)
• decorin is a potent trophic factor that protects neuronal progenitor cells and glioma cells from oxygen and glucose deprivation (PMID:16467781)
• reduced galactosyltransferase I(beta4GalT-7)activity resulting in defective glycosylation of decorin and biglycan may be responsible for the complex molecular pathology in beta4GalT-7 deficient Ehlers-Danlos syndrome patients (PMID:16583246)
• Data show that decorin protein core inhibits tumor xenograft growth and metabolism by hindering epidermal growth factor receptor function and triggering apoptosis via caspase-3 activation. (PMID:16835231)
• hevin can modulate the structure of dermal extracellular matrix, specifically by its regulation of decorin levels and collagen fibril assembly (PMID:16844696)
• This is the second family with congenital stromal corneal dystrophy of the cornea in which a frame shift mutation in the decorin gene has been detected. (PMID:16935612)
• Decorin mRNA was expressed in patients with early B-cell CLL, low expression was found in advanced clinical stages a significant higher expression in patients with non-progressive CLL type. (PMID:16938379)
• decorin and biglycan are increased in DMD skeletal muscle and may have a role in muscle response to dystrophic cell damage (PMID:16989735)
• data demonstrate that decorin can regulate fibrin organization and reveal a novel mechanism by which extracellular matrix components can participate in hemostasis, thrombosis, and wound repair (PMID:17046817)
• The purified recombinant human decorin (rhDecorin) significantly inhibited the proliferation of LX-2 cells, a human HSC cell line, stimulated by TGF-beta1. (PMID:17067743)
• decorin in the umbilical cord vein wall is elevated in pre-eclampsia in comparison to the corresponding control vessels (PMID:17097211)
• Altered expression of decorin mRNA in the different dermal strata and a decrease in the collagen-to-decorin ratio inflicted by both age and ultraviolet irradiation affect collagen bundle diameter and subsequently the mechanical properties of human skin. (PMID:17146610)
• Decorin may play an important role in cases of vulvar lichen sclerosus (PMID:17286067)
• decorin is taken up by more than one endocytic pathway; uptake depends on EGFR signaling rather than trafficking along the same pathway (PMID:17335953)
• The results suggest that a high level of decorin mRNA might be associated with the reduced content of collagen type III, resulting in a less flexible form of extracellular matrix in the connective tissue in stress urinary incontinence and prolapse. (PMID:17396208)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcn	ENSDARG00000012066
mus_musculus	Dcn	ENSMUSG00000019929
rattus_norvegicus	Dcn	ENSRNOG00000004554

Paralogs (22): RTN4R (ENSG00000040608), ASPN (ENSG00000106819), FLRT3 (ENSG00000125848), FLRT1 (ENSG00000126500), LRRC4 (ENSG00000128594), LRRC4B (ENSG00000131409), PODNL1 (ENSG00000132000), LRTM1 (ENSG00000144771), LRRC4C (ENSG00000148948), LRRTM1 (ENSG00000162951), LRRC15 (ENSG00000172061), PODN (ENSG00000174348), LRRTM4 (ENSG00000176204), BGN (ENSG00000182492), LRRC19 (ENSG00000184434), FLRT2 (ENSG00000185070), GP1BA (ENSG00000185245), RTN4RL1 (ENSG00000185924), RTN4RL2 (ENSG00000186907), NYX (ENSG00000188937), LRRC66 (ENSG00000188993), LRRTM3 (ENSG00000198739)

Protein

Protein identifiers

Decorin — P07585 (reviewed: P07585)

Alternative names: Bone proteoglycan II, PG-S2, PG40

All UniProt accessions (13): P07585, A0A7I2PRI8, F8VNV6, F8VNW0, F8VSI3, F8VU58, F8VUF6, F8VWU0, F8VX58, F8VXZ8, H0YI87, H0YIH3, Q6FH10

UniProt curated annotations — full annotation on UniProt →

Function. May affect the rate of fibrils formation.

Subunit / interactions. Binds to type I and type II collagen, fibronectin and TGF-beta. Forms a ternary complex with MFAP2 and ELN. Interacts with DPT.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Detected in placenta (at protein level). Detected in cerebrospinal fluid, fibroblasts and urine (at protein level).

Post-translational modifications. The attached glycosaminoglycan chain can be either chondroitin sulfate or dermatan sulfate depending upon the tissue of origin.

Disease relevance. Corneal dystrophy, congenital stromal (CSCD) [MIM:610048] A corneal dystrophy characterized by congenital corneal opacification consisting of a large number of flakes and spots throughout all layers of the stroma. It results in progressive, painless visual loss. Corneal erosions and photophobia are absent. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.

Isoforms (5)

UniProt ID	Names	Canonical?
P07585-1	A	yes
P07585-2	B
P07585-3	C
P07585-4	D
P07585-5	E

RefSeq proteins (6): NP_001911, NP_598010, NP_598011, NP_598012, NP_598013, NP_598014 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR016352	SLRP_I_decor/aspor/byglycan	Family
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050333	SLRP	Family

Pfam: PF01462, PF13855

UniProt features (31 total): repeat 12, splice variant 5, glycosylation site 4, disulfide bond 3, sequence variant 2, sequence conflict 2, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07585-F1	88.60	0.84

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 (3): 54–60, 58–67, 313–346

Glycosylation sites (4): 34, 211, 262, 303

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022870	CS-GAG biosynthesis
R-HSA-2022923	DS-GAG biosynthesis
R-HSA-2024101	CS/DS degradation
R-HSA-3000178	ECM proteoglycans
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3595172	Defective CHST3 causes SEDCJD
R-HSA-3595174	Defective CHST14 causes EDS, musculocontractural type
R-HSA-3595177	Defective CHSY1 causes TPBS
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1

MSigDB gene sets: 365 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_POSITIVE_REGULATION_OF_MITOCHONDRIAL_FISSION, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, GOBP_REGULATION_OF_MEMBRANE_DEPOLARIZATION, GOBP_POSITIVE_REGULATION_OF_MEMBRANE_DEPOLARIZATION, AMIT_SERUM_RESPONSE_40_MCF10A, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GGGTGGRR_PAX4_03, CEBPB_01, GOBP_MACROAUTOPHAGY, CAIRO_HEPATOBLASTOMA_CLASSES_DN

GO Biological Process (10): animal organ morphogenesis (GO:0009887), positive regulation of autophagy (GO:0010508), negative regulation of endothelial cell migration (GO:0010596), positive regulation of macroautophagy (GO:0016239), negative regulation of angiogenesis (GO:0016525), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of mitochondrial depolarization (GO:0051901), positive regulation of mitochondrial fission (GO:0090141), negative regulation of vascular endothelial growth factor signaling pathway (GO:1900747)

GO Molecular Function (5): RNA binding (GO:0003723), glycosaminoglycan binding (GO:0005539), extracellular matrix structural constituent conferring compression resistance (GO:0030021), extracellular matrix binding (GO:0050840), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), extracellular matrix (GO:0031012), lysosomal lumen (GO:0043202)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	6
Chondroitin sulfate/dermatan sulfate metabolism	3
Extracellular matrix organization	2
Glycosaminoglycan metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
anatomical structure morphogenesis	1
animal organ development	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
positive regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
mitochondrial depolarization	1
regulation of mitochondrial depolarization	1
positive regulation of membrane depolarization	1
mitochondrial fission	1
positive regulation of organelle organization	1
positive regulation of developmental process	1
regulation of mitochondrial fission	1
negative regulation of signal transduction	1
vascular endothelial growth factor signaling pathway	1
regulation of vascular endothelial growth factor signaling pathway	1
negative regulation of cellular response to vascular endothelial growth factor stimulus	1
nucleic acid binding	1
carbohydrate derivative binding	1
extracellular matrix structural constituent	1
cellular anatomical structure	1
Golgi apparatus	1
intracellular organelle lumen	1
external encapsulating structure	1
lysosome	1

Protein interactions and networks

STRING

3040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCN	FN1	P02751	995
DCN	TGFB1	P01137	993
DCN	YBX3	P16989	991
DCN	ELN	P15502	990
DCN	YBX1	P16990	989
DCN	EGFR	P00533	986
DCN	BGN	P13247	976
DCN	HSPG2	P98160	972
DCN	VCAN	P13611	966
DCN	P3H3	Q8IVL6	964
DCN	ACAN	P16112	962
DCN	MFAP2	P55001	953
DCN	VTN	P01141	945
DCN	FGF7	P21781	942
DCN	FGF10	O15520	940

IntAct

33 interactions, top by confidence:

A	B	Type	Score
FAM20B	DCN	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
DCN	FAM20B	psi-mi:“MI:0217”(phosphorylation reaction)	0.620
DCN	FN1	psi-mi:“MI:0407”(direct interaction)	0.600
FN1	DCN	psi-mi:“MI:0407”(direct interaction)	0.600
FN1	DCN	psi-mi:“MI:0914”(association)	0.600
BMP1	DCN	psi-mi:“MI:0570”(protein cleavage)	0.560
DCN	KLHL17	psi-mi:“MI:0914”(association)	0.530
DCN	BMP1	psi-mi:“MI:0570”(protein cleavage)	0.440
DCN	Bmp1	psi-mi:“MI:0570”(protein cleavage)	0.440
APP	DCN	psi-mi:“MI:0407”(direct interaction)	0.440
DCN	INSR	psi-mi:“MI:0407”(direct interaction)	0.440
DCN	IGF2	psi-mi:“MI:0407”(direct interaction)	0.440
DCN	INS	psi-mi:“MI:0407”(direct interaction)	0.440
INS	DCN	psi-mi:“MI:0407”(direct interaction)	0.440
Fgf1	DCN	psi-mi:“MI:0407”(direct interaction)	0.440
Fgf7	DCN	psi-mi:“MI:0407”(direct interaction)	0.440
Fgf8	DCN	psi-mi:“MI:0407”(direct interaction)	0.440
FGF2	DCN	psi-mi:“MI:0407”(direct interaction)	0.440
DCN	CNPY3	psi-mi:“MI:0915”(physical association)	0.400
PPP1CA	ACO2	psi-mi:“MI:0914”(association)	0.350
DCN	ITIH2	psi-mi:“MI:0914”(association)	0.350

BioGRID (36): CHSY1 (Affinity Capture-MS), KLHL17 (Affinity Capture-MS), ZBTB33 (Affinity Capture-MS), LONP2 (Affinity Capture-MS), PLAT (Affinity Capture-MS), CHSY1 (Affinity Capture-MS), KLHL17 (Affinity Capture-MS), DCN (Reconstituted Complex), DCN (Affinity Capture-MS), DCN (Reconstituted Complex), FLNA (Reconstituted Complex), DCN (Reconstituted Complex), DCN (Reconstituted Complex), DCN (Reconstituted Complex), DCN (Reconstituted Complex)

ESM2 similar proteins: O02678, O15335, O35367, O42235, O46390, O46403, O46542, O55226, O60938, O62702, O70210, O75094, O94813, P07585, P19879, P20774, P21793, P21809, P21810, P28653, P28654, P28675, P47853, P51887, P51888, P82963, Q01129, Q27972, Q28888, Q29393, Q3ZBN5, Q5R1V9, Q5RBL2, Q5RI43, Q8MJF1, Q99MQ4, Q9BXN1, Q9DE65, Q9DE66, Q9DE68

Diamond homologs: A3KNN3, A6H789, A6H793, A6NJW4, A8WHP9, E7FE13, F1MLX5, G5EFX6, O02678, O02833, O35367, O46378, O46379, O46542, O60938, O62702, O75093, O75094, O88279, O88280, O94813, P07359, P07585, P21793, P24014, P28654, P28675, P35858, P35859, P51884, P51885, P51886, P51888, P51890, P58874, P59034, P59035, P70186, P70389, P83286

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
DCN	“up-regulates quantity by expression”	FBN1	“transcriptional regulation”
MMP2	“down-regulates quantity by destabilization”	DCN	cleavage
MMP7	“down-regulates quantity by destabilization”	DCN	cleavage
MMP3	“down-regulates quantity by destabilization”	DCN	cleavage

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	26.1×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	66
Likely benign	8
Benign	15

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
126374	NM_001920.5(DCN):c.962del (p.Lys321fs)	Pathogenic
16870	NM_001920.5(DCN):c.967del (p.Ser323fs)	Pathogenic
21302	NM_001920.5(DCN):c.941del (p.Pro314fs)	Pathogenic
65663	NM_001920.5(DCN):c.947del (p.Gly316fs)	Pathogenic
4814126	NM_001920.5(DCN):c.793del (p.Leu265fs)	Likely pathogenic

SpliceAI

1291 predictions. Top by Δscore:

Variant	Effect	Δscore
12:91146060:A:AC	donor_gain	1.0000
12:91146061:C:CC	donor_gain	1.0000
12:91146064:A:AC	donor_gain	1.0000
12:91146065:T:C	donor_gain	1.0000
12:91151652:A:C	donor_loss	1.0000
12:91151653:CCT:C	donor_loss	1.0000
12:91153094:A:AC	donor_gain	1.0000
12:91153095:C:CC	donor_gain	1.0000
12:91153098:A:AC	donor_gain	1.0000
12:91153098:AGC:A	donor_gain	1.0000
12:91153099:G:C	donor_gain	1.0000
12:91153113:T:TA	donor_gain	1.0000
12:91158290:CTGTA:C	donor_loss	1.0000
12:91158291:TGTAC:T	donor_loss	1.0000
12:91158293:TA:T	donor_loss	1.0000
12:91158294:A:C	donor_loss	1.0000
12:91161108:AACAT:A	donor_gain	1.0000
12:91161109:A:C	donor_gain	1.0000
12:91164600:CTTAC:C	donor_loss	1.0000
12:91164602:T:TG	donor_loss	1.0000
12:91164603:A:AC	donor_gain	1.0000
12:91164603:ACGTG:A	donor_loss	1.0000
12:91164604:C:CC	donor_gain	1.0000
12:91178338:TCAC:T	donor_loss	1.0000
12:91178339:CACC:C	donor_loss	1.0000
12:91178340:AC:A	donor_gain	1.0000
12:91178340:ACCCA:A	donor_loss	1.0000
12:91178341:C:CA	donor_loss	1.0000
12:91178341:CC:C	donor_gain	1.0000
12:91146249:CAAC:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000032750 (12:91147392 A>C,G), RS1000101216 (12:91148983 G>A,C), RS1000160519 (12:91175358 G>A,T), RS1000215073 (12:91173328 G>T), RS1000231170 (12:91167052 T>C), RS1000246655 (12:91155999 C>G), RS1000262227 (12:91166783 A>C,G), RS1000325515 (12:91167372 G>C), RS1000326409 (12:91168824 G>T), RS1000493817 (12:91173779 T>C), RS1000555500 (12:91165727 A>G), RS1000667547 (12:91158966 A>T), RS1000677112 (12:91169031 C>A), RS1000691436 (12:91165947 A>G), RS1000712331 (12:91173484 G>C)

Disease associations

OMIM: gene MIM:125255 | disease phenotypes: MIM:610048

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital stromal corneal dystrophy	Definitive	Autosomal dominant

Mondo (1): congenital stromal corneal dystrophy (MONDO:0012401)

Orphanet (1): Congenital stromal corneal dystrophy (Orphanet:101068)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000529	Progressive visual loss
HP:0000613	Photophobia
HP:0001131	Corneal dystrophy
HP:0003623	Neonatal onset
HP:0007709	Band-shaped corneal dystrophy
HP:0011487	Increased corneal thickness
HP:0200020	Corneal erosion

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001104_1	Sudden cardiac arrest	5.000000e-06
GCST005580_290	Intraocular pressure	2.000000e-09
GCST005667_2	Central corneal thickness	1.000000e-10
GCST006585_2493	Blood protein levels	3.000000e-07
GCST006979_1074	Heel bone mineral density	3.000000e-09
GCST010002_219	Refractive error	4.000000e-09
GCST90000654_74	Central corneal thickness	4.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004278	sudden cardiac arrest
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0009270	heel bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566452	Corneal Dystrophy, Congenital Stromal (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	4
Tetrachlorodibenzodioxin	decreases expression, decreases reaction, affects expression, increases expression	4
bisphenol A	decreases methylation, increases methylation, affects cotreatment, increases expression, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Valproic Acid	decreases expression, affects cotreatment, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Arsenic Trioxide	affects cotreatment, decreases expression	2
Calcitriol	decreases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Doxorubicin	decreases response to substance, affects expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
tungsten carbide	affects binding, decreases expression	1
2,4,6-tribromophenol	increases expression	1
methylmercuric chloride	decreases expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
salinomycin	decreases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
decabromobiphenyl ether	increases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
cupric chloride	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
acyline	decreases expression	1
entinostat	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0BI	Ubigene HeLa DCN KO	Cancer cell line	Female

Clinical trials (associated diseases)

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