OPTC

Summary

OPTC (opticin, HGNC:8158) is a protein-coding gene on chromosome 1q32.1, encoding Opticin (Q9UBM4). Inhibits angiogenesis in the vitreous humor of the eye, and therefore represses neovascularization.

Opticin belongs to class III of the small leucine-rich repeat protein (SLRP) family. Members of this family are typically associated with the extracellular matrix. Opticin is present in significant quantities in the vitreous of the eye and also localizes to the cornea, iris, ciliary body, optic nerve, choroid, retina, and fetal liver. Opticin may noncovalently bind collagen fibrils and regulate fibril morphology, spacing, and organization. The opticin gene is mapped to a region of chromosome 1 that is associated with the inherited eye diseases age-related macular degeneration (AMD) and posterior column ataxia with retinosa pigmentosa (AXPC1).

Source: NCBI Gene 26254 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_014359

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8158
Approved symbol	OPTC
Name	opticin
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188770
Ensembl biotype	protein_coding
OMIM	605127
Entrez	26254

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000367222, ENST00000448911, ENST00000715259

RefSeq mRNA: 1 — MANE Select: NM_014359 NM_014359

CCDS: CCDS1439

Canonical transcript exons

ENST00000367222 — 8 exons

Exon	Start	End
ENSE00001372858	203496977	203497115
ENSE00001381292	203494153	203494217
ENSE00001384251	203498681	203498839
ENSE00001614983	203499649	203499851
ENSE00001703497	203495965	203496236
ENSE00001822243	203508646	203508949
ENSE00004026330	203502914	203503009
ENSE00004026332	203503550	203503745

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 82.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.1852 / max 1742.2741, expressed in 59 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
7903	1.1852	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	82.09	silver quality
ileal mucosa	UBERON:0000331	77.50	gold quality
pancreatic ductal cell	CL:0002079	74.87	silver quality
deltoid	UBERON:0001476	70.96	silver quality
cardiac muscle of right atrium	UBERON:0003379	69.44	gold quality
left ventricle myocardium	UBERON:0006566	68.70	gold quality
quadriceps femoris	UBERON:0001377	67.33	gold quality
biceps brachii	UBERON:0001507	66.33	gold quality
germinal epithelium of ovary	UBERON:0001304	65.81	gold quality
vastus lateralis	UBERON:0001379	65.57	gold quality
upper arm skin	UBERON:0004263	64.58	gold quality
vena cava	UBERON:0004087	64.55	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	63.97	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	61.77	gold quality
upper leg skin	UBERON:0004262	60.45	silver quality
esophagus squamous epithelium	UBERON:0006920	59.90	gold quality
heart right ventricle	UBERON:0002080	59.58	gold quality
myocardium	UBERON:0002349	58.96	gold quality
pigmented layer of retina	UBERON:0001782	58.11	gold quality
seminal vesicle	UBERON:0000998	57.96	gold quality
nasal cavity epithelium	UBERON:0005384	57.20	gold quality
epithelial cell of pancreas	CL:0000083	56.45	gold quality
muscle tissue	UBERON:0002385	56.09	gold quality
palpebral conjunctiva	UBERON:0001812	56.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	55.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.10	gold quality
gingiva	UBERON:0001828	55.09	gold quality
kidney epithelium	UBERON:0004819	55.08	gold quality
trabecular bone tissue	UBERON:0002483	54.86	gold quality
gingival epithelium	UBERON:0001949	54.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting OPTC, 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-4673	100.00	66.64	1490
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-3187-3P	97.38	65.80	904
HSA-MIR-631	97.05	66.93	602
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-139-3P	95.24	63.10	316
HSA-MIR-6879-3P	93.93	64.00	759

Literature-anchored findings (GeneRIF, showing 6)

• localization in the human eye and genetic screen of opticin (PMID:12019215)
• OPTC is a candidate gene for primary open-angle glaucoma (PMID:17359525)
• OPTC and EPYC are unlikely to play a major role in high myopia. (PMID:19844586)
• VEGF and hypoxia could decrease opticin protein levels in the human retinal pigment epithelium secretome, and that opticin may be an enzymatic substrate for MMP-2. (PMID:22534113)
• opticin binds to collagen and thereby competitively inhibits endothelial cell interactions with collagen via alpha(1)beta(1) and alpha(2)beta(1) integrins, thereby preventing the strong adhesion that is required for proangiogenic signaling via these integrins. (PMID:22669977)
• An interplay of microglia and matrix metalloproteinase MMP9 under hypoxic stress regulates the opticin expression in retina. (PMID:33811221)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Optc	ENSMUSG00000010311
rattus_norvegicus	Optc	ENSRNOG00000003059
caenorhabditis_elegans		WBGENE00019351

Paralogs (1): LRWD1 (ENSG00000161036)

Protein

Protein identifiers

Opticin — Q9UBM4 (reviewed: Q9UBM4)

Alternative names: Oculoglycan

All UniProt accessions (2): Q5T2G3, Q9UBM4

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits angiogenesis in the vitreous humor of the eye, and therefore represses neovascularization. Binds collagen fibrils. May be involved in collagen fiber organization via regulation of other members of the small leucine-rich repeat proteoglycan superfamily.

Subunit / interactions. Homodimer.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in cartilage and synovial membranes (at protein level). Expressed in the retina, iris, ligament, skin and fetal liver (at protein level). Expressed in the retinal pigment epithelium (at protein level). Expressed in synovial fibroblasts and subchondral bone osteoblasts.

Post-translational modifications. O-glycosylated. Proteolytically cleaved by MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, ADAMTS4, and ADAMTS5. Proteolytically cleaved by MMP13. The degradation of OPTC by proteases may contribute to osteoarthritis pathophysiology. Sulfated on tyrosine residues.

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

RefSeq proteins (1): NP_055174* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR043547	Mimecan/Epiphycan/Opticin	Family

Pfam: PF13855

UniProt features (24 total): repeat 6, site 4, modified residue 3, sequence variant 3, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1, glycosylation site 1, domain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBM4-F1	74.81	0.56

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 (4): 20–21 (cleavage; by mmp7); 32–33 (cleavage; by mmp7); 87–88 (cleavage; by mmp2); 114–115 (cleavage; by mmp13)

Post-translational modifications (3): 65, 71, 139

Disulfide bonds (1): 289–322

Glycosylation sites (1): 312

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix

MSigDB gene sets: 63 (showing top): GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_BONE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_TUBE_MORPHOGENESIS, GOMF_STRUCTURAL_MOLECULE_ACTIVITY

GO Biological Process (5): angiogenesis (GO:0001525), negative regulation of angiogenesis (GO:0016525), collagen fibril organization (GO:0030199), bone development (GO:0060348), articular cartilage development (GO:0061975)

GO Molecular Function (2): extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
extracellular matrix organization	1
skeletal system development	1
animal organ development	1
cartilage development	1
structural molecule activity	1
extracellular matrix	1
binding	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

935 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OPTC	FN1	P02751	845
OPTC	NYX	Q9GZU5	633
OPTC	RTBDN	Q9BSG5	560
OPTC	RBP3	P10745	550
OPTC	MYOC	Q99972	511
OPTC	WDR36	Q8NI36	480
OPTC	AGRN	O00468	461
OPTC	TSKU	Q8WUA8	445
OPTC	GUCY2F	P51841	420
OPTC	ALG5	Q9Y673	420
OPTC	R3HDML	Q9H3Y0	417
OPTC	MYO1F	O00160	404
OPTC	DKK3	Q9UBP4	402
OPTC	VTN	P01141	399
OPTC	LRG1	P02750	398

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CRK	OPTC	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350
OPTC	TCAF2	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): PTPRF (Affinity Capture-MS), B4GALT6 (Affinity Capture-MS), PTPRS (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), TYK2 (Affinity Capture-MS), ITIH2 (Affinity Capture-MS), SLU7 (Affinity Capture-MS), HTRA1 (Affinity Capture-MS), HBA2 (Affinity Capture-MS), AKAP1 (Affinity Capture-MS), GAL (Affinity Capture-MS), MYO18A (Affinity Capture-MS), THBS1 (Affinity Capture-MS), FAM115C (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A2ARI4, A6NDA9, B0BLW3, B4F7C5, D3ZAL8, D3ZTV3, D4A6D8, D4A7P2, E7FE13, F1MT22, O14498, O43155, O43300, P0DM44, P83286, Q149C3, Q5NVQ6, Q5R6B1, Q5R7M3, Q5RAC4, Q6PFC5, Q6RKD8, Q80WD0, Q80XG9, Q80ZD7, Q80ZD8, Q80ZD9, Q810C0, Q810C1, Q86SJ2, Q86UE6, Q86UN2, Q86VH4, Q86VH5, Q86WK6, Q8BGA3, Q8BLU0, Q8BZ81, Q8C2S7

Diamond homologs: A1A4H9, B4F7C5, D3ZAL8, D4A6D8, D4A7P2, O43300, O75093, P58874, Q5R6B1, Q80XG9, Q86UE6, Q86VH4, Q86VH5, Q8BGA3, Q8BZ81, Q8C2S7, Q8K377, Q920A0, Q9BGP6, Q9UBM4, A3KNN3, A6H789, A6H793, A6NJW4, A8WHP9, E7FE13, F1MLX5, G5EFX6, O02678, O02833, O35367, O46378, O46379, O46542, O60938, O62702, O75094, O88279, O88280, O94813

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	27
Benign	16

Top pathogenic / likely-pathogenic (0)

SpliceAI

1239 predictions. Top by Δscore:

Variant	Effect	Δscore
1:203497112:CATGG:C	donor_loss	1.0000
1:203497113:ATGG:A	donor_loss	1.0000
1:203497115:GGTA:G	donor_loss	1.0000
1:203497116:G:GG	donor_gain	1.0000
1:203497116:GTA:G	donor_loss	1.0000
1:203497117:T:G	donor_loss	1.0000
1:203498670:A:AG	acceptor_gain	1.0000
1:203498670:ACCT:A	acceptor_gain	1.0000
1:203498670:ACCTG:A	acceptor_gain	1.0000
1:203498671:C:G	acceptor_gain	1.0000
1:203498673:T:TA	acceptor_gain	1.0000
1:203498674:G:A	acceptor_gain	1.0000
1:203498675:GGCCA:G	acceptor_loss	1.0000
1:203498676:GCCAG:G	acceptor_loss	1.0000
1:203498677:CCAG:C	acceptor_loss	1.0000
1:203498678:CAG:C	acceptor_loss	1.0000
1:203498679:A:AT	acceptor_loss	1.0000
1:203498833:GGGC:G	donor_gain	1.0000
1:203498834:GGC:G	donor_gain	1.0000
1:203498835:GC:G	donor_gain	1.0000
1:203498835:GCTGA:G	donor_gain	1.0000
1:203498836:C:G	donor_gain	1.0000
1:203498836:CTGA:C	donor_loss	1.0000
1:203498838:GA:G	donor_gain	1.0000
1:203498839:AGTA:A	donor_loss	1.0000
1:203498840:G:GG	donor_gain	1.0000
1:203499637:A:AG	acceptor_gain	1.0000
1:203499638:A:G	acceptor_gain	1.0000
1:203499695:C:A	acceptor_gain	1.0000
1:203499850:GG:G	donor_gain	1.0000

AlphaMissense

2166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:203499680:C:A	N187K	0.991
1:203499680:C:G	N187K	0.991
1:203502952:C:A	N257K	0.991
1:203502952:C:G	N257K	0.991
1:203499670:T:C	L184P	0.990
1:203498728:T:A	C140S	0.988
1:203498729:G:C	C140S	0.988
1:203499679:A:T	N187I	0.988
1:203503555:C:A	N278K	0.988
1:203503555:C:G	N278K	0.988
1:203503635:G:C	R305P	0.988
1:203503648:C:A	N309K	0.988
1:203503648:C:G	N309K	0.988
1:203498794:T:C	F162L	0.986
1:203498796:C:A	F162L	0.986
1:203498796:C:G	F162L	0.986
1:203498798:A:T	N163I	0.986
1:203498729:G:A	C140Y	0.985
1:203498828:T:C	F173S	0.985
1:203499655:T:C	L179S	0.985
1:203499678:A:T	N187Y	0.985
1:203499752:C:A	N211K	0.985
1:203499752:C:G	N211K	0.985
1:203498804:T:C	I165T	0.984
1:203499751:A:T	N211I	0.984
1:203498799:C:A	N163K	0.983
1:203498799:C:G	N163K	0.983
1:203499670:T:A	L184H	0.983
1:203499736:T:C	L206P	0.983
1:203502950:A:T	N257Y	0.983

dbSNP variants (sampled 300 via entrez): RS1000191026 (1:203508414 G>A), RS1000428075 (1:203505948 CAG>C,CAGAG), RS1000600219 (1:203506402 C>T), RS1000646284 (1:203499957 T>A,C,G), RS1000793272 (1:203507078 C>T), RS1000863784 (1:203505610 G>A,T), RS1000867917 (1:203501408 A>G), RS1000878419 (1:203494678 TA>T,TAA), RS1001017012 (1:203500233 A>C,T), RS1001030890 (1:203501857 A>G), RS1001468700 (1:203504145 A>G), RS1001485805 (1:203500922 T>G), RS1001547368 (1:203492246 G>A,C), RS1001871147 (1:203493790 G>A,C), RS1001936231 (1:203492497 G>A)

Disease associations

OMIM: gene MIM:605127 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001822_1	Metabolite levels (MHPG)	9.000000e-06
GCST009109_2	Hip circumference variance	6.000000e-11
GCST009123_1	Hip circumference	2.000000e-12
GCST010244_380	Triglyceride levels	1.000000e-10
GCST010988_267	Adult body size	5.000000e-10
GCST90020025_1239	Waist-to-hip ratio adjusted for BMI	2.000000e-11
GCST90020026_662	Hip index	3.000000e-08
GCST90020026_663	Hip index	2.000000e-14
GCST90020026_664	Hip index	6.000000e-31
GCST90020026_665	Hip index	2.000000e-15
GCST90020027_1927	Waist-hip index	2.000000e-11
GCST90020028_452	Hip circumference adjusted for BMI	2.000000e-27
GCST90020028_453	Hip circumference adjusted for BMI	6.000000e-12
GCST90020028_478	Hip circumference adjusted for BMI	3.000000e-08
GCST90020028_479	Hip circumference adjusted for BMI	2.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005133	MHPG measurement
EFO:0004530	triglyceride measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
cobaltous chloride	increases degradation	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Edetic Acid	decreases reaction, increases degradation	1
Estradiol	increases expression	1
Oxygen	decreases reaction, increases degradation	1
Plant Extracts	affects cotreatment, decreases expression	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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