CAPN5

Summary

CAPN5 (calpain 5, HGNC:1482) is a protein-coding gene on chromosome 11q13.5, encoding Calpain-5 (O15484). Calcium-regulated non-lysosomal thiol-protease.

Calpains are calcium-dependent cysteine proteases involved in signal transduction in a variety of cellular processes. A functional calpain protein consists of an invariant small subunit and 1 of a family of large subunits. CAPN5 is one of the large subunits. Unlike some of the calpains, CAPN5 and CAPN6 lack a calmodulin-like domain IV. Because of the significant similarity to Caenorhabditis elegans sex determination gene tra-3, CAPN5 is also called as HTRA3.

Source: NCBI Gene 726 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CAPN5-related vitreoretinopathy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 749 total — 4 pathogenic
• Phenotypes (HPO): 10
• MANE Select transcript: NM_004055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1482
Approved symbol	CAPN5
Name	calpain 5
Location	11q13.5
Locus type	gene with protein product
Status	Approved
Aliases	nCL-3, HTRA3, ADNIV
Ensembl gene	ENSG00000149260
Ensembl biotype	protein_coding
OMIM	602537
Entrez	726

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000456580, ENST00000527066, ENST00000527129, ENST00000529629, ENST00000531028, ENST00000533889, ENST00000648180, ENST00000648752, ENST00000886046, ENST00000886047, ENST00000886048, ENST00000930878

RefSeq mRNA: 4 — MANE Select: NM_004055 NM_001425321, NM_001425322, NM_001425323, NM_004055

CCDS: CCDS8248

Canonical transcript exons

ENST00000648180 — 13 exons

Exon	Start	End
ENSE00000989646	77112589	77112797
ENSE00000989647	77114242	77114434
ENSE00000989648	77115395	77115588
ENSE00000989649	77116226	77116303
ENSE00000989651	77118157	77118352
ENSE00000989652	77119030	77119152
ENSE00000989653	77120713	77120909
ENSE00001762225	77123688	77126155
ENSE00002164961	77066971	77067094
ENSE00002449175	77084852	77085051
ENSE00003534026	77122576	77122712
ENSE00003654501	77093682	77093813
ENSE00003673854	77121934	77122049

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 96.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.1016 / max 230.1648, expressed in 1572 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115969	10.5429	1524
115970	3.5586	1205

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.23	gold quality
rectum	UBERON:0001052	94.93	gold quality
gall bladder	UBERON:0002110	94.21	gold quality
transverse colon	UBERON:0001157	93.79	gold quality
right lobe of liver	UBERON:0001114	93.43	gold quality
stromal cell of endometrium	CL:0002255	91.03	gold quality
esophagus mucosa	UBERON:0002469	90.62	gold quality
lower esophagus mucosa	UBERON:0035834	90.60	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.41	gold quality
duodenum	UBERON:0002114	90.40	gold quality
body of stomach	UBERON:0001161	90.27	gold quality
small intestine	UBERON:0002108	89.86	gold quality
ileal mucosa	UBERON:0000331	89.15	gold quality
colonic mucosa	UBERON:0000317	88.99	gold quality
intestine	UBERON:0000160	88.50	gold quality
cortical plate	UBERON:0005343	88.44	gold quality
large intestine	UBERON:0000059	88.39	gold quality
esophagus squamous epithelium	UBERON:0006920	88.38	gold quality
colon	UBERON:0001155	88.37	gold quality
stomach	UBERON:0000945	88.35	gold quality
palpebral conjunctiva	UBERON:0001812	87.64	gold quality
left testis	UBERON:0004533	87.40	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.35	gold quality
right testis	UBERON:0004534	87.06	gold quality
tibial nerve	UBERON:0001323	86.94	gold quality
mucosa of stomach	UBERON:0001199	86.28	gold quality
dorsal root ganglion	UBERON:0000044	86.24	gold quality
testis	UBERON:0000473	85.80	gold quality
liver	UBERON:0002107	85.79	gold quality
epithelium of esophagus	UBERON:0001976	85.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HOXA10

miRNA regulators (miRDB)

114 targeting CAPN5, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-6733-5P	99.74	67.94	2759

Literature-anchored findings (GeneRIF, showing 26)

• Results describe the cloning and characterization of rat calpain-5, which is highly homologous to human and mouse sequences. (PMID:15464980)
• CAPN5 polymorphisms are associated with a risk of polycystic ovary syndrome. (PMID:16396936)
• CAPN5 seems to influence traits related to increased risk for cardiovascular diseases and play a role as a candidate gene for metabolic syndrome (PMID:17227582)
• We have found significant interaction between CAPN5 and PPARD genes that reduces risk for obesity in 55%. CAPN5 and PPARD gene products may also interact in vivo. (PMID:18657264)
• Data examine possible allelic imbalance in papillary thyroid cancer at EMSY, CAPN5, and PAK1, as candidate genes within 11q13.5-q14 region using a single nucleotide polymorphism-based analysis. (PMID:18787380)
• Calpain5 was expressed in endometrial stromal and glandular cells throughout the menstrual cycle and in decidua, and its expression was decreased in both stromal and glandular cells from women with endometriosis compared with that of fertile controls. (PMID:18829447)
• Calpain-5 mutations cause autoimmune uveitis, retinal neovascularization, and photoreceptor degeneration. (PMID:23055945)
• autosomal dominant neovascular inflammatory vitreoretinopathy is due to CAPN5 gain-of-function rather than haploinsufficiency. (PMID:24381307)
• CAPN5 expression can be suppressed by shRNA-based RNA interference (PMID:25216694)
• A novel CAPN5 (c.750G>T, p.Lys250Asn) missense mutation causes uveitis and neovascular retinal detachment. (PMID:25856303)
• CAPN5 mutation in hereditary uveitis: the R243L mutation increases calpain catalytic activity and triggers intraocular inflammation (PMID:25994508)
• CAPN5 localization at the photoreceptor synapse and with mitochondria explains the neural circuitry phenotype in human CAPN5 disease alleles. (PMID:27152965)
• The relative domain rotation of 60-100 degrees we found for mini-calpain-5 (a non-classical calpain) is significantly greater than the largest rotation previously observed for a classical calpain (PMID:27474374)
• We describe a pediatric patient with severe inflammatory vitreoretinopathy accompanied by hearing loss and developmental delay associated with a novel, de novo CAPN5 missense mutation (c.865C>T, p.Arg289Trp) that shows greater hyperactivation of the calpain protease, indicating a genotype-phenotype correlation. (PMID:29472286)
• The novel CAPN5 mutation (p.R289W) is responsible for the present autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) family. The mutant CAPN5 stimulated secretion and cleavage of SLIT2 fragments that may act as a bystander to regulate abnormal RPE cell proliferation for ADNIV. (PMID:29610848)
• Our findings reveal a comprehensive CD81 network in human liver cells and show that hepatitis C virus and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for hepatitis C virus, to invade cells. (PMID:30024968)
• Capn5 may play a role in CNS development, photoreceptor maintenance, and photoreceptor regeneration. (PMID:30029251)
• Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy. (PMID:31110225)
• Study found 22 loss-of-function (LOF) CAPN5 variants located throughout the gene and in all major protein domains. Structural modeling of coding variants showed these LOF variants were nearby known vitreoretinopathy-causing variants within the proteolytic core and in regions of high homology between human CAPN5 and 150 homologs, yet the LOF of CAPN5 was tolerated as opposed to gain-of-function disease-causing variants. (PMID:31403230)
• Structural Insights into the Unique Activation Mechanisms of a Non-classical Calpain and Its Disease-Causing Variants. (PMID:31968260)
• Whole-Exome Sequencing of Patients With Posterior Segment Uveitis. (PMID:32707200)
• Characterization of mitochondrial calpain-5. (PMID:33607190)
• The C2 domain of calpain 5 contributes to enzyme activation and membrane localization. (PMID:33811937)
• Mitochondrial calpain-5 truncates caspase-4 during endoplasmic reticulum stress. (PMID:35398613)
• Early-onset Neovascular Inflammatory Vitreoretinopathy Due to Two de Novo CAPN5 Mutations in Chinese Patients: A Case Series. (PMID:36369866)
• Role of calpain-5 in cerebral ischemia and reperfusion injury. (PMID:37949151)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	capn5b	ENSDARG00000069748
danio_rerio	capn5a	ENSDARG00000103317
mus_musculus	Capn5	ENSMUSG00000035547
rattus_norvegicus	Capn5	ENSRNOG00000014251
caenorhabditis_elegans		WBGENE00000542
caenorhabditis_elegans	clp-3	WBGENE00000544
caenorhabditis_elegans		WBGENE00000546
caenorhabditis_elegans		WBGENE00000547
caenorhabditis_elegans		WBGENE00006606
caenorhabditis_elegans	clp-8	WBGENE00009695
caenorhabditis_elegans	clpr-3	WBGENE00010417
caenorhabditis_elegans	clpr-1	WBGENE00012233
caenorhabditis_elegans	clpr-3	WBGENE00013184

Paralogs (20): CAPN1 (ENSG00000014216), SRI (ENSG00000075142), CAPN6 (ENSG00000077274), CAPN3 (ENSG00000092529), CAPN15 (ENSG00000103326), GCA (ENSG00000115271), ADGB (ENSG00000118492), CAPNS1 (ENSG00000126247), CAPN7 (ENSG00000131375), CAPN9 (ENSG00000135773), CAPN11 (ENSG00000137225), CAPN10 (ENSG00000142330), PEF1 (ENSG00000162517), CAPN2 (ENSG00000162909), CAPN13 (ENSG00000162949), CAPN12 (ENSG00000182472), CAPN8 (ENSG00000203697), CAPN14 (ENSG00000214711), PDCD6 (ENSG00000249915), CAPNS2 (ENSG00000256812)

Protein

Protein identifiers

Calpain-5 — O15484 (reviewed: O15484)

Alternative names: Calpain htra-3, New calpain 3

All UniProt accessions (5): O15484, A0A140VKH4, A0A3B3IRX8, E7EV01, E9PS73

UniProt curated annotations — full annotation on UniProt →

Function. Calcium-regulated non-lysosomal thiol-protease.

Tissue specificity. Expressed in many tissues. Strong expression in the photoreceptor cells of the retina, with a punctate pattern of labeling over the nuclei and inner segments with less expression along the other segments and outer plexiform layer.

Disease relevance. Vitreoretinopathy, neovascular inflammatory (VRNI) [MIM:193235] An autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. Patients present during the second or third decade of life with posterior uveitis and reduction of the electroretinogram b-wave. They become more symptomatic when cataracts, cystoid macular edema, and disk edema diminish visual acuity during the second stage. Severe vision loss begins during the third stage when proliferative retinal neovascularization and epiretinal membranes appear. There is an ongoing pigmentary retinal degeneration and peripheral visual field loss during all stages. In the fourth stage, proliferative vitreoretinopathy causes tractional retinal detachments at the macula and vitreous base. The fifth or end-stage disease is marked by phthisis. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase C2 family.

RefSeq proteins (4): NP_001412250, NP_001412251, NP_001412252, NP_004046* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000169	Pept_cys_AS	Active_site
IPR001300	Peptidase_C2_calpain_cat	Domain
IPR022682	Calpain_domain_III	Domain
IPR022683	Calpain_III	Domain
IPR022684	Calpain_cysteine_protease	Family
IPR033883	C2_III	Domain
IPR033884	C2_Calpain	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036213	Calpain_III_sf	Homologous_superfamily
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily

Pfam: PF00168, PF00648, PF01067

Enzyme classification (BRENDA):

• EC 3.4.22.B25 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (46 total): helix 18, strand 12, sequence conflict 6, active site 3, domain 2, sequence variant 2, chain 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6P3Q	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15484-F1	91.71	0.77

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 (3): 81; 252; 284

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 271 (showing top): MODULE_172, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, BENPORATH_ES_WITH_H3K27ME3, PAX4_01, TGCGCANK_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOCC_CELL_SURFACE, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, GGGTGGRR_PAX4_03, LIEN_BREAST_CARCINOMA_METAPLASTIC, chr11q13, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS

GO Biological Process (2): proteolysis (GO:0006508), signal transduction (GO:0007165)

GO Molecular Function (5): calcium-dependent cysteine-type endopeptidase activity (GO:0004198), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (5): cytoplasm (GO:0005737), focal adhesion (GO:0005925), cell surface (GO:0009986), synapse (GO:0045202), extracellular exosome (GO:0070062)

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
cellular anatomical structure	2
protein metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cysteine-type endopeptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular anatomical structure	1
cell-substrate junction	1
cell junction	1
extracellular vesicle	1

Protein interactions and networks

STRING

941 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPN5	CBLB	Q13191	633
CAPN5	CALML6	Q8TD86	562
CAPN5	CALML4	Q96GE6	562
CAPN5	CALML3	P27482	561
CAPN5	CALML5	Q9NZT1	561
CAPN5	CAPNS1	P04632	559
CAPN5	CALM1	P02593	555
CAPN5	SRFBP1	Q8NEF9	547
CAPN5	CAST	P20810	544
CAPN5	CAPN3	P20807	498
CAPN5	CD81	P18582	488
CAPN5	FEM1A	Q9BSK4	472
CAPN5	FEM1C	Q96JP0	453
CAPN5	ELOC	Q15369	440
CAPN5	FEM1B	Q9UK73	439

IntAct

15 interactions, top by confidence:

A	B	Type	Score
CAPN5	STIP1	psi-mi:“MI:0915”(physical association)	0.590
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
ZNRD2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PHTF1	CAPN5	psi-mi:“MI:0915”(physical association)	0.400
MLH1	CAPN5	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
AURKB	VWA8	psi-mi:“MI:0914”(association)	0.350
CAPN5	LRBA	psi-mi:“MI:0914”(association)	0.350
DNAJA2	ENC1	psi-mi:“MI:0914”(association)	0.350
PCDH20	CAPN5	psi-mi:“MI:0914”(association)	0.350
PYCR3	ARHGAP32	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): CAPN5 (Affinity Capture-MS), STIP1 (Affinity Capture-MS), CAPN5 (Biochemical Activity), CAPN5 (Co-localization), CAPN5 (Affinity Capture-MS), CAPN5 (Affinity Capture-MS), CAPN5 (Affinity Capture-MS), STIP1 (Affinity Capture-MS), CAPN5 (Affinity Capture-MS), CAPN5 (Affinity Capture-MS), CAPN5 (Negative Genetic), CUL3 (Affinity Capture-Western), KCTD7 (Affinity Capture-Western), PRELID1 (Cross-Linking-MS (XL-MS)), CAPN5 (Affinity Capture-RNA)

ESM2 similar proteins: A5D6R3, A6NHC0, A8MX76, O08529, O08688, O14815, O15484, O35350, O35646, O35920, O88501, P00789, P06814, P06815, P07384, P16259, P17655, P20807, P27730, P35750, P43367, P43368, P51186, P97571, Q07009, Q11002, Q22036, Q27970, Q27971, Q4V8Q1, Q5BK10, Q5NVS7, Q64691, Q6J756, Q6MZZ7, Q6ZSI9, Q78EJ9, Q8R4C0, Q91VA3, Q92177

Diamond homologs: A6NHC0, A8MX76, G3V7W1, O08529, O08688, O14815, O15484, O23184, O35350, O35646, O35920, O75808, O88456, O88501, P00789, P04574, P04632, P05044, P06813, P06814, P06815, P07384, P13135, P16259, P17655, P20807, P27398, P27730, P28676, P30626, P34308, P35750, P43367, P43368, P51186, P97571, Q07009, Q11002, Q22036, Q27970

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	430
Likely benign	243
Benign	38

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
279987	NM_004055.5(CAPN5):c.865C>T (p.Arg289Trp)	Pathogenic
39806	NM_004055.5(CAPN5):c.728G>T (p.Arg243Leu)	Pathogenic
39807	NM_004055.5(CAPN5):c.731T>C (p.Leu244Pro)	Pathogenic
869153	NM_004055.5(CAPN5):c.750G>C (p.Lys250Asn)	Pathogenic

SpliceAI

4198 predictions. Top by Δscore:

Variant	Effect	Δscore
11:77085037:TGG:T	donor_gain	1.0000
11:77085048:CAAGG:C	donor_loss	1.0000
11:77085049:AAG:A	donor_loss	1.0000
11:77085053:T:G	donor_loss	1.0000
11:77093676:CCGCA:C	acceptor_loss	1.0000
11:77093677:CGCA:C	acceptor_loss	1.0000
11:77093678:GCA:G	acceptor_loss	1.0000
11:77093679:CA:C	acceptor_loss	1.0000
11:77093680:AG:A	acceptor_gain	1.0000
11:77093681:GG:G	acceptor_gain	1.0000
11:77093681:GGGC:G	acceptor_gain	1.0000
11:77093809:AAAAG:A	donor_loss	1.0000
11:77093811:AAGGT:A	donor_loss	1.0000
11:77093812:AGGTG:A	donor_loss	1.0000
11:77093813:GGTGA:G	donor_loss	1.0000
11:77093814:G:GA	donor_loss	1.0000
11:77093815:T:A	donor_loss	1.0000
11:77112585:CCAGG:C	acceptor_loss	1.0000
11:77112587:A:C	acceptor_loss	1.0000
11:77112588:GGTC:G	acceptor_gain	1.0000
11:77112758:A:AG	donor_gain	1.0000
11:77112793:GCCAA:G	donor_gain	1.0000
11:77112796:AAGTA:A	donor_loss	1.0000
11:77112797:AG:A	donor_loss	1.0000
11:77112798:G:C	donor_loss	1.0000
11:77112798:G:GG	donor_gain	1.0000
11:77112799:TA:T	donor_loss	1.0000
11:77115390:CACA:C	acceptor_loss	1.0000
11:77115393:A:AG	acceptor_gain	1.0000
11:77115394:G:GA	acceptor_loss	1.0000

AlphaMissense

4217 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:77115566:T:A	W291R	1.000
11:77115566:T:C	W291R	1.000
11:77115568:G:C	W291C	1.000
11:77115568:G:T	W291C	1.000
11:77115578:T:A	W295R	1.000
11:77115578:T:C	W295R	1.000
11:77116236:T:A	W302R	1.000
11:77116236:T:C	W302R	1.000
11:77116299:T:C	F323L	1.000
11:77116301:C:A	F323L	1.000
11:77116301:C:G	F323L	1.000
11:77085037:T:A	W51R	0.999
11:77085037:T:C	W51R	0.999
11:77085039:G:C	W51C	0.999
11:77085039:G:T	W51C	0.999
11:77093741:G:C	Q75H	0.999
11:77093741:G:T	Q75H	0.999
11:77093760:T:A	W82R	0.999
11:77093760:T:C	W82R	0.999
11:77093773:C:A	A86D	0.999
11:77112713:C:A	P141H	0.999
11:77112766:T:A	W159R	0.999
11:77112766:T:C	W159R	0.999
11:77112783:G:C	E164D	0.999
11:77112783:G:T	E164D	0.999
11:77114420:A:C	S229R	0.999
11:77114422:T:A	S229R	0.999
11:77114422:T:G	S229R	0.999
11:77115449:C:G	H252D	0.999
11:77115451:C:A	H252Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000047045 (11:77097368 G>A), RS1000061265 (11:77105838 C>T), RS1000267923 (11:77101079 C>T), RS1000442939 (11:77067915 C>T), RS1000522961 (11:77085143 G>A,C), RS1000634847 (11:77090733 C>A,T), RS1000754447 (11:77094582 C>A,T), RS1000806702 (11:77094778 C>T), RS1000869264 (11:77117609 C>T), RS1000940577 (11:77111897 C>G,T), RS1001075515 (11:77085361 G>T), RS1001169499 (11:77074719 G>C,T), RS1001220245 (11:77074925 T>C), RS1001324367 (11:77112844 G>A), RS1001426262 (11:77118577 C>G,T)

Disease associations

OMIM: gene MIM:602537 | disease phenotypes: MIM:193235, MIM:613587, MIM:248200

GenCC curated gene-disease

Disease	Classification	Inheritance
CAPN5-related vitreoretinopathy	Definitive	Autosomal dominant
autosomal dominant neovascular inflammatory vitreoretinopathy	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
CAPN5-related vitreoretinopathy	Definitive	AD

Mondo (6): CAPN5-related vitreoretinopathy (MONDO:0100450), inherited retinal dystrophy (MONDO:0019118), proliferative vitreoretinopathy (MONDO:0700115), occult macular dystrophy (MONDO:0013316), severe early-childhood-onset retinal dystrophy (MONDO:0009549), (MONDO:0008664)

Orphanet (5): Autosomal dominant neovascular inflammatory vitreoretinopathy (Orphanet:329211), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Occult macular dystrophy (Orphanet:247834), Severe early-childhood-onset retinal dystrophy (Orphanet:364055), Stargardt disease (Orphanet:827)

HPO phenotypes

10 total (11 of 10 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000512	Abnormal electroretinogram
HP:0000541	Retinal detachment
HP:0000554	Uveitis
HP:0000618	Blindness
HP:0007658	Large hyperpigmented retinal spots
HP:0007773	Vitreoretinopathy
HP:0007778	Posterior retinal neovascularization
HP:0007902	Vitreous hemorrhage
HP:0030667	Peripheral retinal neovascularization
HP:0000556	Retinal dystrophy

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000477_43	Cognitive performance	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D018630	Vitreoretinopathy, Proliferative	C11.768.890

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Valproic Acid	affects expression, increases expression, increases methylation	3
sodium arsenite	decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects expression	2
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
OTX015	increases expression	1
bisphenol F	increases expression	1
mivebresib	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	increases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
necrostatin-1	affects cotreatment, affects expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01445028	PHASE4	COMPLETED	Isotretinoin for Proliferative Vitreoretinopathy
NCT01995045	PHASE4	COMPLETED	Postoperative Pain Control Following Vitreoretinal Surgery
NCT07162818	PHASE4	COMPLETED	Effects of 0.1% Nepafenac on Vitreous Inflammatory Biomarkers in Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy
NCT00000140	PHASE3	COMPLETED	The Silicone Study
NCT00370760	PHASE3	UNKNOWN	Oral Colchicine Combined With Intravitreal Infusion of Dexamethasone, LMW Heparin and 5-FU for Management of Proliferative Vitreoretinopathy (PVR)
NCT00371020	PHASE3	UNKNOWN	The Effect of 5-FU and LMW Heparin on the Rate of Retinal Redetachment After Silicone Oil Removal in Cases of PVR
NCT00373282	PHASE3	COMPLETED	Triamcinolone Acetonide in Silicone-Filled Eyes as Adjunctive Treatment for Proliferative Vitreoretinopathy
NCT04136366	PHASE3	COMPLETED	The GUARD Trial - Part 1: A Phase 3 Clinical Trial for Prevention of Proliferative Vitreoretinopathy
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT05244304	PHASE3	COMPLETED	Phase 3, Randomized, Placebo-Controlled Study of Tinlarebant to Explore Safety and Efficacy in Adolescent Stargardt Disease
NCT02192970	PHASE2	COMPLETED	Bevacizumab Against Recurrent Retinal Detachment
NCT04580147	PHASE2	UNKNOWN	Intravitreal Aflibercept for the Prevention of Proliferative Vitreoretinopathy Following Retinal Detachment Repair
NCT04891991	PHASE2	COMPLETED	Intravitreal Infliximab for Proliferative Vitreoretinopathy
NCT06541574	PHASE2	RECRUITING	Prevention of ProliFerative Vitreoretinopathy with Intravitreal MethotreXate in Primary Retinal DEtachment Repair (FIXER) Trial
NCT06818721	PHASE2	NOT_YET_RECRUITING	Intravitreal Topotecan for Prevention or Treatment of Proliferative Vitreoretinopathy in Retinal Detachment
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in Subjects With Stargardt Disease
NCT04830878	PHASE1	WITHDRAWN	Methotrexate For The Prevention and Treatment of Proliferative Vitreoretinopathy in Pediatric Patients
NCT06425419	PHASE1	NOT_YET_RECRUITING	The Safety and Efficacy of Intravitreal Topotecan for the Treatment of Proliferative Vitreoretinopathy
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT03772938	PHASE1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT04482543	PHASE2/PHASE3	UNKNOWN	Repeated Methotrexate for Proliferative Vitreoretinopathy Grade C
NCT05660447	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Multi-Center Study on the Use of Rho-Kinase Inhibitor to Reduce or Prevent PVR in RRD Eyes at High Risk for PVR
NCT06033703	PHASE1/PHASE2	RECRUITING	Topical Netarsudil for the Prevention of Proliferative Vitreoretinopathy in Patients With Retinal Detachment
NCT06289205	PHASE1/PHASE2	UNKNOWN	Comparing Methotrexate Usage Techniques to Prevent Proliferative Vitreoretinopaty After Retinal Detachment Vitrectomy
NCT03727776	EARLY_PHASE1	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Post-op Inflammation in Proliferative Vitreoretinopathy (PVR)
NCT01255293	Not specified	COMPLETED	Comparative Study of 1000 Centistoke Versus 5000 Centistoke Silicone Oil for Repair of Complex Retinal Detachments
NCT02748421	Not specified	UNKNOWN	Optical Coherence Tomography - Rescan During Dissection of Macular Membranes
NCT04490876	Not specified	COMPLETED	Outcomes of Extensive Brilliant Blue G-Assisted Internal Limiting Membrane Peeling in Proliferative Vitreoretinopathy
NCT04682054	Not specified	UNKNOWN	Molecular Taxonomy of Surgically-harvested Ocular Tissues Defined by Single-cell Transcriptomics
NCT05538156	Not specified	NOT_YET_RECRUITING	Internal Limiting Membrane Peeling in Retinal Detachment Surgery
NCT05561569	Not specified	UNKNOWN	Air Versus Gas Tamponade in Primary Retinal Detachment
NCT06166914	Not specified	COMPLETED	Efficacy of 5-fluorouracil and Low Molecular Weight Heparin in High-risk Pediatric Retinal Detachment
NCT07386678	Not specified	NOT_YET_RECRUITING	Study of Imaging and Molecular Biomarkers in Uncomplicated Rhegmatogenous Retinal Detachment
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.