COL8A2

Summary

COL8A2 (collagen type VIII alpha 2 chain, HGNC:2216) is a protein-coding gene on chromosome 1p34.3, encoding Collagen alpha-2(VIII) chain (P25067). Macromolecular component of the subendothelium.

This gene encodes the alpha 2 chain of type VIII collagen. This protein is a major component of the basement membrane of the corneal endothelium and forms homo- or heterotrimers with alpha 1 (VIII) type collagens. Defects in this gene are associated with Fuchs endothelial corneal dystrophy and posterior polymorphous corneal dystrophy type 2. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1296 — RefSeq curated summary.

At a glance

• Gene–disease (curated): posterior polymorphous corneal dystrophy 2 (Strong, GenCC) — +3 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 196 total — 3 pathogenic
• Phenotypes (HPO): 30
• MANE Select transcript: NM_005202

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2216
Approved symbol	COL8A2
Name	collagen type VIII alpha 2 chain
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	PPCD, FECD1, PPCD2
Ensembl gene	ENSG00000171812
Ensembl biotype	protein_coding
OMIM	120252
Entrez	1296

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000303143, ENST00000397799, ENST00000481785

RefSeq mRNA: 2 — MANE Select: NM_005202 NM_001294347, NM_005202

CCDS: CCDS403, CCDS72756

Canonical transcript exons

ENST00000397799 — 4 exons

Exon	Start	End
ENSE00001144083	36095239	36099487
ENSE00001459716	36100050	36100258
ENSE00001530191	36115708	36115752
ENSE00001530192	36125057	36125222

Expression profiles

Bgee: expression breadth ubiquitous, 230 present calls, max score 91.33.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1854 / max 84.5904, expressed in 537 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11704	1.0975	410
11703	1.0879	305

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	91.33	gold quality
tendon of biceps brachii	UBERON:0008188	90.98	gold quality
ascending aorta	UBERON:0001496	90.30	gold quality
pigmented layer of retina	UBERON:0001782	90.30	gold quality
retina	UBERON:0000966	90.28	gold quality
thoracic aorta	UBERON:0001515	90.28	gold quality
descending thoracic aorta	UBERON:0002345	90.11	gold quality
right coronary artery	UBERON:0001625	89.93	gold quality
aorta	UBERON:0000947	89.40	gold quality
popliteal artery	UBERON:0002250	88.80	gold quality
tibial artery	UBERON:0007610	88.80	gold quality
choroid plexus epithelium	UBERON:0003911	88.28	gold quality
cartilage tissue	UBERON:0002418	87.62	gold quality
tibia	UBERON:0000979	85.83	gold quality
tendon	UBERON:0000043	84.93	gold quality
mucosa of stomach	UBERON:0001199	84.92	gold quality
calcaneal tendon	UBERON:0003701	84.83	gold quality
left coronary artery	UBERON:0001626	84.62	gold quality
hair follicle	UBERON:0002073	84.57	gold quality
saphenous vein	UBERON:0007318	84.19	gold quality
coronary artery	UBERON:0001621	84.08	gold quality
blood vessel layer	UBERON:0004797	83.00	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.63	gold quality
tibial nerve	UBERON:0001323	82.12	gold quality
synovial joint	UBERON:0002217	81.57	gold quality
layer of synovial tissue	UBERON:0007616	80.66	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.37	gold quality
lower esophagus	UBERON:0013473	80.35	gold quality
mammary duct	UBERON:0001765	80.17	gold quality
epithelium of mammary gland	UBERON:0003244	79.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.92

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting COL8A2, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
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-98-3P	100.00	74.08	3907
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6086	99.70	65.38	699
HSA-MIR-377-5P	99.70	65.28	712
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-7106-5P	99.53	67.47	3574

Literature-anchored findings (GeneRIF, showing 25)

• Results describe the identification and characterization of nero, the Drosophila melanogaster deoxyhypusine hydroxylase (DOHH) homologue, and indicate that nero and eIF5A are required for cell growth and affect autophagy and protein synthesis. (PMID:19546244)
• eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction. (PMID:33852845)
• The R155Q and T502M mutations of COL8A2 may not be the causative defect in the Japanese Fuchs’ endothelial corneal dystrophy and posterior polymorphous dystrophy patients examined in this study. (PMID:15175909)
• No pathogenic mutations were identified in the COL8A2 gene or in several positional candidate genes in a series of patients, indicating that other genetic factors are involved in the development of this autosomal dominant corneal dystrophy. (PMID:15851557)
• A novel pathogenic L450W COL8A2 mutation was identified and its highly distinctive pathology characterized. This indicates that COL8A2 mutations give rise to a rare subtype of FCD (Fuchs corneal dystrophy). (PMID:15914606)
• Alpha2(VIII) collagen supported endothelial cell attachment in a dose-dependent manner, with an 18-fold higher affinity for endothelial cells. (PMID:16908762)
• The absence of pathogenic mutations identified in the COL8A1 or COL8A2 genes in affected members of 15 pedigrees with familial FECD (Fuchs endothelial corneal dystrophy) indicates that other genetic factors are involved. (PMID:16936088)
• Microscopic and electron microscopic examination revealed pathological changes in Descemet’s membrane of L450W COL8A2 mutants that were consistent with several-fold increased growth of the extracellular matrix. (PMID:17471329)
• The absence of pathogenic mutations in COL8A1 and COL8A2 in patients with keratoconus indicates that other genetic factors are involved in the pathogenesis of this corneal ectatic disorder. (PMID:17721297)
• description of the phenotype of early-onset Fuchs’ endothelial corneal dystrophy in a British family, which is caused by a point mutation (resulting in p.L450W substitution) in COL8A2 (PMID:18024822)
• These data constitute the first report of a heterozygous Q455V mutation of the COL8A2 gene in Korean patients with Fuchs’ corneal dystrophy and Q455V may be the causative defect in the development and progression of Korean FECD patients. (PMID:18464802)
• The previously reported mutations in the COL8A2 gene were not found in the 92 samples tested. (PMID:18502986)
• COL8A2, SLC4A11 genes may not be responsible for Fuchs endothelial corneal dystrophy in patients examined in this study. (PMID:20144242)
• The purpose of this study is to evaluate COL8A1 and COL8A2 as candidate genes for thin central corneal thickness in human primary open angle glaucoma patients. (PMID:21139683)
• Report cellular model in which collagen VIII mutations, which clinically result in Fuchs’ dystrophy, are associated with abnormal cellular accumulation of collagen VIII. (PMID:22020132)
• Single nucleotide polymorphisms in COL8A2 gene is not associated with central corneal thickness in glaucoma. (PMID:22814818)
• Association of central corneal thickness with TCF4 was also significant (p = 6.1x10(-7)), but was abolished with adjustment for FECD grade (p = 0.92). (PMID:23110055)
• mutations in the COL8A2 gene do not contribute to all cases of early-onset early-onset Fuchs’ endothelial corneal dystrophy . (PMID:23601356)
• Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with Eosionophilic esophagitis and inherited connective tissue disorders. (PMID:23608731)
• Variation in the COL8A2, SLC4A11, and ZEB1 genes is present in only a small fraction of African American cases and as such does not appear to significantly contribute to the genetic risk of Fuchs endothelial corneal dystrophy. (PMID:24348007)
• No mutations were identified in COL8A2, in neither the late-onset cohort nor the early-onset family, suggesting genetic heterogeneity in this Late-onset Fuchs endothelial corneal dystrophy (FECD) family. (PMID:25007886)
• Peripheral, anterior microcystic corneal edema represents a characteristic aspect of the phenotype associated with the p.(Leu450Trp) substitution in COL8A2, in at least 2 of 3 known affected families worldwide. (PMID:26989952)
• Analysis of SLC4A11, ZEB1, LOXHD1, COL8A2 and TCF4 gene sequences in a multi-generational family with late-onset Fuchs corneal dystrophy found no evidence for found polymorophisms causing the disease in this specific pedigree. (PMID:27121161)
• COL8A2 Regulates the Fate of Corneal Endothelial Cells. (PMID:32931574)
• Collagen type VIII alpha 2 chain (COL8A2), an important component of the basement membrane of the corneal endothelium, facilitates the malignant development of glioblastoma cells via inducing EMT. (PMID:33405048)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	col8a2	ENSDARG00000060893
mus_musculus	Col8a2	ENSMUSG00000056174
rattus_norvegicus	Col8a2	ENSRNOG00000010841

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), C1QTNF4 (ENSG00000172247), C1QB (ENSG00000173369), C1QA (ENSG00000173372), C1QTNF1 (ENSG00000173918), ADIPOQ (ENSG00000181092), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Collagen alpha-2(VIII) chain — P25067 (reviewed: P25067)

Alternative names: Endothelial collagen

All UniProt accessions (2): P25067, E9PP49

UniProt curated annotations — full annotation on UniProt →

Function. Macromolecular component of the subendothelium. Major component of the Descemet’s membrane (basement membrane) of corneal endothelial cells. Also a component of the endothelia of blood vessels. Necessary for migration and proliferation of vascular smooth muscle cells and thus, has a potential role in the maintenance of vessel wall integrity and structure, in particular in atherogenesis.

Subunit / interactions. Homotrimers, or heterotrimers in association with alpha 2(VIII) type collagens. Four homotrimers can form a tetrahedron stabilized by central interacting C-terminal NC1 trimers.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Tissue specificity. Expressed primarily in the subendothelium of large blood vessels. Also expressed in arterioles and venules in muscle, heart, kidney, spleen, umbilical cord, liver and lung and is also found in connective tissue layers around hair follicles, around nerve bundles in muscle, in the dura of the optic nerve, in cornea and sclera, and in the perichondrium of cartilaginous tissues. In the kidney, expressed in mesangial cells, glomerular endothelial cells, and tubular epithelial cells. Also expressed in mast cells, and in astrocytes during the repair process. Expressed in Descemet’s membrane.

Post-translational modifications. Proteolytically cleaved by neutrophil elastase, in vitro. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.

Disease relevance. Corneal dystrophy, Fuchs endothelial, 1 (FECD1) [MIM:136800] A corneal disease caused by loss of endothelium of the central cornea. It is characterized by focal wart-like guttata that arise from Descemet membrane and develop in the central cornea, epithelial blisters, reduced vision and pain. Descemet membrane is thickened by abnormal collagenous deposition. The disease is caused by variants affecting the gene represented in this entry. Corneal dystrophy, posterior polymorphous, 2 (PPCD2) [MIM:609140] A rare mild subtype of posterior corneal dystrophy characterized by alterations of Descemet membrane presenting as vesicles, opacities or band-like lesions on slit-lamp examination and specular microscopy. Affected patient typically are asymptomatic. The disease is caused by variants affecting the gene represented in this entry.

Induction. Some up-regulation in diabetic nephropathy.

RefSeq proteins (2): NP_001281276, NP_005193* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR050392	Collagen/C1q_domain	Family

Pfam: PF00386, PF01391

UniProt features (35 total): sequence conflict 10, compositionally biased region 9, sequence variant 9, region of interest 4, signal peptide 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25067-F1	58.03	0.21

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-216083	Integrin cell surface interactions
R-HSA-8948216	Collagen chain trimerization

MSigDB gene sets: 185 (showing top): GOCC_COLLAGEN_TRIMER, PEREZ_TP63_TARGETS, GOBP_EXTRACELLULAR_MATRIX_ASSEMBLY, BILD_SRC_ONCOGENIC_SIGNATURE, CHANDRAN_METASTASIS_DN, GOBP_CELL_CELL_ADHESION, PICCALUGA_ANGIOIMMUNOBLASTIC_LYMPHOMA_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, MCLACHLAN_DENTAL_CARIES_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, chr1p34, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOCC_BASEMENT_MEMBRANE

GO Biological Process (7): angiogenesis (GO:0001525), endothelial cell proliferation (GO:0001935), extracellular matrix organization (GO:0030198), camera-type eye morphogenesis (GO:0048593), basement membrane assembly (GO:0070831), cell-cell adhesion (GO:0098609), cell adhesion (GO:0007155)

GO Molecular Function (4): extracellular matrix structural constituent (GO:0005201), extracellular matrix structural constituent conferring tensile strength (GO:0030020), protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), collagen type VIII trimer (GO:0005591), basement membrane (GO:0005604), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), collagen trimer (GO:0005581)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Collagen formation	2
Degradation of the extracellular matrix	1
Extracellular matrix organization	1
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
extracellular matrix	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
epithelial cell proliferation	1
extracellular structure organization	1
external encapsulating structure organization	1
camera-type eye development	1
eye morphogenesis	1
basement membrane organization	1
extracellular matrix assembly	1
cell adhesion	1
cellular process	1
structural molecule activity	1
extracellular matrix structural constituent	1
protein binding	1
molecular adaptor activity	1
binding	1
cellular anatomical structure	1
network-forming collagen trimer	1
hexagonal collagen network	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1
protein-containing complex	1

Protein interactions and networks

STRING

1476 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL8A2	SLC4A11	Q8NBS3	962
COL8A2	GP6	Q9HCN6	949
COL8A2	VSX1	Q9NZR4	894
COL8A2	ZEB1	P37275	871
COL8A2	TCF4	P15884	766
COL8A2	LOXHD1	Q8IVV2	712
COL8A2	AGBL1	Q96MI9	686
COL8A2	DR1	Q01658	669
COL8A2	VWF	P04275	661
COL8A2	ZNF469	Q96JG9	583
COL8A2	CYYR1	Q96J86	572
COL8A2	ADAMTS10	Q9H324	554
COL8A2	F3	P13726	549
COL8A2	ADAMTSL2	Q86TH1	536
COL8A2	SLC8A2	Q9UPR5	523

IntAct

3 interactions, top by confidence:

A	B	Type	Score
COL8A2	P4HA2	psi-mi:“MI:0914”(association)	0.350
COL8A2	PLOD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (65): SGTA (Two-hybrid), CRTAP (Affinity Capture-MS), COLEC12 (Affinity Capture-MS), COL2A1 (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), P3H1 (Affinity Capture-MS), FN1 (Affinity Capture-MS), P4HA2 (Affinity Capture-MS), COL5A1 (Affinity Capture-MS), FKBP14 (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), COL18A1 (Affinity Capture-MS), COL5A1 (Affinity Capture-MS), COL2A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WGB1, A8WR59, B2RNN3, B7Z0K8, C7DZK3, O35167, O35348, O76368, O88207, P0C862, P12107, P13942, P20908, P20909, P23805, P25067, P25318, P25940, P42916, P83371, P98085, Q03637, Q07092, Q07563, Q0II24, Q0VF58, Q17RW2, Q30D77, Q32S24, Q3MI99, Q4ZJM7, Q4ZJN1, Q60467, Q61245, Q64739, Q6UXH8

Diamond homologs: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, O75973, O88992, P02745, P02746, P08125, P0C862, P14106, P14282, P23206, P25067, P25318, P27658, P31720, P31721, P83371, P98085, P98086, Q00780, Q02105, Q03692, Q05306, Q05A80, Q06575, Q06576, Q06577, Q0II24, Q15848, Q2KIU3, Q2KIX7, Q3Y5Z3, Q4ZJM7, Q4ZJM9, Q4ZJN1, Q5E9E3, Q5FVH0, Q5RJ80

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	128
Likely benign	26
Benign	29

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
167868	NM_005202.4(COL8A2):c.1363_1364delinsGT (p.Gln455Val)	Pathogenic
17147	NM_005202.4(COL8A2):c.1363C>A (p.Gln455Lys)	Pathogenic
17148	NM_005202.4(COL8A2):c.1349T>G (p.Leu450Trp)	Pathogenic

SpliceAI

608 predictions. Top by Δscore:

Variant	Effect	Δscore
1:36099485:TTT:T	acceptor_gain	1.0000
1:36100255:CGTG:C	acceptor_gain	1.0000
1:36100257:TG:T	acceptor_gain	1.0000
1:36100259:C:CC	acceptor_gain	1.0000
1:36125051:CTTTA:C	donor_loss	1.0000
1:36125052:TTTA:T	donor_loss	1.0000
1:36125054:TAC:T	donor_loss	1.0000
1:36125055:ACCT:A	donor_loss	1.0000
1:36125056:C:CT	donor_loss	1.0000
1:36125056:CCTG:C	donor_gain	1.0000
1:36099483:CATTT:C	acceptor_gain	0.9900
1:36099484:ATTT:A	acceptor_gain	0.9900
1:36099486:TT:T	acceptor_gain	0.9900
1:36099486:TTC:T	acceptor_loss	0.9900
1:36099488:C:CC	acceptor_gain	0.9900
1:36099488:C:G	acceptor_loss	0.9900
1:36099489:T:C	acceptor_loss	0.9900
1:36100045:CT:C	donor_loss	0.9900
1:36100046:TCA:T	donor_loss	0.9900
1:36100047:CA:C	donor_loss	0.9900
1:36100048:A:AC	donor_gain	0.9900
1:36100048:A:AT	donor_loss	0.9900
1:36100048:AC:A	donor_gain	0.9900
1:36100049:C:CC	donor_gain	0.9900
1:36100049:CC:C	donor_gain	0.9900
1:36100254:ACGTG:A	acceptor_gain	0.9900
1:36100255:CGTGC:C	acceptor_gain	0.9900
1:36100256:GTG:G	acceptor_gain	0.9900
1:36100256:GTGCT:G	acceptor_loss	0.9900
1:36100257:TGC:T	acceptor_loss	0.9900

AlphaMissense

4341 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:36097591:C:T	G697E	1.000
1:36097597:A:G	F695S	1.000
1:36097603:G:A	S693F	1.000
1:36097654:T:G	Q676P	1.000
1:36097663:A:T	V673D	1.000
1:36097771:A:G	L637P	1.000
1:36097811:A:C	Y624D	1.000
1:36097816:A:G	F622S	1.000
1:36097846:A:G	F612S	1.000
1:36097900:A:G	F594S	1.000
1:36097939:A:G	L581P	1.000
1:36097946:C:G	A579P	1.000
1:36097951:A:G	F577S	1.000
1:36097592:C:G	G697R	0.999
1:36097592:C:T	G697R	0.999
1:36097595:A:G	S696P	0.999
1:36097596:A:C	F695L	0.999
1:36097596:A:T	F695L	0.999
1:36097598:A:G	F695L	0.999
1:36097601:A:G	S694P	0.999
1:36097604:A:G	S693P	0.999
1:36097669:T:A	D671V	0.999
1:36097681:A:G	L667P	0.999
1:36097687:A:G	L665P	0.999
1:36097703:A:G	S660P	0.999
1:36097706:C:G	A659P	0.999
1:36097735:T:A	D649V	0.999
1:36097735:T:G	D649A	0.999
1:36097736:C:G	D649H	0.999
1:36097745:A:C	Y646D	0.999

dbSNP variants (sampled 300 via entrez): RS1000138914 (1:36103491 T>C), RS1000296403 (1:36112809 C>G,T), RS1000454044 (1:36106766 C>A,T), RS1000456516 (1:36117541 C>T), RS1000805284 (1:36106532 T>C), RS1000856046 (1:36123338 G>T), RS1000925574 (1:36117285 G>A), RS1000991663 (1:36123550 C>T), RS1000998536 (1:36124596 T>A), RS1001043058 (1:36095207 CCT>C), RS1001145693 (1:36102727 A>G), RS1001307887 (1:36123062 C>T), RS1001408080 (1:36097389 C>A), RS1001502488 (1:36117222 C>A,T), RS1001625101 (1:36117138 T>A,C)

Disease associations

OMIM: gene MIM:120252 | disease phenotypes: MIM:136800, MIM:609140

GenCC curated gene-disease

Disease	Classification	Inheritance
posterior polymorphous corneal dystrophy 2	Strong	Autosomal dominant
corneal dystrophy, Fuchs endothelial, 1	Strong	Autosomal dominant
posterior polymorphous corneal dystrophy	Supportive	Autosomal dominant
Fuchs’ endothelial dystrophy	Supportive	Autosomal dominant

Mondo (4): corneal dystrophy, Fuchs endothelial, 1 (MONDO:0007637), posterior polymorphous corneal dystrophy 2 (MONDO:0012199), posterior polymorphous corneal dystrophy (MONDO:0020364), Fuchs’ endothelial dystrophy (MONDO:0005321)

Orphanet (2): Posterior polymorphous corneal dystrophy (Orphanet:98973), Fuchs endothelial corneal dystrophy (Orphanet:98974)

HPO phenotypes

30 total (30 of 30 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000483	Astigmatism
HP:0000501	Glaucoma
HP:0000533	Chorioretinal atrophy
HP:0000565	Esotropia
HP:0000572	Visual loss
HP:0000613	Photophobia
HP:0000622	Blurred vision
HP:0000632	Lacrimation abnormality
HP:0000646	Amblyopia
HP:0000662	Nyctalopia
HP:0000969	Edema
HP:0001131	Corneal dystrophy
HP:0007663	Reduced visual acuity
HP:0007705	Corneal degeneration
HP:0007906	Ocular hypertension
HP:0007957	Corneal opacity
HP:0009918	Ectopia pupillae
HP:0011483	Anterior synechiae of the anterior chamber
HP:0011488	Abnormal corneal endothelium morphology
HP:0011490	Abnormal Descemet membrane morphology
HP:0011491	Reduced number of corneal endothelial cells
HP:0012038	Corneal guttata
HP:0012039	Descemet Membrane Folds
HP:0012040	Corneal stromal edema
HP:0025358	Uveal ectropion
HP:0030857	Eye movement-induced pain
HP:0032122	Very low visual acuity
HP:0100692	Increased corneal curvature
HP:0200026	Ocular pain

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001806_1	Corneal structure	3.000000e-11
GCST005580_20	Intraocular pressure	2.000000e-14
GCST005580_21	Intraocular pressure	2.000000e-14
GCST005667_25	Central corneal thickness	3.000000e-11
GCST006412_9	Intraocular pressure	2.000000e-11
GCST008178_5	Early spontaneous preterm birth	2.000000e-06
GCST009725_53	Intraocular pressure	1.000000e-09
GCST90000654_1	Central corneal thickness	5.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0006917	spontaneous preterm birth

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D005642	Fuchs’ Endothelial Dystrophy	C11.204.236.438; C11.270.162.438; C16.320.290.162.410
C565176	Corneal Dystrophy, Posterior Polymorphous, 2 (supp.)
C535478	Corneal dystrophy, Fuchs’ endothelial, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Arsenic Trioxide	decreases expression	2
Benzo(a)pyrene	affects methylation	2
Valproic Acid	affects expression, increases methylation	2
GSK-J4	increases expression	1
4-oxoretinoic acid	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentabromodiphenyl ether	increases 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, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Decitabine	increases expression	1
Alitretinoin	increases expression	1
Amiodarone	increases expression	1
Arsenic	increases abundance, decreases expression	1
Atrazine	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Progesterone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
1-Methyl-3-isobutylxanthine	decreases expression, affects cotreatment	1
Isotretinoin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00781027	PHASE4	COMPLETED	Fuchs’ Torsional Phaco Study
NCT03249337	PHASE4	RECRUITING	Glanatec(R) for Descemet Stripping in Fuch’s Endothelial Dystrophy
NCT05716945	PHASE4	RECRUITING	The OPTIMISE Study
NCT03248037	PHASE3	COMPLETED	Trial of Netarsudil for Prevention of Corticosteroid-induced Intraocular Pressure Elevation
NCT05275972	PHASE3	RECRUITING	Descemet Endothelial Thickness Comparison Trial II
NCT06048380	PHASE3	RECRUITING	The Effects of Ripasudil in Patients With FED Undergoing Femtosecond Laser Assisted Cataract Surgery
NCT02834260	PHASE2	COMPLETED	Immunosuppression During Penetrating Keratoplasty, Using a Subconjunctival Implant Releasing Dexamethasone : Tolerance and Safety Pilot Study
NCT03575130	PHASE2	UNKNOWN	Ripasudil 0.4% Eye Drops in Fuchs Endothelial Corneal Dystrophy
NCT03813056	PHASE2	UNKNOWN	Ripasudil for Enhanced Corneal Clearing Following Descemet Membrane Endothelial Keratoplasty in Fuchs’ Dystrophy
NCT04676737	PHASE2	COMPLETED	TTHX1114(NM141) in Combination With DWEK/DSO
NCT04191629	PHASE1	UNKNOWN	Phase 1 Study to Evaluate the Safety and Tolerability of EO1404 in the Treatment of Corneal Edema
NCT04319848	PHASE1	RECRUITING	Safety and Efficacy of Tissue Engineered Endothelial Keratoplasty
NCT05636579	PHASE1	RECRUITING	Study to Assess Safety and Tolerability of Multiple Doses of EO2002
NCT07325097	PHASE1	RECRUITING	PVEK Corneal Implant For Treatment of Corneal Edema
NCT00800111	Not specified	COMPLETED	Study of Endothelial Keratoplasty Outcomes
NCT02020044	Not specified	UNKNOWN	Outcome After Descemet Membrane Endothelial Keratoplasty (DMEK) and Ultra-thin Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)
NCT04387331	Not specified	UNKNOWN	The Postoperative Head Position as a Predictor of the Surgical Outcome After DMEK
NCT03971357	PHASE2/PHASE3	TERMINATED	Trial of Netarsudil for Acceleration of Corneal Endothelial Restoration
NCT04018417	PHASE2/PHASE3	WITHDRAWN	Evaluation of Amphotericin B in Optisol-GS for Prevention of Post-Keratoplasty Fungal Infections.
NCT04051463	PHASE2/PHASE3	COMPLETED	Rhopressa for Corneal Edema Associated With Fuchs Dystrophy
NCT03275896	EARLY_PHASE1	UNKNOWN	Evaluation of the Efficacy of Descemet Membrane Transplantation for the Treatment of Fuchs’ Endothelial Dystrophy
NCT04057053	EARLY_PHASE1	COMPLETED	Netarsudil Use After Descemetorhexis Without Endothelial Keratoplasty
NCT04752020	EARLY_PHASE1	COMPLETED	Netarsudil Use After Descemtorhexis Without Endothelial Keratoplasty
NCT00624221	Not specified	COMPLETED	Study of Eye Bank Pre-cut Donor Grafts for Endothelial Keratoplasty
NCT01206127	Not specified	UNKNOWN	DSAEK- Postoperative Positioning and Transplant Dislocation
NCT01361282	Not specified	TERMINATED	Using the Optovue OCT to Select IOL Power
NCT01586234	Not specified	TERMINATED	OCT-guided DSAEK Graft Shaping and Smoothing
NCT01795001	Not specified	COMPLETED	The Molecular Pathogenesis of Late-onset Fuchs’ Endothelial Corneal Dystrophy
NCT02118922	Not specified	RECRUITING	A Study to Test the Diagnostic Potential of Brillouin Microscopy for Corneal Ectasia
NCT02332109	Not specified	COMPLETED	ODM 5 in the Treatment of Corneal Edematous Fuchs’ Endothelial Dystrophy
NCT02423161	Not specified	COMPLETED	PIONEER: Intraoperative and Perioperative OCT Study
NCT02423213	Not specified	RECRUITING	DISCOVER Study: Microscope-integrated Intraoperative OCT Study
NCT02470793	Not specified	COMPLETED	Technique And Results In Endothelial Keratoplasty
NCT02542644	Not specified	COMPLETED	Assessment of Corneal Graft Attachment in Patients With Fuchs Endothelial Corneal Dystrophy Following DMEK Using Ultra-high Resolution OCT
NCT02793310	Not specified	COMPLETED	DMEK Versus DSAEK Study
NCT02849808	Not specified	COMPLETED	Long Term Cornea Graft Survival Study
NCT02875145	Not specified	COMPLETED	Impact of Cataract Surgery on Keratoplasty Graft Survival
NCT03407755	Not specified	UNKNOWN	Air Versus SF6 for Descemet’s Membrane Endothelial Keratoplasty (DMEK)
NCT04072029	Not specified	COMPLETED	Risk Assessment for Progression to DMEK Following Cataract Surgery in Fuchs Endothelial Corneal Dystrophy
NCT04140422	Not specified	COMPLETED	Eye Drops for Early Morning-Associated Corneal Swelling of the Cornea