COL8A1

Summary

COL8A1 (collagen type VIII alpha 1 chain, HGNC:2215) is a protein-coding gene on chromosome 3q12.1, encoding Collagen alpha-1(VIII) chain (P27658). Macromolecular component of the subendothelium.

This gene encodes one of the two alpha chains of type VIII collagen. The gene product is a short chain collagen and a major component of the basement membrane of the corneal endothelium. The type VIII collagen fibril can be either a homo- or a heterotrimer. Alternatively spliced transcript variants encoding the same protein have been observed.

Source: NCBI Gene 1295 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_020351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2215
Approved symbol	COL8A1
Name	collagen type VIII alpha 1 chain
Location	3q12.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC9568
Ensembl gene	ENSG00000144810
Ensembl biotype	protein_coding
OMIM	120251
Entrez	1295

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 42 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000261037, ENST00000273342, ENST00000452013, ENST00000462604, ENST00000463753, ENST00000474648, ENST00000483969, ENST00000621757, ENST00000652472, ENST00000895751, ENST00000895752, ENST00000895753, ENST00000895754, ENST00000895755, ENST00000895756, ENST00000895757, ENST00000895758, ENST00000895759, ENST00000895760, ENST00000895761, ENST00000895762, ENST00000895763, ENST00000895764, ENST00000895765, ENST00000895766, ENST00000895767, ENST00000895768, ENST00000895769, ENST00000895770, ENST00000895771, ENST00000895772, ENST00000895773, ENST00000895774, ENST00000895775, ENST00000968979, ENST00000968980, ENST00000968981, ENST00000968982, ENST00000968983, ENST00000968984, ENST00000968985, ENST00000968986, ENST00000968987, ENST00000968988, ENST00000968989, ENST00000968990

RefSeq mRNA: 2 — MANE Select: NM_020351 NM_001850, NM_020351

CCDS: CCDS2934

Canonical transcript exons

ENST00000652472 — 4 exons

Exon	Start	End
ENSE00001210506	99744897	99745021
ENSE00003845214	99794230	99799217
ENSE00003850480	99638594	99638664
ENSE00003894636	99790680	99791010

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 99.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 90.3713 / max 5000.3774, expressed in 1082 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37571	89.1414	1080
37576	0.7414	257
37575	0.3169	153
37573	0.1716	99

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
visceral pleura	UBERON:0002401	99.34	gold quality
pigmented layer of retina	UBERON:0001782	99.13	gold quality
right coronary artery	UBERON:0001625	98.85	gold quality
popliteal artery	UBERON:0002250	98.51	gold quality
tibial artery	UBERON:0007610	98.51	gold quality
sural nerve	UBERON:0015488	98.45	gold quality
parietal pleura	UBERON:0002400	98.39	gold quality
germinal epithelium of ovary	UBERON:0001304	98.36	gold quality
aorta	UBERON:0000947	98.33	gold quality
thoracic aorta	UBERON:0001515	98.26	gold quality
ascending aorta	UBERON:0001496	98.23	gold quality
stromal cell of endometrium	CL:0002255	98.22	gold quality
artery	UBERON:0001637	98.21	gold quality
descending thoracic aorta	UBERON:0002345	97.75	gold quality
left coronary artery	UBERON:0001626	97.15	gold quality
pleura	UBERON:0000977	96.96	gold quality
coronary artery	UBERON:0001621	96.76	gold quality
pericardium	UBERON:0002407	96.47	gold quality
tibia	UBERON:0000979	95.35	gold quality
lower lobe of lung	UBERON:0008949	94.27	gold quality
calcaneal tendon	UBERON:0003701	93.87	gold quality
tendon	UBERON:0000043	91.67	gold quality
saphenous vein	UBERON:0007318	91.25	gold quality
tibial nerve	UBERON:0001323	90.61	gold quality
right atrium auricular region	UBERON:0006631	90.44	gold quality
upper lobe of lung	UBERON:0008948	90.34	gold quality
right lung	UBERON:0002167	90.11	gold quality
upper lobe of left lung	UBERON:0008952	89.95	gold quality
left lobe of thyroid gland	UBERON:0001120	89.77	gold quality
tendon of biceps brachii	UBERON:0008188	89.64	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-10290	yes	827.00
E-HCAD-36	yes	706.40
E-GEOD-135922	yes	37.34
E-MTAB-8410	yes	35.03
E-ANND-3	yes	17.02
E-GEOD-130148	yes	5.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KLF4, SP1

miRNA regulators (miRDB)

84 targeting COL8A1, 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-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-223-3P	99.99	70.14	1140
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 25)

• 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)
• 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)
• 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)
• In addition, eight genes classified as ‘second tier’ hits in the original study (PAX7, THADA, COL8A1/FILIP1L, DCAF4L2, GADD45G, NTN1, RBFOX3 and FOXE1) showed evidence of linkage and association in this replication sample. (PMID:23512105)
• The results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions. (PMID:23533600)
• Data indicate that complement factor H (CFH) R1210C and common variants in COL8A1 and RAD51B plus six genes contribute predictive information for advanced macular degeneration (AMD) beyond macular and behavioral phenotypes. (PMID:24498017)
• High COL8A1 expression is associated with early loss of kidney function. (PMID:26110394)
• The COL8A1 rs13095226 polymorphism is not associated with nAMD or PCV, which suggesting this gene maybe not a susceptibility gene locus for neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) in Chinese subjects. (PMID:26617902)
• High COL8A1 level is associated with chronic obstructive pulmonary disease and cancer. (PMID:27234597)
• COL8A1 was identified and proved to be correlated with the progression and prognosis of human colon adenocarcinoma, probably through regulating focal adhesion-related pathways. (PMID:29497907)
• We demonstrated the presence of Col8a1 in Bruch’s membrane, further supporting the role of COL8A1 variants in AMD pathogenesis. Protein-altering variants in COL8A1 may alter the integrity of Bruch’s membrane, contributing to the accumulation of drusen and the development of AMD. (PMID:29706360)
• Polymorphisms in COL8A1 is associated with Polycystic ovary syndrome and type-2 diabetes. (PMID:30555071)
• Serum vastatin (the NC1 domain of human type VIII collagen a1 chain) was detectable in 114 of 115 colorectal cancer (CRC) subjects and was elevated in blood of CRC patients compared to controls. Vastatin correlated with age in controls but not in patients with CRC. Results indicate that vastatin is linked to stromal reactivity and suggests that vastatin has biomarker potential in CRC. (PMID:30626261)
• COL8A1 rs13095226 is strongly associated with exudative age-related macular degeneration risk. (PMID:31191752)
• three polymorphisms located in COL6A5, COL8A1, and COL10A1 were investigated as potential susceptibility biomarkers for atopic eczema. (PMID:31275967)
• Single nucleotide polymorphisms in the COL8A1 gene is associated with idiopathic choroidal neovascularization. (PMID:31512979)
• RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects. (PMID:32326527)
• Serum Levels of ARMS2, COL8A1, RAD51B, and VEGF and their Correlations in Age-related Macular Degeneration. (PMID:34060991)
• COL8A1 facilitates the growth of triple-negative breast cancer via FAK/Src activation. (PMID:35624176)
• Tumor and stroma COL8A1 secretion induces autocrine and paracrine progression signaling in pancreatic ductal adenocarcinoma. (PMID:36375776)
• COL8A1 enhances the invasion/metastasis in MDA-MB-231 cells via the induction of IL1B and MMP1 expression. (PMID:36577251)
• Molecular prognostic of nine parthanatos death-related genes in glioma, particularly in COL8A1 identification. (PMID:38225203)
• COL8A1 Regulates Esophageal Squamous Carcinoma Proliferation and Invasion Through PI3K/AKT Pathway. (PMID:38429534)
• Two patients with Knobloch syndrome due to mutation in COL8A1 gene: case report and review of the literature. (PMID:38575892)
• COL8A1 is a potential prognostic biomarker associated with migration, proliferation, and tumor microenvironment in glioma. (PMID:38719174)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	col8a1b	ENSDARG00000003533
mus_musculus	Col8a1	ENSMUSG00000068196
rattus_norvegicus	Col8a1	ENSRNOG00000039668

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), 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-1(VIII) chain — P27658 (reviewed: P27658)

Alternative names: Endothelial collagen

All UniProt accessions (3): P27658, A0A087WZI0, C9JTN9

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. Vastatin, the C-terminal fragment comprising the NC1 domain, inhibits aortic endothelial cell proliferation and causes cell apoptosis.

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. Specifically expressed in peritoneal fibroblasts and mesothelial cells.

Post-translational modifications. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains. Proteolytically cleaved by neutrophil elastase, in vitro. Proteolytic processing produces the C-terminal NC1 domain fragment, vastatin.

Induction. Up-regulated during vascular injury, in atherosclerosis and in diabetes.

Miscellaneous. Four consecutive Gly-Pro-Pro triplets are present at the C-terminus of the triple-helical region. These may provide the high thermal stability of this region.

RefSeq proteins (2): NP_001841, NP_065084* (*=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 (25 total): sequence conflict 9, compositionally biased region 7, region of interest 5, chain 2, signal peptide 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27658-F1	58.10	0.20

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: 242 (showing top): MORF_ITGA2, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, RNGTGGGC_UNKNOWN, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, BENPORATH_ES_WITH_H3K27ME3, MACLACHLAN_BRCA1_TARGETS_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOCC_COLLAGEN_TRIMER, GCANCTGNY_MYOD_Q6, MCBRYAN_PUBERTAL_TGFB1_TARGETS_UP, GOBP_EXTRACELLULAR_MATRIX_ASSEMBLY, MEF2_02, FOXO4_01, MORF_RAD51L3

GO Biological Process (7): angiogenesis (GO:0001525), endothelial cell proliferation (GO:0001935), cell adhesion (GO:0007155), positive regulation of cell-substrate adhesion (GO:0010811), endodermal cell differentiation (GO:0035987), camera-type eye morphogenesis (GO:0048593), basement membrane assembly (GO:0070831)

GO Molecular Function (2): extracellular matrix structural constituent conferring tensile strength (GO:0030020), protein binding (GO:0005515)

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

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
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
epithelial cell proliferation	1
cellular process	1
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
endoderm formation	1
cell differentiation	1
camera-type eye development	1
eye morphogenesis	1
basement membrane organization	1
extracellular matrix assembly	1
extracellular matrix structural constituent	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
extracellular matrix	1

Protein interactions and networks

STRING

2036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL8A1	GP6	Q9HCN6	945
COL8A1	DR1	Q01658	762
COL8A1	VWF	P04275	644
COL8A1	B3GLCT	Q6Y288	632
COL8A1	ARMS2	P0C7Q2	596
COL8A1	SLC16A8	O95907	580
COL8A1	ITGA2	P17301	538
COL8A1	TGFBR1	P36897	532
COL8A1	ADAMTS2	O95450	521
COL8A1	F3	P13726	519
COL8A1	FILIP1L	Q4L180	505
COL8A1	HAPLN1	P10915	504
COL8A1	ADAMTS4	O75173	500
COL8A1	COL1A1	P02452	494
COL8A1	ADAMTS9	Q9P2N4	483

IntAct

265 interactions, top by confidence:

A	B	Type	Score
VAC14	COL8A1	psi-mi:“MI:0915”(physical association)	0.780
INCA1	COL8A1	psi-mi:“MI:0915”(physical association)	0.780
COL8A1	INCA1	psi-mi:“MI:0915”(physical association)	0.780
COL8A1	VAC14	psi-mi:“MI:0915”(physical association)	0.780
KRTAP10-8	COL8A1	psi-mi:“MI:0915”(physical association)	0.720
CREB5	COL8A1	psi-mi:“MI:0915”(physical association)	0.720
COL8A1	CREB5	psi-mi:“MI:0915”(physical association)	0.720
COL8A1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP26-1	COL8A1	psi-mi:“MI:0915”(physical association)	0.600
COL8A1	KRTAP26-1	psi-mi:“MI:0915”(physical association)	0.600
COL8A1		psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	COL8A1	psi-mi:“MI:0915”(physical association)	0.560
SP4	COL8A1	psi-mi:“MI:0915”(physical association)	0.560
REL	COL8A1	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	KRT40	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.560
KRTAP9-2	COL8A1	psi-mi:“MI:0915”(physical association)	0.560
	COL8A1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (134): REL (Two-hybrid), SP4 (Two-hybrid), CREB5 (Two-hybrid), VAC14 (Two-hybrid), KRTAP9-2 (Two-hybrid), KRT40 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), INCA1 (Two-hybrid), NOTCH2NL (Two-hybrid), KRTAP26-1 (Two-hybrid), KLHL12 (Two-hybrid), KRTAP4-12 (Two-hybrid), EFEMP2 (Two-hybrid)

ESM2 similar proteins: A8WR59, C0HJB4, C0HLL1, C0HLN2, C0HLQ6, C0HM51, E2IYB3, O35167, O35348, O76368, P02456, P08125, P12114, P14282, P18856, P20850, P20909, P22800, P23206, P23805, P25067, P25318, P25508, P27658, P30251, P30252, P53420, P55787, P56683, P58522, P81130, P86290, Q00780, Q03637, Q05306, Q07643, Q14031, Q14055, Q28084, Q60754

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 68 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	20	26.5×	1e-22

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1340 predictions. Top by Δscore:

Variant	Effect	Δscore
3:99638661:CAAGG:C	donor_loss	1.0000
3:99638662:AAGGT:A	donor_loss	1.0000
3:99744895:A:AG	acceptor_gain	1.0000
3:99744896:G:GG	acceptor_gain	1.0000
3:99744962:G:GT	donor_gain	1.0000
3:99745022:G:GG	donor_gain	1.0000
3:99638665:G:GG	donor_gain	0.9900
3:99638666:T:G	donor_loss	0.9900
3:99675637:T:A	acceptor_gain	0.9900
3:99722806:G:GT	donor_gain	0.9900
3:99744893:TTA:T	acceptor_loss	0.9900
3:99744895:A:T	acceptor_loss	0.9900
3:99744896:GA:G	acceptor_gain	0.9900
3:99744896:GAA:G	acceptor_gain	0.9900
3:99744896:GAAGC:G	acceptor_gain	0.9900
3:99745010:TC:T	donor_gain	0.9900
3:99745019:AAT:A	donor_gain	0.9900
3:99745019:AATG:A	donor_loss	0.9900
3:99745020:ATGT:A	donor_loss	0.9900
3:99745021:TG:T	donor_loss	0.9900
3:99745022:GTAA:G	donor_loss	0.9900
3:99745023:TA:T	donor_loss	0.9900
3:99745024:A:AT	donor_loss	0.9900
3:99794225:A:AG	acceptor_gain	0.9900
3:99794226:G:GG	acceptor_gain	0.9900
3:99794226:GTA:G	acceptor_gain	0.9900
3:99794226:GTAGA:G	acceptor_gain	0.9900
3:99744890:A:AG	acceptor_gain	0.9800
3:99744963:A:T	donor_gain	0.9800
3:99745020:AT:A	donor_gain	0.9800

AlphaMissense

4678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:99795754:T:C	F618S	0.999
3:99795859:T:C	F653S	0.999
3:99795882:T:G	Y661D	0.999
3:99795894:T:G	Y665D	0.999
3:99795753:T:C	F618L	0.998
3:99795755:T:A	F618L	0.998
3:99795755:T:G	F618L	0.998
3:99795759:G:C	A620P	0.998
3:99795866:T:G	C655W	0.998
3:99795889:T:C	F663S	0.998
3:99795901:T:A	V667D	0.998
3:99795934:T:C	L678P	0.998
3:99796008:A:C	S703R	0.998
3:99796010:T:A	S703R	0.998
3:99796010:T:G	S703R	0.998
3:99796108:T:C	F736S	0.998
3:99795754:T:G	F618C	0.997
3:99795837:T:G	Y646D	0.997
3:99795865:G:A	C655Y	0.997
3:99795930:G:C	A677P	0.997
3:99796002:T:C	S701P	0.997
3:99796005:G:T	G702W	0.997
3:99796011:G:C	A704P	0.997
3:99796114:G:A	G738E	0.997
3:99795430:G:A	G510E	0.996
3:99795760:C:A	A620D	0.996
3:99795805:T:C	F635S	0.996
3:99795853:G:T	G651V	0.996
3:99795864:T:C	C655R	0.996
3:99795999:G:C	A700P	0.996

dbSNP variants (sampled 300 via entrez): RS1000021566 (3:99738959 A>G), RS1000030487 (3:99646904 C>G), RS1000032184 (3:99690209 T>C), RS1000059084 (3:99649691 G>A), RS1000079132 (3:99745673 A>C), RS1000103889 (3:99685850 C>A,T), RS1000160569 (3:99729328 G>A,C), RS1000171423 (3:99687227 T>G), RS1000186311 (3:99709034 C>G,T), RS1000196260 (3:99670092 T>C), RS1000225609 (3:99774348 AT>A,ATT), RS1000226082 (3:99787525 G>A,C), RS1000230530 (3:99684414 G>A), RS1000233235 (3:99714566 C>T), RS1000237372 (3:99764785 C>T)

Disease associations

OMIM: gene MIM:120251 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000653_1	Age-related macular degeneration	3.000000e-06
GCST001884_18	Age-related macular degeneration	4.000000e-13
GCST002115_7	Axial length	5.000000e-11
GCST002626_2	Vertical cup-disc ratio	7.000000e-10
GCST002663_11	Superior frontal gyrus grey matter volume	9.000000e-06
GCST002762_10	Optic cup area	4.000000e-08
GCST002762_25	Optic cup area	2.000000e-08
GCST003219_17	Advanced age-related macular degeneration	1.000000e-11
GCST003219_18	Advanced age-related macular degeneration	1.000000e-08
GCST003991_15	Childhood ear infection	5.000000e-08
GCST004075_32	Vertical cup-disc ratio	2.000000e-09
GCST004075_33	Vertical cup-disc ratio	9.000000e-12
GCST004076_15	Optic disc area	4.000000e-07
GCST004076_30	Optic disc area	9.000000e-09
GCST004137_2	Optic cup area	6.000000e-06
GCST004137_9	Optic cup area	2.000000e-08
GCST004166_14	Nonsyndromic cleft lip with cleft palate	4.000000e-07
GCST004166_18	Nonsyndromic cleft lip with cleft palate	5.000000e-07
GCST009404_12	Optic cup area	7.000000e-08
GCST009411_14	Optic disc area	4.000000e-08
GCST009412_15	Vertical cup-disc ratio	8.000000e-10
GCST010002_434	Refractive error	5.000000e-25
GCST90011900_84	Serum alkaline phosphatase levels	2.000000e-11
GCST90020024_1250	A body shape index	2.000000e-08
GCST90020026_455	Hip index	2.000000e-10
GCST90020026_456	Hip index	8.000000e-11
GCST90020029_1343	Waist circumference adjusted for body mass index	3.000000e-09

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0005318	axial length measurement
EFO:0006516	superior frontal gyrus grey matter volume measurement
EFO:1001492	atrophic macular degeneration
EFO:0007904	susceptibility to childhood ear infection measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0003959	cleft lip
EFO:0004533	alkaline phosphatase measurement
EFO:0007789	BMI-adjusted waist circumference
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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	3
Cadmium Chloride	decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	3
bisphenol A	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	decreases expression, decreases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
geldanamycin	increases expression	1
methyleugenol	decreases expression	1
sodium arsenate	increases abundance, decreases expression	1
3,4-dichloroaniline	decreases expression	1
beta-lapachone	decreases expression	1
methylparaben	increases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
didecyldimethylammonium	decreases expression	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	increases expression	1
nickel sulfate	decreases expression	1
butylparaben	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
diallyl trisulfide	decreases expression	1
mercuric bromide	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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