COL8A2

collagen type VIII alpha 2 chain, the group of Collagens|C1q domain containing

Basic information

Region (hg38): 1:36095239-36125222

Previous symbols: [ "FECD" ]

Links

ENSG00000171812

∙ NCBI:1296 ∙ OMIM:120252 ∙ HGNC:2216 ∙ Uniprot:P25067 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

posterior polymorphous corneal dystrophy (Supportive), mode of inheritance: AD
Fuchs' endothelial dystrophy (Supportive), mode of inheritance: AD
corneal dystrophy, Fuchs endothelial, 1 (Strong), mode of inheritance: AD
posterior polymorphous corneal dystrophy 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Corneal dystrophy polymorphous posterior, 2; Corneal dystrophy, Fuchs endothelial, 1	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	399801; 11689488; 15914606; 18024822; 18464802

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL8A2 gene.

Inborn_genetic_diseases (102 variants)
not_provided (56 variants)
COL8A2-related_disorder (9 variants)
Posterior_polymorphous_corneal_dystrophy_2 (4 variants)
Corneal_dystrophy,_Fuchs_endothelial,_1 (4 variants)
not_specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL8A2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005202.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				12 clinvar	8 clinvar	20
missense	3 clinvar		111 clinvar	9 clinvar	5 clinvar	128
nonsense						0
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)						0
Total	3	0	114	21	13

Highest pathogenic variant AF is 0.0000028606532

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL8A2	protein_coding	protein_coding	ENST00000397799	2	29985

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.118	0.877	125714	0	14	125728	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	304	391	0.777	0.0000220	4224
Missense in Polyphen		47	72.284	0.65021		768
Synonymous	-1.14	205	185	1.11	0.0000122	1727
Loss of Function	2.45	4	13.8	0.290	7.32e-7	177

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000633	0.0000633
Ashkenazi Jewish	0.00	0.00
East Asian	0.000281	0.000272
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000549	0.0000528
Middle Eastern	0.000281	0.000272
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Macromolecular component of the subendothelium. Major component of the Descemet's membrane (basement membrane) of corneal endothelial cells. Also 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 (By similarity). {ECO:0000250}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:11689488}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:11689488}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Assembly of collagen fibrils and other multimeric structures;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Integrin (Consensus)

Recessive Scores

pRec: 0.185

Haploinsufficiency Scores

pHI: 0.554
hipred: Y
hipred_score: 0.580
ghis: 0.606

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.875

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Col8a2
Phenotype: vision/eye phenotype; cellular phenotype;

Gene ontology

Biological process: angiogenesis;extracellular matrix organization;camera-type eye morphogenesis;epithelial cell proliferation;cell-cell adhesion
Cellular component: extracellular region;collagen trimer;basement membrane;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
Molecular function: extracellular matrix structural constituent;extracellular matrix structural constituent conferring tensile strength;protein binding, bridging