GeneBe

COL8A2

protein-coding

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

Gene summary

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. [provided by RefSeq, Jun 2014]

Previous symbols:
  • FECD

MANE transcript

NM_005202.4

Inheritance

AD

ClinVar variants

P:3U:137B:51

Top phenotype

Corneal dystrophy polymorphous posterior, 2; Corneal dystrophy, Fuchs endothelial, 1

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr1:36,095,239-36,125,222

External References & Databases

Ensembl (ENSG00000171812)NCBI Gene (1296)OMIM (120252)HGNC:2216GenCCUniProt (P25067)AlphaFoldClinVar (COL8A2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~30.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

posterior polymorphous corneal dystrophy 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0012199

Submitter: Labcorp Genetics (formerly Invitae)

corneal dystrophy, Fuchs endothelial, 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007637

Submitter: G2P

posterior polymorphous corneal dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020364

Submitter: Orphanet

Fuchs' endothelial dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0005321

Submitter: Orphanet

Clinical Genomic Database (CGD)

Corneal dystrophy polymorphous posterior, 2; Corneal dystrophy, Fuchs endothelial, 1AD

Manifestation: Ophthalmologic

Intervention: General

Rationale: 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

Refs: 399801; 11689488; 15914606; 18024822; 18464802Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COL8A2 variants in ClinVar

6 Conditions Cataloged
Inborn genetic diseasesTotal: 117
not providedTotal: 71
not specifiedTotal: 17
COL8A2-related disorderTotal: 15
Posterior polymorphous corneal dystrophy 2Total: 6
Corneal dystrophy, Fuchs endothelial, 1Total: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005202.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
28
clinvar
8
clinvar
 38
missense
3
clinvar
132
clinvar
11
clinvar
4
clinvar
 150
nonsense
0
start loss
0
frameshift
3
clinvar
 3
splice donor/acceptor (+/-2bp)
0
Total301373912191

Highest pathogenic variant AF is 0.0000028606532

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_005202.4RefSeqNP_005193.12MANE Select
ENST00000397799.2EnsemblENSP00000380901.12MANE Select
NM_001294347.2RefSeqNP_001281276.11Standard
ENST00000303143.10EnsemblENSP00000305913.42Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Assembly of collagen fibrils and other multimeric structures
  • Collagen chain trimerization
  • Collagen biosynthesis and modifying enzymes
  • Collagen formation
  • Extracellular matrix organization

Biological Process

  • angiogenesis
  • extracellular matrix organization
  • camera-type eye morphogenesis
  • epithelial cell proliferation
  • cell-cell adhesion

Molecular Function

  • extracellular matrix structural constituent
  • extracellular matrix structural constituent conferring tensile strength
  • protein binding, bridging

Cellular Component

  • extracellular region
  • collagen trimer
  • basement membrane
  • extracellular space
  • endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000397799
Coding exons
2
Length
29985
Individuals with no LoFs
125714
Homozygous LoFs
0
Heterozygous LoFs
14
Defined
125728
p
0.0000557
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.573043910.7770.00002204224
Missense (PolyPhen)4772.2840.65021768
Synonymous-1.142051851.110.00001221727
Loss of Function2.45413.80.2907.32e-7177

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000630.000058rare
Ashkenazi Jewish00.0absent
East Asian0.000280.00027rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000550.000053rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.185

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.875

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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