KERA
protein-codingkeratocan, the group of Small leucine rich repeat proteoglycans
Gene summary
The protein encoded by this gene is a keratan sulfate proteoglycan that is involved in corneal transparency. Defects in this gene are a cause of autosomal recessive cornea plana 2 (CNA2).[provided by RefSeq, May 2010]
- CNA2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0018888
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0000733
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0009014
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009014
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009014
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KERA variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_007035.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 11 | 1 | 13 | ||
| missense | 4 | 3 | 57 | 4 | 68 | |
| nonsense | 4 | 2 | 6 | |||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 4 | 6 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 10 | 9 | 60 | 15 | 1 | 95 |
Highest pathogenic variant AF is 0.0003924057
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_008966.1 | 2 | MANE Select | |
| Ensembl | ENSP00000266719.3 | 2 | MANE Select |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| kera | Danio rerio | Structure: whole organism Quality: dead abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Metabolism of carbohydrates
- Keratan sulfate biosynthesis
- Keratan sulfate/keratin metabolism
- Glycosaminoglycan metabolism
- Metabolism
Biological Process
- visual perception
- keratan sulfate biosynthetic process
- keratan sulfate catabolic process
- response to stimulus
- cornea development in camera-type eye
Molecular Function
- molecular_function
Cellular Component
- extracellular region
- Golgi lumen
- extracellular matrix
- lysosomal lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000266719
- Coding exons
- 2
- Length
- 7493
- Individuals with no LoFs
- 125545
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 38
- Defined
- 125583
- p
- 0.000151
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.324 | 191 | 179 | 1.07 | 0.00000837 | 2324 |
| Missense (PolyPhen) | 42 | 42.629 | 0.98525 | 593 | ||
| Synonymous | -1.27 | 79 | 65.8 | 1.20 | 0.00000312 | 673 |
| Loss of Function | 0.305 | 11 | 12.1 | 0.906 | 7.01e-7 | 151 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be important in developing and maintaining corneal transparency and for the structure of the stromal matrix. {ECO:0000305|PubMed:10802664, ECO:0000305|PubMed:11726611}.;
- Disease
- DISEASE: Cornea plana 2, autosomal recessive (CNA2) [MIM:217300]: A severe form of cornea plana, a rare ocular disorder characterized by flattened corneal curvature leading to a decrease in refraction, reduced visual activity, hyperopia, hazy corneal limbus, opacities in the corneal parenchyma, and marked arcus senilis often detected at an early age. CNA2 patients manifest extreme hyperopia and additional ocular anomalies such as malformations of the iris, a slit-like pupil, and adhesions between iris and cornea. {ECO:0000269|PubMed:10802664, ECO:0000269|PubMed:11726611}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.265
Intolerance Scores
- LoFtool
- 0.598
- RVIS EVS
- -0.45
- RVIS percentile EVS
- 24.19
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.219
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |