COBL
protein-codingcordon-bleu WH2 repeat protein
Gene summary
This gene encodes a protein that contains WH2 domains (WASP, Wiskott-Aldrich syndrome protein, homology domain-2) that interact with actin. The encoded actin regulator protein is required for growth and assembly of brush border microvilli that play a role in maintaining intestinal homeostasis. A similar protein in mouse functions in midbrain neural tube closure. A pseudogene of this gene is located on chromosome X. [provided by RefSeq, Oct 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~300.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to COBL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015198.5. 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 | 2 | 3 | 4 | 9 | ||
| missense | 217 | 19 | 3 | 239 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 225 | 22 | 7 | 254 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056013.2 | 13 | MANE Select | |
| Ensembl | ENSP00000265136.7 | 13 | MANE Select | |
| RefSeq | NP_001274365.1 | 14 | Standard | |
| RefSeq | NP_001274367.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cobl | Danio rerio | Structure: ciliated epithelial cell Quality: composition abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- embryonic axis specification
- somite specification
- neural tube closure
- liver development
- actin filament polymerization
Molecular Function
- actin monomer binding
Cellular Component
- ruffle
- actin filament
- plasma membrane
- cell cortex
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000265136
- Coding exons
- 13
- Length
- 300607
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125748
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.521 | 780 | 740 | 1.05 | 0.0000435 | 8165 |
| Missense (PolyPhen) | 242 | 259.55 | 0.9324 | 2958 | ||
| Synonymous | -0.158 | 318 | 314 | 1.01 | 0.0000208 | 2640 |
| Loss of Function | 4.34 | 13 | 44.1 | 0.295 | 0.00000241 | 528 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells (By similarity). Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles. {ECO:0000250, ECO:0000269|PubMed:21816349}.;
Recessive Scores
- pRec
- 0.112
Intolerance Scores
- LoFtool
- 0.417
- RVIS EVS
- 0.55
- RVIS percentile EVS
- 81.55
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.525
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |