CTTN
protein-codingcortactin
Gene summary
This gene is overexpressed in breast cancer and squamous cell carcinomas of the head and neck. The encoded protein is localized in the cytoplasm and in areas of the cell-substratum contacts. This gene has two roles: (1) regulating the interactions between components of adherens-type junctions and (2) organizing the cytoskeleton and cell adhesion structures of epithelia and carcinoma cells. During apoptosis, the encoded protein is degraded in a caspase-dependent manner. The aberrant regulation of this gene contributes to tumor cell invasion and metastasis. Three splice variants that encode different isoforms have been identified for this gene. [provided by RefSeq, May 2010]
- EMS1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.2 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 CTTN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005231.4. 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 | 3 | 2 | 2 | 7 | ||
| missense | 70 | 3 | 73 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 78 | 5 | 2 | 85 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005222.2 | 16 | MANE Select | |
| Ensembl | ENSP00000301843.8 | 16 | MANE Select | |
| RefSeq | NP_001171669.1 | 17 | Standard | |
| RefSeq | NP_612632.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tight junction - Homo sapiens (human)
- Bacterial invasion of epithelial cells - Homo sapiens (human)
- Shigellosis - Homo sapiens (human)
- Pathogenic Escherichia coli infection - Homo sapiens (human)
- Proteoglycans in cancer - Homo sapiens (human)
Biological Process
- intracellular protein transport
- receptor-mediated endocytosis
- substrate-dependent cell migration, cell extension
- actin filament polymerization
- regulation of axon extension
Molecular Function
- protein binding
- profilin binding
- cadherin binding
Cellular Component
- ruffle
- podosome
- cytoplasm
- Golgi apparatus
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376561
- Coding exons
- 17
- Length
- 38181
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125748
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.868 | 352 | 401 | 0.878 | 0.0000256 | 4147 |
| Missense (PolyPhen) | 143 | 200.61 | 0.71281 | 2070 | ||
| Synonymous | -0.479 | 182 | 174 | 1.05 | 0.0000134 | 1168 |
| Loss of Function | 4.34 | 10 | 39.4 | 0.254 | 0.00000203 | 435 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00079 | 0.00079 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Contributes to the organization of the actin cytoskeleton and cell shape (PubMed:21296879). Plays a role in the formation of lamellipodia and in cell migration. Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones (By similarity). Through its interaction with CTTNBP2, involved in the regulation of neuronal spine density (By similarity). Plays a role in the invasiveness of cancer cells, and the formation of metastases (PubMed:16636290). Plays a role in focal adhesion assembly and turnover (By similarity). In complex with ABL1 and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement (PubMed:20861316). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (PubMed:17959782). Plays a role in receptor-mediated endocytosis via clathrin-coated pits (By similarity). Required for stabilization of KCNH1 channels at the cell membrane (PubMed:23144454). {ECO:0000250|UniProtKB:Q60598, ECO:0000250|UniProtKB:Q66HL2, ECO:0000269|PubMed:16636290, ECO:0000269|PubMed:17959782, ECO:0000269|PubMed:21296879, ECO:0000269|PubMed:23144454}.;
Recessive Scores
- pRec
- 0.586
Intolerance Scores
- LoFtool
- 0.542
- RVIS EVS
- -0.51
- RVIS percentile EVS
- 21.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.798
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |