CLSTN1
protein-codingcalsyntenin 1, the group of Cadherin related
Gene summary
This gene is a member of the calsyntenin family, a subset of the cadherin superfamily. The encoded transmembrane protein, also known as alcadein-alpha, is thought to bind to kinesin-1 motors to mediate the axonal anterograde transport of certain types of vesicle. Amyloid precursor protein (APP) is trafficked via these vesicles and so this protein is being investigated to see how it might contribute to the mechanisms underlying Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~95.1 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 CLSTN1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001009566.3. 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 | 5 | 2 | 2 | 9 | ||
| missense | 148 | 5 | 1 | 154 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 159 | 7 | 3 | 169 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001009566.1 | 19 | MANE Select | |
| Ensembl | ENSP00000366513.4 | 19 | MANE Select | |
| RefSeq | NP_001289812.1 | 18 | Standard | |
| RefSeq | NP_055759.3 | 18 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| clstn1 | Danio rerio | Structure: Rohon-Beard neuron Quality: decreased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Splicing factor NOVA regulated synaptic proteins
Biological Process
- regulation of cell growth
- cell adhesion
- homophilic cell adhesion via plasma membrane adhesion molecules
- positive regulation of synaptic transmission
- positive regulation of synapse assembly
Molecular Function
- amyloid-beta binding
- calcium ion binding
- protein binding
- kinesin binding
- X11-like protein binding
Cellular Component
- Golgi membrane
- extracellular region
- nucleus
- endoplasmic reticulum membrane
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000377298
- Coding exons
- 19
- Length
- 95501
- Individuals with no LoFs
- 125736
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 12
- Defined
- 125748
- p
- 0.0000477
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.02 | 525 | 595 | 0.882 | 0.0000384 | 6483 |
| Missense (PolyPhen) | 181 | 230.2 | 0.78626 | 2471 | ||
| Synonymous | -0.807 | 280 | 263 | 1.06 | 0.0000206 | 1886 |
| Loss of Function | 5.26 | 8 | 46.9 | 0.171 | 0.00000235 | 547 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Induces KLC1 association with vesicles and functions as a cargo in axonal anterograde transport. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2- mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation. In complex with APBA2 and C99, a C-terminal APP fragment, abolishes C99 interaction with PSEN1 and thus APP C99 cleavage by gamma-secretase, most probably through stabilization of the direct interaction between APBA2 and APP. The intracellular fragment AlcICD suppresses APBB1-dependent transactivation stimulated by APP C-terminal intracellular fragment (AICD), most probably by competing with AICD for APBB1- binding. May modulate calcium-mediated postsynaptic signals (By similarity). {ECO:0000250, ECO:0000269|PubMed:12972431}.;
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- LoFtool
- 0.289
- RVIS EVS
- -1.05
- RVIS percentile EVS
- 7.6
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.814
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |