FSCN2
protein-codingfascin actin-bundling protein 2, retinal, the group of Fascin family
Gene summary
This gene encodes a member of the fascin protein family. Fascins crosslink actin into filamentous bundles within dynamic cell extensions. This family member is proposed to play a role in photoreceptor disk morphogenesis. A mutation in this gene results in one form of autosomal dominant retinitis pigmentosa and macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019200
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0011935
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0011935
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0011935
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0011935
Submitter: G2P
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 FSCN2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012418.4. 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 | 176 | 11 | 190 | ||
| missense | 1 | 375 | 29 | 3 | 408 | |
| nonsense | 1 | 11 | 12 | |||
| start loss | 0 | |||||
| frameshift | 15 | 1 | 16 | |||
| splice donor/acceptor (+/-2bp) | 1 | 5 | 1 | 1 | 8 | |
| Total | 0 | 3 | 409 | 207 | 15 | 634 |
Highest pathogenic variant AF is 7.3982994e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036550.1 | 5 | MANE Select | |
| Ensembl | ENSP00000388716.2 | 5 | MANE Select | |
| RefSeq | NP_001070650.1 | 5 | Standard | |
| Ensembl | ENSP00000334665.7 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- establishment or maintenance of cell polarity
- visual perception
- anatomical structure morphogenesis
- cell migration
- actin cytoskeleton organization
Molecular Function
- actin binding
- protein binding, bridging
- actin filament binding
Cellular Component
- cytoplasm
- actin cytoskeleton
- stereocilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000334850
- Coding exons
- 5
- Length
- 8735
- Individuals with no LoFs
- 123656
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 330
- Defined
- 123987
- p
- 0.00134
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.114 | 344 | 338 | 1.02 | 0.0000243 | 3251 |
| Missense (PolyPhen) | 138 | 144.8 | 0.95302 | 1466 | ||
| Synonymous | -1.82 | 175 | 147 | 1.19 | 0.0000109 | 1070 |
| Loss of Function | -0.0364 | 19 | 18.8 | 1.01 | 0.00000109 | 181 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000071 | 0.000065 | rare |
| Latino/Admixed American | 0.00085 | 0.00078 | rare |
| Ashkenazi Jewish | 0.00073 | 0.00070 | rare |
| East Asian | 0.012 | 0.012 | notable |
| Finnish | 0.00016 | 0.00014 | rare |
| European (Non-Finnish) | 0.00057 | 0.00050 | rare |
| South Asian | 0.00060 | 0.00056 | rare |
| Other | 0.00088 | 0.00083 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as an actin bundling protein. May play a pivotal role in photoreceptor cell-specific events, such as disk morphogenesis.;
Recessive Scores
- pRec
- 0.143
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.510
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |