GSN
gelsolin, the group of Gelsolin/villins
Basic information
Region (hg38): 9:121207794-121332843
Links
Phenotypes
GenCC
Source:
- Finnish type amyloidosis (Moderate), mode of inheritance: AD
- Finnish type amyloidosis (Supportive), mode of inheritance: AD
- Finnish type amyloidosis (Strong), mode of inheritance: AD
- Finnish type amyloidosis (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Amyloidosis, Finnish type | AD | Cardiovascular | Individuals with cardiac conduction disease have been described, and surveillance (eg, with electocardiogram) may allow early management (eg, with pacemaker) | Cardiovascular; Dermatologic; Neurologic; Ophthalmologic; Renal | 4543600; 2153578; 2176164; 1322359; 1311149; 1315718; 8395367; 8684801; 11754099; 16258946; 22068858; 22622774 |
| Recessive disease has been reported as resulting in a more severe phenotype |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (714 variants)
- Finnish_type_amyloidosis (233 variants)
- Inborn_genetic_diseases (184 variants)
- GSN-related_disorder (26 variants)
- not_specified (20 variants)
- Amyloidosis (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the GSN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000198252.3. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 156 | 162 | ||||
| missense | 340 | 53 | 404 | |||
| nonsense | 7 | |||||
| start loss | 0 | |||||
| frameshift | 18 | 18 | ||||
| splice donor/acceptor (+/-2bp) | 11 | 12 | ||||
| Total | 3 | 2 | 380 | 210 | 8 |
Highest pathogenic variant AF is 0.00000495667
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| GSN | protein_coding | protein_coding | ENST00000373818 | 17 | 125050 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 3.89e-11 | 0.982 | 125664 | 0 | 84 | 125748 | 0.000334 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.962 | 401 | 459 | 0.874 | 0.0000308 | 5034 |
| Missense in Polyphen | 156 | 189.86 | 0.82167 | 2090 | ||
| Synonymous | 0.427 | 189 | 197 | 0.961 | 0.0000146 | 1604 |
| Loss of Function | 2.37 | 23 | 38.9 | 0.591 | 0.00000190 | 433 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000710 | 0.000709 |
| Ashkenazi Jewish | 0.000199 | 0.000198 |
| East Asian | 0.000601 | 0.000598 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000372 | 0.000369 |
| Middle Eastern | 0.000601 | 0.000598 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.000490 | 0.000489 |
dbNSFP
Source:
- Function
- FUNCTION: Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed. Plays a role in ciliogenesis. {ECO:0000269|PubMed:20393563}.;
- Disease
- DISEASE: Amyloidosis 5 (AMYL5) [MIM:105120]: A hereditary generalized amyloidosis due to gelsolin amyloid deposition. It is typically characterized by cranial neuropathy and lattice corneal dystrophy. Most patients have modest involvement of internal organs, but severe systemic disease can develop in some individuals causing peripheral polyneuropathy, amyloid cardiomyopathy, and nephrotic syndrome leading to renal failure. {ECO:0000269|PubMed:1338910, ECO:0000269|PubMed:2176481}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Fc gamma R-mediated phagocytosis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Regulation of Actin Cytoskeleton;Senescence and Autophagy in Cancer;Neutrophil degranulation;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;hiv-1 nef: negative effector of fas and tnf;rho cell motility signaling pathway;Caspase-mediated cleavage of cytoskeletal proteins;Apoptotic cleavage of cellular proteins;Innate Immune System;Immune System;Apoptotic execution phase;Apoptosis;Programmed Cell Death;AndrogenReceptor;EGFR1;Coregulation of Androgen receptor activity;Caspase Cascade in Apoptosis;Osteopontin-mediated events;N-cadherin signaling events
(Consensus)
Recessive Scores
- pRec
- 0.752
Intolerance Scores
- loftool
- 0.888
- rvis_EVS
- 0.61
- rvis_percentile_EVS
- 82.94
Haploinsufficiency Scores
- pHI
- 0.234
- hipred
- Y
- hipred_score
- 0.706
- ghis
- 0.507
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.981
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Gsn
- Phenotype
- mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- phagocytosis, engulfment;aging;positive regulation of gene expression;oligodendrocyte development;striated muscle atrophy;extracellular matrix disassembly;actin filament polymerization;regulation of cell adhesion;protein destabilization;tissue regeneration;sequestering of actin monomers;neutrophil degranulation;cellular protein metabolic process;actin nucleation;response to ethanol;negative regulation of viral entry into host cell;phosphatidylinositol-mediated signaling;actin filament severing;barbed-end actin filament capping;positive regulation of actin nucleation;response to folic acid;actin filament capping;cilium assembly;cellular response to cadmium ion;cellular response to interferon-gamma;regulation of podosome assembly;actin filament reorganization;renal protein absorption;hepatocyte apoptotic process;positive regulation of keratinocyte apoptotic process;regulation of establishment of T cell polarity;regulation of plasma membrane raft polarization;regulation of receptor clustering;positive regulation of protein processing in phagocytic vesicle;amyloid fibril formation;positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
- Cellular component
- ruffle;podosome;extracellular region;extracellular space;nucleus;cytoplasm;cytosol;plasma membrane;focal adhesion;actin cytoskeleton;sarcoplasm;lamellipodium;actin cap;cortical actin cytoskeleton;secretory granule lumen;myelin sheath;phagocytic vesicle;perinuclear region of cytoplasm;extracellular exosome;blood microparticle;ficolin-1-rich granule lumen
- Molecular function
- actin binding;calcium ion binding;protein binding;myosin II binding;actin filament binding