GSN

gelsolin, the group of Gelsolin/villins

Basic information

Region (hg38): 9:121207793-121332843

Links

ENSG00000148180 ∙ NCBI:2934 ∙ OMIM:137350 ∙ HGNC:4620 ∙ Uniprot:P06396 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Finnish type amyloidosis (Moderate), mode of inheritance: AD
• Finnish type amyloidosis (Supportive), mode of inheritance: AD
• Finnish type amyloidosis (Definitive), mode of inheritance: AR
• Finnish type amyloidosis (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the GSN gene.

• not provided (507 variants)
• Meretoja syndrome (161 variants)
• Inborn genetic diseases (134 variants)
• not specified (19 variants)
• Amyloidosis (10 variants)
• GSN-related condition (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	118	7	126
missense	2	1	213	19	10	245
nonsense			5			5
start loss			1			1
frameshift		1	18			19
inframe indel			5			5
splice donor/acceptor (+/-2bp)			8	1		9
splice region			8	17	1	26
non coding			21	53	37	111
Total	2	2	272	191	54

Highest pathogenic variant AF is 0.00000657

Variants in GSN

This is a list of pathogenic ClinVar variants found in the GSN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-121282470-C-T		GSN-related disorder	Likely benign (Feb 09, 2022)
9-121282717-C-T			Benign (May 12, 2021)
9-121285850-C-T			Benign (May 16, 2021)
9-121286020-G-A			Benign (May 12, 2021)
9-121286183-T-C			Benign (May 12, 2021)
9-121286186-G-T		GSN-related disorder	Likely benign (Feb 01, 2021)
9-121286343-A-G			Benign (May 12, 2021)
9-121286733-GAGAGCTGATCTTCATGCCACTGTGTACAGT-G			Uncertain significance (Oct 01, 2023)
9-121286747-A-T			Uncertain significance (Nov 01, 2022)
9-121299557-C-T			Benign (May 12, 2021)
9-121299624-C-T			Benign (May 12, 2021)
9-121299685-G-A			Benign (May 12, 2021)
9-121299826-C-T		Finnish type amyloidosis	Uncertain significance (Jan 13, 2018)
9-121299860-CCATGGCT-C			Uncertain significance (Nov 25, 2022)
9-121299862-A-G			Uncertain significance (Jan 15, 2023)
9-121299868-CCGCACCGCCCCGCGCCCGCGCTGCTTTG-C		Inborn genetic diseases • Finnish type amyloidosis	Conflicting classifications of pathogenicity (Jan 20, 2024)
9-121299869-C-T			Uncertain significance (Sep 07, 2022)
9-121299872-A-C		Inborn genetic diseases	Uncertain significance (Feb 06, 2020)
9-121299872-A-G		Inborn genetic diseases	Uncertain significance (Jun 14, 2022)
9-121299873-C-G		Inborn genetic diseases	Uncertain significance (Feb 05, 2021)
9-121299875-G-A			Uncertain significance (Jul 31, 2022)
9-121299875-G-T		Inborn genetic diseases	Uncertain significance (Sep 09, 2022)
9-121299875-GC-G		Inborn genetic diseases	Uncertain significance (Dec 30, 2023)
9-121299879-C-G			Benign (Jan 27, 2024)
9-121299879-C-T			Likely benign (Aug 31, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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