CST3
cystatin C, the group of Cystatins, type 2
Basic information
Region (hg38): 20:23626706-23638473
Links
Phenotypes
GenCC
Source:
- ACys amyloidosis (Supportive), mode of inheritance: AD
- ACys amyloidosis (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cerebral amyloid angiopathy, CST3 related | AD | General | 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 | Cardiovascular; Neurologic | 4655034; 3495457; 2900981; 11760381; 16612982; 18566660 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (31 variants)
- not_specified (21 variants)
- Hereditary_cerebral_amyloid_angiopathy,_Icelandic_type (6 variants)
- LEUKODYSTROPHY,_ADULT-ONSET,_AUTOSOMAL_DOMINANT,_WITHOUT_AMYLOID_ANGIOPATHY (3 variants)
- CST3-related_Leukodystrophy (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CST3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000099.4. 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 | 12 | |||||
| missense | 26 | 31 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 2 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 1 | 2 | 29 | 9 | 7 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CST3 | protein_coding | protein_coding | ENST00000398411 | 3 | 10577 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00390 | 0.661 | 125726 | 0 | 21 | 125747 | 0.0000835 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.497 | 81 | 69.4 | 1.17 | 0.00000365 | 898 |
| Missense in Polyphen | 30 | 26.62 | 1.127 | 300 | ||
| Synonymous | -0.518 | 33 | 29.4 | 1.12 | 0.00000180 | 291 |
| Loss of Function | 0.581 | 4 | 5.47 | 0.732 | 3.19e-7 | 61 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000185 | 0.000185 |
| Ashkenazi Jewish | 0.0000993 | 0.0000992 |
| East Asian | 0.000109 | 0.000109 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000132 | 0.000132 |
| Middle Eastern | 0.000109 | 0.000109 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity.;
- Disease
- DISEASE: Amyloidosis 6 (AMYL6) [MIM:105150]: A hereditary generalized amyloidosis due to cystatin C amyloid deposition. Cystatin C amyloid accumulates in the walls of arteries, arterioles, and sometimes capillaries and veins of the brain, and in various organs including lymphoid tissue, spleen, salivary glands, and seminal vesicles. Amyloid deposition in the cerebral vessels results in cerebral amyloid angiopathy, cerebral hemorrhage and premature stroke. Cystatin C levels in the cerebrospinal fluid are abnormally low. {ECO:0000269|PubMed:1352269, ECO:0000269|PubMed:2541223}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Macular degeneration, age-related, 11 (ARMD11) [MIM:611953]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:11815350, ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:2764935}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Salivary secretion - Homo sapiens (human);Neutrophil degranulation;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
(Consensus)
Recessive Scores
- pRec
- 0.625
Intolerance Scores
- loftool
- 0.691
- rvis_EVS
- 0.13
- rvis_percentile_EVS
- 62.74
Haploinsufficiency Scores
- pHI
- 0.162
- hipred
- N
- hipred_score
- 0.261
- ghis
- 0.406
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.874
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cst3
- 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); reproductive system 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); 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); neoplasm; muscle phenotype; homeostasis/metabolism phenotype;
Gene ontology
- Biological process
- defense response;negative regulation of peptidase activity;negative regulation of collagen catabolic process;negative regulation of extracellular matrix disassembly;negative regulation of endopeptidase activity;regulation of tissue remodeling;neutrophil degranulation;post-translational protein modification;cellular protein metabolic process;negative regulation of proteolysis;negative regulation of elastin catabolic process;negative regulation of blood vessel remodeling;supramolecular fiber organization
- Cellular component
- extracellular region;extracellular space;endoplasmic reticulum lumen;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
- Molecular function
- amyloid-beta binding;protease binding;endopeptidase inhibitor activity;cysteine-type endopeptidase inhibitor activity;protein binding;identical protein binding