CAST
Basic information
Region (hg38): 5:96525266-96779595
Links
Phenotypes
GenCC
Source:
- peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome (Strong), mode of inheritance: AR
- peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome (Moderate), mode of inheritance: AR
- peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome (Strong), mode of inheritance: AR
- peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome (Supportive), mode of inheritance: AR
- peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (PLACK) | AR | 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 | Dermatologic | 25683118 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (134 variants)
- Inborn genetic diseases (35 variants)
- not specified (8 variants)
- Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome (7 variants)
- CAST-related condition (2 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CAST 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 | 11 | 17 | ||||
missense | 37 | 50 | ||||
nonsense | 4 | |||||
start loss | 0 | |||||
frameshift | 0 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 0 | |||||
splice region ? | 1 | 1 | 2 | 4 | ||
non coding ? | 12 | 77 | 92 | |||
Total | 2 | 2 | 41 | 27 | 92 |
Highest pathogenic variant AF is 0.0000131
Variants in CAST
This is a list of pathogenic ClinVar variants found in the CAST region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
5-96661873-C-CACAG | Benign (Jun 19, 2021) | |||
5-96662496-A-C | Uncertain significance (Jun 04, 2022) | |||
5-96662653-G-GGCAGGTGGCT | Benign (Jun 19, 2021) | |||
5-96662653-G-GGCAGGTGGCAGCAGGTGGCT | Benign (Nov 10, 2018) | |||
5-96662687-C-T | Benign (Jun 18, 2021) | |||
5-96662768-G-A | Benign (Jun 19, 2021) | |||
5-96675319-T-C | Benign (Jun 18, 2021) | |||
5-96695582-A-G | Benign (Nov 11, 2018) | |||
5-96695864-AA-GG | Uncertain significance (Dec 11, 2023) | |||
5-96695865-A-G | Peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome | Benign (Jan 29, 2024) | ||
5-96695918-T-C | Benign (Sep 11, 2023) | |||
5-96696123-G-T | Benign (Nov 10, 2018) | |||
5-96722634-T-C | Likely benign (Mar 30, 2023) | |||
5-96722658-C-G | Inborn genetic diseases | Uncertain significance (Jul 31, 2023) | ||
5-96722706-G-A | CAST-related disorder | Likely benign (May 28, 2019) | ||
5-96722708-ATGCTAATTGAGTGAG-A | Likely benign (Jul 09, 2022) | |||
5-96722934-G-GTTGTT | Benign (Jun 20, 2021) | |||
5-96726913-C-T | Benign (Jun 18, 2021) | |||
5-96727253-T-C | Benign (Nov 10, 2018) | |||
5-96727489-G-C | Inborn genetic diseases | Uncertain significance (Mar 07, 2024) | ||
5-96727507-GAGA-G | Uncertain significance (Sep 23, 2022) | |||
5-96727539-T-C | Benign (Dec 18, 2023) | |||
5-96727798-A-G | Benign (Nov 10, 2018) | |||
5-96728929-A-C | Benign (Nov 10, 2018) | |||
5-96729011-A-T | Benign (Nov 10, 2018) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
CAST | protein_coding | protein_coding | ENST00000395812 | 29 | 254329 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
4.12e-12 | 0.996 | 125691 | 0 | 57 | 125748 | 0.000227 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | -0.384 | 402 | 381 | 1.06 | 0.0000192 | 4827 |
Missense in Polyphen | 141 | 140.13 | 1.0062 | 1991 | ||
Synonymous | 0.515 | 130 | 138 | 0.944 | 0.00000752 | 1434 |
Loss of Function | 2.74 | 26 | 46.1 | 0.564 | 0.00000195 | 665 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000315 | 0.000308 |
Ashkenazi Jewish | 0.000200 | 0.000198 |
East Asian | 0.0000547 | 0.0000544 |
Finnish | 0.00 | 0.00 |
European (Non-Finnish) | 0.000268 | 0.000264 |
Middle Eastern | 0.0000547 | 0.0000544 |
South Asian | 0.000640 | 0.000588 |
Other | 0.000165 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.;
- Disease
- DISEASE: Peeling skin with leukonychia, acral punctate keratoses, cheilitis, and knuckle pads (PLACK) [MIM:616295]: An autosomal recessive disease characterized by generalized, continuous shedding of the outer layers of the epidermis, leukonychia, acral punctate keratosis, cheilitis, knuckle pads with multiple hyperkeratotic micropapules involving the interphalangeal joints, and palmoplantar keratoderma. {ECO:0000269|PubMed:25683118}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;mcalpain and friends in cell motility;Extracellular matrix organization;Degradation of the extracellular matrix
(Consensus)
Recessive Scores
- pRec
- 0.338
Intolerance Scores
- loftool
- 0.963
- rvis_EVS
- 0.71
- rvis_percentile_EVS
- 85.82
Haploinsufficiency Scores
- pHI
- 0.280
- hipred
- N
- hipred_score
- 0.429
- ghis
- 0.387
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.354
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cast
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; 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); skeleton phenotype; immune system phenotype; limbs/digits/tail 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); 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); hematopoietic 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Gene ontology
- Biological process
- inhibition of cysteine-type endopeptidase activity;presynaptic active zone organization;negative regulation of type B pancreatic cell apoptotic process
- Cellular component
- endoplasmic reticulum;cytosol;membrane
- Molecular function
- protease binding;RNA binding;endopeptidase inhibitor activity;protein binding;calcium-dependent cysteine-type endopeptidase inhibitor activity;cadherin binding