CASP10
caspase 10, the group of Caspases|Death inducing signaling complex |Death effector domain containing
Basic information
Region (hg38): 2:201182872-201229428
Links
Phenotypes
GenCC
Source:
- autoimmune lymphoproliferative syndrome (Supportive), mode of inheritance: AD
- autoimmune lymphoproliferative syndrome type 2A (Strong), mode of inheritance: AD
- autoimmune lymphoproliferative syndrome type 2A (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Autoimmune lymphoproliferative syndrome, type IIA | AD | Allergy/Immunology/Infectious; Oncologic | Lymphoproliferation can be suppressed with medications such as corticosteroids, cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil; BMT/HSCT the only curative treatment for ALPS, has to date mostly been reported in patients with severe clinical findings; Surveillance for manifestations of lymphoproliferation and autoimmunity, and specialized imaging studies to detect malignant transformation may be beneficial | Allergy/Immunology/Infectious; Hematologic; Oncologic | 10412980; 16537120; 16446975; 17999750; 20301287 |
| Variants may modify other related disorders |
ClinVar
This is a list of variants' phenotypes submitted to
- Autoimmune_lymphoproliferative_syndrome_type_2A (418 variants)
- not_specified (69 variants)
- not_provided (48 variants)
- CASP10-related_disorder (20 variants)
- Gastric_cancer (9 variants)
- Lymphoma,_non-Hodgkin,_familial (7 variants)
- Autoimmune_lymphoproliferative_syndrome_type_1 (7 variants)
- Non-Hodgkin_lymphoma (3 variants)
- Neoplasm_of_stomach (2 variants)
- Hypomyelination_and_Congenital_Cataract (1 variants)
- See_cases (1 variants)
- Susceptibility_to_severe_COVID-19 (1 variants)
- Diffuse_midline_glioma,_H3_K27-altered (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CASP10 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000032977.4. 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 | 88 | 95 | ||||
| missense | 240 | 13 | 254 | |||
| nonsense | 9 | |||||
| start loss | 0 | |||||
| frameshift | 16 | 20 | ||||
| splice donor/acceptor (+/-2bp) | 7 | |||||
| Total | 4 | 1 | 274 | 102 | 4 |
Highest pathogenic variant AF is 6.840488e-7
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CASP10 | protein_coding | protein_coding | ENST00000286186 | 9 | 46526 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.64e-12 | 0.102 | 125554 | 2 | 192 | 125748 | 0.000772 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0269 | 271 | 272 | 0.995 | 0.0000136 | 3424 |
| Missense in Polyphen | 79 | 84.057 | 0.93984 | 1091 | ||
| Synonymous | -0.232 | 115 | 112 | 1.03 | 0.00000601 | 1022 |
| Loss of Function | 0.529 | 19 | 21.7 | 0.877 | 0.00000109 | 256 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00160 | 0.00160 |
| Ashkenazi Jewish | 0.000502 | 0.000496 |
| East Asian | 0.00155 | 0.00152 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000750 | 0.000747 |
| Middle Eastern | 0.00155 | 0.00152 |
| South Asian | 0.000801 | 0.000752 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Recruited to both Fas- and TNFR-1 receptors in a FADD dependent manner. May participate in the granzyme B apoptotic pathways. Cleaves and activates caspase- 3, -4, -6, -7, -8, and -9. Hydrolyzes the small- molecule substrates, Tyr-Val-Ala-Asp-|-AMC and Asp-Glu-Val-Asp-|-AMC. {ECO:0000269|PubMed:11717445}.; FUNCTION: Isoform C is proteolytically inactive. {ECO:0000269|PubMed:11717445}.;
- Disease
- DISEASE: Autoimmune lymphoproliferative syndrome 2A (ALPS2A) [MIM:603909]: A disorder of apoptosis that manifests in early childhood and results in the accumulation of autoreactive lymphocytes. It is characterized by non-malignant lymphadenopathy with hepatosplenomegaly, and autoimmune hemolytic anemia, thrombocytopenia and neutropenia. {ECO:0000269|PubMed:10412980}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Familial non-Hodgkin lymphoma (NHL) [MIM:605027]: Cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss. {ECO:0000269|PubMed:12010812}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Gastric cancer (GASC) [MIM:613659]: A malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. {ECO:0000269|PubMed:11973654}. Note=The gene represented in this entry is involved in disease pathogenesis.;
- Pathway
- TNF signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Apoptosis - Homo sapiens (human);RIG-I-like receptor signaling pathway - Homo sapiens (human);Apoptosis Modulation and Signaling;Apoptosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Apoptotic Signaling Pathway;TP53 Regulates Transcription of Cell Death Genes;RIG-I-like Receptor Signaling;Signal Transduction;Gene expression (Transcription);caspase cascade in apoptosis;induction of apoptosis through dr3 and dr4/5 death receptors;internal ribosome entry pathway;Generic Transcription Pathway;NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10;DDX58/IFIH1-mediated induction of interferon-alpha/beta;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;DroToll-like;Innate Immune System;Immune System;fas signaling pathway (cd95);TP53 Regulates Transcription of Caspase Activators and Caspases;FasL/ CD95L signaling;TRAIL signaling;Death Receptor Signalling;Transcriptional Regulation by TP53;Direct p53 effectors;TNFalpha;Caspase Cascade in Apoptosis;TRAIL signaling pathway;FAS (CD95) signaling pathway
(Consensus)
Intolerance Scores
- loftool
- 0.454
- rvis_EVS
- -0.09
- rvis_percentile_EVS
- 46.99
Haploinsufficiency Scores
- pHI
- 0.112
- hipred
- N
- hipred_score
- 0.352
- ghis
- 0.463
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.502
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Gene ontology
- Biological process
- proteolysis;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;cell surface receptor signaling pathway;regulation of apoptotic process;positive regulation of I-kappaB kinase/NF-kappaB signaling;apoptotic signaling pathway;execution phase of apoptosis
- Cellular component
- cytoplasm;cytosol;CD95 death-inducing signaling complex;ripoptosome
- Molecular function
- cysteine-type endopeptidase activity;protein binding;ubiquitin protein ligase binding;death effector domain binding;cysteine-type endopeptidase activity involved in apoptotic process;cysteine-type endopeptidase activity involved in apoptotic signaling pathway