CASP10

caspase 10, the group of Caspases|Death inducing signaling complex |Death effector domain containing

Basic information

Region (hg38): 2:201182871-201229428

Links

ENSG00000003400 ∙ NCBI:843 ∙ OMIM:601762 ∙ HGNC:1500 ∙ Uniprot:Q92851 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the CASP10 gene.

• Autoimmune lymphoproliferative syndrome type 2A (362 variants)
• not provided (55 variants)
• Inborn genetic diseases (18 variants)
• not specified (13 variants)
• Autoimmune lymphoproliferative syndrome type 1 (13 variants)
• CASP10-related condition (9 variants)
• Neoplasm of stomach (2 variants)
• Autoimmune lymphoproliferative syndrome type 2A;Lymphoma, non-Hodgkin, familial;Gastric cancer (2 variants)
• Diffuse midline glioma, H3 K27-altered (1 variants)
• Autoimmune lymphoproliferative syndrome type 2A;Neoplasm of stomach (1 variants)
• See cases (1 variants)
• Hypomyelination and Congenital Cataract (1 variants)
• Gastric cancer;Lymphoma, non-Hodgkin, familial;Autoimmune lymphoproliferative syndrome type 2A (1 variants)
• Gastric cancer (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.

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			2	52	5	59
missense			149	4	4	157
nonsense			6			6
start loss						0
frameshift	1		11			12
inframe indel			1			1
splice donor/acceptor (+/-2bp)			6			6
splice region			10	8	1	19
non coding			52	30	56	138
Total	1	0	227	86	65

Variants in CASP10

This is a list of pathogenic ClinVar variants found in the CASP10 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-201182956-T-C		Autoimmune lymphoproliferative syndrome type 2A	Benign (Jan 13, 2018)
2-201183002-G-A		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Jan 13, 2018)
2-201183031-C-T		Autoimmune lymphoproliferative syndrome type 2A	Likely benign (Apr 27, 2017)
2-201183110-C-T		Autoimmune lymphoproliferative syndrome type 2A	Benign (May 10, 2021)
2-201183313-G-A		Autoimmune lymphoproliferative syndrome type 1 • Autoimmune lymphoproliferative syndrome type 2A	Conflicting classifications of pathogenicity (May 28, 2019)
2-201183400-C-T			Benign (May 10, 2021)
2-201183496-C-T			Likely benign (May 10, 2021)
2-201185430-G-A			Benign (Aug 25, 2018)
2-201185788-A-G		Diffuse midline glioma, H3 K27-altered	Uncertain significance (May 19, 2021)
2-201185790-G-A		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Nov 03, 2022)
2-201185797-A-G		Autoimmune lymphoproliferative syndrome type 2A • not specified	Conflicting classifications of pathogenicity (Dec 26, 2023)
2-201185806-C-G		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Aug 29, 2021)
2-201185822-C-T		Autoimmune lymphoproliferative syndrome type 2A	Likely benign (Jan 01, 2024)
2-201185824-G-A		Autoimmune lymphoproliferative syndrome type 2A • not specified	Uncertain significance (Jan 17, 2024)
2-201185826-A-G		Autoimmune lymphoproliferative syndrome type 2A	Conflicting classifications of pathogenicity (Jul 12, 2023)
2-201185834-C-G		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Nov 06, 2022)
2-201185838-C-T		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Oct 08, 2022)
2-201185839-G-A		Autoimmune lymphoproliferative syndrome type 2A • not specified	Uncertain significance (Jan 22, 2024)
2-201185853-A-G		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Sep 05, 2023)
2-201185858-T-C		Autoimmune lymphoproliferative syndrome type 2A	Conflicting classifications of pathogenicity (Aug 14, 2023)
2-201185859-G-C		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Aug 27, 2021)
2-201185863-C-A		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Sep 04, 2023)
2-201185866-A-T		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Jan 11, 2024)
2-201185867-C-T		Autoimmune lymphoproliferative syndrome type 2A	Likely benign (Feb 25, 2022)
2-201185871-G-A		Autoimmune lymphoproliferative syndrome type 2A	Uncertain significance (Jun 03, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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