CASP4

caspase 4, the group of Caspase recruitment domain containing|Caspases

Basic information

Region (hg38): 11:104942866-104969366

Links

ENSG00000196954 ∙ NCBI:837 ∙ OMIM:602664 ∙ HGNC:1505 ∙ Uniprot:P49662 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CASP4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CASP4 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						0
missense			18	2	2	22
nonsense						0
start loss						0
frameshift					1	1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	2	3

Variants in CASP4

This is a list of pathogenic ClinVar variants found in the CASP4 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-104944766-A-G		not specified	Uncertain significance (Apr 07, 2022)
11-104944774-G-GA			Benign (Jul 31, 2018)
11-104944851-C-T		not specified	Uncertain significance (Apr 06, 2024)
11-104947136-T-G		not specified	Uncertain significance (Oct 25, 2022)
11-104948538-G-A		not specified	Uncertain significance (Dec 27, 2023)
11-104948572-C-T		not specified	Uncertain significance (Oct 24, 2023)
11-104948606-C-A			Benign (Dec 31, 2019)
11-104948611-A-G		not specified	Likely benign (Dec 19, 2022)
11-104949648-G-T		not specified	Uncertain significance (Oct 26, 2021)
11-104949740-G-T		not specified	Uncertain significance (Dec 06, 2024)
11-104949777-C-A		not specified	Uncertain significance (Dec 22, 2023)
11-104950996-T-G		not specified	Uncertain significance (Sep 13, 2023)
11-104951064-C-T		not specified	Uncertain significance (Aug 01, 2022)
11-104951089-T-C		not specified	Uncertain significance (Apr 06, 2024)
11-104951922-T-C		not specified	Uncertain significance (Oct 12, 2024)
11-104951974-C-G		not specified	Uncertain significance (Oct 14, 2023)
11-104951975-T-C		not specified	Uncertain significance (Nov 18, 2022)
11-104952002-T-A		not specified	Uncertain significance (Sep 29, 2023)
11-104954755-T-C		not specified	Likely benign (May 26, 2022)
11-104954785-G-C		not specified	Uncertain significance (Aug 17, 2022)
11-104954797-A-G		not specified	Uncertain significance (May 17, 2023)
11-104954812-C-T		not specified	Uncertain significance (Jun 10, 2022)
11-104954870-C-T			Benign (Dec 31, 2019)
11-104954880-C-A		not specified	Uncertain significance (Mar 02, 2023)
11-104954881-T-C		not specified	Uncertain significance (Apr 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CASP4	protein_coding	protein_coding	ENST00000444739	8	26571

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.05e-8	0.525	125521	1	204	125726	0.000816

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.176	201	208	0.966	0.0000107	2497
Missense in Polyphen		57	68.298	0.83458		855
Synonymous	-1.32	88	73.5	1.20	0.00000384	691
Loss of Function	1.01	14	18.7	0.747	9.80e-7	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000370	0.000369
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.00555	0.00551
European (Non-Finnish)	0.000653	0.000642
Middle Eastern	0.000272	0.000272
South Asian	0.0000327	0.0000327
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inflammatory caspase (PubMed:7797510, PubMed:23516580, PubMed:25119034). Essential effector of NLRP3 inflammasome- dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS (PubMed:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352). Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:24879791, PubMed:25964352). Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection (PubMed:25121752). In later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which ultimately results in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Activated by direct binding to LPS without the need of an upstream sensor (PubMed:25119034). Does not directly process IL1B (PubMed:7743998, PubMed:7797592, PubMed:7797510). During non- canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590). {ECO:0000269|PubMed:15123740, ECO:0000269|PubMed:22246630, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:23661706, ECO:0000269|PubMed:24879791, ECO:0000269|PubMed:25119034, ECO:0000269|PubMed:25121752, ECO:0000269|PubMed:25964352, ECO:0000269|PubMed:26173988, ECO:0000269|PubMed:26174085, ECO:0000269|PubMed:26508369, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:7743998, ECO:0000269|PubMed:7797510, ECO:0000269|PubMed:7797592}.
• Pathway: NOD-like receptor signaling pathway - Homo sapiens (human);Apoptosis Modulation and Signaling;Apoptosis;Apoptotic Signaling Pathway;caspase cascade in apoptosis;internal ribosome entry pathway;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;DroToll-like;Innate Immune System;Immune System (Consensus)

Recessive Scores

• pRec: 0.246

Intolerance Scores

• loftool: 0.981
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.44

Haploinsufficiency Scores

• pHI: 0.262
• hipred: N
• hipred_score: 0.318
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Casp4
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; immune system phenotype; renal/urinary system phenotype; digestive/alimentary 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); hematopoietic 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); neoplasm

Gene ontology

• Biological process: proteolysis;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;inflammatory response;innate immune response;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;intrinsic apoptotic signaling pathway;execution phase of apoptosis;positive regulation of tumor necrosis factor-mediated signaling pathway;cellular response to amyloid-beta
• Cellular component: extracellular region;cytoplasm;mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;plasma membrane;protein-containing complex;inflammasome complex
• Molecular function: cysteine-type endopeptidase activity;CARD domain binding;cysteine-type endopeptidase activity involved in apoptotic process;cysteine-type endopeptidase activity involved in apoptotic signaling pathway