CASP9

caspase 9, the group of Apoptosome|Caspases|Caspase recruitment domain containing|Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 1:15490831-15526534

Links

ENSG00000132906 ∙ NCBI:842 ∙ OMIM:602234 ∙ HGNC:1511 ∙ Uniprot:P55211 ∙ 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 CASP9 gene.

• Inborn genetic diseases (22 variants)
• not provided (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CASP9 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				3		3
missense			20	2	3	25
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	20	5	4

Variants in CASP9

This is a list of pathogenic ClinVar variants found in the CASP9 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-15491299-T-C		not specified	Uncertain significance (Nov 28, 2023)
1-15492963-G-T		not specified	Uncertain significance (Jul 20, 2021)
1-15492971-C-T		not specified	Uncertain significance (Jan 26, 2023)
1-15492994-C-A		not specified	Likely benign (Sep 14, 2022)
1-15492997-C-A		not specified	Uncertain significance (Dec 03, 2021)
1-15493007-A-T		not specified	Uncertain significance (Dec 04, 2023)
1-15493898-C-G		CASP9-related disorder	Likely benign (Jun 21, 2019)
1-15493908-T-C		not specified	Uncertain significance (Jun 24, 2022)
1-15493953-G-T		CASP9-related disorder	Benign (Dec 31, 2019)
1-15493997-A-C		not specified	Uncertain significance (Nov 06, 2023)
1-15495299-A-G		not specified	Uncertain significance (Jan 18, 2023)
1-15495350-C-T		not specified	Uncertain significance (Jul 12, 2022)
1-15495401-G-T		not specified	Uncertain significance (Aug 17, 2022)
1-15495452-T-C		not specified	Uncertain significance (Jan 16, 2024)
1-15504656-G-T		not specified	Uncertain significance (Jul 19, 2023)
1-15504674-C-T		not specified	Uncertain significance (May 27, 2022)
1-15504763-A-G		CASP9-related disorder	Benign (Aug 28, 2019)
1-15505981-G-A		CASP9-related disorder	Benign/Likely benign (Dec 31, 2019)
1-15505999-G-A		CASP9-related disorder	Likely benign (Mar 01, 2023)
1-15506028-C-A		not specified	Uncertain significance (Sep 23, 2023)
1-15506048-T-C		CASP9-related disorder	Benign (Oct 18, 2019)
1-15506050-C-T		CASP9-related disorder	Likely benign (Apr 12, 2019)
1-15506969-C-T		not specified	Uncertain significance (Aug 26, 2022)
1-15506973-C-G		not specified	Uncertain significance (Sep 26, 2023)
1-15506983-G-A			Likely benign (Dec 31, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CASP9	protein_coding	protein_coding	ENST00000333868	9	35703

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000738	0.916	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0269	239	240	0.995	0.0000141	2679
Missense in Polyphen		97	95.484	1.0159		1082
Synonymous	0.232	94	96.9	0.970	0.00000590	835
Loss of Function	1.65	11	18.7	0.588	9.47e-7	209

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000529	0.000510
Ashkenazi Jewish	0.00	0.00
East Asian	0.000231	0.000217
Finnish	0.000110	0.0000924
European (Non-Finnish)	0.000342	0.000325
Middle Eastern	0.000231	0.000217
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf- 1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP- ribose) polymerase (PARP).
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Legionellosis - Homo sapiens (human);VEGF signaling pathway - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Apoptosis - multiple species - Homo sapiens (human);Influenza A - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Apoptosis - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Nucleotide-binding Oligomerization Domain (NOD) pathway;miRNA Regulation of DNA Damage Response;Apoptosis Modulation and Signaling;Integrated Breast Cancer Pathway;Alzheimers Disease;TNF alpha Signaling Pathway;AGE-RAGE pathway;Allograft Rejection;Corticotropin-releasing hormone signaling pathway;Parkinsons Disease Pathway;Amyotrophic lateral sclerosis (ALS);Nanomaterial induced apoptosis;Integrated Lung Cancer Pathway;Apoptosis;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Rac1-Pak1-p38-MMP-2 pathway;Apoptotic Signaling Pathway;Hepatitis C and Hepatocellular Carcinoma;Apoptosis Modulation by HSP70;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Oxidative Damage;miRNA regulation of prostate cancer signaling pathways;miRNA regulation of p53 pathway in prostate cancer;NO-cGMP-PKG mediated Neuroprotection;apoptotic signaling in response to dna damage;Endometrial cancer;PI3K-Akt Signaling Pathway;Chromosomal and microsatellite instability in colorectal cancer;DNA Damage Response;Disease;Signal Transduction;trefoil factors initiate mucosal healing;caspase cascade in apoptosis;role of mitochondria in apoptotic signaling;akt signaling pathway;ras signaling pathway;hiv-1 nef: negative effector of fas and tnf;west nile virus;stress induction of hsp regulation;regulation of cell cycle progression by plk3;internal ribosome entry pathway;Fas;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;Caspase activation via extrinsic apoptotic signalling pathway;DroToll-like;Formation of apoptosome;SMAC-mediated dissociation of IAP:caspase complexes ;SMAC-mediated apoptotic response;Apoptotic factor-mediated response;Intrinsic Pathway for Apoptosis;Innate Immune System;Immune System;Apoptosis;Programmed Cell Death;Activation of caspases through apoptosome-mediated cleavage;BCR;EGFR1;SMAC binds to IAPs ;PIP3 activates AKT signaling;Ligand-independent caspase activation via DCC;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;TNF;AKT phosphorylates targets in the cytosol;Cytochrome c-mediated apoptotic response;Intracellular signaling by second messengers;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;Diseases of signal transduction;p75(NTR)-mediated signaling;Class I PI3K signaling events mediated by Akt (Consensus)

Recessive Scores

• pRec: 0.734

Intolerance Scores

• loftool: 0.882
• rvis_EVS: 0.82
• rvis_percentile_EVS: 88.02

Haploinsufficiency Scores

• pHI: 0.188
• hipred: Y
• hipred_score: 0.669
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.971

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Casp9
• Phenotype: growth/size/body region phenotype; taste/olfaction phenotype; endocrine/exocrine gland phenotype; craniofacial phenotype; cellular phenotype; embryo phenotype; respiratory 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); 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); 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); immune system phenotype

Zebrafish Information Network

• Gene name: casp9
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: occurrence

Gene ontology

• Biological process: kidney development;response to ischemia;proteolysis;apoptotic process;cellular response to DNA damage stimulus;aging;intrinsic apoptotic signaling pathway in response to DNA damage;activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c;platelet formation;response to cobalt ion;response to estradiol;response to lipopolysaccharide;glial cell apoptotic process;cellular response to UV;signal transduction in response to DNA damage;positive regulation of apoptotic process;positive regulation of neuron apoptotic process;response to antibiotic;cellular response to dexamethasone stimulus;leukocyte apoptotic process;extrinsic apoptotic signaling pathway in absence of ligand;regulation of response to DNA damage stimulus
• Cellular component: nucleus;cytoplasm;mitochondrion;cytosol;protein-containing complex;apoptosome
• Molecular function: cysteine-type endopeptidase activity;protein binding;enzyme activator activity;peptidase activity;SH3 domain binding;protein kinase binding;cysteine-type endopeptidase activity involved in apoptotic process;cysteine-type endopeptidase activity involved in apoptotic signaling pathway