CASP2

caspase 2, the group of Caspases|Protein phosphatase 1 regulatory subunits|Caspase recruitment domain containing

Basic information

Region (hg38): 7:143288215-143307696

Previous symbols: [ "NEDD2" ]

Links

ENSG00000106144 ∙ NCBI:835 ∙ OMIM:600639 ∙ HGNC:1503 ∙ Uniprot:P42575 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly (Limited), mode of inheritance: AR
• intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly	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	Neurologic	37880421

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CASP2 gene.

• Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly (4 variants)
• Inborn genetic diseases (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CASP2 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	5	7
missense			24			24
nonsense	2					2
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region						0
non coding						0
Total	4	1	24	2	5

Variants in CASP2

This is a list of pathogenic ClinVar variants found in the CASP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-143288487-C-T		not specified	Uncertain significance (Mar 01, 2023)
7-143288510-G-A		CASP2-related disorder	Likely benign (Sep 08, 2022)
7-143288526-G-T		not specified	Uncertain significance (Sep 28, 2022)
7-143291550-G-A		not specified	Uncertain significance (Nov 09, 2023)
7-143291552-G-A			Benign (Feb 01, 2025)
7-143291595-C-T		Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly • Inborn genetic diseases	Pathogenic (Apr 09, 2023)
7-143291615-G-C		not specified	Uncertain significance (Aug 23, 2021)
7-143291627-C-G		not specified	Uncertain significance (Dec 20, 2023)
7-143292656-T-C		not specified	Uncertain significance (Dec 19, 2023)
7-143292676-C-T			Benign (Dec 31, 2019)
7-143292686-C-T		not specified	Uncertain significance (Oct 19, 2024)
7-143294285-G-T		not specified	Uncertain significance (Jul 11, 2023)
7-143294286-C-G		CASP2-related disorder	Likely benign (May 30, 2023)
7-143294298-G-A		not specified	Uncertain significance (Oct 12, 2021)
7-143294309-AAC-A		Inborn genetic diseases	Likely pathogenic (Mar 29, 2018)
7-143294622-G-A		not specified	Uncertain significance (Feb 22, 2023)
7-143294667-A-G		not specified	Uncertain significance (Dec 28, 2023)
7-143299928-G-A		not specified	Uncertain significance (Nov 09, 2023)
7-143299937-A-G			Benign (Nov 20, 2017)
7-143299968-C-G		not specified	Conflicting classifications of pathogenicity (Jun 01, 2022)
7-143299976-G-A			Benign/Likely benign (Mar 01, 2025)
7-143299989-G-A		not specified	Uncertain significance (Dec 02, 2024)
7-143299993-C-T		not specified	Uncertain significance (Apr 01, 2024)
7-143300052-G-T		Inborn genetic diseases • Intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly	Pathogenic (Apr 04, 2023)
7-143300060-A-G		CASP2-related disorder	Likely benign (Oct 28, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CASP2	protein_coding	protein_coding	ENST00000310447	11	19482

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00150	0.997	125720	0	28	125748	0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.497	233	255	0.913	0.0000158	2973
Missense in Polyphen		74	106.89	0.69231		1229
Synonymous	-0.551	107	100	1.07	0.00000632	865
Loss of Function	2.82	9	23.9	0.377	0.00000133	272

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000578	0.000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000791	0.0000703
Middle Eastern	0.000163	0.000163
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. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival.
• Pathway: Apoptosis - Homo sapiens (human);Apoptosis Modulation and Signaling;Parkinsons Disease Pathway;Apoptosis;Apoptotic Signaling Pathway;Apoptosis Modulation by HSP70;Signal Transduction;Gene expression (Transcription);tnfr1 signaling pathway;caspase cascade in apoptosis;hiv-1 nef: negative effector of fas and tnf;tnf/stress related signaling;internal ribosome entry pathway;Generic Transcription Pathway;NOD1/2 Signaling Pathway;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;DroToll-like;Innate Immune System;Immune System;p73 transcription factor network;TP53 Regulates Transcription of Caspase Activators and Caspases;NADE modulates death signalling;Death Receptor Signalling;p75 NTR receptor-mediated signalling;Transcriptional Regulation by TP53;TNFalpha;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;Cell death signalling via NRAGE, NRIF and NADE (Consensus)

Recessive Scores

• pRec: 0.213

Intolerance Scores

• loftool: 0.574
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.44

Haploinsufficiency Scores

• pHI: 0.256
• hipred: Y
• hipred_score: 0.736
• ghis: 0.596

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Casp2
• 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); immune system phenotype; 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); reproductive system phenotype; endocrine/exocrine gland phenotype; cellular phenotype

Gene ontology

• Biological process: luteolysis;neural retina development;apoptotic process;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;brain development;aging;intrinsic apoptotic signaling pathway in response to DNA damage;protein processing;ectopic germ cell programmed cell death;regulation of apoptotic process;positive regulation of apoptotic process;negative regulation of apoptotic process;positive regulation of neuron apoptotic process;cellular response to mechanical stimulus;apoptotic signaling pathway;extrinsic apoptotic signaling pathway in absence of ligand;execution phase of apoptosis;positive regulation of apoptotic signaling pathway
• Cellular component: nucleus;cytoplasm;mitochondrion;cytosol;membrane
• Molecular function: cysteine-type endopeptidase activity;protein binding;enzyme binding;protein domain specific binding;identical protein binding;cysteine-type endopeptidase activity involved in apoptotic process;cysteine-type endopeptidase activity involved in execution phase of apoptosis