CRADD

CASP2 and RIPK1 domain containing adaptor with death domain, the group of Caspase recruitment domain containing

Basic information

Region (hg38): 12:93677374-93894840

Links

ENSG00000169372 ∙ NCBI:8738 ∙ OMIM:603454 ∙ HGNC:2340 ∙ Uniprot:P78560 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 34 (Limited), mode of inheritance: AR
• intellectual disability, autosomal recessive 34 (Strong), mode of inheritance: AR
• intellectual disability, autosomal recessive 34 (Strong), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• syndromic intellectual disability (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 34, 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	22279524; 27773430

ClinVar

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

• not provided (37 variants)
• Intellectual disability, autosomal recessive 34 (7 variants)
• Inborn genetic diseases (6 variants)
• not specified (3 variants)
• Intellectual disability (3 variants)
• Global developmental delay;Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRADD 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				12	2	14
missense	1		15	3	2	21
nonsense						0
start loss	1					1
frameshift	1		1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding		1	1	2	5	9
Total	3	1	17	17	9

Highest pathogenic variant AF is 0.000492

Variants in CRADD

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

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

Position	Type	Phenotype	Significance	ClinVar
12-93678762-T-C		Intellectual disability, autosomal recessive 34	Uncertain significance (Mar 25, 2024)
12-93678773-A-G		Intellectual disability, autosomal recessive 34	Uncertain significance (Nov 22, 2019)
12-93678776-T-C		Intellectual disability	Pathogenic (Oct 16, 2020)
12-93678776-T-G		Intellectual disability, moderate	Pathogenic (-)
12-93678801-C-T			Likely benign (Nov 07, 2023)
12-93678802-C-T			Uncertain significance (Feb 01, 2024)
12-93678813-C-G			Likely benign (Jul 18, 2018)
12-93678817-G-A			Uncertain significance (Oct 03, 2023)
12-93678822-GGGTGCAGA-G			Pathogenic (Aug 30, 2023)
12-93678834-A-C			Likely benign (Oct 28, 2022)
12-93678839-T-C		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
12-93678877-A-G			Benign (Jan 22, 2024)
12-93678884-C-T			Uncertain significance (Aug 07, 2022)
12-93678886-G-A			Uncertain significance (Aug 23, 2022)
12-93678904-A-C		Inborn genetic diseases	Likely benign (May 27, 2022)
12-93678908-A-G		Inborn genetic diseases	Uncertain significance (Nov 21, 2023)
12-93678925-C-A		not specified • CRADD-related disorder	Likely benign (Jan 18, 2024)
12-93678942-C-T			Likely benign (Dec 07, 2022)
12-93678968-G-T		Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
12-93678975-A-G			Likely benign (Sep 23, 2023)
12-93678978-A-G			Likely benign (Aug 29, 2017)
12-93678983-A-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
12-93678985-A-G			Uncertain significance (Dec 01, 2018)
12-93679025-A-G		Inborn genetic diseases	Uncertain significance (May 03, 2023)
12-93679035-G-A			Likely benign (Apr 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRADD	protein_coding	protein_coding	ENST00000542893	2	217466

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.879	0.120	125737	0	10	125747	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0968	118	121	0.975	0.00000736	1280
Missense in Polyphen		44	49.448	0.88983		549
Synonymous	-1.55	67	52.7	1.27	0.00000306	422
Loss of Function	2.43	0	6.87	0.00	2.94e-7	75

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000177	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Apoptotic adaptor molecule specific for caspase-2 and FASL/TNF receptor-interacting protein RIP. In the presence of RIP and TRADD, CRADD recruits caspase-2 to the TNFR-1 signalling complex.
• Disease: DISEASE: Mental retardation, autosomal recessive 34, with variant lissencephaly (MRT34) [MIM:614499]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT34 is a non-syndromic form. Affected individuals have mildly delayed development and significantly impaired cognitive function, precluding independent living and self-care. Speech is rudimentary, but articulate; autism is not present. {ECO:0000269|PubMed:22279524}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Apoptosis Modulation and Signaling;Apoptosis;Apoptotic Signaling Pathway;Gene expression (Transcription);tnfr1 signaling pathway;hiv-1 nef: negative effector of fas and tnf;tnf/stress related signaling;Generic Transcription Pathway;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;ceramide signaling pathway;TP53 Regulates Transcription of Caspase Activators and Caspases;sodd/tnfr1 signaling pathway;Transcriptional Regulation by TP53;TNFalpha;Caspase Cascade in Apoptosis;HIV-1 Nef: Negative effector of Fas and TNF-alpha;Ceramide signaling pathway (Consensus)

Recessive Scores

• pRec: 0.146

Intolerance Scores

• loftool: 0.215
• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.180
• hipred: Y
• hipred_score: 0.610
• ghis: 0.477

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.326

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cradd
• 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); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: activation of cysteine-type endopeptidase activity involved in apoptotic process;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;extrinsic apoptotic signaling pathway via death domain receptors;regulation of apoptotic process;positive regulation of apoptotic process;cellular response to mechanical stimulus;apoptotic signaling pathway;positive regulation of apoptotic signaling pathway
• Cellular component: nucleus;cytoplasm;cytosol
• Molecular function: protease binding;protein binding;protein binding, bridging;death domain binding