CRADD

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

Basic information

Region (hg38): 12:93677375-93894840

Links

ENSG00000169372NCBI:8738OMIM:603454HGNC:2340Uniprot:P78560AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Intellectual developmental disorder, autosomal recessive 34, with variant lissencephalyARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic22279524; 27773430

ClinVar

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

  • not_provided (42 variants)
  • Inborn_genetic_diseases (21 variants)
  • Intellectual_disability,_autosomal_recessive_34 (12 variants)
  • CRADD-related_disorder (6 variants)
  • not_specified (4 variants)
  • Intellectual_disability (3 variants)
  • Intellectual_disability,_moderate (1 variants)
  • Familial_isolated_arrhythmogenic_right_ventricular_dysplasia (1 variants)
  • Global_developmental_delay (1 variants)
  • 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. These statistics are base on transcript: NM_000003805.5. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
17
clinvar
1
clinvar
19
missense
2
clinvar
1
clinvar
28
clinvar
5
clinvar
1
clinvar
37
nonsense
1
clinvar
1
start loss
2
2
frameshift
1
clinvar
2
clinvar
3
splice donor/acceptor (+/-2bp)
0
Total 5 4 29 22 2

Highest pathogenic variant AF is 0.000273903

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CRADDprotein_codingprotein_codingENST00000542893 2217466
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.8790.1201257370101257470.0000398
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.09681181210.9750.000007361280
Missense in Polyphen4449.4480.88983549
Synonymous-1.556752.71.270.00000306422
Loss of Function2.4306.870.002.94e-775

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00005790.0000579
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00001770.0000176
Middle Eastern0.000.00
South Asian0.0001630.000163
Other0.0001630.000163

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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