CRADD CASP2 and RIPK1 domain containing adaptor with death domain [Homo sapiens (human)] - Gene

Summary

Official Symbol: CRADDprovided by HGNC
Official Full Name: CASP2 and RIPK1 domain containing adaptor with death domainprovided by HGNC
Primary source: HGNC:HGNC:2340
See related: Ensembl:ENSG00000169372 MIM:603454; AllianceGenome:HGNC:2340
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MRT34; RAIDD
Summary: This gene encodes a protein containing a death domain (DD) motif. This protein recruits caspase 2/ICH1 to the cell death signal transduction complex, which includes tumor necrosis factor receptor 1 (TNFR1A) and RIPK1/RIP kinase, and acts in promoting apoptosis. A mutation in this gene was associated with cognitive disability. A related pseudogene is found on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
Expression: Ubiquitous expression in heart (RPKM 3.8), liver (RPKM 2.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q22

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (93677375..93894840)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (93658870..93876341)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (94071151..94288616)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CRADD and USP44 mutations in intellectual disability, mild lissencephaly, brain atrophy, developmental delay, strabismus, behavioural problems and skeletal anomalies.
Title: CRADD and USP44 mutations in intellectual disability, mild lissencephaly, brain atrophy, developmental delay, strabismus, behavioural problems and skeletal anomalies.
Twenty two patients were identified with the c.509G>A p.(Arg170His) homozygous variant in ASP2 and RIPK1 domain containing adaptor with death domain protein CRADD (CRADD).
Title: Phenotypic spectrum associated with a CRADD founder variant underlying frontotemporal predominant pachygyria in the Finnish population.
Whole exome sequencing (WES) of an affected fetus, and subsequent Sanger sequencing of the second fetus, revealed a homozygous frameshift variant in CRADD, which encodes an adaptor protein that interacts with PIDD and caspase-2 to initiate apoptosis
Title: Homozygous null variant in CRADD, encoding an adaptor protein that mediates apoptosis, is associated with lissencephaly.
The megalencephaly, lissencephaly variant, and intellectual disability associated with loss of CRADD/caspase-2-mediated apoptosis imply a role for CRADD/caspase-2 signaling in development of the human cerebral cortex.
Title: Mutations in CRADD Result in Reduced Caspase-2-Mediated Neuronal Apoptosis and Cause Megalencephaly with a Rare Lissencephaly Variant.
The adaptor molecule RAIDD coordinates IKKepsilon and IRF7 interaction to ensure efficient expression of type I interferon.
Title: RAIDD Mediates TLR3 and IRF7 Driven Type I Interferon Production.
define a novel function for CRADD in endothelial cells as an inducible suppressor of BCL10, a key mediator of responses to proinflammatory agonists
Title: The adaptor CRADD/RAIDD controls activation of endothelial cells by proinflammatory stimuli.
Crystals are trigonal and belong to space group P3(1)21 (or its enantiomorph P3(2)21) with unit-cell parameters a = 56.3, b = 56.3, c = 64.9 A and gamma = 120 degrees .
Title: Purification, crystallization and preliminary x-ray crystallographic studies of RAIDD Death-Domain (DD).
Study identified sequence variants in the known disease-causing genes SLC6A3 and FLVCR1, and present evidence to strongly support the pathogenicity of variants identified in TUBGCP6, BRAT1, SNIP1, CRADD, and HARS.
Title: Genetic mapping and exome sequencing identify variants associated with five novel diseases.
point mutations on RAIDD (R147E) and on PIDD (Y814A) exert a dominant negative effect on the formation of the PIDDosome, and that this effect cannot be applied after the PIDDosome has been formed
Title: Identification and analysis of dominant negative mutants of RAIDD and PIDD.
The expressions of PIDD and RAIDD are upregulated during tumour progression in renal cell carcinomas.
Title: PIDDosome expression and the role of caspase-2 activation for chemotherapy-induced apoptosis in RCCs.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Intellectual disability, autosomal recessive 34 MedGen: C3281044 OMIM: 614499 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study of the rate of cognitive decline in Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH101930 (e-PCR)
- UniSTS:96265

SHGC-111655 (e-PCR)
- UniSTS:168462

CRADD_3916 (e-PCR)
- UniSTS:462121

SHGC-36307 (e-PCR)
- UniSTS:67888

G64465 (e-PCR)
- UniSTS:163893

G64526 (e-PCR)
- UniSTS:163948

RH11222 (e-PCR)
- UniSTS:42093

D12S394 (e-PCR)
- UniSTS:70517

D12S1346 (e-PCR), detects polymorphism
- UniSTS:26755

G64524 (e-PCR)
- UniSTS:163974

RH46265 (e-PCR)
- UniSTS:78999

G64466 (e-PCR)
- UniSTS:164002

D12S1037 (e-PCR)
- UniSTS:46509

SHGC-54268 (e-PCR)
- UniSTS:83154

RH68127 (e-PCR)
- UniSTS:15841

D12S1044 (e-PCR), detects polymorphism
- UniSTS:38896

G60211 (e-PCR)
- UniSTS:137469

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables death domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables protease binding	IBA Inferred from Biological aspect of Ancestor more info
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	NAS Non-traceable Author Statement more info	PubMed
involved_in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in apoptotic signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to mechanical stimulus	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in extrinsic apoptotic signaling pathway via death domain receptors	IC Inferred by Curator more info	PubMed
involved_in positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of apoptotic signaling pathway	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
part_of endopeptidase complex	IPI Inferred from Physical Interaction more info	PubMed
located_in nucleolus	NAS Non-traceable Author Statement more info	PubMed
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: death domain-containing protein CRADD

Names: CRADD/LYZ fusion; RIP-associated ICH1/CED3-homologous protein with death domain; caspase and RIP adaptor with death domain; death adaptor molecule RAIDD; death domain containing protein CRADD

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032159.2 RefSeqGene

Range

5001..178382

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001320099.2 → NP_001307028.1 death domain-containing protein CRADD isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AA150833, AC012085, AK294986, BC037905

Consensus CDS

CCDS9048.1

UniProtKB/Swiss-Prot

B7Z2Q5, P78560

UniProtKB/TrEMBL

B5BU44, Q53XL1

Related

ENSP00000439068.2, ENST00000542893.2

Conserved Domains (2) summary

cd08319
Location:116 → 198

Death_RAIDD; Death domain of RIP-associated ICH-1 homologous protein with a death domain

cd08327
Location:1 → 94

CARD_RAIDD; Caspase activation and recruitment domain of RIP-associated ICH-1 homologous protein with a death domain
NM_001320100.2 → NP_001307029.1 death domain-containing protein CRADD isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 3' coding region and 3' UTR compared to variant 1. The encoded isoform (2) has a distinct, shorter C-terminus compared to isoform 1.

Source sequence(s)

AK294986, AK296225, HY113325

Consensus CDS

CCDS81722.1

UniProtKB/TrEMBL

B4DJT6, F5H7C2

Related

ENSP00000448685.1, ENST00000548483.5

Conserved Domains (1) summary

cd08327
Location:1 → 94

CARD_RAIDD; Caspase activation and recruitment domain of RIP-associated ICH-1 homologous protein with a death domain
NM_001320101.3 → NP_001307030.1 death domain-containing protein CRADD isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 3' coding region and 3' UTR compared to variant 1. The encoded isoform (3) has a distinct, shorter C-terminus compared to isoform 1.

Source sequence(s)

AC025261, AI417529, AI791547, AK294986, HY113325

Consensus CDS

CCDS81720.1

UniProtKB/TrEMBL

B4DJT6, F8VV49

Related

ENSP00000449664.1, ENST00000552033.5

Conserved Domains (1) summary

cl14633
Location:1 → 94

DD; Death Domain Superfamily of protein-protein interaction domains
NM_001330126.1 → NP_001317055.1 death domain-containing protein CRADD isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR, 3' coding region and 3' UTR compared to variant 1. The encoded isoform (4) has a distinct, shorter C-terminus compared to isoform 1.

Source sequence(s)

AI417529, AK314861, CD108947

Consensus CDS

CCDS81719.1

UniProtKB/TrEMBL

F8VVY5

Conserved Domains (1) summary

cd08327
Location:1 → 94

CARD_RAIDD; Caspase activation and recruitment domain of RIP-associated ICH-1 homologous protein with a death domain
NM_003805.5 → NP_003796.1 death domain-containing protein CRADD isoform 1

See identical proteins and their annotated locations for NP_003796.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). Variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AA150833, BC017042, HY113325

Consensus CDS

CCDS9048.1

UniProtKB/Swiss-Prot

B7Z2Q5, P78560

UniProtKB/TrEMBL

B5BU44, Q53XL1

Related

ENSP00000327647.3, ENST00000332896.8

Conserved Domains (2) summary

cd08319
Location:116 → 198

Death_RAIDD; Death domain of RIP-associated ICH-1 homologous protein with a death domain

cd08327
Location:1 → 94

CARD_RAIDD; Caspase activation and recruitment domain of RIP-associated ICH-1 homologous protein with a death domain

RNA

NR_135147.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an exon and contains two alternate 3' exons compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK294986, HY113325

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

93677375..93894840

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047429805.1 → XP_047285761.1 death domain-containing protein CRADD isoform X3

Related

ENSP00000448425.1, ENST00000551065.5
XM_047429804.1 → XP_047285760.1 death domain-containing protein CRADD isoform X2
XM_024449252.2 → XP_024305020.1 death domain-containing protein CRADD isoform X1

UniProtKB/TrEMBL

F8VVY5

Related

ENSP00000449570.1, ENST00000552983.5

Conserved Domains (1) summary

cd08327
Location:1 → 94

CARD_RAIDD; Caspase activation and recruitment domain of RIP-associated ICH-1 homologous protein with a death domain
XM_017020145.2 → XP_016875634.1 death domain-containing protein CRADD isoform X4

UniProtKB/TrEMBL

B4DJT6

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

93658870..93876341

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054373705.1 → XP_054229680.1 death domain-containing protein CRADD isoform X3
XM_054373704.1 → XP_054229679.1 death domain-containing protein CRADD isoform X2
XM_054373703.1 → XP_054229678.1 death domain-containing protein CRADD isoform X1

UniProtKB/TrEMBL

F8VVY5
XM_054373706.1 → XP_054229681.1 death domain-containing protein CRADD isoform X4