CRADD (CARD and death domain containing adaptor protein)

Gene

• Entrez ID: 8738
• Gene name: CARD and death domain containing adaptor protein
• Gene symbol: CRADD
• Synonyms (NCBI Gene): MRT34, RAIDD
• Chromosome: 12
• Chromosome location: 12q22
• 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 apop

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs141179774	G>A	Pathogenic-likely-pathogenic	Missense variant, downstream transcript variant, intron variant, genic downstream transcript variant, coding sequence variant
rs370916968	T>G	Pathogenic	Genic downstream transcript variant, coding sequence variant, intron variant, missense variant, downstream transcript variant
rs387906861	G>A,C	Pathogenic	Downstream transcript variant, missense variant, genic downstream transcript variant, intron variant, coding sequence variant
rs749655461	C>T	Pathogenic	Coding sequence variant, intron variant, downstream transcript variant, missense variant, genic downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029087	hsa-miR-26b-5p	Microarray	19088304
MIRT514653	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT514652	hsa-miR-8076	PAR-CLIP	23446348
MIRT514651	hsa-miR-1246	PAR-CLIP	23446348
MIRT514650	hsa-miR-3201	PAR-CLIP	23446348
MIRT514649	hsa-miR-4791	PAR-CLIP	23446348
MIRT514648	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT514647	hsa-miR-1277-5p	PAR-CLIP	23446348
MIRT514653	hsa-miR-5011-5p	PAR-CLIP	23446348
MIRT514652	hsa-miR-8076	PAR-CLIP	23446348
MIRT514651	hsa-miR-1246	PAR-CLIP	23446348
MIRT514650	hsa-miR-3201	PAR-CLIP	23446348
MIRT514649	hsa-miR-4791	PAR-CLIP	23446348
MIRT514648	hsa-miR-190a-3p	PAR-CLIP	23446348
MIRT514647	hsa-miR-1277-5p	PAR-CLIP	23446348
MIRT907998	hsa-miR-4683	CLIP-seq
MIRT907999	hsa-miR-4686	CLIP-seq
MIRT2205112	hsa-miR-498	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002020	Function	Protease binding	IBA
GO:0002020	Function	Protease binding	IEA
GO:0002020	Function	Protease binding	IPI	9044836
GO:0005515	Function	Protein binding	IPI	8985253, 11156409, 15073321, 16652156, 17159900, 22458338, 25416956, 25910212, 27107012, 27773430, 31467278, 31515488, 32296183, 37398436
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	ISS
GO:0005730	Component	Nucleolus	NAS	28432080
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0005829	Component	Cytosol	TAS
GO:0006915	Process	Apoptotic process	IEA
GO:0006974	Process	DNA damage response	NAS	15073321
GO:0007165	Process	Signal transduction	IEA
GO:0008625	Process	Extrinsic apoptotic signaling pathway via death domain receptors	IC	9044836
GO:0030330	Process	DNA damage response, signal transduction by p53 class mediator	IBA
GO:0030330	Process	DNA damage response, signal transduction by p53 class mediator	IMP	21726810
GO:0030674	Function	Protein-macromolecule adaptor activity	IPI	9044836
GO:0042981	Process	Regulation of apoptotic process	IEA
GO:0043065	Process	Positive regulation of apoptotic process	IDA	11821383
GO:0043065	Process	Positive regulation of apoptotic process	IEA
GO:0043065	Process	Positive regulation of apoptotic process	NAS	15073321
GO:0070513	Function	Death domain binding	IEA
GO:0070513	Function	Death domain binding	IPI	9044836
GO:0071260	Process	Cellular response to mechanical stimulus	IEP	19593445
GO:0097190	Process	Apoptotic signaling pathway	IMP	8985253
GO:1905369	Component	Endopeptidase complex	IPI	15073321
GO:2001235	Process	Positive regulation of apoptotic signaling pathway	IBA
GO:2001235	Process	Positive regulation of apoptotic signaling pathway	IEA

Other IDs

• MIM: 603454
• HGNC: 2340
• e!Ensembl: ENSG00000169372

Protein

• UniProt ID: P78560
• Protein name: Death domain-containing protein CRADD (Caspase and RIP adapter with death domain) (RIP-associated protein with a death domain)
• Protein function: Adapter protein that associates with PIDD1 and the caspase CASP2 to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis (PubMed:15073321, PubMed:16652156, PubMed:17159900, PubMed:17289572, PubMed:9044836). Also recruits CAS
• PDB: 2O71, 2OF5, 3CRD
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00619	CARD	6 → 89	Caspase recruitment domain	Domain
  PF00531	Death	117 → 195	Death domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Constitutively expressed in most tissues, with particularly high expression in adult heart, testis, liver, skeletal muscle, fetal liver and kidney. {ECO:0000269|PubMed:8985253, ECO:0000269|PubMed:9044836}.
• Sequence:

  MEARDKQVLRSLRLELGAEVLVEGLVLQYLYQEGILTENHIQEINAQTTGLRKTMLLLDI
  LPSRGPKAFDTFLDSLQEFPWVREKLKKAREEAMTDLPAGDRLTGIPSHILNSSPSDRQI
  NQLAQRLGPEWEPMVLSLGLSQTDIYRCKANHPHNVQSQVVEAFIRWRQRFGKQATFQSL
  HNGLRAVEVDPSLLLHMLE

• Sequence length: 199

Pathways

Reactome:

TP53 Regulates Transcription of Caspase Activators and Caspases

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Familial isolated arrhythmogenic right ventricular dysplasia	Likely pathogenic; Pathogenic	rs2540635374	RCV004544211	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability	Pathogenic	rs141179774, rs772665884	RCV001261380 RCV001261379	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability, autosomal recessive 34	Likely pathogenic; Pathogenic	rs2540635374, rs749655461, rs141179774, rs1207931375	RCV004526358 RCV000412552 RCV000412611 RCV005011725	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Moderate intellectual disability	Pathogenic	rs772665884	RCV001089807	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANDROGENETIC ALOPECIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE NON-SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BONE FRACTURE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, RENAL CELL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRADD-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Global developmental delay	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 34, WITH VARIANT LISSENCEPHALY	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, HIP	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OSTEOARTHRITIS, KNEE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seizure	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absence of septum pellucidum	Absence Of Septum Pellucidum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	GWASDB_DG	23535033		★☆☆☆☆ Found in Text Mining only
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	23535033		★☆☆☆☆ Found in Text Mining only
Amyloidosis	Amyloidosis	BEFREE	27773430		★☆☆☆☆ Found in Text Mining only
Aortic Valve Disease	Aortic valve disease	Pubtator	33125279	Associate	★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	31894294	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal recessive non-syndromic intellectual disability	Non-Syndromic Intellectual Disability	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	17934210	Associate	★☆☆☆☆ Found in Text Mining only
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chromophobe Renal Cell Carcinoma	Chromophobe Carcinoma	CTD_human_DG	20208132		★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Collecting Duct Carcinoma of the Kidney	Renal Carcinoma	CTD_human_DG	20208132		★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	CTD_human_DG	20208132		★☆☆☆☆ Found in Text Mining only
Cortical Dysplasia	Cortical Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	GWASCAT_DG	30664745		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	34163010	Associate	★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	34163010	Associate	★☆☆☆☆ Found in Text Mining only
Generalized seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	30914828		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Intellectual developmental disorder	Pubtator	30914828, 34163010	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	16651240		★☆☆☆☆ Found in Text Mining only
Lissencephaly	Lissencephaly	BEFREE	27773430, 28686357, 30914828		★☆☆☆☆ Found in Text Mining only
Lissencephaly	Lissencephaly	Pubtator	30914828, 34163010, 37880421	Associate	★☆☆☆☆ Found in Text Mining only
Lissencephaly	Lissencephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	BEFREE	27773430		★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mantle cell lymphoma	Mantle Cell Lymphoma	BEFREE	11468180		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 34, WITH VARIANT LISSENCEPHALY	Mental retardation	UNIPROT_DG	22279524		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 34, WITH VARIANT LISSENCEPHALY	Mental retardation	GENOMICS_ENGLAND_DG	27773430		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 34, WITH VARIANT LISSENCEPHALY	Mental retardation	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 34, WITH VARIANT LISSENCEPHALY	Mental retardation	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neoplasms	Neoplasms	BEFREE	20208132, 28591699		★☆☆☆☆ Found in Text Mining only
Osteoarthritis of hip	Osteoarthritis Of Hip	GWASCAT_DG	30664745		★☆☆☆☆ Found in Text Mining only
Osteoarthritis, Knee	Knee osteoarthritis	GWASCAT_DG	30664745		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteosarcoma	Osteosarcoma	BEFREE	19125251		★☆☆☆☆ Found in Text Mining only
Pachygyria	Pachygyria	BEFREE	30914828, 31506600		★☆☆☆☆ Found in Text Mining only
Pachygyria	Pachygyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Papillary Renal Cell Carcinoma	Papillary Renal Carcinoma	CTD_human_DG	20208132		★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	CTD_human_DG	20208132		★☆☆☆☆ Found in Text Mining only
Salaam Seizures	Salaam Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sarcomatoid Renal Cell Carcinoma	Renal Carcinoma	CTD_human_DG	20208132		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	30914828	Associate	★☆☆☆☆ Found in Text Mining only
Septicemia	Septicemia	BEFREE	26190521		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	BEFREE	30679432		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	17026852	Associate	★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only
Trigeminal Neuralgia	Trigeminal neuralgia	Pubtator	38158702	Associate	★☆☆☆☆ Found in Text Mining only