Gene Gene information from NCBI Gene database.
Entrez ID 83737
Gene name Itchy E3 ubiquitin protein ligase
Gene symbol ITCH
Synonyms (NCBI Gene)
ADMFDAIF4AIP4NAPP1
Chromosome 20
Chromosome location 20q11.22
Summary This gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases. HECT domain E3 ubiquitin ligases transfer ubiquitin from E2 ubiquitin-conjugating enzymes to protein substrates, thus targeting specific proteins for lysosomal degradation
SNPs SNP information provided by dbSNP.
1
SNP ID Visualize variation Clinical significance Consequence
rs587776592 ->A Pathogenic Coding sequence variant, non coding transcript variant, frameshift variant, 5 prime UTR variant
miRNA miRNA information provided by mirtarbase database.
853
miRTarBase ID miRNA Experiments Reference
MIRT000372 hsa-miR-106b-5p Luciferase reporter assayWestern blot 19096009
MIRT000372 hsa-miR-106b-5p Luciferase reporter assay 19074548
MIRT000372 hsa-miR-106b-5p Microarray 17242205
MIRT042842 hsa-miR-324-3p CLASH 23622248
MIRT475091 hsa-miR-543 PAR-CLIP 23592263
Gene ontology (GO) Gene Ontology (GO) annotations describing the biological processes, molecular functions, and cellular components associated with a gene.
98
GO ID Ontology Definition Evidence Reference
GO:0000209 Process Protein polyubiquitination IEA
GO:0001558 Process Regulation of cell growth NAS 9462742
GO:0002376 Process Immune system process IEA
GO:0002669 Process Positive regulation of T cell anergy IEA
GO:0002683 Process Negative regulation of immune system process IEA
Other IDs Other IDs provides unique identifiers for this gene in OMIM, HGNC, and Ensembl databases.
MIM HGNC e!Ensembl
606409 13890 ENSG00000078747
Protein Protein information from UniProt database.
UniProt ID Unique identifier for the protein in the UniProt database. Click to view detailed protein information.
Q96J02
Protein name E3 ubiquitin-protein ligase Itchy homolog (Itch) (EC 2.3.2.26) (Atrophin-1-interacting protein 4) (AIP4) (HECT-type E3 ubiquitin transferase Itchy homolog) (NFE2-associated polypeptide 1) (NAPP1)
Protein function Acts as an Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:11046148, PubMed:14602072, PubM
PDB 2DMV , 2KYK , 2NQ3 , 2P4R , 2YSF , 3TUG , 4ROF , 5C7M , 5CQ2 , 5DWS , 5DZD , 5SXP
Family and domains

Pfam

Accession ID Position in sequence Description Type
PF00168 C2 18 116 C2 domain Domain
PF00397 WW 328 357 WW domain Domain
PF00397 WW 360 389 WW domain Domain
PF00397 WW 440 469 WW domain Domain
PF00397 WW 480 509 WW domain Domain
PF00632 HECT 598 903 HECT-domain (ubiquitin-transferase) Domain
Tissue specificity TISSUE SPECIFICITY: Widely expressed.
Sequence
MSDSGSQLGSMGSLTMKSQLQITVISAKLKENKKNWFGPSPYVEVTVDGQSKKTEKCNNT
NSPKWKQPLTVIVTPVSKLHFRVWSHQTLKSDVLLGTAALDIYETLKSNNMKLEEV
VVTL
QLGGDKEPTETIGDLSICLDGLQLESEVVTNGETTCSENGVSLCLPRLECNSAISAHCNL
CLPGLSDSPISASRVAGFTGASQNDDGSRSKDETRVSTNGSDDPEDAGAGENRRVSGNNS
PSLSNGGFKPSRPPRPSRPPPPTPRRPASVNGSPSATSESDGSSTGSLPPTNTNTNTSEG
ATSGLIIPLTISGGSGPRPLNPVTQAPLPPGWEQRVDQHGRVYYVDHVEKRTTWDRPEPL
PPGWERRVDNMGRIYYVDHFTRTTTWQRP
TLESVRNYEQWQLQRSQLQGAMQQFNQRFIY
GNQDLFATSQSKEFDPLGPLPPGWEKRTDSNGRVYFVNHNTRITQWEDPRSQGQLNEKPL
PEGWEMRFTVDGIPYFVDHNRRTTTYIDP
RTGKSALDNGPQIAYVRDFKAKVQYFRFWCQ
QLAMPQHIKITVTRKTLFEDSFQQIMSFSPQDLRRRLWVIFPGEEGLDYGGVAREWFFLL
SHEVLNPMYCLFEYAGKDNYCLQINPASYINPDHLKYFRFIGRFIAMALFHGKFIDTGFS
LPFYKRILNKPVGLKDLESIDPEFYNSLIWVKENNIEECDLEMYFSVDKEILGEIKSHDL
KPNGGNILVTEENKEEYIRMVAEWRLSRGVEEQTQAFFEGFNEILPQQYLQYFDAKELEV
LLCGMQEIDLNDWQRHAIYRHYARTSKQIMWFWQFVKEIDNEKRMRLLQFVTGTCRLPVG
GFADLMGSNGPQKFCIEKVGKENWLPRSHTCFNRLDLPPYKSYEQLKEKLLFAIEETEGF
GQE
Sequence length 903
Interactions View interactions
Pathways Pathway information has different metabolic/signaling pathways associated with genes.
  KEGG  Reactome
  Ubiquitin mediated proteolysis
Endocytosis
Notch signaling pathway
TNF signaling pathway
Non-alcoholic fatty liver disease
  Downregulation of ERBB4 signaling
NOD1/2 Signaling Pathway
Activated NOTCH1 Transmits Signal to the Nucleus
Degradation of GLI1 by the proteasome
Hedgehog 'on' state
RUNX1 regulates transcription of genes involved in differentiation of HSCs
Negative regulators of DDX58/IFIH1 signaling
Antigen processing: Ubiquitination & Proteasome degradation
Associated diseases Disease associations from ClinVar (causal & non-causal) and other databases (OMIM, Orphanet, GWAS, etc.).
20
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 Diseases associated with Pathogenic or Likely Pathogenic variants in ClinVar
Phenotype Name Clinical Significance dbSNP ID RCV Accession Evidence Score
Syndromic multisystem autoimmune disease due to ITCH deficiency Pathogenic; Likely pathogenic rs1568998827, rs2146507793, rs587776592, rs2515695390, rs2515940072, rs2515819804, rs2515548244, rs2515866863, rs2515520453, rs2038571383, rs1988702062, rs1988672290, rs1983332740, rs1381447036 RCV001329453
RCV001953515
RCV000004641
RCV002971446
RCV003024828
View all (9 more)
★★★★★
ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Unknown / Other Associations ClinVar entries with uncertain/conflicting evidence, and associations from other databases (OMIM, Orphanet, GWAS, etc.) where the gene is not established as causal.
Phenotype Name Clinical Significance Source Evidence Score
Acute myeloid leukemia Likely benign; Benign ClinVar
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
ANDROGENETIC ALOPECIA GWAS catalog
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE DISEASE, MULTISYSTEM, WITH FACIAL DYSMORPHISM CTD, HPO
CTD, HPO
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Cervical cancer Benign; Likely benign ClinVar
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Associations from Text Mining Disease associations identified through text mining
Disease Name Disease (Merged) Source PMID Relationship Type Evidence Score
Anaplastic thyroid carcinoma Anaplastic thyroid cancer BEFREE 19016753
★☆☆☆☆
Found in Text Mining only
Arthritis Arthritis Pubtator 33894394 Associate
★☆☆☆☆
Found in Text Mining only
Asthma Asthma BEFREE 31091003
★☆☆☆☆
Found in Text Mining only
AUTOIMMUNE DISEASE, MULTISYSTEM, WITH FACIAL DYSMORPHISM MULTISYSTEM AUTOIMMUNE DISEASE WITH FACIAL DYSMORPHISM GENOMICS_ENGLAND_DG 20170897, 27322655
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE DISEASE, MULTISYSTEM, WITH FACIAL DYSMORPHISM MULTISYSTEM AUTOIMMUNE DISEASE WITH FACIAL DYSMORPHISM ORPHANET_DG 20170897
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE DISEASE, MULTISYSTEM, WITH FACIAL DYSMORPHISM MULTISYSTEM AUTOIMMUNE DISEASE WITH FACIAL DYSMORPHISM CLINVAR_DG
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE DISEASE, MULTISYSTEM, WITH FACIAL DYSMORPHISM MULTISYSTEM AUTOIMMUNE DISEASE WITH FACIAL DYSMORPHISM CTD_human_DG
★★☆☆☆
Found in Text Mining + Unknown/Other Associations
Autoimmune Diseases Autoimmune disease Pubtator 20170897 Associate
★☆☆☆☆
Found in Text Mining only
Autoimmune Diseases of the Nervous System Autoimmune nervous system disorder Pubtator 33894394 Associate
★☆☆☆☆
Found in Text Mining only
Behcet Syndrome Behcet disease Pubtator 26890122 Associate
★☆☆☆☆
Found in Text Mining only