CYLD
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CYLD (HGNC:2584) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
CYLD lysine 63 deubiquitinase
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
CYLD1
Alias symbols
KIAA0849, USPL2
%HI
2.21(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.33(Read more about gnomAD LOEUF score)
Cytoband
16q12.1
Genomic Coordinates
GRCh37/hg19: chr16:50775997-50835846 NCBI Ensembl UCSC
GRCh38/hg38: chr16:50742086-50801935 NCBI Ensembl UCSC
MANE Select Transcript
NM_001378743.1 ENST00000427738.8 (Read more about MANE Select)
Function
Deubiquitinase that specifically cleaves 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains and is involved in NF-kappa-B activation and TNF-alpha-induced necroptosis (PubMed:18636086, PubMed:26670046, PubMed:27458237, PubMed:26997266, PubMed:27591049, PubMed:29291351, PubMed:18313383, PubMed:32185393). Negatively regulates NF-kappa-B activation by deubiquitinating upstream signaling factors (PubMed:12917689, PubMed:12917691, PubMed:32185393). Contributes to the regulation of cell survival... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-1226
ClinGen Curation ID:
CCID:006962
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
02/10/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 10835629
    Bignell et al (2000) identified CYLD as the causal gene for familial cylindromatosis (FC), an inherited condition that manifests as benign cutaneous adnexal tumors. Sequence analysis of 21 affected families identified 9 frameshifting mutations, 9 nonsense mutations, and 3 splice site alterations. All variations segregated with the condition, are predicted to result in loss of function variation, and are not observed or observed very infrequently in population databases.
  • PUBMED: 15854031
    Bowen et al (2005) documents three families with familial benign skin tumors with clinical diagnoses of Brooke-Speigler Syndrome (BSS), FC, and two families with multiple familial trichoepitheliomas (MFT). Five families were found to have rare nonsense or frameshift variants in CYLD. No CYLD variant was identified in the sixth family.
  • PUBMED: 20132422
    Kazakov (2010) reports a patient with germline putative splicing variant (c.1684+1G>A) in CYLD and multiple benign lesions. In addition to the benign lesions, the patient had two basal cell carcinomas that demonstrated loss of heterozygosity for the CYLD locus. This case, and others, demonstrates the potential for the benign skin lesions associated with CYLD-associated cutaneous syndromes to transform into malignancies.
HI Evidence Comments:
Transformation of the benign tumors present in CYLD-associated cutaneous syndromes has been reported, starting with Gerretsen et al 1993 (PMID 7688655). Estimated rates of malignant transformation range from 5-10% (Kazakov 2016, PMID 26971504).

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
No evidence for triplosensitivity

Genomic View

Select assembly: (NC_000016.9) (NC_000016.10)