CYLD

Chr 16

CYLD lysine 63 deubiquitinase

Also known as: BRSS, CDMT, CYLD1, CYLDI, EAC, FTDALS8, MFT, MFT1

NCBI Gene: 1540ENSG00000083799UniProt: Q9NQC7

This gene is encodes a cytoplasmic protein with three cytoskeletal-associated protein-glycine-conserved (CAP-GLY) domains that functions as a deubiquitinating enzyme. Mutations in this gene have been associated with cylindromatosis, multiple familial trichoepithelioma, and Brooke-Spiegler syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCylindromatosis, familial
UniProtTrichoepithelioma, multiple familial, 1
UniProtBrooke-Spiegler syndrome
UniProtFrontotemporal dementia and/or amyotrophic lateral sclerosis 8

Clinical highlights

Gene-disease validity (ClinGen)
Brooke-Spiegler syndrome · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
113
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.20
LOEUF· LoF intol.
LOF
Mechanism· G2P
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GeneReview available — CYLD
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.20LOEUF
pLI 1.000
Z-score 5.65
OE 0.09 (0.04–0.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.55Z-score
OE missense 0.55 (0.50–0.61)
277 obs / 500.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.09 (0.04–0.20)
0≤0.351.4
Missense OE?0.55 (0.50–0.61)
0≤0.61.4
Synonymous OE?0.97
0≤1.21.6
LoF obs/exp: 4 / 44.8Missense obs/exp: 277 / 500.1Syn Z: 0.32

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

CYLD · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients