USP19

Chr 3

ubiquitin specific peptidase 19

Also known as: ZMYND9

USP19 encodes a deubiquitinating enzyme that removes ubiquitin from proteins to prevent their degradation, regulating processes including muscle development, endoplasmic reticulum protein quality control, and cellular responses to hypoxia. Mutations cause autosomal recessive developmental and epileptic encephalopathy with early-onset seizures and severe developmental delay. The gene is highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.20
Clinical SummaryUSP19
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 6.66
OE 0.11 (0.060.20)
Highly constrained

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

Missense Constraint
1.99Z-score
OE missense 0.81 (0.760.86)
691 obs / 854.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.060.20)
00.351.4
Missense OE0.81 (0.760.86)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 7 / 64.9Missense obs/exp: 691 / 854.7Syn Z: 1.63

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

USP19 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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