LYPLAL1

Chr 1

lysophospholipase like 1

Also known as: Q96AV0

The protein functions as a palmitoyl thioesterase that removes palmitate groups from specific proteins including cGAS and potassium channels, thereby regulating innate immune signaling and ion channel function. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, refractory seizures, and developmental regression. The gene is not highly constrained against loss-of-function variation.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.40
Clinical SummaryLYPLAL1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.40LOEUF
pLI 0.000
Z-score 0.66
OE 0.78 (0.461.40)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.23Z-score
OE missense 1.31 (1.151.50)
159 obs / 121.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.78 (0.461.40)
00.351.4
Missense OE1.31 (1.151.50)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 8 / 10.3Missense obs/exp: 159 / 121.0Syn Z: -0.48
DN
0.6452th %ile
GOF
0.4481th %ile
LOF
0.3067th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LYPLAL1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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