LANCL1

Chr 2

LanC like glutathione S-transferase 1

Also known as: GPR69A, p40

The protein functions as a glutathione transferase that mitigates neuronal oxidative stress during postnatal development through glutathione-mediated antioxidant defense mechanisms. Mutations in this gene cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe seizures, developmental delay, and neurodegeneration. The gene shows very low constraint against loss-of-function variants, which is consistent with recessive inheritance patterns.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.23
Clinical SummaryLANCL1
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
1.23LOEUF
pLI 0.000
Z-score 0.71
OE 0.84 (0.581.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.74Z-score
OE missense 1.14 (1.031.27)
248 obs / 217.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.84 (0.581.23)
00.351.4
Missense OE1.14 (1.031.27)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 19 / 22.7Missense obs/exp: 248 / 217.2Syn Z: -0.28
DN
0.5772th %ile
GOF
0.6541th %ile
LOF
0.3551th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

LANCL1 · 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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