LANCL1

Chr 2

LanC like glutathione S-transferase 1

Also known as: GPR69A, p40

NCBI Gene: 10314 ENSG00000115365 UniProt: O43813

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a loosely associated peripheral membrane protein related to the LanC family of bacterial membrane-associated proteins involved in the biosynthesis of antimicrobial peptides. This protein may play a role as a peptide-modifying enzyme component in eukaryotic cells. Previously considered a member of the G-protein-coupled receptor superfamily, this protein is now in the LanC family. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2008]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.23

Clinical Summary— LANCL1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

69 VUS of 80 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.23LOEUF

pLI 0.000

Z-score 0.71

OE 0.84 (0.58–1.23)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.74Z-score

OE missense 1.14 (1.03–1.27)

248 obs / 217.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.84 (0.58–1.23)

0≤0.351.4

Missense OE?1.14 (1.03–1.27)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 19 / 22.7Missense obs/exp: 248 / 217.2Syn Z: -0.28

This gene — mechanism propensity

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

80 submitted variants in ClinVar

ClinVar

Classification Summary

VUS69

Benign3

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	69	0	0	69
Likely Benign	0	0	0	0
Benign	1	1	1	3
Total	70	1	1	72

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

23 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap LANCL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →