LCE2D

Chr 1

late cornified envelope 2D

Also known as: LEP12, SPRL1A

NCBI Gene: 353141 ENSG00000187223 UniProt: Q5TA82

Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Jul 2025]

Research

Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.90

Clinical Summary— LCE2D

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Population Constraint (gnomAD)

Low constraint (pLI 0.09) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

21 VUS of 23 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?

1.90LOEUF

pLI 0.085

Z-score -0.13

OE 1.16 (0.28–1.90)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.66Z-score

OE missense 1.23 (1.03–1.48)

81 obs / 65.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.16 (0.28–1.90)

0≤0.351.4

Missense OE?1.23 (1.03–1.48)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 1 / 0.9Missense obs/exp: 81 / 65.9Syn Z: -0.61

This gene — mechanism propensity

0.85top 5%

GOF

0.74top 25%

LOF

0.2874th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

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

23 submitted variants in ClinVar

ClinVar

Classification Summary

VUS21

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	21	0	21
Likely Benign	1	1	2
Benign	0	0	0
Total	22	1	23

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap LCE2D — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →