LCE1B

Chr 1

late cornified envelope 1B

Also known as: LEP2, SPRL2A

NCBI Gene: 353132 ENSG00000196734 UniProt: Q5T7P3 OMIM: 612604

Enables identical protein binding activity. Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

Enables identical protein binding activity. Predicted to be involved in keratinization. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.84

Clinical Summary— LCE1B

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

19 VUS of 19 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.84LOEUF

pLI 0.030

Z-score 0.19

OE 0.86 (0.33–1.84)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.57Z-score

OE missense 1.20 (1.00–1.45)

77 obs / 64.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.86 (0.33–1.84)

0≤0.351.4

Missense OE?1.20 (1.00–1.45)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 2 / 2.3Missense obs/exp: 77 / 64.1Syn Z: -1.26

This gene — mechanism propensity

0.83top 10%

GOF

0.72top 25%

LOF

0.2582th %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

19 submitted variants in ClinVar

ClinVar

Classification Summary

VUS19

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	19	19
Likely Benign	0	0
Benign	0	0
Total	19	19

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap LCE1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →