LCE2B

Chr 1

late cornified envelope 2B

Also known as: LEP10, SPRL1B, XP5

This gene is one of the at least 20 genes expressed during epidermal differentiation and located on chromosomal band 1q21. This gene is involved in epidermal differentiation, and it is expressed at high levels in normal and psoriatic skin, but not in cultured keratinocytes or in any other tested cell types or tissues. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…
MultiplemechanismLOEUF 1.88
Clinical SummaryLCE2B
Population Constraint (gnomAD)
Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
30 VUS of 31 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.88LOEUF
pLI 0.098
Z-score 0.12
OE 0.88 (0.251.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-1.84Z-score
OE missense 1.65 (1.411.91)
104 obs / 62.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.88 (0.251.88)
00.351.4
Missense OE?1.65 (1.411.91)
00.61.4
Synonymous OE?1.59
01.21.6
LoF obs/exp: 1 / 1.1Missense obs/exp: 104 / 62.9Syn Z: -2.23

This gene — mechanism propensity

DN
0.86top 5%
GOF
0.72top 25%
LOF
0.2776th %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

31 submitted variants in ClinVar

Classification Summary

VUS30
Likely Benign1
30
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
30
0
0
30
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total0310031

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap LCE2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

LCE2B · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →