LCE1F

Chr 1

late cornified envelope 1F

Also known as: LEP6

NCBI Gene: 353137 ENSG00000240386 UniProt: Q5T754 OMIM: 612608

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 1.89

Clinical Summary— LCE1F

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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

20 VUS of 25 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.005

Z-score -0.24

OE 1.16 (0.48–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.16Z-score

OE missense 1.05 (0.87–1.27)

75 obs / 71.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.16 (0.48–1.89)

0≤0.351.4

Missense OE?1.05 (0.87–1.27)

0≤0.61.4

Synonymous OE?1.50

0≤1.21.6

LoF obs/exp: 3 / 2.6Missense obs/exp: 75 / 71.3Syn Z: -2.12

This gene — mechanism propensity

0.87top 5%

GOF

0.81top 10%

LOF

0.2971th %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

25 submitted variants in ClinVar

ClinVar

Classification Summary

VUS20

Likely Benign5

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	20	0	20
Likely Benign	1	4	5
Benign	0	0	0
Total	21	4	25

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 LCE1F — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →