LCE5A

Chr 1

late cornified envelope 5A

Also known as: LEP18, SPRL5A

NCBI Gene: 254910 ENSG00000186207 UniProt: Q5TCM9 OMIM: 612619

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— LCE5A

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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

12 VUS of 16 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 0.18

OE 0.87 (0.33–1.84)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.07Z-score

OE missense 0.98 (0.80–1.20)

65 obs / 66.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.87 (0.33–1.84)

0≤0.351.4

Missense OE?0.98 (0.80–1.20)

0≤0.61.4

Synonymous OE?0.70

0≤1.21.6

LoF obs/exp: 2 / 2.3Missense obs/exp: 65 / 66.5Syn Z: 1.18

This gene — mechanism propensity

0.87top 5%

GOF

0.77top 25%

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

16 submitted variants in ClinVar

ClinVar

Classification Summary

VUS12

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	12	12
Likely Benign	1	1
Benign	0	0
Total	13	13

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 16) ClinVar copy-number / structural variants overlap LCE5A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →