LCE2D

Chr 1

late cornified envelope 2D

Also known as: LEP12, SPRL1A

NCBI Gene: 353141 ENSG00000187223 UniProt: Q5TA82 OMIM: 612612

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

OMIM Research

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

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.90

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in LCE2D?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 200

178 rare PASS variants

Rare truncating (LoF)

1 in 6,500

18 rare PASS variants

Rare synonymous (reference)

1 in 1,100

60 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LCE2D. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 510	1 in 26,000
South Asian	~43k	1 in 190	1 in 3,600
Remaining (unassigned)	~30k	1 in 210	1 in 1,000
European (Finnish)	~27k	1 in 460	none seen
Admixed American	~22k	1 in 180	1 in 1,600
African / African American	~21k	1 in 270	1 in 3,300
East Asian	~20k	1 in 300	none seen
Ashkenazi Jewish	~13k	1 in 1,900	none seen
Middle Eastern	~2,884	1 in 260	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓