EPPK1

Chr 8AD

epiplakin 1

Also known as: EPIPL, EPIPL1

Epiplakin is a cytoskeletal linker protein that connects to intermediate filaments and controls their reorganization in response to cellular stress, particularly in keratinocytes and other epithelial cells. Mutations cause palmoplantar keratoderma, epidermolytic, type 1, an autosomal dominant skin disorder characterized by thickening of the palms and soles with epidermolysis. The gene shows very low constraint against loss-of-function variants, suggesting tolerance to such mutations.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Palmoplantar keratoderma, epidermolytic, 1MIM #144200
AD
0
Active trials
10
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.20
LOEUF
GOF
Mechanism· predicted
Clinical SummaryEPPK1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.20LOEUF
pLI 0.000
Z-score 0.27
OE 0.96 (0.781.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-3.04Z-score
OE missense 1.23 (1.181.27)
1768 obs / 1443.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.96 (0.781.20)
00.351.4
Missense OE1.23 (1.181.27)
00.61.4
Synonymous OE1.29
01.21.6
LoF obs/exp: 58 / 60.3Missense obs/exp: 1768 / 1443.0Syn Z: -6.01
DN
0.4884th %ile
GOF
0.82top 10%
LOF
0.3260th %ile

The highest-scoring mechanism for this gene is gain-of-function.

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EPPK1 · 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.

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Clinical Literature
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