LYPD2

Chr 8

LY6/PLAUR domain containing 2

Also known as: LYPDC2, UNQ430

LYPD2 encodes a protein predicted to localize to the extracellular region and plasma membrane, though its specific function remains unclear. Mutations in LYPD2 have been associated with neurodevelopmental disorders, but the clinical phenotype and inheritance pattern are not well-established. The gene shows moderate tolerance to loss-of-function variants (pLI 0.25, LOEUF 1.33), suggesting it may not be under strong selective constraint.

Summary from RefSeq
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0
Active trials
3
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.33
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryLYPD2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.33LOEUF
pLI 0.253
Z-score 1.22
OE 0.29 (0.101.33)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.20Z-score
OE missense 0.94 (0.781.13)
80 obs / 85.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.29 (0.101.33)
00.351.4
Missense OE0.94 (0.781.13)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 1 / 3.4Missense obs/exp: 80 / 85.3Syn Z: 0.50
DN
0.6355th %ile
GOF
0.7029th %ile
LOF
0.2580th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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

LYPD2 · 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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