LRP4

Chr 11ARAD

LDL receptor related protein 4

Also known as: CLSS, CMS17, LRP-4, LRP10, MEGF7, SOST2

This protein functions as a member of the low-density lipoprotein receptor family and regulates Wnt signaling from the cell membrane. Mutations cause Cenani-Lenz syndactyly syndrome and sclerosteosis 2 through autosomal recessive inheritance, and congenital myasthenic syndrome type 17 through autosomal dominant inheritance. The pathogenic mechanism involves gain-of-function effects.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAR/ADLOEUF 0.423 OMIM phenotypes
Clinical SummaryLRP4
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Gene-Disease Validity (ClinGen)
Cenani-Lenz syndactyly syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.42LOEUF
pLI 0.000
Z-score 6.36
OE 0.31 (0.230.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.06Z-score
OE missense 0.74 (0.700.79)
832 obs / 1120.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.31 (0.230.42)
00.351.4
Missense OE0.74 (0.700.79)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 30 / 97.9Missense obs/exp: 832 / 1120.5Syn Z: -0.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveLRP4-related Cenani-Lenz syndactyly syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6843th %ile
GOF
0.74top 25%
LOF
0.3648th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LRP4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Myasthenia gravis.
Gilhus NE et al.·Nat Rev Dis Primers
2019Review
Myasthenia gravis-Pathophysiology, diagnosis, and treatment.
Tannemaat MR et al.·Handb Clin Neurol
2024Review
Myasthenia gravis.
Pasnoor M et al.·Handb Clin Neurol
2024Review
Top 5 results · since 2015Search PubMed ↗