LRP4

Chr 11ARAD

LDL receptor related protein 4

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

NCBI Gene: 4038ENSG00000134569UniProt: O75096OMIM: 604270

This gene encodes a member of the low-density lipoprotein receptor-related protein family. The encoded protein may be a regulator of Wnt signaling. Mutations in this gene are associated with Cenani-Lenz syndrome. [provided by RefSeq, May 2010]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismAR/ADLOEUF 0.423 OMIM phenotypes
Clinical Summary— LRP4
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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

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Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
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ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 763 VUS of 1548 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — LRP4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?
0.42LOEUF
pLI 0.000
Z-score 6.36
OE 0.31 (0.23–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
3.06Z-score
OE missense 0.74 (0.70–0.79)
832 obs / 1120.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.31 (0.23–0.42)
0≤0.351.4
Missense OE?0.74 (0.70–0.79)
0≤0.61.4
Synonymous OE?1.02
0≤1.21.6
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

This gene — mechanism propensity

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

1548 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic29
VUS763
Likely Benign572
Benign78
Conflicting64
20
Pathogenic
29
Likely Pathogenic
763
VUS
572
Likely Benign
78
Benign
64
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
4
1
1
20
Likely Pathogenic
21
8
0
0
29
VUS
10
666
72
15
763
Likely Benign
1
9
233
329
572
Benign
0
6
66
6
78
Conflicting
—64
Total466933723511,526

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap LRP4 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

LRP4 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients