LDLRAD4

Chr 18

low density lipoprotein receptor class A domain containing 4

Also known as: C18orf1

NCBI Gene: 753 ENSG00000168675 UniProt: O15165

The LDLRAD4 protein functions as a negative regulator of TGF-beta signaling by binding to SMAD2 and SMAD3, thereby controlling cell proliferation, differentiation, and migration. Mutations cause autosomal recessive developmental delay with variable intellectual disability and dysmorphic features. The gene is highly constrained against loss-of-function variants (pLI = 1.0), indicating intolerance to protein-truncating mutations.

ResearchSummary from RefSeq, UniProt

Enables R-SMAD binding activity. Involved in negative regulation of cell migration; negative regulation of epithelial to mesenchymal transition; and negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway. Located in early endosome membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.54

LOEUF

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Mechanism

Some data sources returned errors (1)

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