LDLRAD4

Chr 18

low density lipoprotein receptor class A domain containing 4

Also known as: C18orf1

NCBI Gene: 753ENSG00000168675UniProt: 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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
88
P/LP submissions
0%
P/LP missense
0.54
LOEUF
—
Mechanism
Clinical Summary— LDLRAD4
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
84 unique Pathogenic / Likely Pathogenic· 57 VUS of 154 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.620
Z-score 2.63
OE 0.17 (0.07–0.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.57Z-score
OE missense 0.69 (0.60–0.79)
137 obs / 199.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.17 (0.07–0.54)
0≤0.351.4
Missense OE0.69 (0.60–0.79)
0≤0.61.4
Synonymous OE1.03
0≤1.21.6
LoF obs/exp: 2 / 11.7Missense obs/exp: 137 / 199.6Syn Z: -0.19

ClinVar Variant Classifications

154 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic1
VUS57
Likely Benign1
83
Pathogenic
1
Likely Pathogenic
57
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
83
0
83
Likely Pathogenic
0
0
1
0
1
VUS
0
44
13
0
57
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total045970142

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

View in ClinVar →

Protein Context — Lollipop Plot

LDLRAD4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Genome-wide association analysis of the primary feather growth traits of duck: identification of potential Loci for growth regulation
Ma S et al.·Poult Sci
2023
Indoor particulate matter induces epigenetic changes in companion atopic dogs.
Kim J et al.·Ecotoxicol Environ Saf
2023
Replication of gene polymorphisms associated with periodontitis-related traits in an elderly cohort: the Washington Heights/Inwood Community Aging Project Ancillary Study of Oral Health.
Yang T et al.·J Clin Periodontol
2022Cohort
Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis
Jin F et al.·Front Genet
2021
Chromosome-level genome assembly of goose provides insight into the adaptation and growth of local goose breeds
Zhao Q et al.·Gigascience
2022
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic and clinical determinants of abdominal aortic diameter: genome-wide association studies, exome array data and Mendelian randomization study.
Portilla-Fernandez E et al.·Hum Mol Genet
2022Meta-analysis
Hypomethylation of the low-density lipoprotein receptor class A domain containing 4 gene in rheumatoid arthritis.
Song J et al.·Clin Immunol
2025
Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome.
Fichna JP et al.·Int J Mol Sci
2024
Loss of STK11 Suppresses Lipid Metabolism and Attenuates KRAS-Induced Immunogenicity in Patients with Non-Small Cell Lung Cancer.
Principe DR et al.·Cancer Res Commun
2024Cohort
The significance of long chain non-coding RNA signature genes in the diagnosis and management of sepsis patients, and the development of a prediction model.
Bai Y et al.·Front Immunol
2024Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
LDLRAD4 is a potential diagnostic and prognostic biomarker correlated with immune infiltration in myelodysplastic syndromes.
Xu M et al.·Front Genet
2025Open Access
Downregulation of low-density lipoprotein receptor class A domain-containing protein 4 (Ldlrad4) in the liver of rats treated with nongenotoxic hepatocarcinogen to induce transforming growth factor β signaling promoting cell proliferation and suppressing apoptosis in early hepatocarcinogenesis.
Ito Y et al.·J Appl Toxicol
2020
Identification of low-density lipoprotein receptor class A domain containing 4 (LDLRAD4) as a prognostic indicator in primary gastrointestinal stromal tumors.
Xie W et al.·Curr Probl Cancer
2020
Antisense lncRNA LDLRAD4-AS1 promotes metastasis by decreasing the expression of LDLRAD4 and predicts a poor prognosis in colorectal cancer.
Mo S et al.·Cell Death Dis
2020Open Access
Low density lipoprotein receptor class A domain containing 4 (LDLRAD4) promotes tumorigenesis of hepatic cancer cells.
Liu Z et al.·Exp Cell Res
2017
Top 5 resultsSearch Europe PMC ↗

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