VLDLR

Chr 9AR

very low density lipoprotein receptor

Also known as: CAMRQ1, CARMQ1, CHRMQ1, VLDL-R, VLDLRCH

NCBI Gene: 7436ENSG00000147852UniProt: P98155

The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. This gene encodes a lipoprotein receptor that is a member of the LDLR family and plays important roles in VLDL-triglyceride metabolism and the reelin signaling pathway. Mutations in this gene cause VLDLR-associated cerebellar hypoplasia. Alternative splicing generates multiple transcript variants encoding distinct isoforms for this gene. [provided by RefSeq, Aug 2009]

Primary Disease Associations & Inheritance

Cerebellar hypoplasia, impaired intellectual development, and dysequilibrium syndrome 1MIM #224050
AR
UniProtCerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 1
1064
ClinVar variants
53
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— VLDLR
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 Pathogenic / Likely Pathogenic· 78 VUS of 1064 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.72LOEUF
pLI 0.000
Z-score 3.17
OE 0.52 (0.38–0.72)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.12Z-score
OE missense 1.15 (1.07–1.23)
534 obs / 465.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.52 (0.38–0.72)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.15 (1.07–1.23)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.17
0≤1.21.6
LoF obs/exp: 26 / 50.3Missense obs/exp: 534 / 465.9Syn Z: -1.74

ClinVar Variant Classifications

1064 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic18
VUS78
Likely Benign347
Benign5
Conflicting2
35
Pathogenic
18
Likely Pathogenic
78
VUS
347
Likely Benign
5
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
26
0
35
Likely Pathogenic
13
0
5
0
18
VUS
0
72
5
1
78
Likely Benign
0
0
159
188
347
Benign
0
0
5
0
5
Conflicting
—2
Total2272200189485

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

View in ClinVar →

Protein Context — Lollipop Plot

VLDLR · protein map & ClinVar variants

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

Gene2Phenotype Curations

VLDLR-related cerebellar ataxia, intellectual developmental disorder, and dysequilibrium syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebellar hypoplasia, impaired intellectual development, and dysequilibrium syndrome 1

MIM #224050

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Resilience to autosomal dominant Alzheimer's disease in a Reelin-COLBOS heterozygous man.
Lopera F et al.·Nat Med
2023Case report
Neuronal ROS-induced glial lipid droplet formation is altered by loss of Alzheimer's disease-associated genes.
Moulton MJ et al.·Proc Natl Acad Sci U S A
2021
Reelin links Apolipoprotein E4, Tau, and Amyloid-β in Alzheimer's disease.
Yi LX et al.·Ageing Res Rev
2024Review
The receptor VLDLR binds Eastern Equine Encephalitis virus through multiple distinct modes.
Cao D et al.·Nat Commun
2024
Identification of the VLDLR locus associated with giant cell arteritis and the possible causal role of low-density lipoprotein cholesterol in its pathogenesis.
Iwasaki T et al.·Rheumatology (Oxford)
2024Meta-analysis
PCSK9 and cancer: Rethinking the link.
Mahboobnia K et al.·Biomed Pharmacother
2021Review
Midbrain-hindbrain involvement in lissencephalies.
Jissendi-Tchofo P et al.·Neurology
2009
Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.
Wang Y et al.·Genome Med
2025Cohort
PCSK9 Inhibition: From Current Advances to Evolving Future.
Liu C et al.·Cells
2022Review
The risks of RELN polymorphisms and its expression in the development of otosclerosis.
Priyadarshi S et al.·PLoS One
2022Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools