VLDLR

Chr 9AR

very low density lipoprotein receptor

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

NCBI Gene: 7436 ENSG00000147852 UniProt: P98155 OMIM: 192977

The protein functions as a multifunctional cell surface receptor that binds and transports VLDL into cells through endocytosis and serves as a critical component of the Reelin signaling pathway, which controls neuronal migration and positioning during brain development. Mutations cause cerebellar hypoplasia with impaired intellectual development and dysequilibrium syndrome, primarily affecting the cerebellum and cognitive function from early childhood. This condition follows autosomal recessive inheritance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.721 OMIM phenotype

Clinical Summary— VLDLR

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Gene-Disease Validity (ClinGen)

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

66 unique Pathogenic / Likely Pathogenic· 221 VUS of 865 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — VLDLR

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.72LOEUF

pLI 0.000

Z-score 3.17

OE 0.52 (0.38–0.72)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.12Z-score

OE missense 1.15 (1.07–1.23)

534 obs / 465.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.52 (0.38–0.72)

0≤0.351.4

Missense OE?1.15 (1.07–1.23)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 26 / 50.3Missense obs/exp: 534 / 465.9Syn Z: -1.74

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveVLDLR-related cerebellar ataxia, intellectual developmental disorder, and dysequilibrium syndromeLOFAR

This gene — mechanism propensity

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

0.6646th %ile

GOF

0.74top 25%

LOF

0.3260th %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

865 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36

Likely Pathogenic30

VUS221

Likely Benign483

Benign47

Conflicting34

Pathogenic

Likely Pathogenic

221

VUS

483

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	30	2	4	0	36
Likely Pathogenic	27	3	0	0	30
VUS	1	182	32	6	221
Likely Benign	0	6	248	229	483
Benign	0	0	46	1	47
Conflicting	—				34
Total	58	193	330	236	851

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

View in ClinVar →

177 pathogenic / likely-pathogenic (of 206) ClinVar copy-number / structural variants overlap VLDLR — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →