VLDLR

very low density lipoprotein receptor, the group of Low density lipoprotein receptors

Basic information

Region (hg38): 9:2621182-2660056

Links

ENSG00000147852 ∙ NCBI:7436 ∙ OMIM:192977 ∙ HGNC:12698 ∙ Uniprot:P98155 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (Definitive), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (Strong), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium (Supportive), mode of inheritance: AR
• cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellar hypoplasia, impaired intellectual development, and dysequilibrium syndrome 1	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	16080122; 18043714; 18326629; 18364738; 20082205

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VLDLR gene.

• not_provided (610 variants)
• Inborn_genetic_diseases (119 variants)
• Cerebellar_ataxia,_intellectual_disability,_and_dysequilibrium_syndrome_1 (106 variants)
• not_specified (61 variants)
• Congenital_cerebellar_hypoplasia (30 variants)
• VLDLR-related_disorder (23 variants)
• Intellectual_disability (3 variants)
• Dysequilibrium_syndrome (2 variants)
• See_cases (2 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Cerebellar_hypoplasia (1 variants)
• Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VLDLR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003383.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			7	240	1	248
missense	2	3	186	16		207
nonsense	18	5				23
start loss		1				1
frameshift	11	3	1			15
splice donor/acceptor (+/-2bp)	1	18	4			23
Total	32	30	198	256	1

Highest pathogenic variant AF is 0.000016108486

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VLDLR	protein_coding	protein_coding	ENST00000382100	19	38220

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.12	534	466	1.15	0.0000262	5813
Missense in Polyphen		161	186.32	0.86411		2403
Synonymous	-1.74	203	174	1.17	0.0000107	1567
Loss of Function	3.17	26	50.3	0.517	0.00000323	557

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000522	0.000521
Ashkenazi Jewish	0.000893	0.000893
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000202	0.000202
Middle Eastern	0.000326	0.000326
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds VLDL and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. Binding to Reelin induces tyrosine phosphorylation of Dab1 and modulation of Tau phosphorylation (By similarity). {ECO:0000250}.
• Disease: DISEASE: Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 1 (CAMRQ1) [MIM:224050]: A congenital, non-progressive cerebellar ataxia associated with disturbed equilibrium, delayed ambulation, mental retardation, cerebellar hypoplasia and mild cerebral gyral simplification. Additional features include short stature, strabismus, pes planus and, rarely, seizures. {ECO:0000269|PubMed:16080122}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Developmental Biology;VLDL clearance;VLDLR internalisation and degradation;Plasma lipoprotein clearance;Transport of small molecules;Plasma lipoprotein assembly, remodeling, and clearance;Axon guidance;Reelin signalling pathway;Reelin signaling pathway;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Lissencephaly gene (LIS1) in neuronal migration and development (Consensus)

Recessive Scores

• pRec: 0.490

Intolerance Scores

• loftool: 0.0391
• rvis_EVS: -1.06
• rvis_percentile_EVS: 7.55

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.690

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;lipid transport;receptor-mediated endocytosis;signal transduction;nervous system development;axon guidance;memory;cholesterol metabolic process;ventral spinal cord development;low-density lipoprotein particle receptor catabolic process;glycoprotein transport;very-low-density lipoprotein particle clearance;reelin-mediated signaling pathway;positive regulation of protein kinase activity;dendrite morphogenesis;positive regulation of dendrite development
• Cellular component: lysosomal membrane;plasma membrane;clathrin-coated pit;membrane;integral component of membrane;very-low-density lipoprotein particle;receptor complex
• Molecular function: low-density lipoprotein particle receptor activity;calcium ion binding;protein binding;very-low-density lipoprotein particle receptor activity;apolipoprotein binding;very-low-density lipoprotein particle binding;glycoprotein transporter activity;reelin receptor activity;calcium-dependent protein binding