Vhl von Hippel-Lindau tumor suppressor [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Vhlprovided by MGI
Official Full Name: von Hippel-Lindau tumor suppressorprovided by MGI
Primary source: MGI:MGI:103223
See related: Ensembl:ENSMUSG00000033933 AllianceGenome:MGI:103223
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Vhlh; pVHL
Summary: Predicted to enable enzyme binding activity and ubiquitin ligase-substrate adaptor activity. Involved in regulation of postsynapse organization and regulation of protein catabolic process at postsynapse, modulating synaptic transmission. Acts upstream of or within several processes, including camera-type eye morphogenesis; enteroendocrine cell differentiation; and regulation of apoptotic process. Located in several cellular components, including cilium; glutamatergic synapse; and nuclear lumen. Part of Cul2-RING ubiquitin ligase complex. Is expressed in several structures, including eye; genitourinary system; gut; heart; and nervous system. Used to study familial erythrocytosis 2; sudden infant death syndrome; and von Hippel-Lindau disease. Human ortholog(s) of this gene implicated in several diseases, including pancreatic cancer (multiple); pheochromocytoma; polycythemia (multiple); renal cell carcinoma; and von Hippel-Lindau disease. Orthologous to several human genes including VHL (von Hippel-Lindau tumor suppressor). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in testis adult (RPKM 26.4), CNS E14 (RPKM 13.7) and 28 other tissues See more
Orthologs: human all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 6 E3; 6 52.81 cM

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	6	NC_000072.7 (113600955..113608595)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	6	NC_000072.6 (113623994..113631634)

Chromosome 6 - NC_000072.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.
Title: VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.
VHL governs m6A modification and PIK3R3 mRNA stability in clear cell renal cell carcinomas.
Title: VHL governs m6A modification and PIK3R3 mRNA stability in clear cell renal cell carcinomas.
Inhibiting von Hippel-Lindau protein-mediated Dishevelled ubiquitination protects against experimental parkinsonism.
Title: Inhibiting von Hippel‒Lindau protein-mediated Dishevelled ubiquitination protects against experimental parkinsonism.
The von Hippel-Lindau Tumor Suppressor Gene Mutations Modulate Lipocalin-2 Expression in Ferroptotic-Inflammatory Pathways.
Title: The von Hippel-Lindau Tumor Suppressor Gene Mutations Modulate Lipocalin-2 Expression in Ferroptotic-Inflammatory Pathways.
Deletion of Vhl in Dmp1-Expressing Cells Causes Microenvironmental Impairment of B Cell Lymphopoiesis.
Title: Deletion of Vhl in Dmp1-Expressing Cells Causes Microenvironmental Impairment of B Cell Lymphopoiesis.
E3 Ubiquitin Ligase Von Hippel-Lindau Protein Promotes Th17 Differentiation.
Title: E3 Ubiquitin Ligase Von Hippel-Lindau Protein Promotes Th17 Differentiation.
Rb1/Rbl1/Vhl loss induces mouse subretinal angiomatous proliferation and hemangioblastoma.
Title: Rb1/Rbl1/Vhl loss induces mouse subretinal angiomatous proliferation and hemangioblastoma.
promotes follicular helper T cell differentiation via glycolytic-epigenetic control
Title: The E3 ligase VHL promotes follicular helper T cell differentiation via glycolytic-epigenetic control.
a novel role for VHL in mediating nephron progenitor differentiation through metabolic regulation, and suggest that VHL is required for normal kidney development.
Title: Von Hippel-Lindau Acts as a Metabolic Switch Controlling Nephron Progenitor Differentiation.
Study results in transgenic mice demonstrate that the type 2B (murine G518A representing human R167Q) VHL mutation may influence vascular changes and hemangioblastoma formation by accelerating the maturation of larger-caliber arteries in addition to maintaining and expanding capillary density, which could, in turn, worsen pathological progression via blood perfusion defects.
Title: Von Hippel-Lindau mutations disrupt vascular patterning and maturation via Notch.

Submit: New GeneRIF Correction See all GeneRIFs (98)

Variation

Go to the top of the page Help

Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (9) 1 citation
Endonuclease-mediated (5) 1 citation

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

UniSTS:235523 (e-PCR)
- UniSTS:235523

PMC23053P1 (e-PCR)
- UniSTS:272191

PMC23053P2 (e-PCR)
- UniSTS:272192

U12570 (e-PCR)
- UniSTS:163396

Vhlh (e-PCR), detects polymorphism
- UniSTS:144755

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	ISO Inferred from Sequence Orthology more info
enables molecular adaptor activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables transcription elongation factor activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin-like ligase-substrate adaptor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within blood vessel endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within camera-type eye morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within camera-type eye morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within ciliary body morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of endothelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within extracellular matrix organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within eye pigmentation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within homeostasis of number of retina cells	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of hypoxia-inducible factor-1alpha signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within iris morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within iris morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within melanin metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of endothelial cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of hypoxia-inducible factor-1alpha signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of thymocyte apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in neuron differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within pancreatic A cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within proteasomal protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein transport	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of apoptotic signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of catecholamine metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynapse organization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynapse organization	IEP Inferred from Expression Pattern more info	PubMed
involved_in regulation of postsynapse organization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of protein localization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of thymocyte apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation protein catabolic process at postsynapse	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation protein catabolic process at postsynapse	IEP Inferred from Expression Pattern more info	PubMed
involved_in regulation protein catabolic process at postsynapse	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to hypoxia	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within type B pancreatic cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of Cul2-RING ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
part_of VCB complex	IBA Inferred from Biological aspect of Ancestor more info
part_of VCB complex	ISO Inferred from Sequence Orthology more info
located_in cilium	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in endoplasmic reticulum	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IEP Inferred from Expression Pattern more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in intracellular non-membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
is_active_in postsynaptic density	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynaptic density	IEP Inferred from Expression Pattern more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: von Hippel-Lindau disease tumor suppressor

Names: von Hippel-Lindau syndrome protein homolog

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_009507.4 → NP_033533.1 von Hippel-Lindau disease tumor suppressor

See identical proteins and their annotated locations for NP_033533.1

Status: VALIDATED

Source sequence(s)

AC153987

Consensus CDS

CCDS20429.1

UniProtKB/Swiss-Prot

P40338

UniProtKB/TrEMBL

Q3TTE7

Related

ENSMUSP00000039418.8, ENSMUST00000035673.8

Conserved Domains (1) summary

pfam01847
Location:27 → 171

VHL; von Hippel-Lindau disease tumour suppressor protein