Provide a comprehensive cross-database identifier and functional mapping reference for human VHL. This should serve as a definitive lookup resource for researchers. ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 1: GENE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Provide ALL gene-level database identifiers: - HGNC ID and approved symbol - Ensembl gene ID (ENSG) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 2: TRANSCRIPT IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL transcript-level identifiers: - Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.) How many total transcripts? - RefSeq transcripts: ALL NM_ mRNA accessions Mark which is MANE Select (canonical clinical standard) - CCDS IDs: ALL consensus coding sequence identifiers For the CANONICAL/MANE SELECT transcript: - List ALL exon IDs (ENSE) with genomic coordinates - Total exon count ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 3: PROTEIN IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List ALL protein-level identifiers: - UniProt accessions: ALL entries (reviewed and unreviewed) Mark the canonical reviewed entry - RefSeq protein: ALL NP_ accessions Protein domains and families: - List ALL annotated domains/families with identifiers - Include: domain name, type (domain/family/superfamily), and ID ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 4: STRUCTURE IDENTIFIERS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Experimental structures: - List ALL PDB structure IDs - For each: experimental method (X-ray, NMR, Cryo-EM) and resolution - Total PDB structure count Predicted structures: - AlphaFold model ID and confidence metrics (pLDDT) ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 5: CROSS-SPECIES ORTHOLOGS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ List orthologous genes in key model organisms (where available): - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 6: CLINICAL VARIANTS & AI PREDICTIONS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Clinical variant annotations: - Total variant count in clinical databases - Breakdown by classification: Pathogenic, Likely Pathogenic, Uncertain Significance (VUS), Likely Benign, Benign - List TOP 50 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: Total count List TOP 50 predicted splice-altering variants with delta scores - Missense pathogenicity predictions: Total count List TOP 50 predicted pathogenic missense variants with scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Pathway membership: - List ALL biological pathways this gene participates in - Include pathway IDs and names - Total pathway count Gene Ontology annotations: - Biological Process: count and TOP 20 terms with IDs - Molecular Function: count and TOP 20 terms with IDs - Cellular Component: count and TOP 20 terms with IDs ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Protein-protein interactions: - Total interaction count - List TOP 50 highest-confidence interacting proteins with scores Protein similarity (evolutionary and structural): - Structural/embedding similarity: How many similar proteins? List TOP 20 with similarity scores - Sequence homology: How many homologous proteins? List TOP 20 with identity/similarity scores ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene encodes a transcription factor: Downstream targets (genes regulated BY this TF): - Total target gene count - List TOP 50 target genes with regulation type (activates/represses) DNA binding profiles: - List ALL known binding motif IDs - Motif family classification Upstream regulators (TFs that regulate THIS gene): - List known transcriptional regulators with evidence type ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 10: DRUG & PHARMACOLOGY DATA ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ If this gene/protein is a drug target: Targeting molecules: - How many drug/compound molecules target this protein? - List TOP 30 molecules by development phase - Include: molecule ID, name, mechanism, highest development phase Clinical trials: - How many clinical trials involve drugs targeting this gene? - List TOP 20 trials with: trial ID, phase, status, intervention Pharmacogenomics: - Known drug-gene interactions affecting drug response - Dosing guidelines if any exist ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 11: EXPRESSION PROFILES ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Tissue expression: - Which tissues express this gene most highly? - List TOP 30 tissues with expression scores/levels - Note any tissue-specific or tissue-enriched patterns Cell type expression: - Which cell types show highest expression? - List TOP 30 cell types with expression scores - Note any cell type-specific patterns Single-cell expression data (if available): - Which single-cell datasets/experiments include this gene? - Notable cell population patterns ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ SECTION 12: DISEASE ASSOCIATIONS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ Mendelian/monogenic disease links: - What diseases are caused by mutations in this gene? - List ALL associated diseases with: disease name, disease ID, inheritance pattern, evidence level Phenotype associations: - What clinical phenotypes are associated with this gene? - List TOP 50 phenotype terms with IDs Complex trait associations (GWAS): - What traits/diseases are linked via genome-wide association studies? - List TOP 30 GWAS associations with: trait, study ID, p-value, effect size if available ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ FORMATTING REQUIREMENTS ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ - Present each section with clear headers - Use tables for listing multiple items - Always include COUNTS for every category - For lists with 50 items: show total count + TOP 50 - For lists with

Question

Provide a comprehensive cross-database identifier and functional mapping
reference for human VHL. This should serve as a definitive
lookup resource for researchers.

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 1: GENE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Provide ALL gene-level database identifiers:
- HGNC ID and approved symbol
- Ensembl gene ID (ENSG)
- NCBI Entrez Gene ID
- OMIM gene/locus ID
- Genomic location: chromosome, start position, end position, strand

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 2: TRANSCRIPT IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL transcript-level identifiers:
- Ensembl transcripts: ALL ENST IDs with biotype (protein_coding, etc.)
  How many total transcripts?
- RefSeq transcripts: ALL NM_ mRNA accessions
  Mark which is MANE Select (canonical clinical standard)
- CCDS IDs: ALL consensus coding sequence identifiers

For the CANONICAL/MANE SELECT transcript:
- List ALL exon IDs (ENSE) with genomic coordinates
- Total exon count

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 3: PROTEIN IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List ALL protein-level identifiers:
- UniProt accessions: ALL entries (reviewed and unreviewed)
  Mark the canonical reviewed entry
- RefSeq protein: ALL NP_ accessions

Protein domains and families:
- List ALL annotated domains/families with identifiers
- Include: domain name, type (domain/family/superfamily), and ID

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 4: STRUCTURE IDENTIFIERS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Experimental structures:
- List ALL PDB structure IDs
- For each: experimental method (X-ray, NMR, Cryo-EM) and resolution
- Total PDB structure count

Predicted structures:
- AlphaFold model ID and confidence metrics (pLDDT)

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 5: CROSS-SPECIES ORTHOLOGS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
List orthologous genes in key model organisms (where available):
- Mouse (Mus musculus): gene ID, symbol
- Rat (Rattus norvegicus): gene ID, symbol
- Zebrafish (Danio rerio): gene ID, symbol
- Fruit fly (Drosophila melanogaster): gene ID, symbol
- Worm (C. elegans): gene ID, symbol
- Yeast (S. cerevisiae): gene ID, symbol

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 6: CLINICAL VARIANTS & AI PREDICTIONS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Clinical variant annotations:
- Total variant count in clinical databases
- Breakdown by classification: Pathogenic, Likely Pathogenic,
  Uncertain Significance (VUS), Likely Benign, Benign
- List TOP 50 pathogenic/likely pathogenic variants with:
  variant ID, HGVS notation, associated condition

AI-based variant effect predictions:
- Splice effect predictions: Total count
  List TOP 50 predicted splice-altering variants with delta scores
- Missense pathogenicity predictions: Total count
  List TOP 50 predicted pathogenic missense variants with scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 7: BIOLOGICAL PATHWAYS & GENE ONTOLOGY
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Pathway membership:
- List ALL biological pathways this gene participates in
- Include pathway IDs and names
- Total pathway count

Gene Ontology annotations:
- Biological Process: count and TOP 20 terms with IDs
- Molecular Function: count and TOP 20 terms with IDs
- Cellular Component: count and TOP 20 terms with IDs

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 8: PROTEIN INTERACTIONS & MOLECULAR NETWORKS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Protein-protein interactions:
- Total interaction count
- List TOP 50 highest-confidence interacting proteins with scores

Protein similarity (evolutionary and structural):
- Structural/embedding similarity: How many similar proteins?
  List TOP 20 with similarity scores
- Sequence homology: How many homologous proteins?
  List TOP 20 with identity/similarity scores

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 9: TRANSCRIPTION FACTOR REGULATORY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene encodes a transcription factor:

Downstream targets (genes regulated BY this TF):
- Total target gene count
- List TOP 50 target genes with regulation type (activates/represses)

DNA binding profiles:
- List ALL known binding motif IDs
- Motif family classification

Upstream regulators (TFs that regulate THIS gene):
- List known transcriptional regulators with evidence type

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 10: DRUG & PHARMACOLOGY DATA
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
If this gene/protein is a drug target:

Targeting molecules:
- How many drug/compound molecules target this protein?
- List TOP 30 molecules by development phase
- Include: molecule ID, name, mechanism, highest development phase

Clinical trials:
- How many clinical trials involve drugs targeting this gene?
- List TOP 20 trials with: trial ID, phase, status, intervention

Pharmacogenomics:
- Known drug-gene interactions affecting drug response
- Dosing guidelines if any exist

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 11: EXPRESSION PROFILES
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Tissue expression:
- Which tissues express this gene most highly?
- List TOP 30 tissues with expression scores/levels
- Note any tissue-specific or tissue-enriched patterns

Cell type expression:
- Which cell types show highest expression?
- List TOP 30 cell types with expression scores
- Note any cell type-specific patterns

Single-cell expression data (if available):
- Which single-cell datasets/experiments include this gene?
- Notable cell population patterns

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
SECTION 12: DISEASE ASSOCIATIONS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
Mendelian/monogenic disease links:
- What diseases are caused by mutations in this gene?
- List ALL associated diseases with: disease name, disease ID,
  inheritance pattern, evidence level

Phenotype associations:
- What clinical phenotypes are associated with this gene?
- List TOP 50 phenotype terms with IDs

Complex trait associations (GWAS):
- What traits/diseases are linked via genome-wide association studies?
- List TOP 30 GWAS associations with: trait, study ID, p-value,
  effect size if available

━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
FORMATTING REQUIREMENTS
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
- Present each section with clear headers
- Use tables for listing multiple items
- Always include COUNTS for every category
- For lists with >50 items: show total count + TOP 50
- For lists with <50 items: show ALL items
- Always include database identifiers (IDs), not just names
- Mark canonical/primary/reviewed entries where applicable
- If a section has no data available, state "No data available"
  rather than omitting the section

Accepted Answer

VHL Gene: Comprehensive Cross-Database Identifier and Functional Mapping Reference GENE OVERVIEW
A critical tumor suppressor involved in HIF ubiquitination Summary: This gene encodes a component of a ubiquitination complex involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF). VHL plays a central role in the regulation of gene expression by oxygen, cilia formation, cytokine signaling, regulation of senescence, and formation of the extracellular matrix. Variants are …

Database	Identifier	Notes
HGNC	HGNC:12687	Approved symbol: VHL
Ensembl	ENSG00000134086	Human gene
NCBI Entrez	7428	Gene ID
OMIM	608537	Gene/locus MIM
UniGene	Hs.585416	Cluster

Attribute	Value
Chromosome	3
Cytogenetic Band	3p25.3
Start Position	10,141,778 (GRCh38)
End Position	10,153,676 (GRCh38)
Strand	+ (plus/forward)
Genomic Accession	NC_000003.12

Attribute	Value
Locus Type	Gene with protein product
Locus Group	Protein-coding gene
Status	Approved

Transcript ID	Biotype	Start	End	Strand
ENST00000256474	protein_coding	10,141,778	10,153,667	+
ENST00000345392	protein_coding	10,141,788	10,153,667	+
ENST00000477538	retained_intron	10,141,802	10,153,667	+
ENST00000696142	nonsense_mediated_decay	10,141,786	10,153,667	+
ENST00000696143	protein_coding	10,141,816	10,153,667	+
ENST00000696153	protein_coding	10,141,778	10,153,676	+
ENST00000713811	protein_coding	10,141,778	10,153,667	+
ENST00000713812	protein_coding	10,141,786	10,153,667	+
ENST00000713813	retained_intron	10,141,787	10,153,667	+
ENST00000713814	nonsense_mediated_decay	10,141,791	10,153,667	+
ENST00000713815	protein_coding	10,141,797	10,153,667	+
ENST00000713816	protein_coding_CDS_not_defined	10,141,800	10,153,667	+
ENST00000713982	protein_coding	10,141,778	10,153,667	+

Accession	Type	Status	MANE Select
NM_000551	mRNA	REVIEWED	✓ Yes
NM_198156	mRNA	REVIEWED	No
NM_001354723	mRNA	REVIEWED	No
NR_176335	ncRNA	REVIEWED	No

VHL Gene Complete Identifier and Functional Mapping Reference

Structured Data Sources

Accession	Status	MANE Select
NP_000542	REVIEWED	✓ Yes
NP_937799	REVIEWED	No
NP_001341652	REVIEWED	No

Exon ID	Start	End	Strand	Length
ENSE00001930974	10,141,778	10,142,187	+	410 bp
ENSE00004022056	10,146,514	10,146,636	+	123 bp
ENSE00004022057	10,149,787	10,153,667	+	3,881 bp

Accession	Status	Length	Mass	Description
P40337	✓ Reviewed (Swiss-Prot)	213 aa	24,153 Da	Canonical entry
A0A024R2F2	Unreviewed	-	-	TrEMBL
A0A0S2Z4K1	Unreviewed	-	-	TrEMBL
A0A8Q3SIA6	Unreviewed	-	-	TrEMBL
A0A8Q3WL21	Unreviewed	-	-	TrEMBL
A0AAQ5BGZ3	Unreviewed	-	-	TrEMBL
A0AAQ5BGZ5	Unreviewed	-	-	TrEMBL
A0AAQ5BH02	Unreviewed	-	-	TrEMBL
A0AAQ5BH16	Unreviewed	-	-	TrEMBL
A0AAQ5BH56	Unreviewed	-	-	TrEMBL

InterPro ID	Name	Type
IPR022772	VHL_tumour_suppress_b/a_dom	Domain
IPR024048	VHL_alpha_dom	Domain
IPR024053	VHL_beta_dom	Domain
IPR036208	VHL_sf	Homologous Superfamily
IPR037139	VHL_alpha_dom_sf	Homologous Superfamily
IPR037140	VHL_beta_dom_sf	Homologous Superfamily

PDB ID	Method	Resolution	Title
9GIO	X-RAY	1.486 Å	VHL-EloC-EloB complex with covalent compound
7Z76	X-RAY	1.32 Å	SMARCA2/VCB complex with compound 10
7JTO	X-RAY	1.70 Å	Protac MS33 with WDR5 and VCB
4AJY	X-RAY	1.73 Å	VHL-ElonginB-ElonginC with HIF1-alpha peptide
6GMR	X-RAY	1.75 Å	VCB with pyrrolyl-phenylmethanol
6HR2	X-RAY	1.76 Å	PROTAC 2 with SMARCA4 bromodomain and VCB
8BB3	X-RAY	1.80 Å	WDR5/VCB with PROTAC (PEG linker)
6GFX	X-RAY	1.83 Å	VCB with modified HIF-1a CODD peptide
1LM8	X-RAY	1.85 Å	HIF-1a-pVHL-ElonginB-ElonginC Complex
6ZHC	X-RAY	1.92 Å	PROTAC6 VHL:EloB:EloC and Bcl-xL
6GMN	X-RAY	1.94 Å	VCB with furo-pyrrole-carboxylate
7Z77	X-RAY	1.97 Å	SMARCA2/VCB with compound 6
8P0F	X-RAY	1.98 Å	VCB complex with compound 1
9BOL	X-RAY	1.99 Å	VHL/ElonginB/ElonginC with compound 5
1LQB	X-RAY	2.00 Å	Hydroxylated HIF-1 alpha with pVHL/elongin
4B9K	X-RAY	2.00 Å	VCB with hydroxypyrrolidine compound
6BVB	X-RAY	2.00 Å	HIF-2alpha-pVHL-elongin B-elongin C
8BB5	X-RAY	2.05 Å	WDR5/VCB with PROTAC (Aryl linker)
9EQJ	X-RAY	2.05 Å	VCB with MP-1-39
4W9F	X-RAY	2.10 Å	VCB with methylthiazol-benzyl compound
4W9H	X-RAY	2.10 Å	VCB with acetamido compound
4W9K	X-RAY	2.10 Å	VCB with phenylpropanamido compound
5NVV	X-RAY	2.10 Å	VCB with hydroxyacetamido compound
5NW1	X-RAY	2.10 Å	VCB with cyclobutanecarboxamido compound
9DTX	X-RAY	2.11 Å	PRT3789 with BRG1 bromodomain and VCB
7JTP	X-RAY	2.12 Å	Protac MS67 with WDR5 and VCB
9RKC	X-RAY	2.19 Å	ACBI4-KRAS G12D-VCB ternary complex
8QW6	X-RAY	2.20 Å	Compound 3-KRAS G12V-VCB complex
4W9C	X-RAY	2.20 Å	VCB with oxazol-benzyl compound
4W9D	X-RAY	2.20 Å	VCB with methyloxazol compound
4W9J	X-RAY	2.20 Å	VCB with methylpentanamido compound
4W9L	X-RAY	2.20 Å	VCB with dimethylbutanamido compound
5NVW	X-RAY	2.20 Å	VCB with cyclopropanecarboxamido
5NVX	X-RAY	2.20 Å	VCB with fluorocyclopropane compound
5NW2	X-RAY	2.20 Å	VCB with oxetane-carboxamido compound
9HYP	X-RAY	2.20 Å	SMARCA2-VCB with PROTAC P5
7PI4	X-RAY	2.24 Å	FAK-GSK215 PROTAC-VCB
6HAY	X-RAY	2.24 Å	PROTAC 1 with SMARCA2 and VCB
8QVU	X-RAY	2.24 Å	ACBI3 with KRAS G12D and VCB
7KHH	X-RAY	2.28 Å	VHL/BRD4-BD1/Compound9 ternary complex
9QE4	X-RAY	2.28 Å	VCB with compound 114
6GFZ	X-RAY	2.30 Å	VCB with fluoro-hydroxyproline compound
5NW0	X-RAY	2.30 Å	VCB with acetamidocyclopropane compound
9OIO	X-RAY	2.30 Å	VCB with fragments 9 and 14
4BKS	X-RAY	2.20 Å	VCB with ethanoyl-oxazol compound
4BKT	X-RAY	2.35 Å	VCB with methyloxazol compound
6HAX	X-RAY	2.35 Å	PROTAC 2 with SMARCA2 and VCB
8QW7	X-RAY	2.36 Å	Compound 4-KRAS G12V-VCB complex
9HYN	X-RAY	2.37 Å	SMARCA2-VCB with PROTAC P1
8CQL	X-RAY	2.38 Å	VCB with compound 33

Attribute	Value
AlphaFold ID	AF-P40337-F1
Global pLDDT	85.45
Sequence Length	1702
Fraction High Confidence (pLDDT >90)	72%

Organism	Ensembl ID	Symbol	Biotype
Mouse (Mus musculus)	ENSMUSG00000033933	Vhl	protein_coding
Rat (Rattus norvegicus)	ENSRNOG00000010258	Vhl	protein_coding
Zebrafish (Danio rerio)	ENSDARG00000070617	vhl	protein_coding
Fruit fly (Drosophila melanogaster)	FBGN0041174	Vhl	protein_coding
Worm (C. elegans)	-	No data available	-
Yeast (S. cerevisiae)	-	No data available	-

Classification	Count
Pathogenic	~200+
Likely Pathogenic	~50+
Uncertain Significance (VUS)	~400+
Likely Benign	~100+
Benign	~50+
Conflicting Classifications	~50+

ClinVar ID	HGVS Notation	Type	Classification
182977	c.257C>T (p.Pro86Leu)	SNV	Pathogenic (Expert Panel)
182978	c.263G>A (p.Trp88Ter)	SNV	Pathogenic (Expert Panel)
2226	c.191G>C (p.Arg64Pro)	SNV	Pathogenic (Expert Panel)
43597	c.194C>G (p.Ser65Trp)	SNV	Pathogenic (Expert Panel)
428806	c.208G>T (p.Glu70Ter)	SNV	Pathogenic (Expert Panel)
182975	c.194C>T (p.Ser65Leu)	SNV	Pathogenic
193118	c.245G>C (p.Arg82Pro)	SNV	Pathogenic
220414	c.337C>T (p.Arg113Ter)	SNV	Pathogenic
223168	c.233A>C (p.Asn78Thr)	SNV	Pathogenic
223176	c.293A>G (p.Tyr98Cys)	SNV	Pathogenic
2223	c.292T>C (p.Tyr98His)	SNV	Pathogenic
2228	c.334T>A (p.Tyr112Asn)	SNV	Pathogenic
223184	c.320G>A (p.Arg107His)	SNV	Pathogenic
223186	c.332G>A (p.Ser111Asn)	SNV	Pathogenic
223187	c.333C>G (p.Ser111Arg)	SNV	Pathogenic
223190	c.340+1G>A	Splice	Pathogenic
223193	c.340G>C (p.Gly114Arg)	SNV	Pathogenic
2236	c.250G>T (p.Val84Leu)	SNV	Pathogenic
2237	c.277G>A (p.Gly93Ser)	SNV	Pathogenic
229860	c.250G>C (p.Val84Leu)	SNV	Pathogenic
456577	c.262T>A (p.Trp88Arg)	SNV	Pathogenic
496053	c.262T>C (p.Trp88Arg)	SNV	Pathogenic
560741	c.329del (p.His110fs)	Deletion	Pathogenic
583094	c.340G>A (p.Gly114Ser)	SNV	Pathogenic
182986	c.180del (p.Val62fs)	Deletion	Pathogenic
223161	c.194C>A (p.Ser65Ter)	SNV	Pathogenic
223162	c.203C>A (p.Ser68Ter)	SNV	Pathogenic
223164	c.217C>T (p.Gln73Ter)	SNV	Pathogenic
411961	c.226_227del (p.Phe76fs)	Deletion	Pathogenic
220487	c.258del (p.Val87fs)	Deletion	Pathogenic
163dup	c.163dup (p.Glu55fs)	Duplication	Pathogenic
164_171dup	c.164_171dup (p.Arg60fs)	Duplication	Pathogenic
1070179	c.239G>A (p.Ser80Asn)	SNV	Pathogenic/Likely pathogenic
1023005	c.190C>A (p.Arg64Ser)	SNV	Likely pathogenic
1297059	c.244C>G (p.Arg82Gly)	SNV	Pathogenic
1426858	c.193T>A (p.Ser65Thr)	SNV	Pathogenic
1782641	c.191dup (p.Ser65fs)	Duplication	Pathogenic
1785035	c.204dup (p.Arg69fs)	Duplication	Pathogenic
428811	c.278del (p.Gly93fs)	Deletion	Pathogenic
428804	c.286C>T (p.Gln96Ter)	SNV	Pathogenic
496052	c.238A>C (p.Ser80Arg)	SNV	Pathogenic
496055	c.313A>C (p.Thr105Pro)	SNV	Pathogenic
547829	c.193T>C (p.Ser65Pro)	SNV	Pathogenic
565557	c.331A>T (p.Ser111Cys)	SNV	Pathogenic
580847	c.264G>C (p.Trp88Cys)	SNV	Pathogenic
2214	c.223_225del (p.Ile75del)	Deletion	Pathogenic
2220	c.263G>C (p.Trp88Ser)	SNV	Pathogenic
223175	c.277G>T (p.Gly93Cys)	SNV	Pathogenic
2028206	c.231C>A (p.Cys77Ter)	SNV	Pathogenic
2925342	c.202T>C (p.Ser68Pro)	SNV	Pathogenic

Variant	Effect	Delta Score
3:10142188:GT>G	donor_loss	0.98
3:10142185:GAG>G	donor_gain	0.95
3:10142188:G>GG	donor_gain	0.92
3:10142235:TCTG>T	donor_gain	0.87
3:10142222:G>T	donor_gain	0.82
3:10142180:C>G	donor_gain	0.75
3:10142880:G>GT	donor_gain	0.66
3:10142001:G>GT	donor_gain	0.51
3:10142185:G>GT	donor_gain	0.53
3:10142186:AG>A	donor_gain	0.50
3:10142187:GG>G	donor_gain	0.50
3:10145957:T>G	donor_gain	0.49
3:10142069:C>A	donor_gain	0.45
3:10142866:TC>T	donor_gain	0.45
3:10142674:GC>G	donor_gain	0.45
3:10142320:GCTC>G	donor_gain	0.45
3:10142853:G>GT	donor_gain	0.44
3:10143228:TC>T	donor_gain	0.44
3:10144640:T>TA	donor_gain	0.44
3:10144656:C>T	donor_gain	0.43
3:10145954:GCTT>G	donor_gain	0.42
3:10143003:A>C	donor_gain	0.42
3:10143323:C>G	donor_gain	0.41
3:10143774:G>T	donor_gain	0.41
3:10142236:C>A	donor_gain	0.40
3:10142961:T>G	donor_gain	0.40
3:10142895:T>A	donor_gain	0.39
3:10142905:G>T	donor_gain	0.39
3:10141968:G>GT	donor_gain	0.37
3:10142185:GAGGT>G	donor_gain	0.37

Method	Count
X-RAY DIFFRACTION	~125
ELECTRON MICROSCOPY	~14

Organism	UniProt	Length	Identity
Mouse	P40338	181 aa	93.4%
Rat	Q64259	185 aa	93.4%

Variant	Protein Change	AM Score	Class
3:10142081:T>A	N78K	0.999	likely_pathogenic
3:10142081:T>G	N78K	0.999	likely_pathogenic
3:10142109:T>A	W88R	0.999	likely_pathogenic
3:10142109:T>C	W88R	0.999	likely_pathogenic
3:10142085:A>C	S80R	0.999	likely_pathogenic
3:10142087:T>A	S80R	0.999	likely_pathogenic
3:10142087:T>G	S80R	0.999	likely_pathogenic
3:10142074:T>C	F76S	0.999	likely_pathogenic
3:10142079:A>G	N78D	0.998	likely_pathogenic
3:10142104:C>A	P86H	0.997	likely_pathogenic
3:10142073:T>C	F76L	0.996	likely_pathogenic
3:10142075:C>A	F76L	0.996	likely_pathogenic
3:10142075:C>G	F76L	0.996	likely_pathogenic
3:10142104:C>G	P86R	0.995	likely_pathogenic
3:10142080:A>T	N78I	0.994	likely_pathogenic
3:10142083:G>C	R79P	0.993	likely_pathogenic
3:10142068:T>A	V74D	0.993	likely_pathogenic
3:10142098:T>A	V84E	0.992	likely_pathogenic
3:10142079:A>T	N78Y	0.992	likely_pathogenic
3:10142091:C>A	R82S	0.992	likely_pathogenic
3:10142074:T>G	F76C	0.991	likely_pathogenic
3:10142092:G>C	R82P	0.990	likely_pathogenic
3:10142103:C>T	P86S	0.990	likely_pathogenic
3:10142071:T>A	I75N	0.988	likely_pathogenic
3:10142079:A>C	N78H	0.987	likely_pathogenic
3:10142041:C>G	S65W	0.981	likely_pathogenic
3:10142061:T>C	S72P	0.979	likely_pathogenic
3:10142071:T>C	I75T	0.978	likely_pathogenic
3:10142097:G>A	V84M	0.977	likely_pathogenic
3:10142086:G>A	S80N	0.976	likely_pathogenic
3:10142103:C>A	P86T	0.975	likely_pathogenic
3:10142101:T>C	L85P	0.975	likely_pathogenic
3:10142062:C>A	S72Y	0.970	likely_pathogenic
3:10142091:C>G	R82G	0.970	likely_pathogenic
3:10142086:G>T	S80I	0.970	likely_pathogenic
3:10142073:T>G	F76V	0.967	likely_pathogenic
3:10142062:C>T	S72F	0.965	likely_pathogenic
3:10142067:G>T	V74F	0.963	likely_pathogenic
3:10142076:T>C	C77R	0.963	likely_pathogenic
3:10142038:G>C	R64P	0.962	likely_pathogenic

Pathway ID	Name	Disease Pathway
R-HSA-1234176	Oxygen-dependent proline hydroxylation of HIF Alpha	No
R-HSA-3232142	SUMOylation of ubiquitinylation proteins	No
R-HSA-8951664	Neddylation	No
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation	No
R-HSA-9706019	RHOBTB3 ATPase cycle	No
R-HSA-9682706	Replication of the SARS-CoV-1 genome	Yes
R-HSA-9694686	Replication of the SARS-CoV-2 genome	Yes

GO ID	Term
GO:0000122	negative regulation of transcription by RNA polymerase II
GO:0000902	cell morphogenesis
GO:0006355	regulation of DNA-templated transcription
GO:0006508	proteolysis
GO:0008285	negative regulation of cell population proliferation
GO:0009968	negative regulation of signal transduction
GO:0010468	regulation of gene expression
GO:0010507	negative regulation of autophagy
GO:0010629	negative regulation of gene expression
GO:0016567	protein ubiquitination
GO:0034244	negative regulation of transcription elongation by RNA polymerase II
GO:0043066	negative regulation of apoptotic process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0045597	positive regulation of cell differentiation
GO:0045893	positive regulation of DNA-templated transcription
GO:0046426	negative regulation of receptor signaling pathway via JAK-STAT
GO:0050821	protein stabilization
GO:0071456	cellular response to hypoxia
GO:1900037	regulation of cellular response to hypoxia
GO:1904262	negative regulation of TORC1 signaling
GO:1990000	amyloid fibril formation

GO ID	Term
GO:0003711	transcription elongation factor activity
GO:0003714	transcription corepressor activity
GO:0004842	ubiquitin-protein transferase activity
GO:0019899	enzyme binding
GO:0060090	molecular adaptor activity
GO:0120283	protein serine/threonine kinase binding
GO:0140297	DNA-binding transcription factor binding
GO:1990756	ubiquitin-like ligase-substrate adaptor activity

GO ID	Term
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005739	mitochondrion
GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005929	cilium
GO:0015630	microtubule cytoskeleton
GO:0097542	ciliary tip

UniProt B	Gene	Score	Description
Q15369	ELOC	999	Elongin-C
Q13617	CUL2	998	Cullin-2
Q16665	HIF1A	998	Hypoxia-inducible factor 1-alpha
Q15370	ELOB	997	Elongin-B
P62877	RBX1	995	E3 ubiquitin-protein ligase RBX1
Q99814	EPAS1	967	HIF-2-alpha
Q9GZT9	EGLN1	950	Egl nine homolog 1 (PHD2)
O94782	USP1	920	Ubiquitin carboxyl-terminal hydrolase 1
Q8TEY7	USP33	919	Ubiquitin carboxyl-terminal hydrolase 33
P27540	ARNT	901	Aryl hydrocarbon receptor nuclear translocator
Q96KS0	EGLN2	871	Egl nine homolog 2 (PHD1)
Q9H6Z9	EGLN3	870	Egl nine homolog 3 (PHD3)
Q96SL1	TCEB3	817	Transcription elongation factor B polypeptide 3
Q9BT92	TCEB3B	813	Elongin-A2
P61758	VBP1	809	Prefoldin subunit 3
O60841	TCEB3C	801	Elongin-A3
Q9NWT6	HIF3A	781	Hypoxia-inducible factor 3-alpha
Q16790	CA9	761	Carbonic anhydrase 9
Q6IE81	TCEB3CL	758	Elongin-A-like
Q9Y2N7	HIF1AN	753	Hypoxia-inducible factor 1-alpha inhibitor
O43255	SOCS7	732	Suppressor of cytokine signaling 7
Q8IYF1	HIF1AN	715	Factor inhibiting HIF1
Q14241	TCEB1	708	Elongin-B
P04637	TP53	699	Cellular tumor antigen p53
Q9Y2K6	USP20	651	Ubiquitin carboxyl-terminal hydrolase 20
P07954	FH	647	Fumarate hydratase
Q12983	BNIP3	630	BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
P34991	HES1	620	Transcription factor HES-1
Q96F10	SAT1	603	Diamine acetyltransferase 1
P01588	EPO	597	Erythropoietin
Q96CJ1	RHOBTB3	590	Rho-related BTB domain-containing protein 3
P02751	FN1	579	Fibronectin
P11166	SLC2A1	571	Solute carrier family 2 member 1 (GLUT1)
P25388	RRAD	564	GTP-binding protein RAD
O43570	CA12	556	Carbonic anhydrase 12
O15460	PROLYL	551	Prolyl 4-hydroxylase subunit alpha-2
P13674	P4HA1	550	Prolyl 4-hydroxylase subunit alpha-1
P17980	PSMC3	549	26S proteasome regulatory subunit 6A
Q9UGP4	LIMD1	543	LIM domain-containing protein 1
P28300	LOX	539	Protein-lysine 6-oxidase
Q9H3M7	TXNIP	535	Thioredoxin-interacting protein
Q09472	EP300	533	Histone acetyltransferase p300
P21912	SDHB	517	Succinate dehydrogenase iron-sulfur subunit
Q15717	ELAVL1	517	ELAV-like protein 1
P30991	SHC1	515	SHC-transforming protein 1
Q15843	NEDD8	509	NEDD8
O43524	FOXO3	504	Forkhead box protein O3
P24928	POLR2A	500	DNA-directed RNA polymerase II subunit RPB1
P49719	HDAC1	497	Histone deacetylase 1
Q13315	ATM	496	Serine-protein kinase ATM

Partner Gene	Interaction Type	Score
MDFI	physical association	0.670
JADE1	physical association	0.370
CUL2	physical association	-
ELOB	physical association	-
ELOC	physical association	-
NEDD8	physical association	-
RBX1	physical association	-
CDK2	physical association	-
TCP1	direct interaction	0.440

UniProt	Top Similarity	Avg Similarity
P40337 (Human)	0.9972	0.9480
P40338 (Mouse)	0.9982	0.9533
Q5Q9Z2	0.9972	0.9553
Q64259 (Rat)	0.9982	0.9513

UniProt	Top Identity	Top Bitscore
P40337 (Human)	92.60%	318
P40338 (Mouse)	93.40%	339
Q64259 (Rat)	93.40%	340
Q5Q9Z2	91.50%	313
Q6RSH7	70.60%	148

Target Gene	Regulation Type	Confidence
ANGPT2	Repression	-
AR	Activation	-
CA12	Unknown	-
CA9	Unknown	-
CCND1	Unknown	-
CDH1	Unknown	-
CDKN1B	Activation	-
CDKN1C	Activation	-
CENPX	Unknown	-
COL4A2	Unknown	-
CXCR4	Repression	-
DAB2	Activation	-
HIF1A	Repression	-
IGF1R	Repression	-
KLF10	Unknown	-
NMU	Repression	-
PDGFB	Activation	-
SNAI1	Repression	-
SPARC	Activation	-
TCF4	Unknown	-
TFRC	Repression	-
TMEM115	Activation	-
TP53	Unknown	-
VEGFA	Activation	-
ZEB2	-	-

Type	Count
Single Protein	1
Protein Complex	4
Protein-Protein Interaction	151

ChEMBL ID	Target Description	Type
CHEMBL3108660	VHL tumor suppressor	SINGLE PROTEIN
CHEMBL3301400	VHL/Elongin B/Elongin C	PROTEIN COMPLEX
CHEMBL4296117	VHL/Elongin-C/Elongin-B/HIF1A	PROTEIN COMPLEX
CHEMBL4296140	VHL/BRD4	PROTEIN-PROTEIN INTERACTION
CHEMBL4296148	VHL/EloB/EloC/BRD4	PROTEIN-PROTEIN INTERACTION
CHEMBL4523998	VHL/EGFR	PROTEIN-PROTEIN INTERACTION
CHEMBL5169273	VHL/KRAS	PROTEIN-PROTEIN INTERACTION
CHEMBL4748227	VHL/BRG1 (SMARCA4)	PROTEIN-PROTEIN INTERACTION
CHEMBL5169067	VHL/WEE1	PROTEIN-PROTEIN INTERACTION
CHEMBL5169069	VHL/WDR5	PROTEIN-PROTEIN INTERACTION
CHEMBL4748224	VHL/BCL-2	PROTEIN-PROTEIN INTERACTION
CHEMBL4748229	VHL/BCL-XL	PROTEIN-PROTEIN INTERACTION
CHEMBL4630740	VHL/BTK	PROTEIN-PROTEIN INTERACTION
CHEMBL4523741	VHL/FAK	PROTEIN-PROTEIN INTERACTION
CHEMBL4630745	VHL/HDAC1	PROTEIN-PROTEIN INTERACTION
CHEMBL4630743	VHL/HDAC2	PROTEIN-PROTEIN INTERACTION
CHEMBL4630741	VHL/HDAC3	PROTEIN-PROTEIN INTERACTION
CHEMBL4630737	VHL/HISTONE DEACETYLASE 6	PROTEIN-PROTEIN INTERACTION
CHEMBL4523730	VHL/Androgen receptor	PROTEIN-PROTEIN INTERACTION
CHEMBL4523726	VHL/Estrogen receptor	PROTEIN-PROTEIN INTERACTION
CHEMBL5291692	VHL/MDM2	PROTEIN-PROTEIN INTERACTION
CHEMBL4748223	VHL/PARP1	PROTEIN-PROTEIN INTERACTION
CHEMBL4748233	VHL/PARP2	PROTEIN-PROTEIN INTERACTION
CHEMBL5169073	VHL/EZH2	PROTEIN-PROTEIN INTERACTION
CHEMBL4748216	VHL/Aurora kinase A	PROTEIN-PROTEIN INTERACTION
CHEMBL5291691	VHL/VEGFR2	PROTEIN-PROTEIN INTERACTION
CHEMBL4523743	VHL/ALK	PROTEIN-PROTEIN INTERACTION
CHEMBL4523725	VHL/ABL1	PROTEIN-PROTEIN INTERACTION
CHEMBL4523735	VHL/FLT3	PROTEIN-PROTEIN INTERACTION
CHEMBL5291688	VHL/FGFR1	PROTEIN-PROTEIN INTERACTION

Attribute	Value
Expression Breadth	Ubiquitous
Total Tissues with Expression	186
Max Expression Score	94.86
Average Expression Score	76.78
Gold Quality Observations	258

Tissue/Cell Type	ID	Score	Quality
Cortical plate	UBERON:0005343	94.86	Gold
Monocyte	CL:0000576	94.31	Gold
Mononuclear cell	CL:0000842	93.09	Gold
Leukocyte	CL:0000738	92.90	Gold
Ganglionic eminence	UBERON:0004023	92.23	Gold
Stromal cell of endometrium	CL:0002255	89.57	Gold
Ventricular zone	UBERON:0003053	89.00	Gold
Buccal mucosa cell	CL:0002336	87.61	Gold
Adrenal tissue	UBERON:0018303	87.40	Gold
Granulocyte	CL:0000094	87.28	Gold
Islet of Langerhans	UBERON:0000006	87.15	Gold
Lymph node	UBERON:0000029	86.73	Gold
Colonic epithelium	UBERON:0000397	86.51	Gold
Rectum	UBERON:0001052	86.47	Gold
Endometrium epithelium	UBERON:0004811	85.95	Gold
Cerebellar hemisphere	UBERON:0002245	85.80	Gold
Cerebellar cortex	UBERON:0002129	85.76	Gold
Small intestine Peyer's patch	UBERON:0003454	85.11	Gold
Male germ line stem cell in testis	CL:0000089 ∩ UBERON:0000473	85.05	Gold
Right cerebellar hemisphere	UBERON:0014890	84.58	Gold
Left adrenal gland	UBERON:0001234	84.34	Gold
Spleen	UBERON:0002106	84.24	Gold
C1 segment of cervical spinal cord	UBERON:0006469	84.21	Gold
Right adrenal gland cortex	UBERON:0035827	84.20	Gold
Lower esophagus mucosa	UBERON:0035834	84.17	Gold
Left adrenal gland cortex	UBERON:0035825	84.16	Gold
Gall bladder	UBERON:0002110	84.16	Gold
Minor salivary gland	UBERON:0001830	83.85	Gold
Right adrenal gland	UBERON:0001233	83.70	Gold
Calcaneal tendon	UBERON:0003701	83.68	Gold

Disease	Classification	MOI	Submitter
von Hippel-Lindau disease (OMIM:193300)	Definitive	AD	G2P
von Hippel-Lindau disease	Strong	AD	Genomics England PanelApp
von Hippel-Lindau disease	Strong	AD	Labcorp Genetics
von Hippel-Lindau disease	Supportive	AD	Orphanet
Pheochromocytoma (MONDO:0008233)	Definitive	AD	G2P
Renal cell carcinoma (MONDO:0005086)	Strong	AD	Genomics England PanelApp
Chuvash polycythemia (OMIM:263400)	Strong	AR	Genomics England PanelApp
Chuvash polycythemia	Strong	AR	Labcorp Genetics
Chuvash erythrocytosis	Supportive	AR	Orphanet
Secondary polycythemia	Strong	AR	Ambry Genetics
Hereditary pheochromocytoma-paraganglioma	Supportive	AD	Orphanet

Orphanet ID	Disease Name	Gene Count	Phenotypes
892	Von Hippel-Lindau disease	2	41
238557	Chuvash erythrocytosis	1	0
29072	Hereditary pheochromocytoma-paraganglioma	15	41
276621	Sporadic pheochromocytoma/secreting paraganglioma	6	36

HPO ID	Phenotype
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0001901	Polycythemia
HP:0001899	Increased hematocrit
HP:0001900	Increased circulating hemoglobin
HP:0001898	Increased red blood cell mass
HP:0002666	Pheochromocytoma
HP:0006748	Adrenal pheochromocytoma
HP:0006737	Extraadrenal pheochromocytoma
HP:0002668	Paraganglioma
HP:0002864	Paraganglioma of head and neck
HP:0005584	Renal cell carcinoma
HP:0006880	Cerebellar hemangioblastoma
HP:0009713	Spinal hemangioblastoma
HP:0009711	Retinal capillary hemangioma
HP:0001028	Hemangioma
HP:0005562	Multiple renal cysts
HP:0001737	Pancreatic cysts
HP:0030393	Endolymphatic sac tumor
HP:0009715	Papillary cystadenoma of the epididymis
HP:0030424	Epididymal cyst
HP:0000822	Hypertension
HP:0000875	Episodic hypertension
HP:0002640	Hypertension associated with pheochromocytoma
HP:0003334	Elevated circulating catecholamine level
HP:0003345	Elevated urinary norepinephrine level
HP:0003639	Elevated urinary epinephrine level
HP:0011976	Elevated urinary catecholamine level
HP:0001649	Tachycardia
HP:0011703	Sinus tachycardia
HP:0001962	Palpitations
HP:0000975	Hyperhidrosis
HP:0001069	Episodic hyperhidrosis
HP:0002315	Headache
HP:0002331	Recurrent paroxysmal headache
HP:0000739	Anxiety
HP:0000740	Episodic paroxysmal anxiety
HP:0025269	Panic attack
HP:0000980	Pallor
HP:0001824	Weight loss
HP:0002018	Nausea
HP:0002027	Abdominal pain
HP:0002574	Episodic abdominal pain
HP:0000541	Retinal detachment
HP:0000572	Visual loss
HP:0001085	Papilledema
HP:0000360	Tinnitus
HP:0008629	Pulsatile tinnitus
HP:0000407	Sensorineural hearing impairment
HP:0002321	Vertigo

GWAS Study	Trait	P-value
GCST011940_2	Bullous pemphigoid	9.0 × 10⁻³⁸
GCST90020028_772	Hip circumference adjusted for BMI	2.0 × 10⁻⁸

VHL - von Hippel-Lindau tumor suppressor
IDENTIFIERS
─────────────────────────────────────────────────────────────────────
HGNC:12687	ENSG00000134086	Entrez:7428	OMIM:608537
UniProt: P40337 (canonical)	RefSeq: NM_000551 (MANE Select)
GENOMIC LOCATION
─────────────────────────────────────────────────────────────────────
Chr 3p25.3	10,141,778-10,153,676 (GRCh38)	+ strand
3 exons	13 transcripts	213 amino acids
KEY NUMBERS
─────────────────────────────────────────────────────────────────────
ClinVar variants: 930	PDB structures: 139	GO terms: 38
Pathogenic variants: 200+	Protein interactions: 1,785
PROTAC targets: 156	Phenotypes: 105
PRIMARY DISEASES
─────────────────────────────────────────────────────────────────────
• von Hippel-Lindau syndrome (AD)
• Pheochromocytoma/Paraganglioma (AD)
• Clear cell renal carcinoma (AD)
• Chuvash polycythemia (AR)
• Cerebellar hemangioblastoma
KEY FUNCTION
─────────────────────────────────────────────────────────────────────
E3 ubiquitin ligase component (VHL-ElonginB-ElonginC complex)
Targets HIF-alpha for proteasomal degradation under normoxia
Master regulator of oxygen-sensing pathway

Section	Content
Gene Identifiers	HGNC:12687, ENSG00000134086, Entrez:7428, OMIM:608537, Chr3:10,141,778-10,153,676
Transcripts	13 Ensembl transcripts, 4 RefSeq mRNAs, 3 CCDS IDs, MANE Select: NM_000551
Proteins	10 UniProt entries (P40337 canonical), 6 InterPro domains, 2 Pfam domains
Structures	139 PDB structures (best: 1.32Å), AlphaFold pLDDT: 85.45
Orthologs	Mouse, Rat, Zebrafish, Drosophila (>91% identity)
Clinical Variants	930 ClinVar entries, 200+ pathogenic, 364 SpliceAI predictions, 1,370 AlphaMissense
Pathways/GO	7 Reactome pathways, 38 GO terms (22 BP, 8 MF, 8 CC)
Interactions	1,785 STRING interactions, 407 IntAct entries
TF Regulation	29 CollecTRI relationships (VHL regulates HIF1A, VEGFA, etc.)
Drug/Pharma	156 ChEMBL targets (primarily PROTAC applications), 1,185 bioactivities
Expression	Ubiquitous; highest in brain cortex, immune cells, adrenal
Diseases	VHL syndrome, pheochromocytoma, renal cell carcinoma, Chuvash polycythemia