Provide a comprehensive cross-database identifier and functional mapping reference for human BRAF. 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 BRAF. 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

DatabaseIdentifierNotes HGNCHGNC:1097Approved symbol: BRAF Ensembl GeneENSG00000157764 NCBI Entrez Gene673 OMIM164757Gene/locus entry PharmGKBPA25408VIP gene (Very Important Pharmacogene) Full Gene Name: B-Raf proto-oncogene, serine/threonine kinase Previous Names: v-raf murine sarcoma viral oncogene homolog B Aliases: BRAF1, BRAF-1 Gene Groups: Mitogen-activated protein kinase kinase kinases, RAF family Locus Type: Protein-coding gene Genomic Location PropertyValue Chromosome7 Cytogenetic …

Property	Value
Chromosome	7
Cytogenetic Band	7q34
Start Position	140,719,327
End Position	140,924,976
Strand	- (minus/reverse)
Gene Length	~205.6 kb
Genome Assembly	GRCh38

Transcript ID	Biotype	Start	End
ENST00000288602	protein_coding	140,734,486	140,924,732
ENST00000469930	protein_coding	140,833,972	140,924,742
ENST00000496384	protein_coding	140,719,327	140,924,810
ENST00000644969	protein_coding	140,719,337	140,924,929
ENST00000646891	protein_coding	140,730,665	140,924,929
ENST00000867090	protein_coding	140,734,016	140,924,712
ENST00000867091	protein_coding	140,734,490	140,924,947
ENST00000867092	protein_coding	140,734,565	140,924,712
ENST00000912600	protein_coding	140,734,012	140,924,976
ENST00000912601	protein_coding	140,733,847	140,924,744
ENST00000944245	protein_coding	140,734,485	140,924,713
ENST00000479537	nonsense_mediated_decay	140,734,521	140,781,677
ENST00000497784	nonsense_mediated_decay	140,734,597	140,924,709
ENST00000642228	nonsense_mediated_decay	140,734,314	140,924,712
ENST00000644650	nonsense_mediated_decay	140,734,558	140,800,437
ENST00000646730	nonsense_mediated_decay	140,734,487	140,924,708
ENST00000647434	nonsense_mediated_decay	140,734,558	140,800,384
ENST00000642272	retained_intron	140,799,054	140,924,726
ENST00000642875	retained_intron	140,725,325	140,808,338
ENST00000643356	retained_intron	140,801,020	140,808,271
ENST00000644905	retained_intron	140,732,563	140,924,712
ENST00000645443	retained_intron	140,734,487	140,741,717
ENST00000646334	retained_intron	140,780,359	140,783,464
ENST00000646427	retained_intron	140,833,969	140,836,233
ENST00000642808	protein_coding_CDS_not_defined	140,808,892	140,924,703
ENST00000643790	protein_coding_CDS_not_defined	140,822,385	140,924,706
ENST00000644120	protein_coding_CDS_not_defined	140,725,145	140,824,398

Accession	Status	MANE Select
NM_004333	REVIEWED	YES (Canonical)
NM_001354609	REVIEWED	No
NM_001374244	REVIEWED	No
NM_001374258	REVIEWED	No
NM_001378467	REVIEWED	No
NM_001378468	REVIEWED	No
NM_001378469	REVIEWED	No
NM_001378470	REVIEWED	No
NM_001378471	REVIEWED	No
NM_001378472	REVIEWED	No
NM_001378473	REVIEWED	No
NM_001378474	REVIEWED	No
NM_001378475	REVIEWED	No
XM_017012559	PREDICTED	No

Exon ID	Start	End	Length
ENSE00003826734	140,924,566	140,924,732	167 bp
ENSE00003603715	140,850,111	140,850,212	102 bp
ENSE00001035295	140,834,609	140,834,872	264 bp
ENSE00001034889	140,808,892	140,808,995	104 bp
ENSE00003603742	140,807,960	140,808,062	103 bp
ENSE00003687908	140,801,412	140,801,560	149 bp
ENSE00003487759	140,800,362	140,800,481	120 bp
ENSE00003569635	140,794,308	140,794,467	160 bp
ENSE00003680515	140,787,548	140,787,584	37 bp
ENSE00003829283	140,785,689	140,785,808	120 bp
ENSE00003685923	140,783,021	140,783,157	137 bp
ENSE00003559218	140,781,576	140,781,693	118 bp
ENSE00003521664	140,777,991	140,778,075	85 bp
ENSE00003527888	140,776,912	140,777,088	177 bp
ENSE00003649805	140,754,187	140,754,233	47 bp
ENSE00003485507	140,753,275	140,753,393	119 bp
ENSE00003587655	140,749,287	140,749,418	132 bp
ENSE00003551608	140,739,812	140,739,946	135 bp
ENSE00001034876	140,734,486	140,734,770	285 bp

Accession	Status	Notes
P15056	Reviewed (Swiss-Prot)	Canonical entry
H7C4S5	Unreviewed (TrEMBL)	Isoform
H7C560	Unreviewed (TrEMBL)	Isoform
H7C5K3	Unreviewed (TrEMBL)	Isoform
A0A2R8Y467	Unreviewed (TrEMBL)
A0A2R8Y492	Unreviewed (TrEMBL)
A0A2R8Y679	Unreviewed (TrEMBL)
A0A2R8Y8E0	Unreviewed (TrEMBL)
A0A2R8YDP5	Unreviewed (TrEMBL)
A0A2R8YES9	Unreviewed (TrEMBL)
A0A2U3TZI2	Unreviewed (TrEMBL)

BRAF Gene Complete Identifier and Functional Mapping Reference

Structured Data Sources

Database	Identifier	Notes
HGNC	HGNC:1097	Approved symbol: BRAF
Ensembl Gene	ENSG00000157764
NCBI Entrez Gene	673
OMIM	164757	Gene/locus entry
PharmGKB	PA25408	VIP gene (Very Important Pharmacogene)

Accession	Status	MANE Select
NP_004324	REVIEWED	YES
NP_001341538	REVIEWED	No
NP_001361173	REVIEWED	No
NP_001361187	REVIEWED	No
NP_001365396	REVIEWED	No
NP_001365397	REVIEWED	No
NP_001365398	REVIEWED	No
NP_001365399	REVIEWED	No
NP_001365400	REVIEWED	No
NP_001365401	REVIEWED	No
NP_001365402	REVIEWED	No
NP_001365403	REVIEWED	No
NP_001365404	REVIEWED	No
XP_016868048	PREDICTED	No

InterPro ID	Short Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR002219	PKC_DAG/PE	Domain
IPR003116	RBD_dom	Domain (Ras-binding)
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020454	DAG/PE-bd	Domain
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR046349	C1-like_sf	Homologous_superfamily
IPR051681	Ser/Thr_Kinases-Pseudokinases	Family

PDB ID	Method	Resolution	Description
8C7X	X-ray	1.65 Å	BRAF with hybrid compound 6
8C7Y	X-ray	1.65 Å	BRAF V600E with hybrid compound 6
5VYK	X-ray	1.749 Å	BRS domain with KSR1 CC-SAM
9BP8	X-ray	1.73 Å	BRAF kinase with PF-07799933
9BFB	X-ray	1.92 Å	BRAF kinase with PF-07284890
7K0V	X-ray	1.93 Å	BRAF with GNE-0749
5ITA	X-ray	1.95 Å	BRAF kinase with AZ-VEM
3NY5	X-ray	1.99 Å	RBD domain
4XV9	X-ray	2.0 Å	BRAF kinase with PLX5568
6XFP	X-ray	2.0 Å	BRAF with Belvarafenib
6N0Q	X-ray	2.04 Å	BRAF with benzimidazole inhibitor
9AXX	X-ray	2.07 Å	BRAF/MEK1 with NST-628
5VAM	X-ray	2.1 Å	BRAF with RAF709
6P3D	X-ray	2.11 Å	BRAF V600E with ponatinib
5JSM	X-ray	2.19 Å	BRAF V600E with VEM-3-VEM
5VAL	X-ray	2.26 Å	BRAF with morpholinopyrimidine
5JRQ	X-ray	2.29 Å	BRAF V600E with VEM-6-VEM
4CQE	X-ray	2.3 Å	BRAF V600E with diarylthiazole
3OG7	X-ray	2.45 Å	BRAF V600E with PLX4032 (Vemurafenib)
4XV1	X-ray	2.47 Å	BRAF V600E with PLX7904
4XV2	X-ray	2.5 Å	BRAF V600E with Dabrafenib
5CSX	X-ray	2.51 Å	BRAF with BI 882370
3C4C	X-ray	2.57 Å	BRAF with PLX4720
6PP9	X-ray	2.59 Å	BRAF:MEK1 complex
5CSW	X-ray	2.66 Å	BRAF with Dabrafenib
5C9C	X-ray	2.7 Å	BRAF V600E with LY3009120

PDB ID	Resolution	Description
8VYP	3.29 Å	BRAF V600E monomer
7ZR0	3.4 Å	HSP90-CDC37-BRAF(V600E) complex
7MFD	3.66 Å	Autoinhibited BRAF:(14-3-3)2:MEK complex
8VYO	3.74 Å	BRAF WT monomer
7MFF	3.89 Å	Dimeric (BRAF)2:(14-3-3)2 with SB590885
6UAN	3.9 Å	BRAF:14-3-3 complex
8DGT	3.9 Å	RAS/RAF complex
7MFE	4.07 Å	Autoinhibited BRAF:(14-3-3)2
6NYB	4.1 Å	MAPK pathway complex

PDB ID	Description
2L05	Ras-binding domain (RBD)
5J17	RBD solution structure
5J18	RBD with Rigosertib
5J2R	RBD solution structure

Organism	Gene ID	Symbol	Biotype
Mouse (Mus musculus)	ENSMUSG00000002413	Braf	protein_coding
Rat (Rattus norvegicus)	ENSRNOG00000010957	Braf	protein_coding
Zebrafish (Danio rerio)	ENSDARG00000017661	braf	protein_coding
Fruit fly (Drosophila melanogaster)	No direct ortholog	-	-
Worm (C. elegans)	No direct ortholog	-	-
Yeast (S. cerevisiae)	No direct ortholog	-	-

Classification	Count
Pathogenic	62
Likely Pathogenic	38
Uncertain Significance (VUS)	~200+
Likely Benign	~500+
Benign	~300+
Conflicting	~100+

ClinVar ID	HGVS Notation	Protein Change	Review Status
13964	c.1391G>A	p.Gly464Glu	expert panel
13965	c.736G>C	p.Ala246Pro	expert panel
13973	c.770A>G	p.Gln257Arg	expert panel
13974	c.1406G>A	p.Gly469Glu	expert panel
13975	c.1455G>C	p.Leu485Phe	expert panel
13979	c.1741A>G	p.Asn581Asp	expert panel
177672	c.1785T>G	p.Phe595Leu	expert panel
177844	c.1455G>T	p.Leu485Phe	expert panel
180784	c.739T>C	p.Phe247Leu	expert panel
280033	c.1796C>G	p.Thr599Arg	expert panel
40346	c.730A>C	p.Thr244Pro	expert panel
40347	c.735A>C	p.Leu245Phe	expert panel
40348	c.735A>T	p.Leu245Phe	expert panel
40387	c.1787G>T	p.Gly596Val	expert panel
40388	c.1796C>T	p.Thr599Ile	expert panel
40389	c.1799T>G	p.Val600Gly	expert panel
44829	c.722C>A	p.Thr241Lys	expert panel
55793	c.741T>G	p.Phe247Leu	expert panel
375946	c.1781A>T	p.Asp594Val	expert panel
13966	c.1801A>G	p.Lys601Glu	single submitter
13969	c.1789C>G	p.Leu597Val	multiple submitters
13971	c.1406G>C	p.Gly469Ala	single submitter
13972	c.1781A>G	p.Asp594Gly	multiple submitters
162793	c.1794_1796dup	p.Thr599dup	multiple submitters
162797	c.1914T>G	p.Asp638Glu	multiple submitters
1685577	c.1591T>C	p.Trp531Arg	multiple submitters
180789	c.1785T>A	p.Phe595Leu	multiple submitters
29806	c.722C>G	p.Thr241Arg	multiple submitters
29808	c.1593G>C	p.Trp531Cys	multiple submitters
372572	c.1390G>A	p.Gly464Arg	multiple submitters
40373	c.1502A>C	p.Glu501Ala	multiple submitters
40375	c.1513C>T	p.Leu505Phe	multiple submitters
41446	c.1801A>C	p.Lys601Gln	multiple submitters
44818	c.1802A>C	p.Lys601Thr	multiple submitters
1210729	c.2125C>G	p.Gln709Glu	single submitter
1317489	c.1738A>G	p.Asn580Asp	single submitter
1325840	c.1454T>G	p.Leu485Trp	single submitter
13962	c.1385G>T	p.Arg462Ile	no criteria
13963	c.1388T>G	p.Ile463Ser	no criteria
13967	c.1397G>T	p.Gly466Val	no criteria
13968	c.1790T>G	p.Leu597Arg	no criteria
180788	c.1722C>A	p.His574Gln	single submitter
223138	c.1399T>G	p.Ser467Ala	single submitter
2430770	c.1591T>A	p.Trp531Arg	single submitter
2501901	c.1396G>C	p.Gly466Arg	single submitter
265358	c.1593G>T	p.Trp531Cys	single submitter
279992	c.1390G>C	p.Gly464Arg	single submitter
3373467	c.721A>G	p.Thr241Ala	single submitter
3572914	c.2126A>G	p.Gln709Arg	single submitter
372626	c.1574T>G	p.Leu525Arg	single submitter

ClinVar ID	HGVS Notation	Protein Change
40349	c.740T>C	p.Phe247Ser
40370	c.1454T>C	p.Leu485Ser
40380	c.1595G>A	p.Cys532Tyr
44830	c.739T>G	p.Phe247Val
44832	c.793G>C	p.Gly265Arg
1163474	c.1402T>C	p.Phe468Leu
1198003	c.1448A>T	p.Lys483Ile
1320917	c.708C>G	p.Asn236Lys
177776	c.1742A>G	p.Asn581Ser
2769805	c.1695T>A	p.Asp565Glu
279935	c.1493T>A	p.Phe498Tyr
3220902	c.1749T>G	p.Phe583Leu
3338728	c.1099C>G	p.Pro367Ala
3343956	c.2132T>C	p.Leu711Pro
3393207	c.794G>C	p.Gly265Ala
372757	c.1765A>C	p.Thr589Pro
40365	c.1391G>C	p.Gly464Ala
40368	c.1411G>A	p.Val471Ile
40379	c.1592G>T	p.Trp531Leu
4072207	c.1082A>T	p.Asp361Val
44804	c.1409C>G	p.Thr470Arg
44807	c.1501G>C	p.Glu501Gln
44813	c.1780G>A	p.Asp594Asn
44815	c.1798G>A	p.Val600Met
44816	c.1798G>T	p.Val600Leu
44817	c.1799_1801del	p.Val600_Lys601delinsGlu
575127	c.1505_1507dup	p.Val502dup
599445	c.1388_1408dup	p.Ile463_Gly469dup
636502	c.1441_1442delinsAA	p.Ala481Lys
645347	c.1096G>C	p.Ala366Pro
802372	c.2276G>A	p.Gly759Glu
802377	c.644C>T	p.Ser215Phe
976167	c.1475_1477del	p.Pro492del

CCDS ID
CCDS5863
CCDS87555
CCDS94218
CCDS94219

Variant ID	Gene	Effect	Delta Score
7:140720925:T:G	BRAF	acceptor_gain	0.94
7:140720900:A:G	BRAF	acceptor_gain	0.91
7:140720923:T:G	BRAF	acceptor_gain	0.88
7:140720885:C:CA	BRAF	acceptor_gain	0.79
7:140720899:A:AG	BRAF	acceptor_gain	0.76
7:140719812:T:A	BRAF	acceptor_gain	0.74
7:140719977:G:GT	BRAF	donor_gain	0.72
7:140720871:A:AG	BRAF	acceptor_gain	0.64
7:140720872:G:GG	BRAF	acceptor_gain	0.64
7:140720922:ATAT:A	BRAF	acceptor_gain	0.60
7:140720922:A:AG	BRAF	acceptor_gain	0.54
7:140720886:G:A	BRAF	acceptor_gain	0.46
7:140720732:G:T	BRAF	acceptor_gain	0.46
7:140719813:G:A	BRAF	acceptor_gain	0.45
7:140720730:TAG:T	BRAF	acceptor_gain	0.42
7:140720861:A:T	BRAF	acceptor_gain	0.39
7:140719810:ACT:A	BRAF	acceptor_gain	0.38
7:140720729:CTAG:C	BRAF	acceptor_gain	0.37
7:140720872:GACC:G	BRAF	acceptor_gain	0.37
7:140720873:ACCCT:A	BRAF	acceptor_gain	0.35
7:140719762:A:T	BRAF	acceptor_gain	0.35
7:140720855:A:AG	BRAF	acceptor_gain	0.35
7:140720856:A:G	BRAF	acceptor_loss	0.34
7:140720857:T:G	BRAF	acceptor_loss	0.34
7:140720874:C:T	BRAF	acceptor_gain	0.33

Variant	Protein Change	AM Score	AM Class
7:140734647:G:A	P751S	0.981	likely_pathogenic
7:140734646:G:T	P751Q	0.984	likely_pathogenic
7:140734646:G:C	P751R	0.978	likely_pathogenic
7:140734646:G:A	P751L	0.974	likely_pathogenic
7:140734637:G:T	P754H	0.989	likely_pathogenic
7:140734637:G:C	P754R	0.978	likely_pathogenic
7:140734637:G:A	P754L	0.977	likely_pathogenic
7:140734638:G:A	P754S	0.977	likely_pathogenic
7:140734638:G:T	P754T	0.974	likely_pathogenic
7:140734640:G:A	T753I	0.986	likely_pathogenic
7:140734640:G:C	T753R	0.963	likely_pathogenic
7:140734640:G:T	T753K	0.961	likely_pathogenic
7:140734642:T:A	K752N	0.955	likely_pathogenic
7:140734642:T:G	K752N	0.955	likely_pathogenic
7:140734643:T:A	K752I	0.968	likely_pathogenic
7:140734643:T:G	K752T	0.901	likely_pathogenic
7:140734644:T:C	K752E	0.936	likely_pathogenic
7:140734641:T:A	T753S	0.828	likely_pathogenic
7:140734641:T:C	T753A	0.905	likely_pathogenic
7:140734641:T:G	T753P	0.874	likely_pathogenic
7:140734634:A:C	I755S	0.778	likely_pathogenic
7:140734634:A:G	I755T	0.892	likely_pathogenic
7:140734634:A:T	I755N	0.860	likely_pathogenic
7:140734644:T:G	K752Q	0.720	likely_pathogenic
7:140734617:C:G	G761R	0.646	likely_pathogenic
7:140734623:C:G	G759R	0.696	likely_pathogenic
7:140734623:C:T	G759R	0.696	likely_pathogenic
7:140734626:C:A	G758W	0.686	likely_pathogenic
7:140734626:C:G	G758R	0.694	likely_pathogenic
7:140734626:C:T	G758R	0.694	likely_pathogenic
7:140734638:G:C	P754A	0.897	likely_pathogenic
7:140734609:A:C	F763L	0.571	likely_pathogenic
7:140734609:A:T	F763L	0.571	likely_pathogenic
7:140734611:A:G	F763L	0.571	likely_pathogenic

Pathway ID	Pathway Name	Disease Pathway
R-HSA-5673000	RAF activation	No
R-HSA-5674135	MAP2K and MAPK activation	No
R-HSA-5674499	Negative feedback regulation of MAPK pathway	No
R-HSA-5675221	Negative regulation of MAPK pathway	No
R-HSA-1295596	Spry regulation of FGF signaling	No
R-HSA-170968	Frs2-mediated activation	No
R-HSA-170984	ARMS-mediated activation	No
R-HSA-187706	Signalling to p38 via RIT and RIN	No
R-HSA-6802946	Signaling by moderate kinase activity BRAF mutants	Yes
R-HSA-6802948	Signaling by high-kinase activity BRAF mutants	Yes
R-HSA-6802952	Signaling by BRAF and RAF1 fusions	Yes
R-HSA-6802955	Paradoxical activation of RAF signaling by kinase inactive BRAF	Yes
R-HSA-9649948	Signaling downstream of RAS mutants	Yes
R-HSA-9656223	Signaling by RAF1 mutants	Yes
R-HSA-9726840	SHOC2 M1731 mutant abolishes MRAS complex function	Yes
R-HSA-9726842	Gain-of-function MRAS complexes activate RAF signaling	Yes

GO ID	Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004708	MAP kinase kinase activity
GO:0004709	MAP kinase kinase kinase activity
GO:0005509	calcium ion binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0042802	identical protein binding
GO:0097110	scaffold protein binding
GO:0106310	protein serine kinase activity

GO ID	Term
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005929	cilium
GO:0034451	centriolar satellite
GO:0036064	ciliary basal body
GO:0043005	neuron projection
GO:0044297	cell body
GO:0097225	sperm midpiece
GO:0097228	sperm principal piece
GO:0097229	sperm end piece
GO:0098793	presynapse
GO:0098794	postsynapse
GO:0098978	glutamatergic synapse

GO ID	Term
GO:0000165	MAPK cascade
GO:0006468	protein phosphorylation
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0070371	ERK1 and ERK2 cascade
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0050852	T cell receptor signaling pathway
GO:0033077	T cell differentiation in thymus
GO:0043367	CD4-positive, alpha-beta T cell differentiation
GO:0043369	CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
GO:0045580	regulation of T cell differentiation
GO:0048538	thymus development
GO:0030878	thyroid gland development
GO:0043066	negative regulation of apoptotic process
GO:0043524	negative regulation of neuron apoptotic process
GO:0048680	positive regulation of axon regeneration
GO:0050772	positive regulation of axonogenesis
GO:0060291	long-term synaptic potentiation
GO:0009887	animal organ morphogenesis
GO:0060323	head morphogenesis
GO:0060324	face development

UniProt	Gene	Score	Description
P04049	RAF1	983	RAF proto-oncogene
Q02750	MAP2K1	983	MEK1
P01116	KRAS	974	GTPase KRas
P01111	NRAS	973	GTPase NRas
P01112	HRAS	953	GTPase HRas
P07900	HSP90AA1	933	Heat shock protein 90
P08238	HSP90AB1	931	Heat shock protein 90β
P42336	PIK3CA	931	PI3K catalytic subunit alpha
P60484	PTEN	928	Phosphatase and tensin homolog
P46940	IQGAP1	919	IQ motif containing GTPase activating protein
Q9HCM3	KIAA1549	908	KIAA1549 (BRAF fusion partner)
P21359	NF1	895	Neurofibromin
P42771	CDKN2A	886	p16/INK4a
P04637	TP53	883	Tumor protein p53
Q07889	SOS1	881	Son of sevenless homolog 1
P40692	MLH1	876	DNA mismatch repair protein
P24385	CCND1	864	Cyclin D1
P07557	EGFR	861	Epidermal growth factor receptor
Q06124	PTPN11	853	Tyrosine-protein phosphatase non-receptor type 11
P36507	MAP2K2	836	MEK2
P54278	PMS2	834	PMS1 homolog 2
P49815	TSC2	832	Tuberin
Q9UBS0	RPS6KB1	826	Ribosomal protein S6 kinase beta-1
P52701	MSH6	805	MutS homolog 6
P29992	GNA11	797	Guanine nucleotide-binding protein G(q)
Q9NZQ7	PDCD4	792	Programmed cell death protein 4
O75874	IDH1	789	Isocitrate dehydrogenase
Q8IVT5	KSR1	780	Kinase suppressor of Ras 1
Q13315	ATM	779	Ataxia telangiectasia mutated
O14746	TERT	777	Telomerase reverse transcriptase
P16410	CTLA4	773	Cytotoxic T-lymphocyte protein 4
P35222	CTNNB1	771	Beta-catenin
P10415	BCL2	759	Apoptosis regulator Bcl-2
P40763	STAT3	756	Signal transducer and activator of transcription 3
P01266	TG	750	Thyroglobulin
Q9UQ13	LECT2	746	Leukocyte cell-derived chemotaxin 2
P03372	ESR1	738	Estrogen receptor
Q13485	SMAD4	738	Mothers against DPP homolog 4
Q01726	MUC2	736	Mucin-2
Q13905	RAPGEF1	729	Rap guanine nucleotide exchange factor 1
Q9HC35	EML4	729	Echinoderm microtubule-associated protein-like 4
P43246	MSH2	724	DNA mismatch repair protein
P50148	GNAQ	720	Guanine nucleotide-binding protein G(q)
P48735	IDH2	718	Isocitrate dehydrogenase
O75030	MITF	717	Microphthalmia-associated transcription factor
P01106	MYC	717	Myc proto-oncogene protein
Q969H0	FBXW7	706	F-box/WD repeat-containing protein 7
Q06710	PAX8	698	Paired box protein Pax-8
Q15116	PDCD1	696	Programmed cell death 1
O14497	ARID1A	695	AT-rich interactive domain-containing protein 1A

UniProt	Top Similarity	Average Similarity
P04049 (RAF1)	1.0000	0.9853
Q99N57 (Braf mouse)	1.0000	0.9856
P11345 (Raf1 rat)	1.0000	0.9855
Q5R5M7 (RAF1 macaque)	1.0000	0.9853
P27037 (ACVR1)	1.0000	0.9704
P27038 (ACVR1B)	1.0000	0.9707
A7E3S4	0.9999	0.9857
O88382	0.9999	0.9746
P04627 (ARAF)	0.9999	0.9788
P05625	0.9995	0.9847
P38444	0.9999	0.9711
P14056 (ARAF mouse)	0.9999	0.9788
O94806	0.9996	0.9762
O94967	0.9997	0.9784
P34908	0.9993	0.9833
Q04982	0.9993	0.9820
Q8IVH8 (KSR2)	0.9998	0.9791
Q8BPM2	0.9998	0.9778
P53668 (MAP3K4)	0.9999	0.9790
P53669 (MAP3K5)	0.9999	0.9789

UniProt	Identity	Bit Score	Description
P04049	100%	1303	RAF1 (human)
Q5R5M7	100%	1303	RAF1 (macaque)
Q99N57	98.9%	1287	Braf (mouse)
A7E3S4	97.7%	1278	BRAF (bovine)
P11345	98.9%	1285	Raf1 (rat)
P27966	100%	754	(kinase domain homolog)
P00531	98.9%	745	(kinase domain homolog)
Q5S006	86.1%	4259	(extended homolog)
Q5S007	86.1%	4260	(extended homolog)
Q3UH66	78.7%	2726	(extended homolog)
Q9Y3S1	86.3%	2712	(extended homolog)
A7J1T2	91.3%	1712
A7J1T0	91.3%	1710
A7MBB4	93.8%	1731
Q60700	98.4%	1699	Braf (mouse)
Q63796	98.4%	1695	Braf (rat)
Q07292	92.4%	1491
Q61UC4	92.4%	1492
Q12852	90.6%	1531
Q1HKZ5	87.6%	1650

Target Gene	Regulation	Evidence
NFE2L2 (NRF2)	Activation	Direct target
SLC5A5 (NIS)	Repression	Direct target

ChEMBL Target ID	Name	Type
CHEMBL5145	Serine/threonine-protein kinase B-raf	SINGLE PROTEIN
CHEMBL3559685	RAF serine/threonine protein kinase	PROTEIN FAMILY
CHEMBL3883317	B-raf/RAF proto-oncogene	PROTEIN FAMILY
CHEMBL4106189	BRAF/CRAF	PROTEIN COMPLEX
CHEMBL4523687	Protein cereblon/BRAF	PROTEIN-PROTEIN INTERACTION
CHEMBL5291967	von Hippel-Lindau/BRAF	PROTEIN-PROTEIN INTERACTION

ChEMBL ID	Drug Name	Type	Phase
CHEMBL1229517	VEMURAFENIB	Small molecule	4 (Approved)
CHEMBL2028663	DABRAFENIB	Small molecule	4 (Approved)
CHEMBL3301612	ENCORAFENIB	Small molecule	4 (Approved)
CHEMBL3348923	TOVORAFENIB	Small molecule	4 (Approved)
CHEMBL1336	SORAFENIB	Small molecule	4 (Approved)
CHEMBL1946170	REGORAFENIB	Small molecule	4 (Approved)
CHEMBL1171837	PONATINIB	Small molecule	4 (Approved)
CHEMBL1421	DASATINIB	Small molecule	4 (Approved)
CHEMBL5416410	DASATINIB ANHYDROUS	Small molecule	4 (Approved)
CHEMBL941	IMATINIB	Small molecule	4 (Approved)
CHEMBL255863	NILOTINIB	Small molecule	4 (Approved)
CHEMBL553	ERLOTINIB	Small molecule	4 (Approved)
CHEMBL939	GEFITINIB	Small molecule	4 (Approved)
CHEMBL477772	PAZOPANIB	Small molecule	4 (Approved)
CHEMBL1789941	RUXOLITINIB	Small molecule	4 (Approved)
CHEMBL1287853	FEDRATINIB	Small molecule	4 (Approved)
CHEMBL1834657	INFIGRATINIB PHOSPHATE	Small molecule	4 (Approved)
CHEMBL1852688	INFIGRATINIB	Small molecule	4 (Approved)
CHEMBL2146883	COBIMETINIB	Small molecule	4 (Approved)
CHEMBL3301610	ABEMACICLIB	Small molecule	4 (Approved)
CHEMBL1908391	MASITINIB	Small molecule	3
CHEMBL3264002	AVUTOMETINIB	Small molecule	3
CHEMBL4583691	NAPORAFENIB (LXH254)	Small molecule	3
CHEMBL50	QUERCETIN	Small molecule	3
CHEMBL572881	MOTESANIB	Small molecule	3

Drug	Clinical Annotations	Variant Annotations
Sorafenib	40	80
Cetuximab	15	87
FOLFIRI	4	66
FOLFOX	2	38
XELOX	1	22
Vemurafenib	0	2
Dabrafenib	0	3
Pembrolizumab	0	12
Selumetinib	0	12
Nivolumab	0	11
Atezolizumab	0	7

Tissue/Cell Type	Entity ID	Score	Quality
Buccal mucosa cell	CL:0002336	97.92	gold
Colonic epithelium	UBERON:0000397	92.55	gold
Calcaneal tendon	UBERON:0003701	91.78	gold
Middle temporal gyrus	UBERON:0002771	90.64	gold
Sperm	CL:0000019	90.53	gold
Sural nerve	UBERON:0015488	90.26	gold
Male germ line stem cell (testis)	CL:0000089	89.82	gold
Adrenal tissue	UBERON:0018303	88.84	gold
Tendon	UBERON:0000043	88.76	gold
Male germ cell	CL:0000015	87.85	gold
Lateral nuclear group of thalamus	UBERON:0002736	86.90	gold
Cortical plate	UBERON:0005343	86.80	gold
Lower esophagus mucosa	UBERON:0035834	86.17	gold
Postcentral gyrus	UBERON:0002581	86.09	gold
Left testis	UBERON:0004533	86.02	gold
Testis	UBERON:0000473	85.96	gold
Right testis	UBERON:0004534	85.87	gold
Brodmann area 23	UBERON:0013554	85.86	gold
Tendon of biceps brachii	UBERON:0008188	85.56	gold
Superior frontal gyrus	UBERON:0002661	85.12	gold
Ganglionic eminence	UBERON:0004023	85.07	gold
Corpus callosum	UBERON:0002336	84.91	gold
Parietal lobe	UBERON:0001872	84.79	gold
Primordial germ cell (gonad)	CL:0000670	84.37	gold
Bone marrow	UBERON:0002371	84.16	gold
Upper leg skin	UBERON:0004262	84.08	gold
Ventricular zone	UBERON:0003053	83.63	gold
Islet of Langerhans	UBERON:0000006	83.40	gold
Primary visual cortex	UBERON:0002436	83.24	gold
Cerebellar cortex	UBERON:0002129	83.23	gold

Disease	OMIM/MONDO	Inheritance	Evidence Level
Cardiofaciocutaneous syndrome 1	OMIM:115150	Autosomal dominant	Definitive
Noonan syndrome 7	OMIM:613706	Autosomal dominant	Definitive
LEOPARD syndrome 3	OMIM:613707	Autosomal dominant	Definitive
Anaplastic astrocytoma	MONDO:0016684	Autosomal dominant	Limited

Orphanet ID	Disease Name	Type	Gene Count
1340	Cardiofaciocutaneous syndrome	Malformation syndrome	4
500	Noonan syndrome with multiple lentigines	Malformation syndrome	3
648	Noonan syndrome	Malformation syndrome	15
146	Differentiated thyroid carcinoma	Disease	29
389	Langerhans cell histiocytosis	Disease	3
58017	Classic hairy cell leukemia	Disease	1
626	Large/giant congenital melanocytic nevus	Disease	7
54595	Craniopharyngioma	Disease	2
251615	Pilomyxoid astrocytoma	Histopathological subtype	8
840	Syringocystadenoma papilliferum	Disease	1
96253	Cushing disease	Disease	7

HPO ID	Phenotype
HP:0000006	Autosomal dominant inheritance
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000431	Wide nasal bridge
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000767	Pectus excavatum
HP:0000768	Pectus carinatum
HP:0000957	Cafe-au-lait spot
HP:0000962	Hyperkeratosis
HP:0001007	Hirsutism
HP:0001249	Intellectual disability
HP:0001250	Seizures
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001634	Mitral valve prolapse
HP:0001642	Pulmonic stenosis
HP:0001679	Abnormal aortic morphology
HP:0001680	Coarctation of aorta
HP:0002205	Recurrent respiratory infections
HP:0002564	Malformation of the heart and great vessels
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0003196	Short nose
HP:0004322	Short stature
HP:0007018	Attention deficit hyperactivity disorder
HP:0007565	Multiple lentigines
HP:0008066	Abnormal blistering of the skin
HP:0008070	Sparse hair
HP:0008501	Median cleft lip and palate
HP:0010880	Increased nuchal translucency
HP:0011830	Abnormal oral mucosa morphology
HP:0025502	Overweight
HP:0028388	Sparse or absent eyebrows
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000486	Strabismus
HP:0000717	Autism

Study ID	Trait/Disease	P-value
GCST004894_108	Type 2 diabetes	1.0×10⁻⁹
GCST010118_100	Type 2 diabetes	2.0×10⁻¹⁰
GCST008103_6	Bipolar disorder	6.0×10⁻¹⁰
GCST009600_25	Psychiatric disorder pleiotropy	5.0×10⁻⁹
GCST003124_32	Mild influenza (H1N1) infection	3.0×10⁻⁸
GCST003070_2	Cerebrospinal T-tau levels	3.0×10⁻⁷
GCST004894_16	Type 2 diabetes	4.0×10⁻⁷
GCST012210_2	Longevity	1.0×10⁻⁶
GCST001450_7	Response to Vitamin E supplementation	4.0×10⁻⁶
GCST003079_5	CSF t-tau:AB1-42 ratio	7.0×10⁻⁶

Category	Count
Ensembl Transcripts	27
RefSeq Transcripts (human)	14
CCDS IDs	4
Exons (canonical)	19
UniProt Entries	11
InterPro Domains	11
PDB Structures	131
Orthologs (key species)	3
ClinVar Variants	1,473
- Pathogenic	62
- Likely Pathogenic	38
SpliceAI Predictions	3,893
AlphaMissense Predictions	4,976
Reactome Pathways	16
GO Terms	66
STRING Interactions	6,138+
IntAct Interactions	846+
Approved Drugs (targeting BRAF)	4
Phase 3+ Molecules	25
HPO Phenotypes	391+
Orphanet Diseases	11
GWAS Associations	10