Provide a comprehensive cross-database identifier and functional mapping reference for human CDKN2A. 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 CDKN2A. 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

DatabaseIdentifierDescription HGNC IDHGNC:1787Approved symbol HGNC SymbolCDKN2Acyclin dependent kinase inhibitor 2A Ensembl GeneENSG00000147889Human gene NCBI Entrez1029Gene ID OMIM600160Gene/locus entry Genomic Location AttributeValue Chromosome9 Cytogenetic Band9p21.3 Start Position21,967,752 (GRCh38) End Position21,995,301 (GRCh38) StrandMinus (-) Genomic AccessionNC_000009.12 Gene Nomenclature CategoryValues Approved Namecyclin dependent kinase inhibitor 2A Locus Typegene with protein …

Category	Values
Approved Name	cyclin dependent kinase inhibitor 2A
Locus Type	gene with protein product
Locus Group	protein-coding gene
Previous Symbols	CDKN2, MLM
Aliases	CDK4I, p16, INK4a, MTS1, CMM2, ARF, p19, p14, INK4, p16INK4a, p19Arf, p14ARF, P16-INK4A, CAI2

Transcript ID	Biotype	Start	End	Strand
ENST00000304494	protein_coding	21,967,752	21,974,857	-
ENST00000380150	protein_coding_CDS_not_defined	21,970,442	21,971,332	-
ENST00000380151	nonsense_mediated_decay	21,968,180	21,974,827	-
ENST00000470819	protein_coding_CDS_not_defined	21,989,340	21,994,873	-
ENST00000479692	protein_coding	21,969,569	21,971,346	-
ENST00000494262	protein_coding	21,968,182	21,995,269	-
ENST00000497750	protein_coding	21,970,716	21,971,400	-
ENST00000498124	protein_coding	21,968,056	21,974,866	-
ENST00000498628	protein_coding	21,968,105	21,995,301	-
ENST00000530628	protein_coding	21,968,001	21,994,411	-
ENST00000577854	protein_coding_CDS_not_defined	21,969,583	21,970,467	-
ENST00000578845	protein_coding	21,967,996	21,971,332	-
ENST00000579122	protein_coding	21,967,991	21,974,858	-
ENST00000579755	protein_coding	21,967,752	21,994,392	-

Accession	Status	MANE Select	Description
NM_000077	REVIEWED	✓ Yes	Canonical clinical standard
NM_001195132	REVIEWED	No	Alternate transcript
NM_001363763	REVIEWED	No	Alternate transcript
NM_058195	REVIEWED	No	p14ARF transcript
NM_058197	REVIEWED	No	Alternate transcript

CCDS ID	Description
CCDS6510	Consensus CDS
CCDS6511	Consensus CDS
CCDS56565	Consensus CDS
CCDS87644	Consensus CDS

Exon ID	Start	End	Strand	Seq Region
ENSE00001833804	21,974,678	21,974,857	-	9
ENSE00003496053	21,970,902	21,971,208	-	9
ENSE00003529527	21,967,752	21,968,242	-	9

CDKN2A Gene Complete Identifier and Functional Mapping Reference

Structured Data Sources

Database	Identifier	Description
HGNC ID	HGNC:1787	Approved symbol
HGNC Symbol	CDKN2A	cyclin dependent kinase inhibitor 2A
Ensembl Gene	ENSG00000147889	Human gene
NCBI Entrez	1029	Gene ID
OMIM	600160	Gene/locus entry

Attribute	Value
Chromosome	9
Cytogenetic Band	9p21.3
Start Position	21,967,752 (GRCh38)
End Position	21,995,301 (GRCh38)
Strand	Minus (-)
Genomic Accession	NC_000009.12

Accession	Name	Status	Mass	Length
P42771 ★	Cyclin-dependent kinase inhibitor 2A (p16INK4a)	Reviewed (Canonical)	16,533 Da	156 aa
Q8N726 ★	Tumor suppressor ARF (p14ARF)	Reviewed	13,903 Da	132 aa
J3QRG6	Isoform	Unreviewed	-	-
K7ENC6	Isoform	Unreviewed	-	-
K7ES20	Isoform	Unreviewed	-	-
K7PML8	Isoform	Unreviewed	-	-

Accession	Status	MANE Select
NP_000068	REVIEWED	✓ Yes
NP_001182061	REVIEWED	No
NP_001350692	REVIEWED	No
NP_478102	REVIEWED	No
NP_478104	REVIEWED	No

InterPro ID	Name	Type
IPR036770	Ankyrin_rpt-contain_sf	Homologous superfamily
IPR050776	Ank_Repeat/CDKN_Inhibitor	Family

PDB ID	Method	Resolution	Title
1A5E	Solution NMR	-	Solution NMR structure of tumor suppressor p16INK4A (18 structures)
1BI7	X-ray Diffraction	3.4 Å	CDK6-p16INK4A tumor suppressor complex
1DC2	Solution NMR	-	Solution NMR structure of tumor suppressor p16INK4A (20 structures)
2A5E	Solution NMR	-	Restrained minimized mean structure
7OZT	X-ray Diffraction	1.74 Å	Nanobodies restore stability to cancer-associated mutants of p16INK4a

Metric	Value
AlphaFold ID	AF-P42771-F1
Global pLDDT	77.02
Sequence Length	1160
Fraction pLDDT Very High	0.01

Metric	Value
AlphaFold ID	AF-Q8N726-F1
Global pLDDT	64.69
Sequence Length	978
Fraction pLDDT Very High	0.02

Species	Ensembl Gene ID	Symbol	Biotype
Mouse (Mus musculus)	ENSMUSG00000044303	Cdkn2a	protein_coding
Rat (Rattus norvegicus)	ENSRNOG00000059837	Cdkn2a	protein_coding
Zebrafish (Danio rerio)	No ortholog available	-	-
Fruit fly (D. melanogaster)	No ortholog available	-	-
Worm (C. elegans)	No ortholog available	-	-
Yeast (S. cerevisiae)	No ortholog available	-	-

Classification	Count
Pathogenic	100+
Likely Pathogenic	41
Uncertain Significance (VUS)	~1,000+
Likely Benign	~200+
Benign	~100+
Conflicting Classifications	~50+

ClinVar ID	HGVS Notation	Type	Classification
1068946	c.34del (p.Ser12fs)	Deletion	Pathogenic
1069074	c.126dup (p.Ser43Ter)	Duplication	Pathogenic
142061	c.47_50del (p.Leu16fs)	Microsatellite	Pathogenic
182409	c.131_132insAA (p.Tyr44Ter)	Insertion	Pathogenic
182412	c.240_253del (p.Pro81fs)	Deletion	Pathogenic
182416	c.151-1G>C	SNV	Pathogenic
183759	c.335_337dup (p.Arg112dup)	Duplication	Pathogenic
220711	c.148C>T (p.Gln50Ter)	SNV	Pathogenic
230421	c.44G>A (p.Trp15Ter)	SNV	Pathogenic
236984	c.260G>C (p.Arg87Pro)	SNV	Pathogenic
279749	c.307_308del (p.Arg103fs)	Microsatellite	Pathogenic
376303	c.330G>A (p.Trp110Ter)	SNV	Pathogenic
376304	c.329G>A (p.Trp110Ter)	SNV	Pathogenic
376305	c.262G>T (p.Glu88Ter)	SNV	Pathogenic
376310	c.172C>T (p.Arg58Ter)	SNV	Pathogenic
406710	c.358del (p.Glu120fs)	Deletion	Pathogenic
429111	c.132del (p.Ser43_Tyr44insTer)	Deletion	Pathogenic
429112	c.45dup (p.Leu16fs)	Duplication	Pathogenic
463512	c.79G>T (p.Glu27Ter)	SNV	Pathogenic
483336	c.131dup (p.Tyr44Ter)	Duplication	Pathogenic
483337	c.132C>G (p.Tyr44Ter)	SNV	Pathogenic
630390	c.35C>A (p.Ser12Ter)	SNV	Pathogenic
635365	c.151-1G>A	SNV	Pathogenic
644262	c.189del (p.Leu64fs)	Deletion	Pathogenic
655275	c.132C>A (p.Tyr44Ter)	SNV	Pathogenic
1059393	c.172C>T (p.Gln58Ter)	SNV	Likely Pathogenic
1215320	c.281T>C (p.Leu94Pro)	SNV	Likely Pathogenic
1467708	c.157A>G (p.Met53Val)	SNV	Likely Pathogenic
1491259	c.193+2T>C	SNV	Likely Pathogenic
1773995	c.150+2T>G	SNV	Likely Pathogenic
1786538	c.213C>A (p.Asn71Lys)	SNV	Likely Pathogenic
182423	c.322G>T (p.Asp108Tyr)	SNV	Likely Pathogenic
187713	c.149A>C (p.Gln50Pro)	SNV	Likely Pathogenic
230375	c.202_203delinsTT (p.Ala68Leu)	Indel	Likely Pathogenic
406707	c.259C>T (p.Arg87Trp)	SNV	Likely Pathogenic
418121	c.212A>G (p.Asn71Ser)	SNV	Likely Pathogenic
429108	c.67G>A (p.Gly23Ser)	SNV	Likely Pathogenic
429109	c.67G>T (p.Gly23Cys)	SNV	Likely Pathogenic
491572	c.296G>C (p.Arg99Pro)	SNV	Likely Pathogenic
833629	c.242C>T (p.Pro81Leu)	SNV	Likely Pathogenic

Variant ID	Effect	Delta Score
9:21968240:TGT:T	acceptor_gain	0.99
9:21968346:A:AC	donor_gain	0.98
9:21968347:T:C	donor_gain	0.97
9:21968241:GT:G	acceptor_gain	0.95
9:21968239:ATGTC:A	acceptor_loss	0.95
9:21968240:TGTCT:T	acceptor_loss	0.95
9:21968241:GTC:G	acceptor_loss	0.95
9:21968242:TCTGC:T	acceptor_loss	0.95
9:21968244:T:A	acceptor_loss	0.95
9:21968238:GATGT:G	acceptor_gain	0.93
9:21968245:G:C	acceptor_loss	0.89
9:21968253:C:CT	acceptor_gain	0.88
9:21968239:ATGT:A	acceptor_gain	0.87
9:21968342:A:AC	donor_gain	0.87
9:21968343:C:CC	donor_gain	0.87
9:21968246:C:CT	acceptor_gain	0.86
9:21968247:A:T	acceptor_gain	0.86
9:21968254:A:T	acceptor_gain	0.83

Variant	Protein Change	AM Score	Class
9:21971037:C:G	D108H	0.992	likely_pathogenic
9:21971036:T:A	D108V	0.989	likely_pathogenic
9:21971018:G:T	P114H	0.989	likely_pathogenic
9:21971035:A:C	D108E	0.984	likely_pathogenic
9:21971089:G:C	F90L	0.983	likely_pathogenic
9:21971037:C:A	D108Y	0.981	likely_pathogenic
9:21971006:G:T	A118D	0.980	likely_pathogenic
9:21971018:G:C	P114R	0.973	likely_pathogenic
9:21971078:A:G	L94P	0.969	likely_pathogenic
9:21971024:C:G	R112P	0.967	likely_pathogenic
9:21971061:C:G	A100P	0.967	likely_pathogenic
9:21970974:A:C	Y129D	0.966	likely_pathogenic
9:21971054:G:T	A102E	0.957	likely_pathogenic
9:21970974:A:T	Y129N	0.956	likely_pathogenic
9:21970970:A:G	L130P	0.954	likely_pathogenic
9:21971036:T:C	D108G	0.953	likely_pathogenic
9:21971069:A:G	L97P	0.958	likely_pathogenic
9:21971078:A:C	L94R	0.949	likely_pathogenic
9:21971081:G:T	T93K	0.950	likely_pathogenic
9:21971058:C:A	G101W	0.950	likely_pathogenic

Pathway ID	Pathway Name	Disease Pathway
R-HSA-69231	Cyclin D associated events in G1	No
R-HSA-2559580	Oxidative Stress Induced Senescence	No
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)	No
R-HSA-2559585	Oncogene Induced Senescence	No
R-HSA-8853884	Transcriptional Regulation by VENTX	No
R-HSA-9825892	Regulation of MITF-M-dependent genes in cell cycle	No
R-HSA-9630791	Evasion of OIS Due to Defective p16INK4A binding to CDK4	Yes
R-HSA-9630794	Evasion of OIS Due to Defective p16INK4A binding to CDK4/6	Yes
R-HSA-9632697	Evasion of Oxidative Stress Senescence (CDK4)	Yes
R-HSA-9632700	Evasion of Oxidative Stress Senescence (CDK4/6)	Yes

GO ID	Term Name
GO:0000122	negative regulation of transcription by RNA polymerase II
GO:0001953	negative regulation of cell-matrix adhesion
GO:0007265	Ras protein signal transduction
GO:0008285	negative regulation of cell population proliferation
GO:0009303	rRNA transcription
GO:0030216	keratinocyte differentiation
GO:0030308	negative regulation of cell growth
GO:0033598	mammary gland epithelial cell proliferation
GO:0033600	negative regulation of mammary gland epithelial cell proliferation
GO:0034393	positive regulation of smooth muscle cell apoptotic process
GO:0035019	somatic stem cell population maintenance
GO:0042593	glucose homeostasis
GO:0043616	keratinocyte proliferation
GO:0045736	negative regulation of cyclin-dependent protein kinase activity
GO:0045892	negative regulation of DNA-templated transcription
GO:0046822	regulation of nucleocytoplasmic transport
GO:0051726	regulation of cell cycle
GO:0070301	cellular response to hydrogen peroxide
GO:0090398	cellular senescence
GO:2000045	regulation of G1/S transition of mitotic cell cycle

GO ID	Term Name
GO:0003723	RNA binding
GO:0004861	cyclin-dependent protein serine/threonine kinase inhibitor activity
GO:0019901	protein kinase binding
GO:0051059	NF-kappaB binding

GO ID	Term Name
GO:0005634	nucleus
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0035985	senescence-associated heterochromatin focus

GO ID	Term Name
GO:0002039	p53 binding
GO:0019789	SUMO transferase activity
GO:0055104	ligase inhibitor activity
GO:0055105	ubiquitin-protein transferase inhibitor activity
GO:0097371	MDM2/MDM4 family protein binding
GO:0005759	mitochondrial matrix
GO:0043065	positive regulation of apoptotic process

Interaction ID	Partner Gene	Interaction Type	Confidence
EBI-1255289	CDK4	physical association	0.960
EBI-1542324	CDK4	physical association	0.960
EBI-375269	CDK4	direct interaction	0.960
EBI-1027142	CDK6	direct interaction	0.950
EBI-1542347	CDK6	physical association	0.950
EBI-375266	CDK6	direct interaction	0.950
EBI-1641785	PCNA	association	0.610
EBI-375275	GMNN	direct interaction	0.590
EBI-3935272	DEAF1	physical association	0.510
EBI-3927672	HNRNPU	physical association	0.510
EBI-1641832	MCM6	physical association	0.500
EBI-375281	ORC4	direct interaction	0.440
EBI-375323	CDC6	direct interaction	0.440
EBI-375338	ORC5	direct interaction	0.440
EBI-375356	CDC45	direct interaction	0.440
EBI-375362	CDC7	direct interaction	0.440
EBI-375365	MCM2	direct interaction	0.440
EBI-375374	MCM10	direct interaction	0.440
EBI-375398	MCM5	direct interaction	0.440

Partner UniProt	Gene	Score
P42771	CDKN2A (self)	999
P11802	CDK4	999
Q00534	CDK6	999
Q00987	MDM2	999
P06748	NPM1	995
P24941	CDK2	993
Q15438	CYTH1	976
P04637	TP53	970
Q96S94	-	962
P24385	CCND1	947
P10947	-	936
P38936	CDKN1A	934
P01106	MYC	929
Q16665	HIF1A	928
Q01094	E2F1	921
P01116	KRAS	918

UniProt ID	Top Similarity	Avg Similarity
P55271	0.9987	0.9780
P55272	0.9987	0.9784
P55273	0.9980	0.9802
P42772	0.9974	0.9768
P51480	0.9962	0.9809
Q60773	0.9951	0.9808
Q9R0Z3	0.9962	0.9816
Q29RV0	0.9980	0.9801

UniProt ID	Top Identity	Top Bitscore
P55272	96.9%	255
P55271	96.9%	254
P42773 (CDKN2C)	85.7%	246
Q60772	85.7%	246
Q9R0Z3	78.0%	238
Q29RV0	89.2%	238
P51480	76.2%	235
P42772 (CDKN2B)	88.3%	228

TF Gene	Regulation Type	Confidence
E2F1	Activation	High
E2F2	Activation	Low
E2F3	Activation	High
MYC	Activation	High
JUN	Activation	High
HBP1	Activation	High
ATF2	Activation	High
ID1/ID2/ID3	Activation	High
JDP2	Activation	High
FOXO1	Activation	Low
NFKB	Activation	High
PAX6	Activation	Low
PBX1	Activation	Low
DNMT1	Repression	High
EZH2	Repression	Low
FOXM1	Repression	Low
HDAC1/3/4	Repression	-
HMGA2	Repression	-
MITF	Repression	High
PAX3	Repression	High
CTCF	Repression	High
CTBP1	Repression	-
BMI1	Unknown	-
DNMT3A	Unknown	High
ETS1/ETS2	Unknown	High
FOXA1	Unknown	High
NR3C1	Unknown	High

Regulator	Target	Effect	Mechanism	Score
CDKN2A	CDK4	down-regulates	binding	0.91
CDKN2A	CDK6	down-regulates	binding	0.87
CDKN2A	CDK2	down-regulates	binding	0.48
CDKN2A	CyclinD/CDK4	down-regulates activity	binding	0.83
CDKN2A	CyclinD1/CDK6	down-regulates	binding	0.81
MYC	CDKN2A	down-regulates quantity	transcriptional regulation	0.77
BMI1	CDKN2A	down-regulates quantity	transcriptional regulation	0.46
IKBKB	CDKN2A	down-regulates	phosphorylation	0.40
UV stress	CDKN2A	up-regulates	-	0.70

Attribute	Value
Expression Pattern	Ubiquitous
Total Present Calls	220
Maximum Expression Score	93.57

Tissue/Cell Type	Expression	Score	Quality
Parotid gland	present	93.57	silver
Cervix squamous epithelium	present	92.83	silver
Pituitary gland	present	92.49	gold
Male germ line stem cell (testis)	present	92.11	gold
Adenohypophysis	present	91.60	gold
Subthalamic nucleus	present	88.38	silver
Tongue	present	88.36	silver
Ventral tegmental area	present	88.11	silver
Pharyngeal mucosa	present	87.98	gold
Superior surface of tongue	present	87.97	gold
Lateral globus pallidus	present	87.93	silver
Dorsal+ventral thalamus	present	87.71	silver
Pericardium	present	87.62	gold
Inferior vagus X ganglion	present	87.61	silver
Nipple	present	87.43	silver
Lower esophagus mucosa	present	87.34	gold
Trigeminal ganglion	present	86.57	gold
Dorsal root ganglion	present	86.51	gold
Nasal cavity epithelium	present	85.99	silver
Trachea	present	85.88	silver
Left testis	present	85.09	gold
Right testis	present	84.12	gold
Stromal cell of endometrium	present	83.84	gold
Testis	present	82.27	gold
Adrenal cortex	present	81.71	gold
Choroid plexus epithelium	present	81.62	gold
Pancreatic ductal cell	present	81.43	silver
Buccal mucosa cell	present	81.38	gold
Olfactory nasal mucosa	present	81.21	gold
Synovial joint	present	80.50	gold

Experiment ID	Description	Species	Cell Count
E-MTAB-6308	Lung tumor endothelial cell heterogeneity	H. sapiens	113,132
E-CURD-84	Tumor-infiltrating lymphocytes in metastatic uveal melanoma	H. sapiens	40,656
E-MTAB-8559	Ovarian cancer ex vivo models	H. sapiens	20,982
E-GEOD-84465	Glioblastoma migrating front cells	H. sapiens	3,588
E-MTAB-6911	Induced Neural Plate Border Stem Cells	H. sapiens	336
E-GEOD-81383	Human melanoma cell lines	H. sapiens	226

Disease	Classification	Inheritance	Submitter
Melanoma-pancreatic cancer syndrome (OMIM:606719)	Definitive	AD	Ambry Genetics
Melanoma-pancreatic cancer syndrome (OMIM:606719)	Strong	AD	Genomics England
Melanoma-pancreatic cancer syndrome (OMIM:606719)	Strong	AD	Labcorp/Invitae
Cutaneous malignant melanoma, susceptibility to 2 (OMIM:155601)	Definitive	AD	G2P
Melanoma and neural system tumor syndrome (OMIM:155755)	Limited	AD	Ambry Genetics
Familial atypical multiple mole melanoma syndrome	Supportive	AD	Orphanet

Orphanet ID	Disease Name	Type	Gene Count
618	Familial melanoma	Disease	11
1333	Familial pancreatic carcinoma	Disease	9
404560	Familial atypical multiple mole melanoma syndrome	Disease	1
1501	Adrenocortical carcinoma	Disease	7
524	Li-Fraumeni syndrome	Disease	4
252206	Melanoma and neural system tumor syndrome	Disease	1
99861	Precursor T-cell acute lymphoblastic leukemia	Disease	23
585909	B-lymphoblastic leukemia/lymphoma with t(9;22)	Subtype	7

HPO ID	Phenotype
HP:0002861	Melanoma
HP:0012056	Cutaneous melanoma
HP:0002894	Neoplasm of the pancreas
HP:0006725	Pancreatic adenocarcinoma
HP:0002664	Neoplasm
HP:0001909	Leukemia
HP:0004808	Acute myeloid leukemia
HP:0006721	Acute lymphoblastic leukemia
HP:0002665	Lymphoma
HP:0012189	Hodgkin lymphoma
HP:0012539	Non-Hodgkin lymphoma
HP:0009592	Astrocytoma
HP:0012174	Glioblastoma multiforme
HP:0003002	Breast carcinoma
HP:0003003	Colon cancer
HP:0012125	Prostate cancer
HP:0002890	Thyroid carcinoma
HP:0006744	Adrenocortical carcinoma
HP:0002859	Rhabdomyosarcoma
HP:0002669	Osteosarcoma
HP:0002860	Squamous cell carcinoma
HP:0030078	Lung adenocarcinoma
HP:0009726	Renal neoplasm
HP:0100615	Ovarian neoplasm
HP:0025318	Ovarian carcinoma
HP:0010788	Testicular neoplasm
HP:0002896	Neoplasm of the liver
HP:0006753	Neoplasm of the stomach
HP:0007378	Neoplasm of the gastrointestinal tract
HP:0000006	Autosomal dominant inheritance

Study ID	Trait	Mapped Gene	P-value
GCST010118_115	Type 2 diabetes	CDKN2B-AS1	4×10⁻¹⁶⁴
GCST009379_256	Type 2 diabetes	CDKN2B-AS1	1×10⁻¹¹⁵
GCST007847_110	Type 2 diabetes	CDKN2B-AS1	1×10⁻⁸⁷
GCST90002400_4	Plateletcrit	CDKN2A	4×10⁻⁸⁹
GCST90002388_504	Lymphocyte count	CDKN2A	1×10⁻⁷¹
GCST90002402_175	Platelet count	CDKN2A	9×10⁻⁶⁵
GCST004347_7	Glioma	CDKN2B-AS1	1×10⁻⁴⁵
GCST004349_7	Glioblastoma	CDKN2B-AS1	7×10⁻⁴⁵
GCST000340_1	Myocardial infarction (early onset)	CDKN2B-AS1	3×10⁻⁴⁴
GCST009638_3	B-cell acute lymphoblastic leukaemia	CDKN2A	8×10⁻³⁵
GCST003400_44	Type 2 diabetes	CDKN2B-AS1	5×10⁻³³
GCST90002393_240	Monocyte count	CDKN2A	2×10⁻²⁹
GCST000383_2	Type 2 diabetes	CDKN2B-AS1	2×10⁻²⁹
GCST005832_4	ALL in childhood (B cell precursor)	CDKN2A	1×10⁻²⁷
GCST002352_52	Type 2 diabetes	CDKN2B-AS1	1×10⁻²⁷
GCST000998_24	Coronary heart disease	CDKN2B-AS1	1×10⁻²²
GCST000646_5	Intracranial aneurysm	CDKN2B-AS1	2×10⁻²²
GCST000030_1	Myocardial infarction	CDKN2B-AS1	1×10⁻²⁰
GCST002128_6	Type 2 diabetes	CDKN2B-AS1	1×10⁻¹⁸
GCST001058_3	Glioma	CDKN2B-AS1	5×10⁻¹⁶
GCST004988_267	Breast cancer	CDKN2B-AS1	1×10⁻¹⁵
GCST004348_11	Non-glioblastoma glioma	CDKN2B-AS1	1×10⁻¹⁵
GCST000024_7	Type 2 diabetes	CDKN2B-AS1	8×10⁻¹⁵
GCST000439_7	Glioma	CDKN2B-AS1	7×10⁻¹⁵
GCST000945_3	Coronary artery disease	CDKN2B-AS1	5×10⁻¹⁴
GCST001337_19	Platelet count	CDKN2A	6×10⁻¹⁴
GCST004483_5	Multiple myeloma	CDKN2A	2×10⁻¹³
GCST001084_4	Coronary heart disease (SNP×SNP)	CDKN2B-AS1	7×10⁻¹⁴
GCST003683_1	Intracranial/aortic aneurysm (pleiotropy)	CDKN2B-AS1	2×10⁻¹³
GCST000262_3	Intracranial aneurysm	CDKN2B-AS1	1×10⁻¹⁰

Category	Count
Ensembl Transcripts	14
RefSeq mRNA Transcripts (Human)	5 reviewed
CCDS Identifiers	4
UniProt Accessions	6 (2 reviewed)
PDB Structures	5
Cross-species Orthologs	2 (mouse, rat)
ClinVar Variants	1,594
Pathogenic Variants	100+
Likely Pathogenic Variants	41
SpliceAI Predictions	1,710
AlphaMissense Predictions	983
Reactome Pathways	10
GO Annotations (p16)	35
GO Annotations (ARF)	47
IntAct Interactions	146+
STRING Interactions	8,510+
TF Regulators	166
HPO Phenotypes	96
GWAS Associations	93
Orphanet Diseases	8
GenCC Diseases	6