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

Section 1: Gene Identifiers Primary Gene Identifiers
DatabaseIdentifierNotes HGNC IDHGNC:11892Approved HGNC SymbolTNFApproved symbol Ensembl GeneENSG00000232810Human NCBI Entrez Gene7124Human OMIM191160Gene/Locus Gene Names and Aliases Approved Name: tumor necrosis factor Previous Name: tumor necrosis factor (TNF superfamily, member 2) Aliases: TNFSF2, DIF, TNF-alpha, TNFA, TNLG1F, IMD127 Previous Symbol: TNFA Locus Group: protein-coding gene Gene Group: Tumor necrosis factor superfamily Genomic …

Feature	Value
Chromosome	6
Cytogenetic Band	6p21.33
Start Position	31,575,565 (GRCh38)
End Position	31,578,336 (GRCh38)
Strand	+ (positive)
Genomic Accession	NC_000006.12
Gene Length	2,772 bp

Transcript ID	Biotype	Start	End	Strand	5'UTR	3'UTR
ENST00000449264 ★	protein_coding	31,575,565	31,578,336	+	31,575,565-31,575,741	31,577,538-31,578,336
ENST00000699334	protein_coding	31,575,742	31,577,537	+	-	31,577,116-31,577,537

RefSeq ID	Symbol	Type	Status	MANE Select
NM_000594 ★	TNF	mRNA	REVIEWED	Yes
(Alternative transcripts from related genes also mapped)

Exon ID	Start	End	Strand	Chromosome
ENSE00001939157	31,575,565	31,575,927	+	6
ENSE00001610044	31,576,534	31,576,579	+	6
ENSE00001691672	31,576,767	31,576,814	+	6
ENSE00001933375	31,577,116	31,578,336	+	6

InterPro ID	Name	Type
IPR002959	TNF_alpha	Family
IPR006052	TNF_dom	Domain
IPR006053	TNF	Family
IPR008983	Tumour_necrosis_fac-like_dom	Homologous Superfamily
IPR021184	TNF_CS	Conserved Site

TNF Gene Complete Identifier and Functional Mapping Reference

Structured Data Sources

Database	Identifier	Notes
HGNC ID	HGNC:11892	Approved
HGNC Symbol	TNF	Approved symbol
Ensembl Gene	ENSG00000232810	Human
NCBI Entrez Gene	7124	Human
OMIM	191160	Gene/Locus

PDB ID	Title	Method	Resolution (Å)
9OJO	TNF alpha in complex with compound 1	X-ray	1.358
5UUI	Spin-Labeled T77C TNFa	X-ray	1.4
4Y6O	SIRT2 with myristoylated TNF-alpha peptide	X-ray	1.6
2E7A	TNFR1-selective TNF Mutant	X-ray	1.8
4TSV	Human TNF-alpha mutant (high resolution)	X-ray	1.8
9OJS	TNF alpha in complex with compound 4	X-ray	1.849
5M2J	TNF alpha with Llama VHH2	X-ray	1.9
9BN7	TNFa-VNAR C4 complex	X-ray	1.92
2AZ5	TNF-alpha with small molecule inhibitor	X-ray	2.1
3L9J	TNFalpha with antagonist	X-ray	2.1
7JRA	TNF-ALPHA with quinoline compound	X-ray	2.1
5M2I	TNF with Llama VHH1	X-ray	2.15
7KP9	Asymmetric hTNF-alpha	X-ray	2.15
9OJY	TNF alpha with compound 3	X-ray	2.158
1A8M	TNF-alpha R31D mutant	X-ray	2.3
5M2M	TNF alpha with Llama VHH3	X-ray	2.3
7KPA	Asymmetric hTNF-alpha	X-ray	2.3
2ZJC	TNFR1 selective TNF mutant R1-6	X-ray	2.5
6OOY	Asymmetric hTNF-alpha	X-ray	2.5
5TSW	Human TNF-alpha mutant	X-ray	2.5
7TA3	TNF-alpha with alpha-peptide-3	X-ray	2.5
6OP0	Asymmetric hTNF-alpha	X-ray	2.55
8ZUI	TNF-TNFR1 ectodomain complex	Cryo-EM	2.56
8Z8M	TNF alpha with ozoralizumab VHH domain	X-ray	2.59
4G3Y	TNF-alpha with Infliximab Fab	X-ray	2.6
1TNF	TNF-alpha structure (classic)	X-ray	2.6
6RMJ	Human NGR-TNF	X-ray	2.65
7TA6	TNF-alpha with alpha/beta-peptide-1	X-ray	2.67
5YOY	TNF with golimumab Fv	X-ray	2.727
9OK6	TNF alpha with compound 19	X-ray	2.776
3IT8	TNF alpha with poxvirus TNF binding protein	X-ray	2.8
6OOZ	Asymmetric hTNF-alpha	X-ray	2.8
6X81	TNFalpha with isoquinoline compound 2	X-ray	2.81
2ZPX	TNFR1-selective TNF mutant R1antTNF-T8	X-ray	2.83
6X83	TNFalpha with fragment compound 6	X-ray	2.83
4TWT	TNFa dimer with bicyclic peptide M21	X-ray	2.85
6X85	TNFalpha with indolinone compound 9	X-ray	2.85
5WUX	TNFalpha-certolizumab Fab	X-ray	2.9
6X86	TNFalpha with indolinone compound 11	X-ray	2.93
3ALQ	TNF-TNFR2 complex	X-ray	3.0
5MU8	TNF-ALPHA with JNJ525	X-ray	3.0
7KPB	TNF-TNFR1 with antibody	X-ray	3.0
2TUN	TNF-alpha Ala-84-Val mutant	X-ray	3.1
3WD5	TNFalpha with Adalimumab Fab	X-ray	3.101
9DJW	TNFa-VNAR D1 complex	X-ray	3.43
7ASY	TNF-alpha transmembrane helix	NMR	-
7AT7	TNF-alpha TM helix S34P mutant	NMR	-
7ATB	TNF-alpha TM helix AGALLL mutant	NMR	-
7QLF	Solnatide conformational ensemble	NMR	-

Species	Gene ID	Symbol	Chromosome	Position
Mouse (Mus musculus)	ENSMUSG00000024401	Tnf	17	35,418,357-35,420,983 (-)
Rat (Rattus norvegicus)	ENSRNOG00000070745	Tnf	20	3,626,532-3,629,303 (+)
Zebrafish (Danio rerio)	554167 (Entrez)	tnfa/tnfb	-	-
Fruit fly (Drosophila)	36054 (Entrez)	eiger	-	(Functional homolog)
Worm (C. elegans)	No direct ortholog	-	-	-
Yeast (S. cerevisiae)	No ortholog	-	-	-

Classification	Count
Pathogenic	3
Likely Pathogenic	0
Uncertain Significance (VUS)	11
Likely Benign	4
Benign	2
Risk Factor	2
Protective	1
Drug Response	1
Not Provided	2

ClinVar ID	Variant	HGVS	Classification	Review Status
12385	L29S	L29S	Pathogenic	no assertion criteria
12386	R108W	NM_000594.4(TNF):c.322C>T (p.Arg108Trp)	Pathogenic	no assertion criteria
3362893	20-BP INS	TNF, 20-BP INS, NT190	Pathogenic	no assertion criteria

ClinVar ID	Variant	Classification
12387	g.31575186G>A	Risk factor
12389	g.31574705C>T	Risk factor
12390	g.31574699C>A	Protective
225964	g.31575254G>A	Drug response (expert reviewed)

Variant	Effect	Delta Score
6:31575924:AGAG:A	donor_gain	1.00
6:31575924:AGAGG:A	donor_loss	1.00
6:31575925:GAG:G	donor_gain	1.00
6:31575925:GAGG:G	donor_gain	1.00
6:31575925:GAGGT:G	donor_loss	1.00
6:31575926:AG:A	donor_gain	1.00
6:31575927:GG:G	donor_gain	1.00
6:31575927:GGTG:G	donor_loss	1.00
6:31575928:G:GG	donor_gain	1.00
6:31576532:A:AG	acceptor_gain	1.00
6:31576533:G:GG	acceptor_gain	1.00
6:31576576:GTCA:G	donor_gain	1.00
6:31576580:G:GG	donor_gain	1.00
6:31575922:G:T	donor_gain	0.99
6:31575923:AAGAG:A	donor_gain	0.99
6:31576530:ACAGT:A	acceptor_loss	0.99
6:31576532:A:C	acceptor_loss	0.99
6:31576533:GT:G	acceptor_gain	0.99
6:31576533:GTT:G	acceptor_gain	0.99
6:31576533:GTTC:G	acceptor_gain	0.99
6:31576533:GTTCC:G	acceptor_gain	0.99

Variant	Protein Change	AM Score	Classification
6:31575745:A:C	S2R	0.913	likely_pathogenic
6:31575746:G:T	S2I	0.853	likely_pathogenic
6:31575761:T:C	I7T	0.906	likely_pathogenic
6:31575761:T:G	I7S	0.844	likely_pathogenic
6:31575759:G:A	M6I	0.836	likely_pathogenic
6:31575758:T:C	M6T	0.758	likely_pathogenic
6:31575761:T:A	I7N	0.770	likely_pathogenic
6:31575766:G:C	D9H	0.765	likely_pathogenic
6:31575767:A:T	D9V	0.737	likely_pathogenic
6:31575767:A:C	D9A	0.680	likely_pathogenic
6:31575749:C:T	T3I	0.673	likely_pathogenic
6:31575774:G:C	E11D	0.655	likely_pathogenic
6:31575758:T:A	M6K	0.645	likely_pathogenic
6:31575745:A:T	S2C	0.629	likely_pathogenic
6:31575758:T:G	M6R	0.622	likely_pathogenic
6:31575766:G:A	D9N	0.622	likely_pathogenic
6:31575768:C:A	D9E	0.617	likely_pathogenic
6:31575772:G:A	E11K	0.610	likely_pathogenic
6:31575767:A:G	D9G	0.606	likely_pathogenic
6:31575773:A:T	E11V	0.595	likely_pathogenic
6:31575752:A:T	E4V	0.589	likely_pathogenic

Pathway ID	Pathway Name
R-HSA-75893	TNF signaling
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-5357786	TNFR1-induced proapoptotic signaling
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5626978	TNFR1-mediated ceramide production
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9942503	Differentiation of naive CD+ T cells to Th1 cells

GO ID	Term
GO:0006954	inflammatory response
GO:0006955	immune response
GO:0033209	tumor necrosis factor-mediated signaling pathway
GO:0007249	canonical NF-kappaB signal transduction
GO:0043065	positive regulation of apoptotic process
GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors
GO:0045944	positive regulation of transcription by RNA polymerase II
GO:0070374	positive regulation of ERK1 and ERK2 cascade
GO:0043507	positive regulation of JUN kinase activity
GO:0050729	positive regulation of inflammatory response
GO:0031622	positive regulation of fever generation
GO:0030316	osteoclast differentiation
GO:0032755	positive regulation of interleukin-6 production
GO:0032731	positive regulation of interleukin-1 beta production
GO:0043123	positive regulation of canonical NF-kappaB signal transduction
GO:0001774	microglial cell activation
GO:0002281	macrophage activation involved in immune response
GO:0045672	positive regulation of osteoclast differentiation
GO:0048661	positive regulation of smooth muscle cell proliferation
GO:0097527	necroptotic signaling pathway

GO ID	Term
GO:0005125	cytokine activity
GO:0005164	tumor necrosis factor receptor binding
GO:0048018	receptor ligand activity
GO:0038177	death receptor agonist activity
GO:0042802	identical protein binding
GO:0002020	protease binding
GO:0000976	transcription cis-regulatory region binding
GO:0140072	histone H3K9ac reader activity

GO ID	Term
GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005886	plasma membrane
GO:0009986	cell surface
GO:0009897	external side of plasma membrane
GO:0045121	membrane raft
GO:0001891	phagocytic cup
GO:0043025	neuronal cell body
GO:0055037	recycling endosome

UniProt ID	Gene	Score	Description
P19438	TNFRSF1A	999	TNF receptor superfamily member 1A
P20333	TNFRSF1B	998	TNF receptor superfamily member 1B
O00220	TNFRSF10A	997	TNF receptor superfamily member 10A (TRAIL-R1)
O14763	TNFRSF10B	997	TNF receptor superfamily member 10B (TRAIL-R2)
P25445	FAS	997	Fas cell surface death receptor
P14778	IL1R1	996	Interleukin 1 receptor type 1
Q15628	TRADD	996	TNFRSF1A associated via death domain
P19838	NFKB1	995	Nuclear factor kappa B subunit 1
Q9Y4K3	TRAF6	995	TNF receptor associated factor 6
P01584	IL1B	993	Interleukin 1 beta
P01579	IFNG	990	Interferon gamma
P05231	IL6	989	Interleukin 6
P78507	EDN1	987	Endothelin 1
P22301	IL10	984	Interleukin 10
P25942	CD40	984	CD40 molecule
P48023	FASLG	984	Fas ligand
P08887	IL6R	977	Interleukin 6 receptor
P01583	IL1A	976	Interleukin 1 alpha
Q13158	FADD	973	Fas associated via death domain
P02751	FN1	970	Fibronectin 1
O00206	TLR4	966	Toll like receptor 4
P01730	CD4	966	CD4 molecule
P10145	CXCL8	965	C-X-C motif chemokine ligand 8 (IL-8)
P05112	IL4	963	Interleukin 4
P01732	CD8A	957	CD8a molecule
Q16552	IL17A	957	Interleukin 17A
P01585	IL2	956	Interleukin 2
P13500	CCL2	953	C-C motif chemokine ligand 2
P50591	TNFSF10	944	TNF superfamily member 10 (TRAIL)
Q04206	RELA	944	RELA proto-oncogene, NF-kB subunit
O60603	TLR2	943	Toll like receptor 2
Q13546	RIPK1	943	Receptor interacting serine/threonine kinase 1
P02741	CRP	938	C-reactive protein
P25963	NFKBIA	937	NF-kappa-B inhibitor alpha
Q14116	IL18	937	Interleukin 18
P01137	TGFB1	936	Transforming growth factor beta 1
O14920	IKBKB	934	Inhibitor of NF-kappa B kinase subunit beta
P78397	STING1	933	Stimulator of interferon genes
P42574	CASP3	932	Caspase 3
P35225	IL13	931	Interleukin 13

Interaction ID	Partner A	Partner B	Classification
CPI-SS04B4619D0	TNF (P01375)	TNFRSF1A (P19438)	Ligand-Receptor
CPI-SS0E7D5974D	TNF (P01375)	TNFRSF1B (P20333)	Ligand-Receptor

UniProt ID	Similarity Count	Top Similarity	Avg Similarity
P59684	50	1.000	0.994
P59693	50	1.000	0.994
P59694	50	1.000	0.995
P63182	50	1.000	0.973
P63306	50	1.000	0.987
P63307	50	1.000	0.987
P63308	50	1.000	0.987
P86437	50	1.000	0.973
Q06599	50	1.000	0.994
Q2MH05	50	1.000	0.994
Q75N23	50	1.000	0.995

UniProt ID	Identity (%)	Bitscore	Description
P59684	100.0	472	TNF (Macaca mulatta)
Q06599	100.0	472	TNF (Chlorocebus aethiops)
Q2MH05	100.0	472	TNF (Pan troglodytes)
P63306	100.0	509	TNF (Bos taurus)
P63307	100.0	509	TNF (Capra hircus)
P63308	100.0	509	TNF (Ovis aries)
O77510	99.6	466	TNF (Macaca fascicularis)
P59694	99.6	466	TNF (Hylobates lar)
Q75N23	99.6	466	TNF (Gorilla gorilla)
P01374	99.5	407	LTA (Homo sapiens, lymphotoxin-alpha)
P61125	99.5	407	LTA (Pan troglodytes)
P48094	99.6	466	TNF (Pongo pygmaeus)
P33620	98.3	456	TNF (Canis lupus familiaris)
Q8WNR1	98.3	454	TNF (Felis catus)
Q9BEA1	98.3	453	TNF (Sus scrofa)
P13296	97.9	461	TNF (Oryctolagus cuniculus)
P23383	97.9	461	TNF (Equus caballus)

TF Gene	Regulation	Confidence
NFKB1/RELA (NfKb-p65/p50)	Activation	High
JUN	Activation	High
FOS	Activation	High
AP1	Activation	High
CREB1	Activation	High
ATF2	Activation	High
ATF3	Activation	High
EGR1	Activation	High
ELK1	Activation	High
ETS1	Activation	High
IRF1	Activation	High
IRF3	Activation	High
IRF8	Activation	High
HIF1A	Activation	High
FOXO1	Activation	High
BCL3	Activation	High
LITAF	Activation	High
JUND	Activation	High
FOSB	Activation	High
JUNB	Activation	Low
ESR1	Activation	High
AHR	Activation	High
CREM	Activation	High
SP1	Activation	High
CEBPB	Unknown	High
CEBPD	Unknown	High
CTCF	-	High
DNMT1	-	High
HSF1	Unknown	High
KLF4	Repression	-
CEBPA	Repression	-
EZH2	Repression	-
HDAC11	Repression	-
FUBP1	Repression	Low
LRRFIP1	Repression	High
APP	Repression	-
MFGE8	Repression	-

Source	Target	Effect	Mechanism
ADAM17	TNF	up-regulates	cleavage
SIRT6	TNF	up-regulates	deacetylation
IRF5	TNF	up-regulates	transcriptional
NfKb-p65/p50	TNF	up-regulates	transcriptional
IL1A	TNF	up-regulates	transcriptional
KLF4	TNF	down-regulates	transcriptional
FUBP1	TNF	down-regulates	transcriptional
MFGE8	TNF	down-regulates	transcriptional

ChEMBL ID	Drug Name	Type	Highest Phase	Mechanism
CHEMBL131	PREDNISOLONE	Small molecule	4 (Approved)	Glucocorticoid
CHEMBL628	PENTOXIFYLLINE	Small molecule	4 (Approved)	Phosphodiesterase inhibitor
CHEMBL704	MESALAMINE	Small molecule	4 (Approved)	Anti-inflammatory
CHEMBL848	LENALIDOMIDE	Small molecule	4 (Approved)	Immunomodulator
CHEMBL43452	POMALIDOMIDE	Small molecule	4 (Approved)	Immunomodulator
CHEMBL279785	MARIMASTAT	Small molecule	3	MMP inhibitor
CHEMBL3989927	IBERDOMIDE	Small molecule	3	Immunomodulator

Drug	Mechanism	Type
Infliximab (Remicade)	TNF binding/neutralization	Monoclonal antibody
Etanercept (Enbrel)	TNF binding/neutralization	Fusion protein
Adalimumab (Humira)	TNF binding/neutralization	Monoclonal antibody
Golimumab (Simponi)	TNF binding/neutralization	Monoclonal antibody
Certolizumab (Cimzia)	TNF binding/neutralization	PEGylated Fab
Doramapimod	MAPK14/p38 inhibition	Small molecule

Drug	Clinical Annotations	Variant Annotations
Carbamazepine	52	403
Cyclosporine	26	157
Rifampin	24	182
Isoniazid	23	237
Infliximab	21	128
Mycophenolate mofetil	20	99
Tenofovir	17	109
Sirolimus	14	44
Sufentanil	12	68
Rituximab	10	55
Pyrazinamide	9	130
Ethambutol	8	130
Ibuprofen	8	46
Sumatriptan	8	29
Diclofenac	7	53
Omeprazole	5	183
Glucocorticoids (class)	48	203
Certolizumab pegol	4	15

Metric	Value
Expression Breadth	Ubiquitous
Total Present Calls	119
Max Expression Score	96.17

Rank	Tissue/Cell Type	Expression Score	Quality
1	Granulocyte	96.17	Gold
2	Male germ line stem cell (testis)	87.11	Gold
3	Bone marrow	86.37	Gold
4	Leukocyte	85.79	Gold
5	Monocyte	85.61	Gold
6	Bone marrow cell	84.38	Gold
7	Blood	77.44	Gold
8	Lymph node	77.13	Gold
9	Spleen	72.08	Gold
10	Vermiform appendix	71.58	Gold
11	Duodenum	68.35	Gold
12	Gall bladder	65.81	Gold
13	Apex of heart	63.92	Gold
14	Smooth muscle tissue	62.41	Gold
15	Primordial germ cell (gonad)	61.57	Gold
16	Tonsil	61.23	Gold
17	Placenta	60.86	Gold
18	Rectum	60.33	Gold
19	Upper lobe of left lung	59.23	Gold
20	Metanephros cortex (kidney)	59.03	Gold
21	Small intestine	58.30	Gold
22	Islet of Langerhans	58.08	Gold
23	Peyer's patch	57.98	Gold
24	Skin of abdomen	57.84	Gold
25	Lung	57.39	Gold
26	Heart left ventricle	57.27	Gold
27	Omental fat pad	57.27	Gold
28	Right coronary artery	56.43	Gold
29	Transverse colon mucosa	56.20	Gold
30	Olfactory nasal mucosa	56.13	Gold

HPO ID	Phenotype	Inheritance Pattern
HP:0000006	Autosomal dominant inheritance	-
HP:0000007	Autosomal recessive inheritance	-
HP:0001426	Non-Mendelian inheritance	-
HP:0002077	Migraine with aura	-
HP:0002083	Migraine without aura	-
HP:0002099	Asthma	-
HP:0000613	Photophobia	-
HP:0002183	Phonophobia	-
HP:0002013	Vomiting	-
HP:0002018	Nausea	-
HP:0002202	Pleural effusion	-
HP:0010516	Thymus hyperplasia	-
HP:0011462	Young adult onset	-
HP:0031273	Shock	-
HP:0032262	Pulmonary tuberculosis	-
HP:0032933	Airway hyperresponsiveness	-
HP:4000007	Bronchoconstriction	-

GWAS Study	Disease/Trait	Mapped Gene Region	P-value
GCST004133_30	Ulcerative colitis	HLA-DQA1	5×10⁻⁶⁵
GCST004131_25	Inflammatory bowel disease	HLA-DQA1	2×10⁻³¹
GCST008916_130	Asthma	NFKBIL1 - LTA	1×10⁻⁹
GCST007269_18	Pulse pressure	LTA - TNF	8×10⁻¹⁹
GCST000308_1	AIDS progression	HCP5	3×10⁻¹⁹
GCST004521_14	Autism/schizophrenia	HCG27 - HLA-C	3×10⁻¹⁷
GCST008921_1	Asthma + major depression	MICB	2×10⁻¹⁶
GCST004521_229	Autism/schizophrenia	SFTA2	8×10⁻²⁰
GCST004521_209	Autism/schizophrenia	LINC02571 - HLA-B	5×10⁻¹⁶
GCST004521_211	Autism/schizophrenia	HCP5, MICB-DT	5×10⁻¹⁵
GCST004521_53	Autism/schizophrenia	LINC00243	2×10⁻¹⁵
GCST004521_17	Autism/schizophrenia	FGFR3P1 - ZDHHC20P2	3×10⁻¹⁵
GCST004521_156	Autism/schizophrenia	TSBP1-AS1	1×10⁻¹⁴
GCST008916_32	Asthma	HLA-B	2×10⁻¹⁴
GCST004521_265	Autism/schizophrenia	PSORS1C1	7×10⁻¹⁴
GCST004521_213	Autism/schizophrenia	PPT2	5×10⁻¹³
GCST012230_545	Waist-to-hip ratio (BMI adj)	LTA - TNF	3×10⁻¹²
GCST000879_48	Crohn's disease	LTA - TNF	4×10⁻¹¹
GCST000738_5	Neonatal lupus	HCP5, MICB-DT	5×10⁻¹⁰
GCST004521_76	Autism/schizophrenia	TNXB	2×10⁻¹⁰
GCST008916_35	Asthma	NFKBIL1 - LTA	1×10⁻⁹
GCST004521_188	Autism/schizophrenia	RNU6-1133P - C6orf15	1×10⁻⁹
GCST004833_9	Cervical cancer	LTA	6×10⁻⁹
GCST011773_10	Type 1 diabetes (age at diagnosis)	TNF	3×10⁻⁷
GCST008917_2	Childhood onset asthma	MICB	4×10⁻⁷
GCST010725_71	Malaria	MICB-DT, HCP5	5×10⁻⁷
GCST002211_10	Psychosis (atypical)	PRRC2A, SNORA38	4×10⁻⁶
GCST010725_96	Malaria	MICB-DT, HCP5	3×10⁻⁶

Category	Count
Gene Identifiers	5 primary databases
Transcripts	2 Ensembl, 1 MANE Select
Exons	4
Protein Entries	1 reviewed UniProt
Protein Domains	5 InterPro annotations
PDB Structures	50
Orthologs	Mouse, Rat (direct); Zebrafish, Fly (functional)
ClinVar Variants	26
SpliceAI Predictions	205
AlphaMissense Predictions	1,498
Reactome Pathways	10
GO Annotations	193
STRING Interactions	10,273+
IntAct Interactions	212
ESM2 Similar Proteins	77
DIAMOND Homologs	54
TF Regulators	248
Approved Drugs (Phase 4)	5 small molecules + 5 biologics
PharmGKB Drug Associations	32
Bgee Tissue Profiles	119 tissues
HPO Phenotypes	17
GWAS Associations	28