TAP1

Summary

TAP1 (transporter 1, ATP binding cassette subfamily B member, HGNC:43) is a protein-coding gene on chromosome 6p21.32, encoding Antigen peptide transporter 1 (Q03518). ABC transporter associated with antigen processing.

The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is involved in the pumping of degraded cytosolic peptides across the endoplasmic reticulum into the membrane-bound compartment where class I molecules assemble. Mutations in this gene may be associated with ankylosing spondylitis, insulin-dependent diabetes mellitus, and celiac disease. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 6890 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MHC class I deficiency (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 11
• Clinical variants (ClinVar): 475 total — 24 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 10
• Druggable target: yes
• MANE Select transcript: NM_000593

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:43
Approved symbol	TAP1
Name	transporter 1, ATP binding cassette subfamily B member
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	PSF1, RING4, D6S114E
Ensembl gene	ENSG00000168394
Ensembl biotype	protein_coding
OMIM	170260
Entrez	6890

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000354258, ENST00000486332, ENST00000487296, ENST00000643049, ENST00000643923, ENST00000645078, ENST00000698420, ENST00000698421, ENST00000698422, ENST00000698423, ENST00000698424, ENST00000875704, ENST00000875705, ENST00000875706, ENST00000920267, ENST00000920268

RefSeq mRNA: 2 — MANE Select: NM_000593 NM_000593, NM_001292022

CCDS: CCDS4758

Canonical transcript exons

ENST00000354258 — 11 exons

Exon	Start	End
ENSE00001640106	32852109	32852239
ENSE00003506325	32845209	32845785
ENSE00003509703	32847068	32847204
ENSE00003660988	32847513	32847675
ENSE00003682157	32852388	32852502
ENSE00003685439	32847919	32848092
ENSE00003973601	32853039	32853704
ENSE00003973603	32850320	32850517
ENSE00003973606	32848652	32848840
ENSE00003973607	32850944	32851149
ENSE00003973608	32848990	32849118

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.4062 / max 628.0976, expressed in 1724 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73036	23.2770	1722
73034	2.4270	209
73037	0.2705	87
73035	0.2620	97
73033	0.0869	38
73032	0.0827	32

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.88	gold quality
vermiform appendix	UBERON:0001154	98.36	gold quality
lymph node	UBERON:0000029	98.15	gold quality
blood	UBERON:0000178	97.89	gold quality
spleen	UBERON:0002106	97.71	gold quality
leukocyte	CL:0000738	96.87	gold quality
monocyte	CL:0000576	96.71	gold quality
duodenum	UBERON:0002114	96.53	gold quality
skin of abdomen	UBERON:0001416	96.24	gold quality
zone of skin	UBERON:0000014	96.14	gold quality
skin of leg	UBERON:0001511	96.08	gold quality
upper lobe of left lung	UBERON:0008952	95.80	gold quality
mucosa of transverse colon	UBERON:0004991	95.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.32	gold quality
rectum	UBERON:0001052	95.29	gold quality
right lung	UBERON:0002167	95.13	gold quality
gall bladder	UBERON:0002110	95.05	gold quality
small intestine	UBERON:0002108	94.61	gold quality
apex of heart	UBERON:0002098	94.29	gold quality
smooth muscle tissue	UBERON:0001135	94.03	gold quality
transverse colon	UBERON:0001157	93.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.52	gold quality
lung	UBERON:0002048	93.21	gold quality
omental fat pad	UBERON:0010414	93.17	gold quality
stromal cell of endometrium	CL:0002255	92.81	gold quality
myometrium	UBERON:0001296	92.76	gold quality
left uterine tube	UBERON:0001303	92.74	gold quality
intestine	UBERON:0000160	92.51	gold quality
adipose tissue	UBERON:0001013	92.50	gold quality
placenta	UBERON:0001987	92.50	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	18.43
E-HCAD-1	yes	18.22
E-MTAB-9543	yes	17.58
E-ANND-3	yes	12.52
E-MTAB-9801	yes	7.78
E-MTAB-6678	yes	7.59
E-GEOD-110499	no	710.74
E-HCAD-8	no	54.12
E-CURD-112	no	3.26

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDX1, CDX2, EGR1, IRF1, IRF2, IRF6, KAT7, NFKB1, RELA, STAT1, TAPBP, TP53

miRNA regulators (miRDB)

31 targeting TAP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-20A-3P	99.44	69.10	1575
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-532-5P	98.43	67.53	760
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-3678-5P	96.64	74.02	93
HSA-MIR-4453	95.61	65.84	436

Literature-anchored findings (GeneRIF, showing 40)

• Regulation of transporters associated with antigen processing (TAPs) by nucleotide binding to, and hydrolysis by, Walker consensus sequences (PMID:11774612)
• a high-frequency TAP1/LMP2 promoter polymorphism in human tumors (PMID:11788900)
• There was a significant difference in the frequencies at positions 333 and 637 of TAP 1 gene. TAP genes might have modifying effects on the cystic fibrosis phenotype (PMID:12026214)
• examination of TAP1 and TAP2 gene polymorphisms in rheumatoid arthritis patients revealed an association between a particular amino acid residue, namely Thr565 in the TAP2 gene, and rheumatoid arthritis (PMID:12047361)
• IFN-gamma and LPS upregulated the expression of TAP1 and TAP2 in primary human macrophages (PMID:12234057)
• cysteine-less TAP1 and TAP2 are functional with respect to adenosine triphosphate (ATP)-dependent peptide transport (PMID:12505156)
• A single-nucleotide deletion of the TAP-1 gene resulted in a >2-fold decrease in the half-life of TAP-1 mRNA, the first evidence that the degradation of mRNA of an antigen presentation gene is involved in HLA class I down-regulation in malignant cells. (PMID:12582163)
• A major role for tapasin as a stabilizer of the TAP peptide transporter and consequences for MHC class I expression (PMID:12594855)
• Mutations in the ABC-transporter signature motifs of TAP2 inhibit the translocation of peptide without affecting binding of either peptide or ATP by TAP. This motif is required after peptide binding to facilitate peptide translocation by TAP. (PMID:12645939)
• The binding sites contributing to the substrate specificity and subcellular localization of this protein are identified. (PMID:12682044)
• peptide binding induces a conformation that triggers ATP hydrolysis in both subunits of the TAP complex within the catalytic cycle (PMID:12777379)
• TAP1 plays an important role in the melanoma-associated antigen-specific cytotoxic T-lymphocyte response, which has been suggested to underlie the spontaneous regression of primary melanoma. (PMID:12777979)
• the G alleles of TAP1-1 and TAP1-2 were significantly more common than the A alleles in serositis of SLE patients. (PMID:12827444)
• hepatitis C virus core protein induces p53-dependent gene expression of TAP1 protein and MHC class I upregulation in liver cells and thus impairs NK cell cytotoxicity (PMID:12857899)
• TAP1 polymorphism in an indigenous Zimbabwean population (Shona ethnic group) (PMID:12878362)
• The TAP1 gene is associated with vitiligo. (PMID:14551602)
• There exists decreased expression of TAP in both childhood ALL and AML, which probably contributes to the escape of leukemia cells from immune surveillance. (PMID:14558951)
• the N-terminal domains of TAP1 and TAP2 are essential for recruitment of tapasin, consequently mediating assembly of the macromolecular peptide-loading complex (PMID:14679198)
• peptidoglycan signaling through TLR2 and bacterial CpG DNA signaling through TLR9 are functionally equivalent at synergizing with IFN-gamma in regulating Tap-1 expression in macrophages (PMID:14694183)
• Severity of disease in a patient with recurrent respiratory papillomatosis might be determined by sequencing TAP1, in conjunction with HLA class II genes. (PMID:14976605)
• TAP1*D allele could lead to genetic susceptibility to psoriasis vulgaris in Poland. (PMID:15306733)
• the serine of the C-loop is not essential for TAP function but rather coordinates, together with other residues of the C-loop, the ATP hydrolysis in both nucleotide-binding sites. (PMID:15322097)
• Evidence is provided that that the extended haplotype of TAP1 is distinct in pauciarticular and polyarticular rheumatoid factor negative juvenile idiopathic arthritis patients. (PMID:15343265)
• interaction of TAP1 and TAP2 and P-glycoprotein with proteasome subunits beta-5 and beta-5i suggest direct targeting of antigenic peptides to the ER via a TAP-proteasome association and a possible role for P-glycoprotein (PMID:15488952)
• The single-site polymorphism of the TAP1 gene at codon 637 may be an indicator for predicting development of Graves’ Disease. (PMID:15711027)
• TPO and IFN-gamma activate the expression of TAP1 via a new mechanism that involves functional cooperation between STAT1 and IRF-2 on the TAP1 promoter (PMID:15778351)
• TAP1-1 gene polymorphisms may, by way of post-transcriptional changes and altered regulation of gene expression, be involve the immune system in the development of primary open-angle glaucoma (PMID:15887980)
• A TAP-1 polymorphism adjacent to the signature motif may be a contributing factor for MHC class I down-regulation in colon cancer (PMID:15897556)
• Epstein-Barr virus (EBV)-induced interference with TAP function is a specific mechanism contributing to reduced levels of cell surface HLA class I in productively EBV-infected B cells. (PMID:15905524)
• Transmembrane segment 1 (TM1) of core-TAP1 is critical for its heterodimerization with core-TAP2. (PMID:16061226)
• Results suggest the possible role of TAP1 gene polymorphism in the genetic susceptibility to systemic sclerosis . (PMID:16112028)
• N-terminal domains of TAP1 and TAP2 are important for tapasin binding and for optimal peptide loading onto major histocompatibility complex class I molecules. (PMID:16174096)
• allelic frequency of TAP1 and TAP2 and the alleles shared in mother-infant were compared in pre-eclampsia and controls (PMID:16191421)
• The data revealed a nonanalogous multipolar bridging of the transporter associated with antigen processing (TAP) transmembrane domains by cytomegalovirus glycoprotein US6 (PMID:16356928)
• study provides a first-time map of the structural organization of the TAP1 machinery within the macromolecular major histocompatibility complex (MHC) class I peptide-loading complex. (PMID:16407277)
• review summarizes the structural organization and function of the ABC transporter TAP and discusses human diseases and viral evasion strategies associated with TAP function (PMID:16691491)
• different functions of UL49.5, editing of glycoprotein M processing and inhibition of TAP1, can be combined during BHV-1 infection (PMID:16731921)
• analysis of ATPase activity in the isolated ABC cassette of human TAP1 by protein engineering (PMID:16864587)
• HLA-DR up-regulation is affected in TAP-deficient skin fibroblasts through an unknown mechanism probably independent from TAP. (PMID:16956670)
• TAP1 nucleotide binding domain is critical for optimal nucleotide binding to the TAP2 site and for initiating the early steps of the TAP catalytic cycle. (PMID:17068338)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	tap1	ENSDARG00000079766
mus_musculus	Tap1	ENSMUSG00000037321
rattus_norvegicus	Tap1	ENSRNOG00000000457
caenorhabditis_elegans		WBGENE00001817
caenorhabditis_elegans		WBGENE00001818
caenorhabditis_elegans		WBGENE00003995
caenorhabditis_elegans		WBGENE00004000
caenorhabditis_elegans		WBGENE00004001
caenorhabditis_elegans		WBGENE00004002
caenorhabditis_elegans		WBGENE00004003
caenorhabditis_elegans		WBGENE00004006
caenorhabditis_elegans		WBGENE00004008

Paralogs (10): ABCB5 (ENSG00000004846), ABCB4 (ENSG00000005471), ABCB11 (ENSG00000073734), ABCB1 (ENSG00000085563), ABCB6 (ENSG00000115657), ABCB7 (ENSG00000131269), ABCB10 (ENSG00000135776), ABCB9 (ENSG00000150967), ABCB8 (ENSG00000197150), TAP2 (ENSG00000204267)

Protein

Protein identifiers

Antigen peptide transporter 1 — Q03518 (reviewed: Q03518)

Alternative names: ATP-binding cassette sub-family B member 2, Peptide supply factor 1, Peptide transporter PSF1, Peptide transporter TAP1, Peptide transporter involved in antigen processing 1, Really interesting new gene 4 protein

All UniProt accessions (8): Q03518, A0A2R8Y4Y0, A0A8V8TLN3, A0A8V8TLQ7, A0A8V8TM76, A0A8V8TN61, A0A8V8TNH0, X5CKB3

UniProt curated annotations — full annotation on UniProt →

Function. ABC transporter associated with antigen processing. In complex with TAP2 mediates unidirectional translocation of peptide antigens from cytosol to endoplasmic reticulum (ER) for loading onto MHC class I (MHCI) molecules. Uses the chemical energy of ATP to export peptides against the concentration gradient. During the transport cycle alternates between ‘inward-facing’ state with peptide binding site facing the cytosol to ‘outward-facing’ state with peptide binding site facing the ER lumen. Peptide antigen binding to ATP-loaded TAP1-TAP2 induces a switch to hydrolysis-competent ‘outward-facing’ conformation ready for peptide loading onto nascent MHCI molecules. Subsequently ATP hydrolysis resets the transporter to the ‘inward facing’ state for a new cycle. Typically transports intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome. Binds peptides with free N- and C-termini, the first three and the C-terminal residues being critical. Preferentially selects peptides having a highly hydrophobic residue at position 3 and hydrophobic or charged residues at the C-terminal anchor. Proline at position 2 has the most destabilizing effect. As a component of the peptide loading complex (PLC), acts as a molecular scaffold essential for peptide-MHCI assembly and antigen presentation.

Subunit / interactions. Heterodimer of TAP1 and TAP2 (TAP1-TAP2). A component of the peptide loading complex (PLC), interacts via TAPBP with MHCI heterodimer; this interaction mediates peptide-MHCI assembly. Recruits TAPBP in a 1:1 stoichiometry. Interacts with classical MHCI such as HLA-A*02-B2M; this interaction is obligatory for the loading of peptide epitopes. Interacts with non-classical MHCI molecules including HLA-E-B2M and HLA-F-B2M as well as PLC component CALR before the peptide loading. Interacts with PSMB5 and PSMB8. (Microbial infection) Interacts with Epstein-Barr virus BNLF2a. (Microbial infection) Interacts with herpes simplex virus US12/ICP47. (Microbial infection) Interacts with adenovirus E3-19K glycoprotein, which binds TAP1-TAP2 and acts as a TAPBP inhibitor, preventing TAP1-TAP2 association with MHCI.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in professional APCs monocytes and dendritic cells as well as in lymphocyte subsets T cells, B cells and NK cells.

Disease relevance. MHC class I deficiency 1 (MHC1D1) [MIM:604571] An autosomal recessive immunologic disorder characterized by chronic bacterial infections of the respiratory tract, beginning in the first or second decade of life and usually progressing to bronchiectasis. Patients have nasal polyps and may develop chronic necrotizing granulomatous lesions affecting the nasal cavity, upper respiratory tract, and skin. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited at high ER lumenal peptide concentrations. (Microbial infection) Inhibited by herpes simplex virus US12/ICP47 protein, which blocks the peptide-binding site of TAP1-TAP2. (Microbial infection) Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of TAP1-TAP2 complex and inhibits peptide translocation by specifically blocking ATP-binding and preventing TAP1-TAP2 conformational rearrangement induced by peptide binding.

Domain organisation. The peptide-binding site is shared between the cytoplasmic loops of TAP1 and TAP2. The nucleotide-binding domain (NBD) mediates ATP hydrolysis coupled to peptide translocation. Two ATP molecules are accommodated at distinct nucleotide binding sites (NBS) at TAP1-TAP2 dimer interface. Each NBS is formed by Walker A (GxxGxGKST) and Q-loop motifs from NBD of one subunit, while the NBD from the second subunit completes the active site by contributing the C loop motif (LSGGQ). Each ATP molecule is coordinated via the beta- and gamma-phosphates to a Mg2+ ion, which is necessary for ATP hydrolysis.

Induction. Up-regulated by IFNG. Down-regulated by IL10. (Microbial infection) Down-regulated by BCRF1/viral IL10.

Polymorphism. There are five common alleles; TAP101:01 (PSF1A), TAP102:01 (PSF1B), TAP103:01 (PSF1C), TAP101:04 and TAP1x. The sequence of TAP101:01 is shown here.

Similarity. Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q03518-1	1	yes
Q03518-2	2

RefSeq proteins (2): NP_000584, NP_001278951 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR011527	ABC1_TM_dom	Domain
IPR013305	ABC_Tap-like	Family
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR039421	Type_1_exporter	Family

Pfam: PF00005, PF00664

Enzyme classification (BRENDA):

• EC 7.4.2.14 — ABC-type antigen peptide transporter (BRENDA: 10 organisms, 90 substrates, 37 inhibitors, 4 Km, 0 kcat entries)
• EC 7.4.2.5 — bacterial ABC-type protein transporter (BRENDA: 33 organisms, 105 substrates, 44 inhibitors, 13 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.05–2.33	11
8-AZIDO-ATP	0.103	1
ATP	0.197	1
RRYNASTEL	0.0006	1
RRYQKSTEL	0.0002	1

Catalyzed reactions (Rhea), 1 shown:

• a peptide antigen(in) + ATP + H2O = a peptide antigen(out) + ADP + phosphate + H(+) (RHEA:65972)

UniProt features (85 total): helix 25, sequence variant 14, topological domain 11, strand 11, transmembrane region 10, binding site 4, domain 2, region of interest 2, mutagenesis site 2, chain 1, site 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
1JJ7	X-RAY DIFFRACTION	2.4
9O9D	ELECTRON MICROSCOPY	2.44
9RCV	ELECTRON MICROSCOPY	2.7
9OCJ	ELECTRON MICROSCOPY	3
9N63	ELECTRON MICROSCOPY	3.1
9O94	ELECTRON MICROSCOPY	3.1
9N66	ELECTRON MICROSCOPY	3.2
9OCH	ELECTRON MICROSCOPY	3.3
9OCI	ELECTRON MICROSCOPY	3.3
9N62	ELECTRON MICROSCOPY	3.4
8T4E	ELECTRON MICROSCOPY	3.5
8T4F	ELECTRON MICROSCOPY	3.5
8T4G	ELECTRON MICROSCOPY	3.5
8T46	ELECTRON MICROSCOPY	3.6
9N61	ELECTRON MICROSCOPY	3.6
9N64	ELECTRON MICROSCOPY	3.7
9N65	ELECTRON MICROSCOPY	3.7
8T4H	ELECTRON MICROSCOPY	3.8
9OCG	ELECTRON MICROSCOPY	3.8
8T4J	ELECTRON MICROSCOPY	3.9
5U1D	ELECTRON MICROSCOPY	3.97
8T4I	ELECTRON MICROSCOPY	5.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03518-F1	79.03	0.27

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 32 (inter-subunit salt bridge with tapbp)

Ligand- & substrate-binding residues (4): 538–546; 545; 641–647; 701

Mutagenesis-validated functional residues (2):

Position	Phenotype
32	complete loss of interaction with tapbp, resulting in impaired plc assembly and antigen presentation.
674	impairs allosteric coupling of peptide transport to atp hydrolysis, converting the unidirectional active pump into a pas

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 481 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, BENPORATH_ES_WITH_H3K27ME3, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, BROWNE_HCMV_INFECTION_12HR_UP, KEGG_ABC_TRANSPORTERS, HINATA_NFKB_TARGETS_KERATINOCYTE_UP, BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS, IRF7_01, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, RICKMAN_METASTASIS_DN

GO Biological Process (9): adaptive immune response (GO:0002250), defense response (GO:0006952), protein transport (GO:0015031), peptide transport (GO:0015833), antigen processing and presentation of endogenous peptide antigen via MHC class I (GO:0019885), cytosol to endoplasmic reticulum transport (GO:0046967), transmembrane transport (GO:0055085), immune system process (GO:0002376), peptide antigen assembly with MHC class I protein complex (GO:0002502)

GO Molecular Function (17): ATP binding (GO:0005524), ABC-type peptide antigen transporter activity (GO:0015433), ATP hydrolysis activity (GO:0016887), MHC class Ib protein binding (GO:0023029), MHC class I protein binding (GO:0042288), peptide antigen binding (GO:0042605), protein homodimerization activity (GO:0042803), ADP binding (GO:0043531), metal ion binding (GO:0046872), TAP1 binding (GO:0046978), TAP2 binding (GO:0046979), peptide transmembrane transporter activity (GO:1904680), nucleotide binding (GO:0000166), protein binding (GO:0005515), ABC-type peptide transporter activity (GO:0015440), MHC protein binding (GO:0042287), ABC-type transporter activity (GO:0140359)

GO Cellular Component (11): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), phagocytic vesicle membrane (GO:0030670), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), centriolar satellite (GO:0034451), MHC class I peptide loading complex (GO:0042824), TAP complex (GO:0042825), cytoplasm (GO:0005737), endomembrane system (GO:0012505), organelle membrane (GO:0031090)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	2
Antigen processing-Cross presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transport	3
antigen processing and presentation of peptide antigen via MHC class I	2
adenyl ribonucleotide binding	2
MHC protein binding	2
TAP binding	2
membrane protein complex	2
endoplasmic reticulum protein-containing complex	2
immune response	1
response to stress	1
intracellular protein localization	1
establishment of protein localization	1
antigen processing and presentation of endogenous peptide antigen	1
intercellular transport	1
intracellular transport	1
transmembrane transport	1
cellular process	1
biological_process	1
MHC class I protein complex assembly	1
peptide antigen assembly with MHC protein complex	1
purine ribonucleoside triphosphate binding	1
ABC-type peptide transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
antigen binding	1
peptide binding	1
identical protein binding	1
protein dimerization activity	1
anion binding	1
cation binding	1
transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
peptide transport	1
ABC-type transporter activity	1
peptide transmembrane transporter activity	1
signaling receptor binding	1
ATPase-coupled transmembrane transporter activity	1
cytoplasm	1

Protein interactions and networks

STRING

1748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAP1	TAP2	Q03519	987
TAP1	PSMB9	P28065	852
TAP1	PSMB8	P28062	834
TAP1	ADM2	Q7Z4H4	670
TAP1	TAPBP	O15533	640
TAP1	SRPRA	P08240	610
TAP1	HLA-DQB1	P01917	607
TAP1	B2M	P01884	532
TAP1	ABCF3	Q9NUQ8	526
TAP1	Q5Y7H0	Q5Y7H0	524
TAP1	LAMP2	P13473	511
TAP1	ABCD4	O14678	483
TAP1	HLA-B	P01889	479
TAP1	HLA-DOB	P13765	476
TAP1	LAMP1	P11279	473

IntAct

209 interactions, top by confidence:

A	B	Type	Score
TAP2	TAP1	psi-mi:“MI:0915”(physical association)	0.940
TAP1	TAP2	psi-mi:“MI:0407”(direct interaction)	0.940
BCL2	BCL2L11	psi-mi:“MI:0914”(association)	0.930
TAP1	TAPBP	psi-mi:“MI:0914”(association)	0.800
TAP1	TAPBP	psi-mi:“MI:0915”(physical association)	0.800
TAPBP	TAP1	psi-mi:“MI:0915”(physical association)	0.800
TAPBP	TAP1	psi-mi:“MI:0914”(association)	0.800
ARMC8	HTRA2	psi-mi:“MI:0914”(association)	0.750
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
TAP1	gN	psi-mi:“MI:0915”(physical association)	0.680
gN	TAP1	psi-mi:“MI:0915”(physical association)	0.680
TAP2	TAPBP	psi-mi:“MI:0914”(association)	0.680
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
TAP1		psi-mi:“MI:0403”(colocalization)	0.670
	TAP1	psi-mi:“MI:0915”(physical association)	0.670
TAP1		psi-mi:“MI:0915”(physical association)	0.670
TAP1	PDIA3	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (182): TAP1 (Affinity Capture-MS), KRTAP4-12 (Two-hybrid), TAP1 (Two-hybrid), TAP1 (Proximity Label-MS), TAP1 (Two-hybrid), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS), TAP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, B0BNF0, B0BNG2, B6CZ46, B6CZ56, C1BKZ7, F1RMN2, O88269, O95255, P86243, Q03518, Q28433, Q32L10, Q32LM8, Q3MHQ7, Q3T0W0, Q497J1, Q499P8, Q49LS7, Q4VV71, Q5KR61, Q5R8F6, Q5REM8, Q5T3U5, Q61672, Q6AZ83, Q6NVG1, Q6UW68, Q767L9, Q7TPN3, Q86VD9, Q8AVI9, Q8C0T0, Q8C3X8, Q8K0H7, Q8N2M4, Q8N661, Q8R1J1, Q8R4P9

Diamond homologs: A0A179H0T5, A0A1U8QG99, A0A3G9H9H1, A1B9K8, A1USS5, I1RF50, I1S2J9, K3VYH8, O06967, O07550, O52618, P08716, P0A2V0, P0A2V1, P10089, P18767, P21958, P22638, P23596, P23702, P23886, P26050, P29018, P36370, P40416, P44407, P63392, P63394, P70864, P77265, P9WER4, P9WQJ6, P9WQJ7, P9WQJ8, P9WQJ9, Q03024, Q03518, Q03519, Q080T2, Q0BFU0

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
IRF2	“up-regulates quantity by expression”	TAP1	“transcriptional regulation”
STAT1	“up-regulates quantity by expression”	TAP1	“transcriptional regulation”
regorafenib	“down-regulates activity”	TAP1	“chemical inhibition”
TAP1	“down-regulates quantity”	oligopeptide	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 179 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	8	29.7×	9e-08
ER-Phagosome pathway	9	11.0×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	8	9.7×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

475 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	3
Uncertain significance	204
Likely benign	190
Benign	12

Top pathogenic / likely-pathogenic (27)

Variant ID	HGVS	Classification
1074323	NM_000593.6(TAP1):c.1866_1879del (p.His622fs)	Pathogenic
13732	NM_000593.6(TAP1):c.599-1G>A	Pathogenic
1455001	NM_000593.6(TAP1):c.1005del (p.Pro336fs)	Pathogenic
2054486	NC_000006.12:g.32853728dup	Pathogenic
2096743	NM_000593.6(TAP1):c.335T>A (p.Leu112Ter)	Pathogenic
2419034	NM_000593.6(TAP1):c.934C>T (p.Arg312Ter)	Pathogenic
2572421	NM_000593.6(TAP1):c.884del (p.Leu295fs)	Pathogenic
2705098	NM_000593.6(TAP1):c.1217_1218del (p.Val406fs)	Pathogenic
2743049	NM_000593.6(TAP1):c.1789G>T (p.Glu597Ter)	Pathogenic
2780812	NM_000593.6(TAP1):c.676C>T (p.Arg226Ter)	Pathogenic
2792573	NM_000593.6(TAP1):c.1738C>T (p.Gln580Ter)	Pathogenic
2796271	NM_000593.6(TAP1):c.1699A>T (p.Lys567Ter)	Pathogenic
2848869	NM_000593.6(TAP1):c.1813C>T (p.Gln605Ter)	Pathogenic
3648549	NM_000593.6(TAP1):c.1845_1858dup (p.Gly620delinsValGlnTer)	Pathogenic
3656608	NM_000593.6(TAP1):c.1047C>A (p.Tyr349Ter)	Pathogenic
3657001	NM_000593.6(TAP1):c.195G>A (p.Trp65Ter)	Pathogenic
3673432	NM_000593.6(TAP1):c.1945C>T (p.Gln649Ter)	Pathogenic
3727231	NM_000593.6(TAP1):c.1679dup (p.Gln561fs)	Pathogenic
4706862	NM_000593.6(TAP1):c.366_372del (p.Gly123fs)	Pathogenic
4712019	NM_000593.6(TAP1):c.268del (p.Gln90fs)	Pathogenic
4731139	NM_000593.6(TAP1):c.924G>A (p.Trp308Ter)	Pathogenic
642101	NM_000593.6(TAP1):c.971C>G (p.Ser324Ter)	Pathogenic
839821	NM_000593.6(TAP1):c.1564C>T (p.Gln522Ter)	Pathogenic
937533	NM_000593.6(TAP1):c.1132C>T (p.Arg378Ter)	Pathogenic
2778172	NM_000593.6(TAP1):c.1740+2T>C	Likely pathogenic
4755454	NM_000593.6(TAP1):c.1997del (p.Leu666fs)	Likely pathogenic
4796687	NM_000593.6(TAP1):c.1963C>T (p.Arg655Ter)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

5133 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32849026:A:C	F507L	0.969
6:32849026:A:T	F507L	0.969
6:32849028:A:G	F507L	0.969
6:32852128:A:C	F335L	0.966
6:32852128:A:T	F335L	0.966
6:32852130:A:G	F335L	0.966
6:32848688:A:C	F570L	0.961
6:32848688:A:T	F570L	0.961
6:32848690:A:G	F570L	0.961
6:32852239:A:C	S298R	0.960
6:32852239:A:T	S298R	0.960
6:32852389:T:G	S298R	0.960
6:32849033:A:T	V505D	0.959
6:32850438:A:T	V437D	0.959
6:32850428:A:C	F440L	0.949
6:32850428:A:T	F440L	0.949
6:32850430:A:G	F440L	0.949
6:32849024:A:T	V508D	0.947
6:32850398:A:C	F450L	0.947
6:32850398:A:T	F450L	0.947
6:32850400:A:G	F450L	0.947
6:32849036:A:T	L504H	0.934
6:32850435:C:G	R438P	0.932
6:32850355:C:G	A465P	0.927
6:32852487:G:T	P265Q	0.926
6:32851057:C:G	G373R	0.925
6:32849036:A:G	L504P	0.924
6:32852475:C:T	G269D	0.919
6:32849087:A:T	L487H	0.915
6:32852487:G:C	P265R	0.915

dbSNP variants (sampled 300 via entrez): RS1000072525 (6:32855413 T>C), RS1000709566 (6:32853996 G>T), RS1001073856 (6:32853755 G>A), RS1001339551 (6:32854447 G>A,T), RS1001542046 (6:32850675 C>T), RS1001590779 (6:32848567 G>A,T), RS1001653737 (6:32844953 A>G), RS1002664055 (6:32846935 A>G), RS1003272544 (6:32846099 A>C), RS1003289311 (6:32846364 A>G), RS1003907769 (6:32845882 G>A,C), RS1004105767 (6:32849651 T>C), RS1004640079 (6:32854169 T>C), RS1005094831 (6:32853817 T>C), RS1005398881 (6:32850645 C>G)

Disease associations

OMIM: gene MIM:170260 | disease phenotypes: MIM:604571

GenCC curated gene-disease

Disease	Classification	Inheritance
MHC class I deficiency	Definitive	Autosomal recessive
MHC class I deficiency 1	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
MHC class I deficiency	Definitive	AR

Mondo (2): MHC class I deficiency (MONDO:0011476), MHC class I deficiency 1 (MONDO:0971006)

Orphanet (1): Immunodeficiency by defective expression of MHC class I (Orphanet:34592)

HPO phenotypes

10 total (10 of 10 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000389	Chronic otitis media
HP:0001083	Ectopia lentis
HP:0002097	Emphysema
HP:0002110	Bronchiectasis
HP:0002837	Recurrent bronchitis
HP:0011109	Chronic sinusitis
HP:0011950	Bronchiolitis
HP:0100582	Nasal polyposis
HP:0200042	Skin ulcer

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001009_2	Nephropathy	2.000000e-12
GCST002655_18	IgA nephropathy	2.000000e-09
GCST004521_126	Autism spectrum disorder or schizophrenia	2.000000e-10
GCST004521_150	Autism spectrum disorder or schizophrenia	2.000000e-08
GCST004521_170	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_296	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_81	Autism spectrum disorder or schizophrenia	1.000000e-14
GCST008916_27	Asthma	5.000000e-31
GCST008916_90	Asthma	4.000000e-15
GCST009391_149	Metabolite levels	3.000000e-06
GCST012227_935	Hip circumference adjusted for BMI	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010476	dimethylglycine measurement
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4523275 (SINGLE PROTEIN), CHEMBL4523654 (PROTEIN COMPLEX)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — ABCB subfamily

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.20	Kd	63.85	nM	CHEMBL3752910
7.20	ED50	63.85	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149544: Binding affinity to human TAP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0639	uM

CTD chemical–gene interactions

86 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, increases expression	6
Aflatoxin B1	increases expression, affects expression, affects cotreatment	6
Benzo(a)pyrene	increases expression	5
Tretinoin	increases expression	4
Valproic Acid	affects expression, increases expression	3
Camptothecin	increases expression	2
Dactinomycin	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Etoposide	increases expression	2
Fluorouracil	increases expression, increases reaction	2
Methyl Methanesulfonate	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
2,2,2-trichloroethanol	affects cotreatment, increases expression, decreases reaction	1
deoxynivalenol	decreases expression	1
perfosfamide	affects response to substance	1
sulforaphane	increases expression	1
2-tert-butylhydroquinone	increases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases expression, decreases reaction, increases expression	1
perfluorooctanoic acid	decreases expression	1
aflatoxin G1	decreases expression	1
nickel sulfate	increases expression	1
andrographolide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
celastrol	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4341444	Binding	Binding affinity to TAP1 in human A549 cells lysates grown on SILAC media at 10 uM incubated for 1 hr by LC-MS/MS analysis relative to untreated control	Profiling withanolide A for therapeutic targets in neurodegenerative diseases. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 3 transformed cell line, 2 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A282	BRE-169	Transformed cell line	Male
CVCL_A5NF	BRE	Finite cell line	Male
CVCL_DP24	TND-3	Transformed cell line	Female
CVCL_DP25	TND-4	Transformed cell line	Male
CVCL_E2LG	HAP1 TAP1 (-) 1	Cancer cell line	Male
CVCL_E2LH	HAP1 TAP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.