TAPBP

Summary

TAPBP (TAP binding protein, HGNC:11566) is a protein-coding gene on chromosome 6p21.32, encoding Tapasin (O15533). Involved in the association of MHC class I with transporter associated with antigen processing (TAP) and in the assembly of MHC class I with peptide (peptide loading).

This gene encodes a transmembrane glycoprotein which mediates interaction between newly assembled major histocompatibility complex (MHC) class I molecules and the transporter associated with antigen processing (TAP), which is required for the transport of antigenic peptides across the endoplasmic reticulum membrane. This interaction is essential for optimal peptide loading on the MHC class I molecule. Up to four complexes of MHC class I and this protein may be bound to a single TAP molecule. This protein contains a C-terminal double-lysine motif (KKKAE) known to maintain membrane proteins in the endoplasmic reticulum. This gene lies within the major histocompatibility complex on chromosome 6. Alternative splicing results in three transcript variants encoding different isoforms.

Source: NCBI Gene 6892 — RefSeq curated summary.

At a glance

• Gene–disease (curated): MHC class I deficiency (Moderate, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 396 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_003190

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11566
Approved symbol	TAPBP
Name	TAP binding protein
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	TAPA, TPN, TPSN, NGS17
Ensembl gene	ENSG00000231925
Ensembl biotype	protein_coding
OMIM	601962
Entrez	6892

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 15 protein_coding, 11 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000426633, ENST00000434618, ENST00000437116, ENST00000467025, ENST00000475304, ENST00000476333, ENST00000480730, ENST00000489157, ENST00000699647, ENST00000699648, ENST00000699649, ENST00000699650, ENST00000699651, ENST00000699652, ENST00000699653, ENST00000699654, ENST00000699655, ENST00000699656, ENST00000699657, ENST00000699658, ENST00000699659, ENST00000699660, ENST00000699661, ENST00000699662, ENST00000699663, ENST00000699664, ENST00000910118, ENST00000925535, ENST00000948440

RefSeq mRNA: 4 — MANE Select: NM_003190 NM_001410875, NM_003190, NM_172208, NM_172209

CCDS: CCDS34426, CCDS34427, CCDS34428, CCDS93889

Canonical transcript exons

ENST00000374572 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 98.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 107.3720 / max 1302.3162, expressed in 1826 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73141	75.1223	1814
73145	11.3641	1777
73144	7.2372	1694
73136	2.6358	495
73143	2.4228	1247
73135	1.9754	373
73139	1.7705	1050
73140	1.1536	773
73127	0.9311	410
73147	0.9061	456

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	98.12	gold quality
granulocyte	CL:0000094	98.03	gold quality
blood	UBERON:0000178	97.87	gold quality
spleen	UBERON:0002106	97.73	gold quality
leukocyte	CL:0000738	97.06	gold quality
mucosa of transverse colon	UBERON:0004991	96.99	gold quality
monocyte	CL:0000576	96.96	gold quality
vermiform appendix	UBERON:0001154	96.66	gold quality
lymph node	UBERON:0000029	96.64	gold quality
colonic epithelium	UBERON:0000397	96.50	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.45	gold quality
small intestine	UBERON:0002108	96.44	gold quality
right adrenal gland	UBERON:0001233	96.40	gold quality
right adrenal gland cortex	UBERON:0035827	96.39	gold quality
left adrenal gland cortex	UBERON:0035825	96.35	gold quality
left adrenal gland	UBERON:0001234	96.31	gold quality
right uterine tube	UBERON:0001302	96.31	gold quality
duodenum	UBERON:0002114	96.28	gold quality
upper lobe of left lung	UBERON:0008952	96.10	gold quality
tonsil	UBERON:0002372	95.95	gold quality
metanephros cortex	UBERON:0010533	95.93	gold quality
transverse colon	UBERON:0001157	95.79	gold quality
right lobe of liver	UBERON:0001114	95.76	gold quality
apex of heart	UBERON:0002098	95.75	gold quality
liver	UBERON:0002107	95.52	gold quality
right lung	UBERON:0002167	95.52	gold quality
minor salivary gland	UBERON:0001830	95.51	gold quality
bone marrow	UBERON:0002371	95.51	gold quality
saliva-secreting gland	UBERON:0001044	95.50	gold quality
adrenal gland	UBERON:0002369	95.50	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.69
E-MTAB-10137	no	184.08

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
TAP1	Unknown
TAP2	Unknown

Upstream regulators (CollecTRI, top): E2F1, EP300, IRF1, NFKB1, NFKB, RELA

Literature-anchored findings (GeneRIF, showing 40)

• recruits MHC class I molecules to TAP complex during antigen processing (PMID:11823531)
• tapasin is a modified Mhc class I molecule (PMID:11862402)
• MHC class I molecules can optimize their peptide repertoire over time and that this process is dependent on tapasin. (PMID:11970875)
• tapasin is not required for calreticulin to bind to the alpha1 domain of MHC class I molecules (PMID:11972874)
• results suggest that tapasin deficiency is another cause of type I bare lymphocyte syndrome (PMID:12149238)
• Tapasin enhances the structural stability of TAP1.TAP2 complexes. (PMID:12213826)
• The domain organization of tapasin is an assembly of two core regions of different sizes loosely connected by a linker or loop comprising residues ~85-93. (PMID:12463753)
• tapasin has a essential function of tapasin in quality control of HLA-G molecules (PMID:12582157)
• A major role for tapasin as a stabilizer of the TAP peptide transporter and consequences for MHC class I expression. (PMID:12594855)
• Downregulation of tapasin in advanced stages of human melanoma may reflect accumulation of alterations in antigen-presenting/processing machinery associated with neoplastic progression. May contribute to immune escape phenotype of human melanoma cells. (PMID:12682852)
• The ERp57-tapasin conjugate can also be modified with the oxidizing agent diamide, indicating that within the pool of ERp57-tapasin complexes the free, non-tapasin-linked CXXC motif exists in both oxidized and reduced states (PMID:13678524)
• Defects in tapasin and HLA class I antigen expression in primary maxillary sinus SCC lesions may play a role in the clinical course of the maxillary sinus cancer, because these defects were associated with poor prognosis. (PMID:14519625)
• In its role as peptide facilitator, tapasin stabilizes the peptide-free conformation of class I major histocompatibility (MHC) complex molecules in the endoplasmic reticulum and thus increases the number and variety of peptides bound to class I MHC. (PMID:14607930)
• Mutational analysis of tapasin provides insight into aspects of tapasin structure that are crucial to its ability to assist major histocompatibility complex class I assembly. (PMID:14978101)
• Transfection of tapasin into the Panc02 cells did not quantitatively increase MHC class I surface expression or detectably affect MHC class I association with tumor-specific peptides and beta(2)-microglubulin (beta(2)m). (PMID:15163903)
• Defective tapasin transcription and thus absence of HLA-B44 expression is associateed with colorectal tumors. (PMID:15455354)
• Substitutions at position lysine-408 in tapasin are shown to affect the expression of major histocompatibility complex class I molecules at the cell surface, by down-regulating tapasin stabilization of TAP. (PMID:15634919)
• Tapasin association specifically inhibits the escape pathway required for disulfide-bond isomerization within conventional protein substrates, suggesting a specific structural role for ERp57 within the MHC class I peptide-loading complex. (PMID:16193070)
• Down-regulation of tapasin expression was associated with glioblastoma multiforme (PMID:16322289)
• Besides beta(2)m and tapasin, an extra unidentified component is also critical for the expression of certain human class I alleles. (PMID:17498802)
• A ternary complex between heavy chain, ERp57, and tapasin was observed and shown to be stabilized by a disulfide between both tapasinheavy chain and tapasin-ERp57. (PMID:18039656)
• Transgenic tapasin establishes hierarchical responses in vivo according to peptide-major histocompatibility complex class I stability. (PMID:18196518)
• In this review, interaction of accessory protein tapasin with HLA-DM crucially influences the selection of peptides that bind to major histocompatibility complex (MHC) molecules during antigen presentation. (PMID:18261958)
• These data reveal a novel “feed-forward” mechanism induced by NF-kappaB which ensures that acutely synthesized IRF-1 operates in concert with NF-kappaB to amplify the immunoproteasome and antigen-processing functions of CD40. (PMID:18694960)
• the 2.6 A resolution structure of the tapasin-ERp57 core of the peptide-loading complex (PMID:19119025)
• HLA-B27 polymorphism drives the tapasin dependency, rates of intracellular maturation and expressions of homodimers. (PMID:19167761)
• tapasin conjugation with ERp57 is as critical as its integration into the membrane for efficient MHC class I assembly, surface expression, and Ag presentation to CD8+ T cells. (PMID:19701894)
• The N-terminal region of Tapasin (Tpn) can be recombinantly expressed and adopt a structure, which at least partially resembles that of wild-type Tpn. This region of Tpn features chaperone activity facilitating peptide binding of MHC-I. (PMID:19728311)
• find that in a competitive situation between high- and low-affinity peptides, tapasin mediates the binding of the high-affinity peptide to class I by accelerating the dissociation of the peptide from an unstable intermediate of the binding reaction. (PMID:20017190)
• The interactions of tapasin with both TAP and ERp57 are correlated with strong MHC class I recruitment and assembly enhancement. (PMID:20070606)
• Downregulation of tapasin is associated with a poor clinical outcome for oral squamous cell carcinoma patients and may serve as a prognostic biomarker (PMID:20532727)
• On infection with human cytomegalovirus tapasin mRNA levels were continuously downregulated during infection, while tapasin transcripts remained stable and long-lived. (PMID:21248040)
• Tapasin discriminates peptide-human leukocyte antigen-A*02:01 complexes formed with natural ligands. (PMID:21518758)
• Data indicate that the peptide-loading complex (PLC) consists maximally of 2x tapasin-ERp57/MHC I per TAP complex, but one tapasin-ERp57/MHC I in the PLC is essential and sufficient for antigen processing. (PMID:22923333)
• isoform lacking exon 3 affects MHC class I-peptide binding (PMID:23519916)
• Modified TAPBP gene function may contribute to the development of refractory chronic rhinosinusitis via reduction of circulating CD8 lymphocytes. (PMID:23640800)
• TAPBP polymorphisms may play a role in the development of aspirin-exacerbated respiratory disease. (PMID:23736108)
• Targeted re-sequencing identified rs3106189 at the 5’ UTR of TAPBP and rs1052918 at the 3’ UTR of TCF3 to be associated with the overall survival of colorectal cancer patients. (PMID:23940558)
• the data indicate that TAPBPR and tapasin bind in a similar orientation to the same face of MHC class I. (PMID:24163410)
• Analysis of expression of tapasin and/or HLA-I may be of value as prognostic tool for glioblastoma multiforme patients, especially when considering immunotherapy. (PMID:25175688)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tapbp.2	ENSDARG00000045011
danio_rerio	tapbp.1	ENSDARG00000079402
mus_musculus	Tapbp	ENSMUSG00000024308
rattus_norvegicus	Tapbp	ENSRNOG00000029500

Paralogs (2): TAPBPL (ENSG00000139192), NCR3LG1 (ENSG00000188211)

Protein

Protein identifiers

Tapasin — O15533 (reviewed: O15533)

Alternative names: NGS-17, TAP-associated protein, TAP-binding protein

All UniProt accessions (13): O15533, A0A024RCT1, A0A0A0MSV9, A0A0A0MT98, A0A8V8TNS3, A0A8V8TP19, A0A8V8TP24, A0A8V8TPY1, A0A8V8TPY6, A0A8V8TQC1, A0A8V8TQC5, A2AB90, C9JA35

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the association of MHC class I with transporter associated with antigen processing (TAP) and in the assembly of MHC class I with peptide (peptide loading).

Subunit / interactions. Heterodimer with PDIA3; disulfide-linked. Obligatory mediator for the interaction between newly assembled MHC class I molecules, calreticulin, PDIA3 and TAP. Up to 4 MHC class I/tapasin complexes bind to 1 TAP. Interacts with HLA-G-B2M complex; this interaction is required for loading of high affinity peptides. On its own or as part of MHC class I peptide loading complex, interacts with ligand-free MR1 or MR1-B2M complex, providing for stable MR1 pools ready for metabolite antigen processing.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Neutrophils, mostly in fully differentiated cells.

Disease relevance. MHC class I deficiency 3 (MHC1D3) [MIM:620814] An autosomal recessive disorder characterized by glomerulonephritis and markedly reduced cell surface expression of class I HLA antigens. Additional features are herpes zoster infection and polyps of the stomach and colon. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminus is required for efficient association with MHC class I molecule and for a stable interaction between MHC I and calreticulin. Binding to TAP is mediated by the C-terminal region.

Polymorphism. The 2 alleles of TAPBP; TAPBP01 (Tapasin01) (shown here) and TAPBP02 (Tapasin02); are in linkage disequilibria with the HLA-DRB1 locus in a Japanese population.

Miscellaneous. Due to a partial intron retention.

Isoforms (4)

UniProt ID	Names	Canonical?
O15533-1	1	yes
O15533-2	2
O15533-3	3
O15533-4	4, tpsnDeltaEx3

RefSeq proteins (4): NP_001397804, NP_003181, NP_757345, NP_757346 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003597	Ig_C1-set	Domain
IPR007110	Ig-like_dom	Domain
IPR008056	Tapasin	Family
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050380	Immune_Resp_Modulators	Family

Pfam: PF07654

UniProt features (65 total): strand 29, mutagenesis site 8, helix 7, disulfide bond 3, splice variant 3, sequence conflict 3, topological domain 2, turn 2, site 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, domain 1, glycosylation site 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
3F8U	X-RAY DIFFRACTION	2.6
7QNG	X-RAY DIFFRACTION	2.7
9RCV	ELECTRON MICROSCOPY	2.7
7TUF	X-RAY DIFFRACTION	2.8
7TUE	X-RAY DIFFRACTION	3.1
7QPD	ELECTRON MICROSCOPY	3.73
7TUG	X-RAY DIFFRACTION	3.9
6ENY	ELECTRON MICROSCOPY	5.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15533-F1	87.71	0.66

Antibody-complex structures (SAbDab): 2 — 7TUF, 7TUG

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 (2): 428 (inter-subunit salt bridge with tap1-tap2. essential peptide loading complex assembly); 428 (may be involved in interaction with tap)

Disulfide bonds (3): 115, 315–382, 27–91

Glycosylation sites (1): 253

Mutagenesis-validated functional residues (8):

Position	Phenotype
115	abolishes the recruitment of pdia3, calr and b2m to the peptide-loading complex.
205	decreases cell surface expression of mr1-metabolite antigen complex; when associated with e-207, s-209 and s-281.
207	decreases cell surface expression of mr1-metabolite antigen complex; when associated with e-205, s-209 and s-281.
209	decreases cell surface expression of mr1-metabolite antigen complex; when associated with e-205, s-207 and s-281.
253	reduces the recruitment of pdia3 to tap1-tap2 transporter.
270	decreases cell surface expression of mr1-metabolite antigen complex.
281	decreases cell surface expression of mr1-metabolite antigen complex; when associated with e-205, s-207 and s-209.
428	restores interaction with tap1-tap2; when associated with tap1 k-92 or tap2 k-16.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1236974	ER-Phagosome pathway
R-HSA-983170	Antigen Presentation: Folding, assembly and peptide loading of class I MHC

MSigDB gene sets: 316 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, WANG_CLIM2_TARGETS_UP, MORF_RAB5A, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_ANTIGEN_PRESENTATION_FOLDING_ASSEMBLY_AND_PEPTIDE_LOADING_OF_CLASS_I_MHC, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_ANTIGEN, WIELAND_UP_BY_HBV_INFECTION, GOBP_PEPTIDE_METABOLIC_PROCESS, IRF7_01, GOBP_PROTEIN_MATURATION, ONKEN_UVEAL_MELANOMA_UP, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION

GO Biological Process (11): MHC class Ib protein complex assembly (GO:0002398), antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent (GO:0002479), peptide antigen assembly with MHC class I protein complex (GO:0002502), retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum (GO:0006890), regulation of gene expression (GO:0010468), antigen processing and presentation of endogenous peptide antigen via MHC class I (GO:0019885), peptide antigen stabilization (GO:0050823), regulation of protein complex stability (GO:0061635), protein-containing complex assembly (GO:0065003), antigen processing and presentation of peptide antigen via MHC class I (GO:0002474), protein folding (GO:0006457)

GO Molecular Function (10): MHC class I protein complex binding (GO:0023024), MHC class I protein binding (GO:0042288), peptide antigen binding (GO:0042605), protein folding chaperone (GO:0044183), TAP1 binding (GO:0046978), TAP2 binding (GO:0046979), obsolete unfolded protein binding (GO:0051082), molecular adaptor activity (GO:0060090), TAP complex binding (GO:0062061), protein binding (GO:0005515)

GO Cellular Component (10): Golgi membrane (GO:0000139), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), phagocytic vesicle membrane (GO:0030670), endoplasmic reticulum-Golgi intermediate compartment membrane (GO:0033116), MHC class I peptide loading complex (GO:0042824), Tapasin-ERp57 complex (GO:0061779), lumenal side of endoplasmic reticulum membrane (GO:0098553), endomembrane system (GO:0012505), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Antigen processing-Cross presentation	1
Class I MHC mediated antigen processing & presentation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
antigen processing and presentation of peptide antigen via MHC class I	2
antigen processing and presentation of peptide antigen	2
molecular_function	2
TAP binding	2
binding	2
bounding membrane of organelle	2
endoplasmic reticulum membrane	2
membrane protein complex	2
endoplasmic reticulum protein-containing complex	2
cellular anatomical structure	2
MHC protein complex assembly	1
antigen processing and presentation of exogenous peptide antigen via MHC class I	1
MHC class I protein complex assembly	1
peptide antigen assembly with MHC protein complex	1
Golgi vesicle transport	1
gene expression	1
regulation of macromolecule biosynthetic process	1
antigen processing and presentation of endogenous peptide antigen	1
peptide stabilization	1
regulation of biological quality	1
cellular component assembly	1
protein-containing complex organization	1
cellular process	1
protein maturation	1
MHC protein complex binding	1
MHC protein binding	1
antigen binding	1
peptide binding	1
protein folding	1
protein-containing complex binding	1
Golgi apparatus	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
endocytic vesicle membrane	1
phagocytic vesicle	1
endoplasmic reticulum-Golgi intermediate compartment	1

Protein interactions and networks

STRING

2046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TAPBP	CALR	P27797	998
TAPBP	PDIA3	P30101	997
TAPBP	CANX	P27824	993
TAPBP	B2M	P01884	992
TAPBP	ZBTB22	O15209	884
TAPBP	PSMB8	P28062	855
TAPBP	WDR46	O15213	851
TAPBP	PSMB9	P28065	846
TAPBP	ERAP1	Q9NZ08	809
TAPBP	HLA-B	P01889	802
TAPBP	PSMB10	P40306	794
TAPBP	HLA-C	P04222	786
TAPBP	RGL2	O15211	776
TAPBP	KIFC1	Q9BW19	751
TAPBP	PFDN6	O15212	708

IntAct

115 interactions, top by confidence:

A	B	Type	Score
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
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
TAPBP	HLA-A	psi-mi:“MI:0915”(physical association)	0.690
HLA-A	TAPBP	psi-mi:“MI:0915”(physical association)	0.690
HLA-A	TAPBP	psi-mi:“MI:0914”(association)	0.690
TAPBP	TAP2	psi-mi:“MI:0915”(physical association)	0.680
TAP2	TAPBP	psi-mi:“MI:0914”(association)	0.680
	TAPBP	psi-mi:“MI:0915”(physical association)	0.620

BioGRID (92): TAPBP (Affinity Capture-RNA), TAPBP (Affinity Capture-RNA), TAPBP (Affinity Capture-MS), TAPBP (Reconstituted Complex), TAPBP (Affinity Capture-Western), TAPBP (Affinity Capture-Western), TAPBP (Affinity Capture-Western), TAPBP (Affinity Capture-MS), TAPBP (Affinity Capture-MS), TAPBP (Affinity Capture-MS), TAPBP (Affinity Capture-MS), CALR (Proximity Label-MS), TAPBP (Proximity Label-MS), TAPBP (Affinity Capture-MS), TAPBP (Affinity Capture-Western)

ESM2 similar proteins: A0A140LHF2, A0EQL2, D3YZF7, D7PDD4, O15533, O55237, O70394, O70540, O95866, P04278, P05111, P07994, P08689, P0C6B3, P0DP72, P15196, P17490, P18627, P40238, P55101, P60882, P97497, Q00657, Q08351, Q14393, Q14773, Q16671, Q3SWY4, Q5BK54, Q5NKT8, Q5TJE4, Q61790, Q61826, Q62588, Q6PZD2, Q6UVK1, Q6UWB1, Q7Z7M0, Q7Z7M1, Q86VR7

Diamond homologs: O15533, O73895, Q5R8H1, Q5TJE4, Q6PZD2, Q8VD31, Q9BX59, Q9R233, A2AJ76, P01889, P01893, P01894, P01898, P01901, P01902, P03991, P04223, P04439, P06140, P06339, P10321, P13747, P13748, P13749, P13750, P13751, P14427, P14428, P14429, P14430, P15978, P16209, P16210, P16211, P16215, P16391, P17693, P18466, P28068, P30375

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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	52.5×	4e-10
ER-Phagosome pathway	8	17.3×	2e-06
Interferon gamma signaling	7	14.6×	3e-05
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	10.2×	2e-04
Neutrophil degranulation	11	4.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptide antigen assembly with MHC class II protein complex	5	69.3×	2e-06
antigen processing and presentation of exogenous peptide antigen via MHC class II	5	35.8×	4e-05
positive regulation of T cell mediated cytotoxicity	5	33.6×	4e-05
positive regulation of immune response	5	31.7×	5e-05
positive regulation of T cell activation	5	29.2×	6e-05
transmembrane transport	5	11.1×	3e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	7	10.4×	3e-04
adaptive immune response	8	8.9×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	228
Likely benign	128
Benign	14

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
7606	NM_003190.5(TAPBP):c.469+3326_1336-732del	Pathogenic
4845722	NM_003190.5(TAPBP):c.948del (p.Val317fs)	Likely pathogenic

SpliceAI

834 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33305385:CCA:C	acceptor_gain	1.0000
6:33305386:CAC:C	acceptor_gain	1.0000
6:33305388:C:CC	acceptor_gain	1.0000
6:33313955:C:A	donor_gain	1.0000
6:33313965:C:A	donor_gain	1.0000
6:33304987:A:AC	donor_gain	0.9900
6:33304988:C:CC	donor_gain	0.9900
6:33305383:TACCA:T	acceptor_gain	0.9900
6:33305384:ACCA:A	acceptor_gain	0.9900
6:33305385:CCAC:C	acceptor_gain	0.9900
6:33305387:AC:A	acceptor_loss	0.9900
6:33305388:C:CG	acceptor_loss	0.9900
6:33305399:A:T	acceptor_gain	0.9900
6:33305424:A:C	acceptor_gain	0.9900
6:33313687:GACT:G	donor_loss	0.9900
6:33313688:ACTC:A	donor_loss	0.9900
6:33313689:CT:C	donor_loss	0.9900
6:33313690:TCAC:T	donor_loss	0.9900
6:33313691:CACC:C	donor_loss	0.9900
6:33313692:A:C	donor_loss	0.9900
6:33313693:C:CT	donor_loss	0.9900
6:33313964:T:TA	donor_gain	0.9900
6:33314038:T:TA	donor_gain	0.9900
6:33314054:T:TA	donor_gain	0.9900
6:33303987:CAG:C	acceptor_gain	0.9800
6:33304988:CTGTA:C	donor_gain	0.9800
6:33305386:CA:C	acceptor_gain	0.9800
6:33305398:C:CT	acceptor_gain	0.9800
6:33305405:A:C	acceptor_gain	0.9800
6:33305413:T:TC	acceptor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000566047 (6:33301891 A>G), RS1000694617 (6:33308557 A>G), RS1000726351 (6:33300253 A>G), RS1000999105 (6:33301233 C>G), RS1001638786 (6:33306240 C>T), RS1001907055 (6:33308063 A>C), RS1001939308 (6:33307684 G>A), RS1002067359 (6:33306612 C>T), RS1002103424 (6:33300013 G>A), RS1002171692 (6:33300908 G>A), RS1002581155 (6:33312653 A>G), RS1002641687 (6:33312472 C>T), RS1002644640 (6:33304709 G>C,T), RS1002782828 (6:33311716 T>C), RS1003079429 (6:33312069 A>G)

Disease associations

OMIM: gene MIM:601962 | disease phenotypes: MIM:604571, MIM:620814

GenCC curated gene-disease

Disease	Classification	Inheritance
MHC class I deficiency 1	Moderate	Autosomal recessive
MHC class I deficiency	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
MHC class I deficiency	Moderate	AR

Mondo (3): MHC class I deficiency (MONDO:0011476), MHC class I deficiency 1 (MONDO:0971006), MHC class I deficiency 3 (MONDO:0971012)

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

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000099	Glomerulonephritis
HP:0002205	Recurrent respiratory infections
HP:0003596	Middle age onset
HP:0032275	Recurrent shingles

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004521_251	Autism spectrum disorder or schizophrenia	6.000000e-12
GCST004521_287	Autism spectrum disorder or schizophrenia	5.000000e-08
GCST006585_1887	Blood protein levels	3.000000e-96

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1059288	Toxicity	3	aspirin	Asthma
rs2071888	Toxicity	3	aspirin	Asthma

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1059288	RGL2, TAPBP	3	3.00	1	aspirin
rs2071888	TAPBP	3	3.00	1	aspirin
rs3130100	TAPBP, ZBTB22	3	3.00	1	aspirin

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	4
Nickel	increases expression	3
Valproic Acid	affects expression, decreases expression	3
bisphenol A	increases expression, affects cotreatment, decreases methylation	2
Arsenic	decreases expression, increases abundance, increases expression, affects methylation, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Doxorubicin	decreases expression, affects response to substance	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
obeticholic acid	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
pyrachlostrobin	decreases expression	1
gardiquimod	increases expression, decreases reaction	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
Zoledronic Acid	increases expression	1
Vinorelbine	affects response to substance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7ZS	Abcam Raji TAPBP KO	Cancer cell line	Male
CVCL_C0AK	Abcam THP-1 TAPBP KO	Cancer cell line	Male
CVCL_C7C8	Abcam PC-3 TAPBP KO	Cancer cell line	Male

Clinical trials (associated diseases)

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