TAPBP

protein-coding

TAP binding protein, the group of C1-set domain containing

Gene summary

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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003190.5

Inheritance

ClinVar variants

P:3U:233B:113

Top phenotype

MHC class I deficiency 3

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr6:33,299,694-33,314,284

External References & Databases

Ensembl (ENSG00000231925)

Transcript & Mutation Effects

hg38 • Region Span ~14.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

MHC class I deficiency 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0971006

Submitter: PanelApp Australia

MHC class I deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0011476

Submitter: Ambry Genetics

MHC class I deficiencyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0011476

Submitter: Labcorp Genetics (formerly Invitae)

MHC class I deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011476

Submitter: Orphanet

MHC class I deficiencyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011476

Submitter: ClinGen

A TAPBP germline loss of function variant was first identified in a woman with type I bare lymphocyte syndrome (BLS) (PMID: 12149238), the only report of a germline TAPBP variant. Other somatic TAPBP variants have been identified in cancers. Autosomal recessive TAPBP deficiency was associated with reduction of class I MHC expression and reductions in CD8 T cell and NK cell numbers in peripheral blood. Herpes zoster infection was noted in this adult patient, but no other immune deficiency was noted. This phenotype contrasts with type I BLS due to biallelic loss of function variants in TAP1, where patients show respiratory inflammation and skin ulcers. The indel variant identified in the single patient resulted in the loss of exon 4-7 of TAPBP, resulting in loss of expression of the protein and loss of function. Heterozygous carriers have not been reported in the literature. TAPBP plays a critical role in the peptide loading and resultant stable expression of cell surface MHC class I. In vitro data show that TAPBP is found in a complex with TAP1, TAP2, MHC, ERp57, and calreticulin, and is required for expression of class I MHC on the surface of cell lines (PMID: 9271576). Studies of cancer cell lines have found that variants in TAPBP reduce the expression of MHC class I on the surface of cells, potentially as a mechanism of immune evasion (PMID: 26381407). Class I MHC expression in these cell lines can be rescued with the transfection of WT TAPBP (PMID: 26381407). TAPBP knockout mice recapitulate the phenotype seen in the reported patient, with loss of stable class I MHC expression and reduced CD8 T cells (PMID:10973281, 12594855). TAPBP KO mice also show alterations in NK cell function and the ability of dendritic cells to cross-present antigens (PMID:10973281). TAPBP heterozygous KO mice show normal expression of MHC I (PMID: 10973281). While there is no evidence against the gene-disease relationship of TAPBP and type I BLS, there was only one patient identified that supports the relationship. Based on this,TAPBP has limited association with type I bare lymphocyte deficiency. This classification was originally approved by the ClinGen SCID-CID GCEP on 10/20/2022 (SOP Version 9). It was re-evaluated on June 19th, 2025 with no additional cases identified. Therefore, there is no change in this gene disease relationship.

Clinical Genomic Database (CGD)

MHC class I deficiency 3AR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Although the described individual did not have the same types of infections as other individuals with TAP deficiency, antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial

Refs: 10074495; 12149238

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TAPBP variants in ClinVar

7 Conditions Cataloged

MHC class I deficiencyTotal: 350

not specifiedTotal: 70

not providedTotal: 12

TAPBP-related disorderTotal: 11

MHC class I deficiency 1Total: 3

MHC class I deficiency 3Total: 2

Kartagener syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003190.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	93 clinvar	6 clinvar	102
missense			195 clinvar	13 clinvar	1 clinvar	209
nonsense		1 clinvar	7 clinvar			8
start loss			1 clinvar			1
frameshift		2 clinvar	15 clinvar			17
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	3	233	106	7	349

Highest pathogenic variant AF is 0.00018970485

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003190.5	RefSeq	NP_003181.3	8	MANE Select
ENST00000434618.7	Ensembl	ENSP00000395701.2	8	MANE Select
NM_001410875.1	RefSeq	NP_001397804.1	7	Standard
NM_172208.3	RefSeq	NP_757345.2	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antigen processing and presentation - Homo sapiens (human)
Immune System
Adaptive Immune System
Antigen processing-Cross presentation
Class I MHC mediated antigen processing & presentation

Biological Process

MHC class Ib protein complex assembly
antigen processing and presentation of peptide antigen via MHC class I
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum
immune response

Molecular Function

protein binding
peptide antigen-transporting ATPase activity
MHC class I protein binding
peptide antigen binding
TAP1 binding

Cellular Component

Golgi membrane
endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane
phagocytic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000426633
Coding exons: 7
Length: 14694
Individuals with no LoFs: 125637
Homozygous LoFs: 1
Heterozygous LoFs: 110
Defined: 125748
p: 0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.764	258	295	0.875	0.0000154	3156
Missense (PolyPhen)		81	97.312	0.83237		1081
Synonymous	0.977	113	127	0.890	0.00000677	1144
Loss of Function	0.949	15	19.5	0.768	0.00000105	182

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00038	0.00037	rare
Latino/Admixed American	0.00078	0.00075	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000052	0.000046	rare
European (Non-Finnish)	0.00061	0.00058	rare
South Asian	0.00026	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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). {ECO:0000269|PubMed:10636848}.;
Disease: DISEASE: Bare lymphocyte syndrome 1 (BLS1) [MIM:604571]: A HLA class I deficiency. Contrary to bare lymphocyte syndromes type 2 and type 3, which are characterized by early-onset severe combined immunodeficiency, class I antigen deficiencies are not accompanied by particular pathologic manifestations during the first years of life. Systemic infections have not been described. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract. {ECO:0000269|PubMed:12149238}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.977
RVIS EVS: 0.13
RVIS percentile EVS: 63.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.992

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium