TAP1

transporter 1, ATP binding cassette subfamily B member, the group of ATP binding cassette subfamily B

Basic information

Region (hg38): 6:32845208-32853816

Previous symbols: [ "ABCB2" ]

Links

ENSG00000168394 ∙ NCBI:6890 ∙ OMIM:170260 ∙ HGNC:43 ∙ Uniprot:Q03518 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MHC class I deficiency (Moderate), mode of inheritance: AR
• MHC class I deficiency (Supportive), mode of inheritance: AR
• MHC class I deficiency (Strong), mode of inheritance: AR
• MHC class I deficiency (Strong), mode of inheritance: AR
• MHC class I deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bare lymphocyte syndrome, type I	AR	Allergy/Immunology/Infectious; Pulmonary	Individuals may manifest with frequent and severe infections (including early-onset severe bacterial infections), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; For pulmonary manifestations, treatment recommendations analogous to those in individuals cystic fibrosis have been recommended; Immunosuppressive therapy may be contraindicated	Allergy/Immunology/Infectious; Pulmonary	3891604; 10074495; 10074494; 10931128; 17498556; 17982230; 17315195; 18668571
The condition has been reported as possibly related to increased risk of malignancy as well as infectious manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TAP1 gene.

• MHC class I deficiency (345 variants)
• Inborn genetic diseases (27 variants)
• not provided (10 variants)
• not specified (6 variants)
• PEPTIDE TRANSPORTER PSF1 POLYMORPHISM (2 variants)
• TAP1 deficiency, somatic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TAP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	88	7	98
missense		1	147	9	9	166
nonsense	6		2			8
start loss						0
frameshift	4					4
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			6	6		12
non coding	1	1	21	40	5	68
Total	11	2	176	137	21

Highest pathogenic variant AF is 0.0000460

Variants in TAP1

This is a list of pathogenic ClinVar variants found in the TAP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-32845503-T-G			Likely benign (Dec 01, 2023)
6-32845587-G-A		not specified	Uncertain significance (Jun 16, 2023)
6-32845602-C-G		MHC class I deficiency	Uncertain significance (Sep 12, 2021)
6-32845607-A-G		MHC class I deficiency	Uncertain significance (Nov 29, 2022)
6-32845611-T-C		Inborn genetic diseases	Uncertain significance (May 11, 2022)
6-32845613-G-A		MHC class I deficiency • Inborn genetic diseases	Uncertain significance (Mar 25, 2022)
6-32845639-G-A		MHC class I deficiency	Likely benign (Apr 13, 2023)
6-32845644-G-T		MHC class I deficiency	Benign (Jan 16, 2024)
6-32845659-C-A		MHC class I deficiency • Inborn genetic diseases	Uncertain significance (Jan 19, 2022)
6-32845659-C-G		MHC class I deficiency	Uncertain significance (Dec 10, 2020)
6-32845671-C-T		MHC class I deficiency	Uncertain significance (May 20, 2022)
6-32845672-G-A		MHC class I deficiency	Likely benign (Aug 30, 2023)
6-32845677-C-A		MHC class I deficiency	Uncertain significance (Oct 16, 2019)
6-32845681-C-A		MHC class I deficiency	Likely benign (Aug 17, 2023)
6-32845682-A-C		MHC class I deficiency	Uncertain significance (Nov 22, 2021)
6-32845686-A-G		MHC class I deficiency	Uncertain significance (Oct 03, 2023)
6-32845687-G-T		MHC class I deficiency	Likely benign (Oct 13, 2023)
6-32845695-G-C		MHC class I deficiency	Uncertain significance (Oct 13, 2023)
6-32845705-C-T		MHC class I deficiency	Likely benign (Feb 24, 2022)
6-32845721-T-TG		MHC class I deficiency	Pathogenic (May 21, 2024)
6-32845731-T-C		MHC class I deficiency	Uncertain significance (Apr 07, 2022)
6-32845732-G-A		MHC class I deficiency	Likely benign (Oct 22, 2021)
6-32845745-C-T		MHC class I deficiency	Uncertain significance (Jul 08, 2022)
6-32845746-G-A		MHC class I deficiency	Uncertain significance (Mar 29, 2022)
6-32845749-A-T		MHC class I deficiency	Uncertain significance (Sep 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TAP1	protein_coding	protein_coding	ENST00000354258	11	8770

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000534	1.00	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.77	327	430	0.760	0.0000239	5053
Missense in Polyphen		79	133.67	0.59101		1653
Synonymous	1.22	168	189	0.887	0.0000105	1794
Loss of Function	3.16	15	35.2	0.426	0.00000199	358

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000351	0.000337
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.000383	0.000381
Finnish	0.000237	0.000231
European (Non-Finnish)	0.000233	0.000229
Middle Eastern	0.000383	0.000381
South Asian	0.0000653	0.0000653
Other	0.000328	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules. Also acts as a molecular scaffold for the final stage of MHC class I folding, namely the binding of peptide. Nascent MHC class I molecules associate with TAP via tapasin. Inhibited by the covalent attachment of herpes simplex virus ICP47 protein, which blocks the peptide-binding site of TAP. Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1 and prevents the conformational rearrangement of TAP induced by peptide binding. Inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex and acts as a tapasin inhibitor, preventing MHC class I/TAP association. Expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules.
• 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:10074494}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Antigen processing and presentation - Homo sapiens (human);Primary immunodeficiency - Homo sapiens (human);Phagosome - Homo sapiens (human);ABC transporters - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);MECP2 and Associated Rett Syndrome;The human immune response to tuberculosis;Type II interferon signaling (IFNG);antigen processing and presentation;Immune System;Adaptive Immune System;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;Direct p53 effectors;ER-Phagosome pathway;Antigen Presentation: Folding, assembly and peptide loading of class I MHC (Consensus)

Intolerance Scores

• loftool: 0.0865
• rvis_EVS: 2.13
• rvis_percentile_EVS: 97.95

Haploinsufficiency Scores

• pHI: 0.0610
• hipred: N
• hipred_score: 0.493
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.953

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tap1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: adaptive immune response;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;defense response;protein transport;peptide transport;viral process;antigen processing and presentation of endogenous peptide antigen via MHC class I;cytosol to endoplasmic reticulum transport;vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;microtubule organizing center;membrane;integral component of membrane;integral component of endoplasmic reticulum membrane;phagocytic vesicle membrane;endoplasmic reticulum-Golgi intermediate compartment membrane;MHC class I peptide loading complex;TAP complex
• Molecular function: protein binding;ATP binding;peptide antigen-transporting ATPase activity;MHC class Ib protein binding;MHC class I protein binding;peptide antigen binding;ATPase activity, coupled to transmembrane movement of substances;protein homodimerization activity;ADP binding;TAP1 binding;TAP2 binding;peptide transmembrane transporter activity