TAP2

transporter 2, ATP binding cassette subfamily B member, the group of ATP binding cassette subfamily B

Basic information

Region (hg38): 6:32821833-32838739

Previous symbols: [ "ABCB3" ]

Links

ENSG00000204267 ∙ NCBI:6891 ∙ OMIM:170261 ∙ HGNC:44 ∙ Uniprot:Q03519 ∙ 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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
MHC class I deficiency 2	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	7517574; 10074495; 10931128; 12644316; 17879436; 17879452; 20083708; 36229627
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 TAP2 gene.

• MHC class I deficiency (15 variants)
• MHC CLASS I DEFICIENCY 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TAP2 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			2	94	13	109
missense			179	6	11	196
nonsense	7		3			10
start loss			2			2
frameshift	7	2				9
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	3	1			5
splice region			6	10	6	22
non coding			6	35	15	56
Total	15	5	195	135	39

Highest pathogenic variant AF is 0.0000197

Variants in TAP2

This is a list of pathogenic ClinVar variants found in the TAP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-32822282-T-C		TAP2-related disorder	Benign (Apr 29, 2019)
6-32822312-G-A		not specified • TAP2-related disorder	Benign (Mar 28, 2016)
6-32822322-G-GA		not specified	Benign (Mar 28, 2016)
6-32822322-G-GAAA		TAP2-related disorder	Likely benign (Jun 25, 2019)
6-32828188-G-A			Benign (Apr 20, 2019)
6-32828868-C-T		MHC class I deficiency	Uncertain significance (Sep 02, 2021)
6-32828876-C-A		not specified • MHC class I deficiency	Benign (Feb 01, 2024)
6-32828876-C-C		MHC class I deficiency	Benign (Feb 01, 2024)
6-32828883-C-T		MHC class I deficiency	Uncertain significance (Aug 09, 2022)
6-32828887-A-T		MHC class I deficiency	Uncertain significance (May 28, 2022)
6-32828897-C-T		MHC class I deficiency	Likely benign (Dec 12, 2023)
6-32828906-C-T		MHC class I deficiency	Likely benign (Feb 11, 2023)
6-32828908-A-G		not specified • MHC class I deficiency	Benign (Feb 01, 2024)
6-32828908-A-A		PEPTIDE TRANSPORTER PSF2 POLYMORPHISM • MHC class I deficiency	Benign (Feb 01, 2024)
6-32828914-G-A		MHC class I deficiency	Uncertain significance (Aug 02, 2021)
6-32828916-G-A		MHC class I deficiency	Uncertain significance (Sep 07, 2022)
6-32828921-C-T		MHC class I deficiency	Likely benign (Aug 09, 2022)
6-32828938-C-T		MHC class I deficiency	Uncertain significance (Jun 15, 2021)
6-32828947-C-T		MHC class I deficiency	Uncertain significance (Nov 01, 2022)
6-32828962-C-T		MHC class I deficiency	Uncertain significance (Jul 09, 2023)
6-32828963-G-A		MHC class I deficiency	Likely benign (Oct 13, 2023)
6-32828968-G-A		MHC class I deficiency	Uncertain significance (Feb 05, 2022)
6-32828974-T-C		not specified • MHC class I deficiency	Benign (Feb 01, 2024)
6-32828974-T-T		PEPTIDE TRANSPORTER PSF2 POLYMORPHISM • MHC class I deficiency	Benign (Feb 01, 2024)
6-32828983-T-G		MHC class I deficiency	Likely benign (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TAP2	protein_coding	protein_coding	ENST00000374899	11	16948

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.80e-8	0.994	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.39	281	355	0.792	0.0000219	4124
Missense in Polyphen		88	115.89	0.75933		1372
Synonymous	0.581	148	157	0.941	0.00000944	1438
Loss of Function	2.51	17	32.4	0.525	0.00000205	322

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00109	0.00108
Ashkenazi Jewish	0.00	0.00
East Asian	0.000177	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000167	0.000158
Middle Eastern	0.000177	0.000163
South Asian	0.000164	0.000163
Other	0.00	0.00

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.
• 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:7517574}. 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);antigen processing and presentation;Immune System;Adaptive Immune System;Antigen processing-Cross presentation;Class I MHC mediated antigen processing & presentation;ER-Phagosome pathway;Antigen Presentation: Folding, assembly and peptide loading of class I MHC (Consensus)

Recessive Scores

• pRec: 0.487

Intolerance Scores

• loftool: 0.0606
• rvis_EVS: 1.53
• rvis_percentile_EVS: 95.56

Haploinsufficiency Scores

• pHI: 0.150
• hipred: N
• hipred_score: 0.332
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.799

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tap2
• Phenotype: hematopoietic system phenotype; immune system phenotype

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;antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent;protein transport;viral process;antigen processing and presentation of endogenous peptide antigen via MHC class I;cytosol to endoplasmic reticulum transport;peptide antigen transport;vesicle fusion with endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane;nuclear speck;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: transporter activity;protein binding;ATP binding;peptide antigen-transporting ATPase activity;MHC class Ib protein binding;ATPase activity, coupled to transmembrane movement of substances;TAP1 binding;tapasin binding;peptide transmembrane transporter activity