MHC class I deficiency 1

Summary

MHC class I deficiency 1 (MONDO:0971006) is a disease caused by variants in TAP1 and TAP2, with 4 cohort genes. The dominant Reactome pathway is Antigen Presentation: Folding, assembly and peptide loading of class I MHC (3 cohort genes).

At a glance

• Causal genes: TAP1 (GenCC Strong), TAP2 (GenCC Strong)
• Cohort genes: 4
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	MHC class I deficiency 1
Mondo ID	MONDO:0971006
OMIM	604571
GARD	0027100
Is cancer (heuristic)	no

Data availability: 11 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › combined immunodeficiency › MHC class I deficiency › MHC class I deficiency 1

Related subtypes (2): MHC class I deficiency 2, MHC class I deficiency 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 2 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
937533	NM_000593.6(TAP1):c.1132C>T (p.Arg378Ter)	TAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
4755454	NM_000593.6(TAP1):c.1997del (p.Leu666fs)	TAP1	Likely pathogenic	criteria provided, single submitter
4796687	NM_000593.6(TAP1):c.1963C>T (p.Arg655Ter)	TAP1	Likely pathogenic	criteria provided, single submitter
656048	NM_003190.5(TAPBP):c.312del (p.Lys104fs)	TAPBP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
574783	NM_001290043.2(TAP2):c.701T>A (p.Leu234Gln)	LOC107648851	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436953	NM_000593.6(TAP1):c.2149G>T (p.Gly717Ter)	PSMB8-AS1	Uncertain significance	criteria provided, single submitter
2165422	NM_000593.6(TAP1):c.217T>G (p.Cys73Gly)	TAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
842574	NM_000593.6(TAP1):c.1783C>G (p.Leu595Val)	TAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
836733	NM_001290043.2(TAP2):c.1733C>T (p.Ala578Val)	TAP2	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436954	NM_003190.5(TAPBP):c.1345T>G (p.Ter449Gly)	TAPBP	Uncertain significance	criteria provided, single submitter
850117	NM_003190.5(TAPBP):c.997C>T (p.Arg333Trp)	TAPBP	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TAP1	Definitive	Autosomal recessive	MHC class I deficiency	6
TAP2	Strong	Autosomal recessive	MHC class I deficiency	4
TAPBP	Moderate	Autosomal recessive	MHC class I deficiency 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TAPBP	Orphanet:34592	Immunodeficiency by defective expression of MHC class I
TAP1	Orphanet:34592	Immunodeficiency by defective expression of MHC class I
TAP2	Orphanet:34592	Immunodeficiency by defective expression of MHC class I

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TAPBP	HGNC:11566	ENSG00000231925	O15533	Tapasin	gencc,clinvar
TAP1	HGNC:43	ENSG00000168394	Q03518	Antigen peptide transporter 1	gencc,clinvar
TAP2	HGNC:44	ENSG00000204267	Q03519	Antigen peptide transporter 2	gencc,clinvar
PSMB8-AS1	HGNC:39758	ENSG00000204261		PSMB8 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TAPBP	Tapasin	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).
TAP1	Antigen peptide transporter 1	ABC transporter associated with antigen processing.
TAP2	Antigen peptide transporter 2	ABC transporter associated with antigen processing.

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.75

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	2	38.9×	0.003
Antibody/Immunoglobulin	1	7.3×	0.195
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TAPBP	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, Tapasin
TAP1	Transporter	yes	7.4.2.14	ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC1_TM_dom
TAP2	Transporter	yes	7.4.2.14	ABC_transporter-like_ATP-bd, AAA+_ATPase, Tap2/ABCB3
PSMB8-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	3
lymph node	2
vermiform appendix	2
monocyte	2
blood	1
bone marrow cell	1
leukocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TAPBP	133	ubiquitous	marker	bone marrow cell, granulocyte, blood
TAP1	134	ubiquitous	marker	granulocyte, vermiform appendix, lymph node
TAP2	134	ubiquitous	yes	vermiform appendix, lymph node, monocyte
PSMB8-AS1	132	ubiquitous	marker	granulocyte, leukocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TAPBP	2,253
TAP1	2,139
TAP2	1,507
PSMB8-AS1	0

Intra-cohort edges

A	B	Sources
TAP1	TAP2	biogrid_interaction, intact, string_interaction
TAP1	TAPBP	biogrid_interaction, intact, string_interaction
TAP2	TAPBP	biogrid_interaction, intact, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TAP1	Q03518	22
TAP2	Q03519	21
TAPBP	O15533	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 4 evidence-associated genes (3 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	3	393.8×	9e-08	TAPBP, TAP1, TAP2
ER-Phagosome pathway	3	129.8×	1e-06	TAPBP, TAP1, TAP2
Antigen processing-Cross presentation	2	211.5×	6e-05	TAP1, TAP2
Class I MHC mediated antigen processing & presentation	2	46.7×	9e-04	TAP1, TAP2
Adaptive Immune System	2	19.9×	0.004	TAP1, TAP2
Immune System	2	8.6×	0.017	TAP1, TAP2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
antigen processing and presentation of endogenous peptide antigen via MHC class I	3	2106.5×	2e-09	TAPBP, TAP1, TAP2
cytosol to endoplasmic reticulum transport	2	5617.3×	2e-07	TAP1, TAP2
MHC class Ib protein complex assembly	1	5617.3×	7e-04	TAPBP
antigen processing and presentation of endogenous peptide antigen via MHC class Ib via ER pathway, TAP-dependent	1	5617.3×	7e-04	TAP2
peptide antigen stabilization	1	5617.3×	7e-04	TAPBP
transmembrane transport	2	112.3×	7e-04	TAP1, TAP2
antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent	1	2808.7×	1e-03	TAP2
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent	1	2808.7×	1e-03	TAP2
peptide antigen transport	1	1872.4×	0.001	TAP2
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	1	1404.3×	0.001	TAPBP
peptide transport	1	1404.3×	0.001	TAP1
peptide antigen assembly with MHC class I protein complex	1	936.2×	0.002	TAPBP
response to molecule of bacterial origin	1	702.2×	0.002	TAP2
protein transport	2	29.3×	0.002	TAP1, TAP2
T cell mediated cytotoxicity	1	374.5×	0.004	TAP2
regulation of protein complex stability	1	351.1×	0.004	TAPBP
positive regulation of T cell mediated cytotoxicity	1	170.2×	0.008	TAP2
retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum	1	112.3×	0.011	TAPBP
defense response	1	72.0×	0.016	TAP1
protein-containing complex assembly	1	38.0×	0.029	TAPBP
adaptive immune response	1	28.1×	0.036	TAP1
regulation of gene expression	1	27.8×	0.036	TAPBP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TAPBP	0	0
TAP1	0	0
TAP2	0	0
PSMB8-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TAP1	4	Binding:4
TAP2	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TAP1	7.4.2.14, 7.4.2.5	ABC-type antigen peptide transporter, bacterial ABC-type protein transporter
TAP2	7.4.2.14, 7.4.2.5	ABC-type antigen peptide transporter, bacterial ABC-type protein transporter

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	TAPBP, TAP1, TAP2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PSMB8-AS1

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
TAPBP	0	—
TAP1	4	—
TAP2	3	—
PSMB8-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.