MHC class I deficiency 2

Summary

MHC class I deficiency 2 (MONDO:0971011) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	MHC class I deficiency 2
Mondo ID	MONDO:0971011
OMIM	620813
UMLS	C5935617
MedGen	1862135
GARD	0027104
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants.

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 2

Related subtypes (2): MHC class I deficiency 1, 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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
13727	NM_001290043.2(TAP2):c.817C>T (p.Arg273Ter)	TAP2	Pathogenic	no assertion criteria provided
1456619	NM_001290043.2(TAP2):c.373del (p.Gln125fs)	TAP2	Pathogenic	criteria provided, single submitter
2727952	NM_001290043.2(TAP2):c.1636-1G>A	TAP2	Pathogenic	criteria provided, multiple submitters, no conflicts
3899339	NM_001290043.2(TAP2):c.494-1G>A	LOC107648851	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

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

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TAP2	HGNC:44	ENSG00000204267	Q03519	Antigen peptide transporter 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

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

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TAP2	Transporter	yes	7.4.2.14	ABC_transporter-like_ATP-bd, AAA+_ATPase, Tap2/ABCB3

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
lymph node	1
monocyte	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TAP2	134	ubiquitous	yes	vermiform appendix, lymph node, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TAP2	1,507

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TAP2	Q03519	21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 evidence-associated genes (1 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 1 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	1	393.8×	0.009	TAP2
Antigen processing-Cross presentation	1	317.2×	0.009	TAP2
ER-Phagosome pathway	1	129.8×	0.015	TAP2
Class I MHC mediated antigen processing & presentation	1	70.1×	0.021	TAP2
Adaptive Immune System	1	29.8×	0.040	TAP2
Immune System	1	13.0×	0.077	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 1 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 Ib via ER pathway, TAP-dependent	1	16852.0×	3e-04	TAP2
antigen processing and presentation of exogenous protein antigen via MHC class Ib, TAP-dependent	1	8426.0×	3e-04	TAP2
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent	1	8426.0×	3e-04	TAP2
cytosol to endoplasmic reticulum transport	1	8426.0×	3e-04	TAP2
peptide antigen transport	1	5617.3×	4e-04	TAP2
response to molecule of bacterial origin	1	2106.5×	7e-04	TAP2
antigen processing and presentation of endogenous peptide antigen via MHC class I	1	2106.5×	7e-04	TAP2
T cell mediated cytotoxicity	1	1123.5×	0.001	TAP2
positive regulation of T cell mediated cytotoxicity	1	510.7×	0.002	TAP2
transmembrane transport	1	168.5×	0.007	TAP2
protein transport	1	43.9×	0.023	TAP2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TAP2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TAP2	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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: 1; 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	1	TAP2
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TAP2	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.