Autoimmune disease with susceptibility to mycobacterium tuberculosis

Summary

Autoimmune disease with susceptibility to mycobacterium tuberculosis (MONDO:0975847) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoimmune disease with susceptibility to mycobacterium tuberculosis
Mondo ID	MONDO:0975847
OMIM	621004
DOID	DOID:0061163
UMLS	C5975515
MedGen	1875045
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › autoimmune disease › autoimmune disease with susceptibility to mycobacterium tuberculosis

Related subtypes (46): autoimmune disease, multisystem, infantile-onset, autoimmune disorder of endocrine system, autoimmune disorder of exocrine system, autoimmune disease of ear, nose and throat, autoimmune disorder of gastrointestinal tract, autoimmune disorder of musculoskeletal system, autoimmune disorder of blood, autoimmune disorder of cardiovascular system, phacolytic glaucoma, Jaccoud syndrome, autoimmune disorder of the nervous system, lupus erythematosus, anti-neutrophil antibody associated vasculitis, cryoglobulinemia, CNS demyelinating autoimmune disease, type III hypersensitivity disease, vitiligo, anti-glomerular basement membrane disease, autoimmune pulmonary alveolar proteinosis, Reynolds syndrome, overlapping connective tissue disease, tempi syndrome, immunoglobulin G4-related sclerosing disease, rheumatic fever, autoerythrocyte sensitization syndrome, autoimmune lymphoproliferative syndrome, secondary neonatal autoimmune disease, euthyroid Graves orbitopathy, Kimura disease, autoimmune thrombocytopenia, autoimmune bullous skin disease, scleroderma, Susac syndrome, undifferentiated connective tissue syndrome, type II hypersensitivity reaction disease, autoimmune urticaria, autoimmune glomerulonephritis, multisystem autoimmune disease due to IKAROS gain of function, autoimmune pulmonary disease due to PD-1 deficiency, non-specific autoimmune supratentorial encephalitis with characteristic antibodies, non-specific autoimmune supratentorial encephalitis without characteristic antibodies, non-specific autoimmune brainstem encephalitis with characteristic antibodies, non-specific autoimmune brainstem encephalitis without characteristic antibodies, non-specific autoimmune cerebellar ataxia with characteristic antibodies, non-specific autoimmune cerebellar ataxia without characteristic antibodies, antiphospholipid syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3376502	PDCD1, 1-BP DUP, 105C	PDCD1	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
PDCD1	Limited	Autosomal recessive	autoimmune disease with susceptibility to mycobacterium tuberculosis	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDCD1	Orphanet:536	Systemic lupus erythematosus

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
PDCD1	HGNC:8760	ENSG00000188389	Q15116	Programmed cell death protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PDCD1	Programmed cell death protein 1	Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PDCD1	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set

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
granulocyte	1
lymph node	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDCD1	114	broad	yes	lymph node, granulocyte, spleen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDCD1	3,029

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDCD1	Q15116	37

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Co-inhibition by PD-1	1	519.1×	0.003	PDCD1
PD-L1(CD274) glycosylation and translocation to plasma membrane	1	519.1×	0.003	PDCD1
Potential therapeutics for SARS	1	114.2×	0.009	PDCD1

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
negative regulation of tolerance induction	1	16852.0×	4e-04	PDCD1
regulatory T cell apoptotic process	1	16852.0×	4e-04	PDCD1
negative regulation of T cell mediated immune response to tumor cell	1	2106.5×	0.002	PDCD1
positive regulation of T cell apoptotic process	1	2106.5×	0.002	PDCD1
negative regulation of B cell apoptotic process	1	1532.0×	0.002	PDCD1
B cell apoptotic process	1	1404.3×	0.002	PDCD1
negative regulation of immune response	1	1053.2×	0.002	PDCD1
negative regulation of T cell activation	1	526.6×	0.003	PDCD1
regulation of immune response	1	495.6×	0.003	PDCD1
negative regulation of T cell receptor signaling pathway	1	366.4×	0.004	PDCD1
humoral immune response	1	280.9×	0.005	PDCD1
negative regulation of inflammatory response	1	137.0×	0.009	PDCD1
adaptive immune response	1	84.3×	0.013	PDCD1
apoptotic process	1	28.7×	0.035	PDCD1

Therapeutics

Drug target analysis

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

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

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
PDCD1	PYRVINIUM

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDCD1	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PYRVINIUM	4	PDCD1
RIFABUTIN	4	PDCD1
EVIXAPODLIN	1	PDCD1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PDCD1	327	Binding:327

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PDCD1	327

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
PYRVINIUM	4	PDCD1
RIFABUTIN	4	PDCD1
EVIXAPODLIN	1	PDCD1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDCD1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.