Autoimmune polyendocrinopathy

Summary

Autoimmune polyendocrinopathy (MONDO:0017278) is a disease with 1 cohort gene and 93 clinical trials. Top therapeutic interventions include hydroxychloroquine, warfarin, and belimumab.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 93

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autoimmune polyendocrinopathy
Mondo ID	MONDO:0017278
Orphanet	282196
DOID	DOID:14040
ICD-10-CM	E31.0
ICD-11	548357900
NCIT	C129726, C84576
SNOMED CT	41864002
UMLS	C0085409
MedGen	39042
GARD	0021116
NORD	790
Is cancer (heuristic)	no

Also known as: Antiphospholipid Syndrome · APS · autoimmune polyendocrine syndrome · autoimmune polyendocrine syndrome; polyglandular autoimmune syndrome · autoimmune polyendocrinopathy · autoimmune polyendocrinopathy syndrome · autoimmune polyglandular failure · autoimmune polyglandular syndrome · autoimmune polyglandular syndrome(s)

Data availability: 1 ClinVar variant · 18 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › autoimmune disorder of endocrine system › autoimmune polyendocrinopathy

Related subtypes (12): type 1 diabetes mellitus, autoimmune thyroid disease, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome, autoimmune pancreatitis, autoimmune hepatitis, autoimmune hypoparathyroidism, insulin autoimmune syndrome, IgG4-related sclerosing cholangitis, lymphocytic hypophysitis, autoimmune oophoritis, autoimmune primary ovarian failure

Subtypes (4): autoimmune polyendocrine syndrome type 1, autoimmune polyendocrinopathy type 2, autoimmune polyendocrinopathy type 3, autoimmune polyendocrinopathy type 4

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/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3309	NM_000383.4(AIRE):c.967_979del (p.Leu323fs)	AIRE	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AIRE	Orphanet:189466	Familial isolated hypoparathyroidism due to impaired PTH secretion
AIRE	Orphanet:3453	Autoimmune polyendocrinopathy type 1

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
AIRE	HGNC:360	ENSG00000160224	O43918	Autoimmune regulator	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AIRE	Autoimmune regulator	Transcription factor playing an essential role to promote self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the pe…

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AIRE	Transcription factor	no		SAND_dom, Znf_PHD, HSR_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
gluteal muscle	1
triceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AIRE	105	tissue_specific	marker	triceps brachii, diaphragm, gluteal muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AIRE	3,001

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
AIRE	O43918	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
peripheral T cell tolerance induction	1	16852.0×	2e-04	AIRE
central tolerance induction to self antigen	1	16852.0×	2e-04	AIRE
regulation of thymocyte migration	1	16852.0×	2e-04	AIRE
thymus epithelium morphogenesis	1	8426.0×	4e-04	AIRE
negative thymic T cell selection	1	1404.3×	0.002	AIRE
positive regulation of chemokine production	1	374.5×	0.005	AIRE
humoral immune response	1	280.9×	0.006	AIRE
transcription by RNA polymerase II	1	70.5×	0.021	AIRE
immune response	1	47.1×	0.028	AIRE
regulation of DNA-templated transcription	1	31.6×	0.038	AIRE
positive regulation of DNA-templated transcription	1	27.9×	0.039	AIRE
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	AIRE

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
AIRE	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	AIRE

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)
AIRE	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 93.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	57
PHASE2	11
PHASE1	9
PHASE4	8
PHASE3	3
PHASE1/PHASE2	2
EARLY_PHASE1	2
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05995600	PHASE4	RECRUITING	Comparison of Clopidogrel-based Antiplatelet Therapy Versus Warfarin As Secondary Prevention Strategy for AntiPhospholipid Syndrome-related STROKE
NCT07087912	PHASE4	RECRUITING	Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases
NCT01104337	PHASE4	COMPLETED	Drug Interaction Between Paracetamol and Warfarin
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT02295475	PHASE4	COMPLETED	Apixaban for Secondary Prevention of Thromboembolism Among Patients With AntiphosPholipid Syndrome
NCT02303171	PHASE4	UNKNOWN	Use of Warfarin After the First Trimester in Pregnant Women With APS
NCT02326051	PHASE4	COMPLETED	Timing of Initiation of LMWH Administration in Pregnant Women With APS
NCT04624269	PHASE4	UNKNOWN	A Study of Hydroxychloroquine Sulfate in the Treatment of Recurrent Spontaneous Abortion With Antiphospholipid Syndrome
NCT01784523	PHASE3	TERMINATED	Hydroxychloroquine for the First Thrombosis Prevention in Antiphospholipid Antibody Positive Patients
NCT02157272	PHASE3	TERMINATED	Rivaroxaban in Thrombotic Antiphospholipid Syndrome
NCT02926170	PHASE3	COMPLETED	Rivaroxaban for Patients With Antiphospholipid Syndrome
NCT05020782	PHASE2/PHASE3	UNKNOWN	The BeLimumab Antiphospholipid Syndrome Trial (BLAST)
NCT05199909	PHASE2	RECRUITING	Safety and Efficacy of Zanubrutinib in the Treatment of Antiphospholipid Syndrome With Secondary Thrombocytopenia
NCT05983952	PHASE2	RECRUITING	Anti-CD38 Antibody Treating APS With Thrombocytopenia
NCT06747312	PHASE2	RECRUITING	Effect of Belimumab on Antibody Titers in Primary APS Patients
NCT06794008	PHASE2	RECRUITING	BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT06828042	PHASE1/PHASE2	RECRUITING	Safety and Efficacy of Universal CD19-targeting CAR-γδT Cells in Refractory Autoimmune Diseases
NCT07584083	PHASE2	NOT_YET_RECRUITING	Anifrolumab in Adults With Primary Antiphospholipid Syndrome (AnifAPS Trial)
NCT00180778	PHASE1/PHASE2	WITHDRAWN	Steroids and Antiphospholipid Syndrome- Related Pregnancy Loss
NCT00537290	PHASE2	COMPLETED	A Pilot Study of Rituximab for the Anticoagulation Resistant Manifestations of Antiphospholipid Syndrome
NCT00674297	PHASE2	COMPLETED	Effects of Fluvastatin on Proinflammatory and Prothrombotic Markers in Antiphospholipid Syndrome Patients
NCT02595346	PHASE2	TERMINATED	Study of the Efficiency of Hydroxychloroquine on the Endothelial Dysfunction and Its Vascular Consequences During the Antiphospholipid Syndrome
NCT03684564	PHASE2	COMPLETED	RIvaroxaban for Stroke Patients With AntiPhospholipid Syndrome
NCT06315530	PHASE2	COMPLETED	Effect of Telitacicept on Antibody Titers in Primary APS Patients
NCT07172022	PHASE2	WITHDRAWN	A Study to Evaluate Crovalimab in People With Antiphospholipid Syndrome (APS)
NCT06371417	PHASE1	RECRUITING	Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)
NCT06723106	PHASE1	ENROLLING_BY_INVITATION	Phase 1b Long-term Extension Trial of RAY121 in Immunological Diseases (RAINBOW-LTE Trial)
NCT06978647	PHASE1	RECRUITING	A Clinical Study of YTS109 Cell in R/R Autoimmune Diseases
NCT07104721	PHASE1	RECRUITING	A Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
NCT07123519	PHASE1	RECRUITING	A Clinical Study of YTS109 Cells for the Treatment of R/R Autoimmune Diseases
NCT07236762	PHASE1	RECRUITING	An Exploratory Clinical Study of YTS109 Cell for R/R Autoimmune Diseases
NCT07236801	PHASE1	RECRUITING	Exploratory Clinical Study on YTS109 Cell Therapy for Autoimmune Diseases
NCT07439029	PHASE1	NOT_YET_RECRUITING	YTS109 in Pediatric Relapsed/Refractory Autoimmune Diseases
NCT00278616	PHASE1	WITHDRAWN	Hematopoietic Stem Cell Transplantation in Patients With Antiphospholipid Syndrome
NCT06420154	EARLY_PHASE1	NOT_YET_RECRUITING	The Safety and Efficacy of Anti-CD19 CAR-T Cells in Patients With Relapsed/Refractory Autoimmune Diseases
NCT07301164	EARLY_PHASE1	NOT_YET_RECRUITING	Clinical Study of BCT301 Cell Injection Therapy for Refractory Autoimmune Diseases
NCT00198068	Not specified	RECRUITING	Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS)
NCT00482794	Not specified	RECRUITING	Genetic Risk Factors Associated With Antiphospholipid Antibody Syndrome
NCT00616317	Not specified	RECRUITING	Register for Pediatric Patients With Antiphospholipid Syndrome (APS): European Project Extended Internationally Study
NCT01787305	Not specified	ACTIVE_NOT_RECRUITING	Pilot Study of Gut Commensals in Antiphospholipid Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
HYDROXYCHLOROQUINE	4	3
WARFARIN	4	3
BELIMUMAB	4	2
ENOXAPARIN SODIUM	4	2
ACENOCOUMAROL	4	1
ACETAMINOPHEN	4	1
ANIFROLUMAB	4	1
APIXABAN	4	1
CROVALIMAB	4	1
FLUVASTATIN	4	1
ZANUBRUTINIB	4	1
TELITACICEPT	3	2
ENOXAPARIN	0	2
CHEMBL5592090	0	1
CHEMBL350239	0	1
CHEMBL4781824	0	1
CHEMBL5193128	0	1