Type 1 diabetes mellitus 1

Summary

Type 1 diabetes mellitus 1 (MONDO:0009100) is a disease with 1 cohort gene and 1,820 clinical trials. Top therapeutic interventions include insulin aspart, insulin detemir, and insulin lispro.

At a glance

• Cohort genes: 1
• Clinical trials: 1,820

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	type 1 diabetes mellitus 1
Mondo ID	MONDO:0009100
UMLS	C5435660
MedGen	1734436
Is cancer (heuristic)	no

Also known as: diabetes mellitus, insulin-dependent · diabetes mellitus, insulin-dependent, 1 · diabetes mellitus, insulin-dependent-1 · diabetes mellitus, type 1 · IDDM · IDDM1 · insulin-dependent diabetes mellitus 1 · juvenile-onset diabetes · type 1 diabetes mellitus

Data availability: 1 GenCC gene-disease record · 155 cell lines.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › diabetes mellitus, insulin-dependent, X-linked, susceptibility to › type 1 diabetes mellitus 1

Related subtypes (20): type 1 diabetes mellitus 2, type 1 diabetes mellitus 3, type 1 diabetes mellitus 4, type 1 diabetes mellitus 5, type 1 diabetes mellitus 7, type 1 diabetes mellitus 8, type 1 diabetes mellitus 11, type 1 diabetes mellitus 13, type 1 diabetes mellitus 12, type 1 diabetes mellitus 15, type 1 diabetes mellitus 6, type 1 diabetes mellitus 10, type 1 diabetes mellitus 17, type 1 diabetes mellitus 18, type 1 diabetes mellitus 19, type 1 diabetes mellitus 20, type 1 diabetes mellitus 21, type 1 diabetes mellitus 22, type 1 diabetes mellitus 23, type 1 diabetes mellitus 24

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 6 · 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
PTPN22	Limited	Autosomal recessive	type 1 diabetes mellitus 1	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PTPN22	Orphanet:3437	Vogt-Koyanagi-Harada disease
PTPN22	Orphanet:397	Giant cell arteritis
PTPN22	Orphanet:536	Systemic lupus erythematosus
PTPN22	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
PTPN22	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
PTPN22	Orphanet:900	Granulomatosis with polyangiitis

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
PTPN22	HGNC:9652	ENSG00000134242	Q9Y2R2	Tyrosine-protein phosphatase non-receptor type 22	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPN22	Tyrosine-protein phosphatase non-receptor type 22	Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPN22	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

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
bone marrow	1
bone marrow cell	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPN22	190	broad	marker	bone marrow cell, bone marrow, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPN22	2,480

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPN22	Q9Y2R2	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Translocation of ZAP-70 to Immunological synapse	1	634.4×	0.002	PTPN22
Phosphorylation of CD3 and TCR zeta chains	1	543.8×	0.002	PTPN22

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
phosphoanandamide dephosphorylation	1	16852.0×	0.002	PTPN22
regulation of natural killer cell proliferation	1	8426.0×	0.002	PTPN22
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	1	4213.0×	0.002	PTPN22
regulation of B cell receptor signaling pathway	1	2808.7×	0.002	PTPN22
positive regulation of toll-like receptor 3 signaling pathway	1	2407.4×	0.002	PTPN22
negative regulation of JUN kinase activity	1	2407.4×	0.002	PTPN22
positive regulation of protein K63-linked ubiquitination	1	2106.5×	0.002	PTPN22
negative regulation of p38MAPK cascade	1	2106.5×	0.002	PTPN22
cellular response to muramyl dipeptide	1	1685.2×	0.002	PTPN22
regulation of non-canonical NF-kappaB signal transduction	1	1532.0×	0.002	PTPN22
negative regulation of interleukin-8 production	1	991.3×	0.003	PTPN22
positive regulation of toll-like receptor 4 signaling pathway	1	991.3×	0.003	PTPN22
regulation of innate immune response	1	648.1×	0.004	PTPN22
positive regulation of NLRP3 inflammasome complex assembly	1	581.1×	0.004	PTPN22
lipopolysaccharide-mediated signaling pathway	1	526.6×	0.004	PTPN22
negative regulation of T cell activation	1	526.6×	0.004	PTPN22
positive regulation of type I interferon production	1	421.3×	0.004	PTPN22
T cell differentiation	1	383.0×	0.004	PTPN22
negative regulation of T cell receptor signaling pathway	1	366.4×	0.004	PTPN22
negative regulation of interleukin-6 production	1	351.1×	0.004	PTPN22
negative regulation of autophagy	1	259.3×	0.005	PTPN22
negative regulation of tumor necrosis factor production	1	251.5×	0.005	PTPN22
positive regulation of type II interferon production	1	224.7×	0.006	PTPN22
T cell receptor signaling pathway	1	151.8×	0.008	PTPN22
response to lipopolysaccharide	1	124.8×	0.010	PTPN22
autophagy	1	110.1×	0.010	PTPN22
lipid metabolic process	1	91.6×	0.012	PTPN22
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.013	PTPN22
negative regulation of gene expression	1	69.1×	0.015	PTPN22
positive regulation of gene expression	1	38.7×	0.026	PTPN22

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
PTPN22	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
PTPN22	137	Binding:122, Functional:10, ADMET:5

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPN22	3.1.3.48	protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PTPN22	137

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	PTPN22
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)
PTPN22	137	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,820.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	310
PHASE1	202
PHASE2	187
PHASE3	183
PHASE4	111
PHASE1/PHASE2	68
PHASE2/PHASE3	23
EARLY_PHASE1	16

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03463564	PHASE4	RECRUITING	Insulin Pump vs Multiple Daily Injections of Insulin and Glyco-metabolic Control in Type 1 Diabetic Patients
NCT03570632	PHASE4	ACTIVE_NOT_RECRUITING	Metformin for Preeclampsia Prevention in Pregnant Women With Type 1 Diabetes Mellitus
NCT03878459	PHASE4	RECRUITING	Dapagliflozin Plus Pioglitazone in T1DM
NCT04698330	PHASE4	NOT_YET_RECRUITING	Effects Of Berberine Plus Inulin On Diabetes Care in Patients With LADA
NCT05585983	PHASE4	RECRUITING	INfluenza VaccInation To Mitigate typE 1 Diabetes
NCT05757713	PHASE4	ACTIVE_NOT_RECRUITING	Teplizumab in Pediatric Stage 2 Type 1 Diabetes
NCT06452654	PHASE4	RECRUITING	Anti-viral Action Against Type 1 Diabetes Autoimmunity
NCT07427251	PHASE4	NOT_YET_RECRUITING	The Postprandial Hypo-Avoid Study
NCT00069537	PHASE4	COMPLETED	Continuous Glucose Monitors for Children With Diabetes Mellitus
NCT00069615	PHASE4	COMPLETED	Pilot Study of the GlucoWatch G2 Biographer for the Management of Type 1 Diabetes in Children
NCT00069628	PHASE4	COMPLETED	Randomized Clinical Trial to Assess the Effectiveness of the GlucoWatch Biographer
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00117780	PHASE4	COMPLETED	Comparison of Insulin Detemir Given Once or Twice Daily in Type 1 Diabetes
NCT00118937	PHASE4	COMPLETED	Effect of Metformin in Patients With Type-1 Diabetes With Inadequate Glycaemic Control by Insulin and Diet
NCT00131755	PHASE4	COMPLETED	Efficacy of Diazoxide in Type 1 Diabetes
NCT00145353	PHASE4	UNKNOWN	Insulin NovoRapid Versus Actrapid in Treatment of Type 1 Diabetic Patients During Daily Adjustment of Insulin Dose
NCT00145379	PHASE4	COMPLETED	The Effect of Metformin in Overweight Patients With Dysregulated Type 1 Diabetes Mellitus
NCT00284232	PHASE4	COMPLETED	Metabolic Effects of Accurate Blood Sugar Results and Education in Type 1 Diabetes
NCT00313742	PHASE4	COMPLETED	The Effect of Exercise on Blood Glucose Levels in Patients With Type 1 Diabetes: A Comparison of 3 Long-acting Insulins
NCT00313937	PHASE4	COMPLETED	SAM - Skip a Meal - Insulin Glargine, Diabetes Mellitus Type 1
NCT00315952	PHASE4	COMPLETED	Study to Estimate the Effects of Inhaled Versus Intravenous (IV) Infusion of Human Insulin in Subjects With Type 1 Diabetes
NCT00356421	PHASE4	TERMINATED	A Clinical Trial Comparing Efficacy and Safety of Exubera® and Humalog®
NCT00360984	PHASE4	COMPLETED	Prevention of Severe Hypoglycemia in Type 1 Diabetes
NCT00365170	PHASE4	COMPLETED	Efficacy and Safety of Insulin Aspart vs. Human Insulin During Pregnancy by Women With Type 1 Diabetes
NCT00374270	PHASE4	COMPLETED	Improving Blood Pressure Management in Patients With Diabetes
NCT00390728	PHASE4	COMPLETED	Insulin Glargine in Type I Diabetes Mellitus> Main Study AT.LANTUS: A Trial Comparing Lantus Algorithms to Achieve Normal Blood Glucose Targets in Subjects With Uncontrolled Blood Sugar. Sub-study: HALT(Hypoglycaemia Avoidance With Lantus Trial)
NCT00420095	PHASE4	COMPLETED	A Study for Patients With Diabetes Mellitus (IOPA)
NCT00442767	PHASE4	COMPLETED	Post-meal Insulin Dosing With Adjuvant Pre-meal Pramlintide in Children With Type 1 Diabetes Mellitus
NCT00461331	PHASE4	COMPLETED	Comparison of Insulins Aspart and Lispro in Insulin Pumps
NCT00462371	PHASE4	COMPLETED	Comparison Between Insulin Pump Treatment and Multiple Daily Insulin Injections in Diabetic Type 1 Children
NCT00472875	PHASE4	UNKNOWN	Do Sulphonylureas Preserve Cortical Function During Hypoglycaemia?
NCT00489190	PHASE4	COMPLETED	APIDRA Registration Study
NCT00497536	PHASE4	COMPLETED	Pharmacokinetics of IAsp Following CSII in Patients With T1DM
NCT00502138	PHASE4	COMPLETED	A Pilot Study of Continuous Subcutaneous Pramlintide Infusion Therapy in Patients With Type 1 Diabetes
NCT00509925	PHASE4	TERMINATED	Effect of Insulin Detemir on Use of Energy in Type 1 Diabetes
NCT00539448	PHASE4	COMPLETED	Gulf, Lantus, Apidra Evaluation in Type 1 Diabetics Study
NCT00542399	PHASE4	COMPLETED	Comparing the Metabolic Control of Once to Twice-daily Insulin Detemir Injections
NCT00542620	PHASE4	COMPLETED	Comparison of Insulin Detemir and Insulin Aspart in 2 Separate Injections Twice Daily to Extemporaneous Mixing Injection Regimen Twice Daily - The Paediatric Mixing Trial
NCT00564395	PHASE4	COMPLETED	Detemir: Role in Type 1 Diabetes
NCT00569426	PHASE4	COMPLETED	Evaluating the Use of Two Different Needles in Subjects With Diabetes

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INSULIN ASPART	4	120
INSULIN DETEMIR	4	36
INSULIN LISPRO	4	35
INSULIN DEGLUDEC	4	21
INSULIN GLULISINE	4	20
GLUCAGON	4	19
PRAMLINTIDE	4	11
TEPLIZUMAB	4	10
INSULIN HUMAN	4	9
SOTAGLIFLOZIN	4	9
INSULIN GLARGINE	4	8
ETANERCEPT	4	6
BASILIXIMAB	4	4
INSULIN ICODEC	4	4
ABATACEPT	4	3
BELATACEPT	4	3
DACLIZUMAB	4	3
DAPAGLIFLOZIN PROPANEDIOL	4	3
DIAZOXIDE	4	3
EFALIZUMAB	4	3
FIBRINOGEN I 125	4	3
GLUCAGON HYDROCHLORIDE	4	3
GLYBURIDE	4	3
GOLIMUMAB	4	3
ALCOHOL	4	2
ANAKINRA	4	2
BARICITINIB	4	2
DEXTROSE	4	2
EMPAGLIFLOZIN	4	2
LIRAGLUTIDE	4	2