Thyroiditis

Summary

Thyroiditis (MONDO:0004126) is a disease with 1 cohort gene (15 GWAS associations across 14 studies) and 9 clinical trials. Top therapeutic interventions include colchicine.

At a glance

• Cohort genes: 1
• GWAS associations: 15
• ClinVar variants: 1
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	thyroiditis
Mondo ID	MONDO:0004126
MeSH	D013966
DOID	DOID:7166
ICD-10-CM	E06
ICD-11	587793334
NCIT	C26894
SNOMED CT	82119001
UMLS	C0040147
MedGen	21548
Is cancer (heuristic)	no

Also known as: inflammation of thyroid gland · thyroid gland inflammation · thyroiditis · thyroiditis (disease)

Data availability: 1 ClinVar variant · 15 GWAS associations (14 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › thyroid gland disorder › thyroiditis

Related subtypes (11): thyrocalcitonin secretion disease, hyperthyroidism, thyroid malformation, hyperthyroxinemia, goiter, hypothyroidism, C-cell hyperplasia, atrophy of thyroid, euthyroid sick syndrome, thyroid tumor, inherited thyroid metabolism disease

Subtypes (3): suppurative thyroiditis, acute thyroiditis, autoimmune thyroid disease

Genetics & variants

GWAS landscape

15 GWAS associations across 14 studies. Top hits map to 7 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9501117	1e-46	MICA - LINC01149	?
rs9295987	6e-17	ZDHHC20P2 - HLA-S	?
rs902084651	3e-13	PDE10A	G	3.7
rs549207705	2e-12	RPL36AP6 - RNA5SP293	C	1.53
rs572792123	2e-12	NXPH1 - GAPDHP68	G	4.35
rs185773423	4e-12	TPRKB	C	2.85
rs147250301	5e-12	SF3A3	G	2.8
rs541866506	8e-12	IMPDH1 - RNU7-54P	C	3.36
rs549432880	9e-12	STK32A	G	2.76
rs542203472	1e-11	RNU6-649P - LINC01248	C	5
rs528828146	2e-11	PPM1H	T	3.78
rs183703108	2e-11	RBBP4P4 - PRIM2BP	C	2.24
rs78775620	2e-11	TG	C	0.63
rs372836892	4e-11	PGAP4	A	4.15
rs28366353	5e-10	HLA-DRB1 - HLA-DQA1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90651198	Liu TY	2025	2,007	212,391	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90477304	Verma A	2024	1,904	447,836	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651278	Liu TY	2025	1,585	212,391	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90473162	UK Biobank Whole-Genome Sequencing Consortium	2025	1,391	457,049	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90481573	Verma A	2024	1,254	449,243	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481574	Verma A	2024	1,174	449,481	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479871	Verma A	2024	392	121,065	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481572	Verma A	2024	392	121,065	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90435696	Zhou W	2018	293	391,429	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651147	Liu TY	2025	275	212,391	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	15

MAF distribution

Bucket	Variants
common (>=0.05)	3
low_freq (0.01-0.05)	1
rare (<0.01)	11
unknown	0

Functional consequences

Consequence	Count
intron_variant	9
intergenic_variant	6

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9501117	6	31430814	A>G	0.05	intron_variant	MICA - LINC01149	1e-46	Tier 4: intronic/intergenic
rs9295987	6	31382067	A>G	0.05	intergenic_variant	ZDHHC20P2 - HLA-S	6e-17	Tier 4: intronic/intergenic
rs902084651	6	165969374	G>A	0.001	intron_variant	PDE10A	3e-13	Tier 4: intronic/intergenic
rs549207705	9	107900624	C>G	0.007	intergenic_variant	RPL36AP6 - RNA5SP293	2e-12	Tier 4: intronic/intergenic
rs572792123	7	8988324	G>A	0	intergenic_variant	NXPH1 - GAPDHP68	2e-12	Tier 4: intronic/intergenic
rs185773423	2	73734715	C>G,T	0.001	intron_variant	TPRKB	4e-12	Tier 4: intronic/intergenic
rs147250301	1	37972001	G>A	0.001	intron_variant	SF3A3	5e-12	Tier 4: intronic/intergenic
rs541866506	7	128429905	C>T	0	intron_variant	IMPDH1 - RNU7-54P	8e-12	Tier 4: intronic/intergenic
rs549432880	5	147294363	G>A	0	intron_variant	STK32A	9e-12	Tier 4: intronic/intergenic
rs542203472	2	5357321	C>T	0	intergenic_variant	RNU6-649P - LINC01248	1e-11	Tier 4: intronic/intergenic
rs528828146	12	62793893	T>C	0.001	intron_variant	PPM1H	2e-11	Tier 4: intronic/intergenic
rs183703108	6	58414288	C>G,T	0.001	intron_variant	RBBP4P4 - PRIM2BP	2e-11	Tier 4: intronic/intergenic
rs78775620	8	132869226	C>T	0.019	intron_variant	TG	2e-11	Tier 4: intronic/intergenic
rs372836892	9	101495853	A>C,G	0	intergenic_variant	PGAP4	4e-11	Tier 4: intronic/intergenic
rs28366353	6	32597227	A>G	0.05	intergenic_variant	HLA-DRB1 - HLA-DQA1	5e-10	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3238621	NM_002771.4(PRSS3):c.74T>C (p.Val25Ala)	PRSS3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
PRSS3	HGNC:9486	ENSG00000010438	P35030	Trypsin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRSS3	Trypsin-3	Digestive protease that cleaves proteins preferentially after an Arg residue and has proteolytic activity toward Kunitz-type trypsin inhibitors.

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRSS3	Protease	yes		Trypsin_dom, Peptidase_S1A, Peptidase_S1_PA

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
body of pancreas	1
lower esophagus mucosa	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRSS3	232	broad	marker	body of pancreas, pancreas, lower esophagus mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRSS3	99

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRSS3	P35030	16

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Uptake of dietary cobalamins into enterocytes	1	1142.0×	0.002	PRSS3
Alpha-defensins	1	1038.2×	0.002	PRSS3
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	278.5×	0.006	PRSS3
Antimicrobial peptides	1	223.9×	0.006	PRSS3
Neutrophil degranulation	1	23.1×	0.043	PRSS3

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
antimicrobial humoral response	1	1532.0×	0.003	PRSS3
zymogen activation	1	674.1×	0.003	PRSS3
digestion	1	624.1×	0.003	PRSS3
endothelial cell migration	1	411.0×	0.003	PRSS3
proteolysis	1	34.2×	0.029	PRSS3

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
PRSS3	ARGATROBAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRSS3	12	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ARGATROBAN	4	PRSS3
MELAGATRAN	4	PRSS3
SULFAGUANIDINE	4	PRSS3
BEROTRALSTAT	4	PRSS3
RUTIN	3	PRSS3
MILVEXIAN	3	PRSS3
DABIGATRAN	3	PRSS3
QUERCETIN	3	PRSS3
CAMOSTAT	3	PRSS3
SILIBININ	3	PRSS3
SEPIMOSTAT	2	PRSS3
BAICALEIN	2	PRSS3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PRSS3	393	Binding:342, ADMET:51

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
PRSS3	393

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

12 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)
ARGATROBAN	4	PRSS3
MELAGATRAN	4	PRSS3
SULFAGUANIDINE	4	PRSS3
BEROTRALSTAT	4	PRSS3
RUTIN	3	PRSS3
MILVEXIAN	3	PRSS3
DABIGATRAN	3	PRSS3
QUERCETIN	3	PRSS3
CAMOSTAT	3	PRSS3
SILIBININ	3	PRSS3
SEPIMOSTAT	2	PRSS3
BAICALEIN	2	PRSS3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PRSS3
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: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	8
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07571681	PHASE2/PHASE3	NOT_YET_RECRUITING	Colchicine for Autoimmune and Subacute Thyroiditis
NCT01227499	Not specified	COMPLETED	Differential Diagnosis of STA-PSV in Thyrotoxicosis
NCT01320813	Not specified	TERMINATED	Trial Comparing Complication Rates Associated With Robot-assisted Thyroidectomy to External Thyroidectomy
NCT02778412	Not specified	TERMINATED	ctDNA in Patients With Thyroid Nodules
NCT03009357	Not specified	COMPLETED	Clinical Application of Pulse Rate-monitoring Activity Trackers in Thyrotoxicosis
NCT04410601	Not specified	UNKNOWN	Post-thyroidectomy Dysphagia: An International Multicentric CONSORT - Compatible RCT
NCT04754607	Not specified	COMPLETED	Effects of Low-Level Laser Therapy on Oxidative Stress Levels
NCT05252884	Not specified	COMPLETED	Calcium+Calcitriol Versus PTH for the Prevention of Hypocalcemia in Thyroidectomy. Randomized Clinical Trial
NCT06735040	Not specified	COMPLETED	Effect of Photobiomodulation Therapy in Patients With Hashimoto’s Thyroiditis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
COLCHICINE	4	1