Hashimoto thyroiditis

Summary

Hashimoto thyroiditis (MONDO:0007699) is a disease with 14 cohort genes (130 GWAS associations across 17 studies) and 35 clinical trials. Top therapeutic interventions include cosyntropin and dexamethasone.

At a glance

• Cohort genes: 14
• GWAS associations: 130
• ClinVar variants: 5
• Clinical trials: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hashimoto thyroiditis
Mondo ID	MONDO:0007699
EFO	EFO:0003779
MeSH	D050031
OMIM	140300
Orphanet	855
DOID	DOID:7188
ICD-10-CM	E06.3
ICD-11	972507934
NCIT	C27191
UMLS	C0677607
MedGen	151769
Is cancer (heuristic)	no

Also known as: chronic lymphocytic thyroiditides · chronic lymphocytic thyroiditis · disease, Hashimoto · disease, Hashimoto’s · Hashimoto disease · Hashimoto hypothyroidism · Hashimoto struma · Hashimoto syndrome · Hashimoto thyroiditides · Hashimoto thyroiditis · Hashimoto’s disease · Hashimoto’s struma · Hashimoto’s syndrome · Hashimoto’s syndromes · Hashimoto’s thyroiditis · Hashimotos disease · Hashimotos syndrome · HT · hypothyroidism, autoimmune thyroid autoantibodies, included · lymphocytic thyroiditides, chronic (+8 more)

Data availability: 5 ClinVar variants · 130 GWAS associations (17 studies) · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › autoimmune disorder of endocrine system › autoimmune thyroid disease › Hashimoto thyroiditis

Related subtypes (4): Graves disease, atrophic thyroiditis, IgG4-related thyroid disease, postpartum thyroiditis

Genetics & variants

GWAS landscape

130 GWAS associations across 17 studies. Top hits map to 32 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6679677	1e-93	PHTF1 - RSBN1	A	0.41
rs9271365	3e-77	HLA-DRB1 - HLA-DQA1	G	0.23
rs7137828	2e-55	ATXN2	T	0.21
rs7847663	1e-50	PTCSC2	T	0.2
rs2476601	3e-45	AP4B1-AS1, PTPN22	G	0.33
rs10739496	1e-43	PTCSC2	T	0.2
rs11571302	5e-43	CTLA4 - ICOS	T	0.17
rs3087243	9e-39	CTLA4 - ICOS	A	0.18
rs80173139	2e-37	VAV3	G	0.24
rs7030280	6e-31	PTCSC2	T	0.21
rs3184504	1e-25	ATXN2, SH2B3	C	0.18
rs11571297	2e-23	CTLA4 - ICOS	G	1.37
rs3756838	3e-22	RNASET2 - MIR3939	A	0.14
rs7073236	2e-19	IL2RA - RPL32P23	C	0.11
rs75143612	2e-19	PHF20L1	C	0.38
rs114322847	1e-18	TG	T	0.37
rs17020139	3e-18	VAV3	A	0.21
rs71508903	7e-17	ARID5B	T	0.12
rs201758905	1e-16	CD69 - GCNAP1	C	0.12
rs72928038	8e-16	BACH2	A	0.14
rs1993945	1e-15	PDE8B	T	0.13
rs13098877	2e-15	LPP	T	0.1
rs661713	4e-15	BACH2	A	0.11
rs705704	4e-15	RPS26	A	0.1
rs117295261	6e-15	SFTA2	T	0.83
rs10168266	9e-15	STAT4	T	0.11
rs706778	1e-14	IL2RA	T	0.11
rs796395	1e-14	LINC02869	A	0.12
rs34636506	2e-14	RNU6-474P - CTLA4	G	0.13
rs12575636	1e-13	LNCRNA-IUR - FAM76B	G	0.11

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90428825	Yu X	2024	15,654	396,652	Shared genetic architecture between autoimmune disorders and B-cell acute lymphoblastic leukemia: insights from large-scale genome-wide cross-trait analysis.
GCST90018855	Sakaue S	2021	15,654	379,986	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90627754	White SL	2026	15,106	1,405,552	Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases.
GCST90627771	White SL	2026	12,023	1,331,755	Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases.
GCST005524	Cooper JD	2012	2,282	0	Seven newly identified loci for autoimmune thyroid disease.
GCST90651262	Liu TY	2025	1,571	212,391	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90627752	White SL	2026	1,142	59,393	Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases.
GCST90627753	White SL	2026	703	183,005	Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases.
GCST90627751	White SL	2026	625	85,422	Global multi-ancestry genome-wide analyses identify genes and biological pathways associated with thyroid cancer and benign thyroid diseases.
GCST90018635	Sakaue S	2021	537	172,656	A cross-population atlas of genetic associations for 220 human phenotypes.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	43

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	32
intergenic_variant	11
missense_variant	4
regulatory_region_variant	1
5_prime_UTR_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6679677	1	113761186	C>A,T	0.085	intergenic_variant	PHTF1 - RSBN1	1e-93	Tier 4: intronic/intergenic
rs9271365	6	32619017	T>A,C,G	0.423	intergenic_variant	HLA-DRB1 - HLA-DQA1	3e-77	Tier 4: intronic/intergenic
rs7137828	12	111494996	C>A,G,T	0.495	intron_variant	ATXN2	2e-55	Tier 4: intronic/intergenic
rs7847663	9	97782586	C>A,G,T	0.314	intron_variant	PTCSC2	1e-50	Tier 4: intronic/intergenic
rs2476601	1	113834946	A>G,T	0.05	missense_variant	AP4B1-AS1, PTPN22	3e-45	Tier 1: coding
rs10739496	9	97790277	C>A,G,T	0.34	intron_variant	PTCSC2	1e-43	Tier 4: intronic/intergenic
rs11571302	2	203878211	G>A,T	0.448	intergenic_variant	CTLA4 - ICOS	5e-43	Tier 4: intronic/intergenic
rs3087243	2	203874196	G>A,T	0.448	intergenic_variant	CTLA4 - ICOS	9e-39	Tier 4: intronic/intergenic
rs80173139	1	107822516	A>G	0.112	intron_variant	VAV3	2e-37	Tier 4: intronic/intergenic
rs7030280	9	97772985	C>T	0.05	intron_variant	PTCSC2	6e-31	Tier 4: intronic/intergenic
rs3184504	12	111446804	T>A,C,G	0.05	missense_variant	ATXN2, SH2B3	1e-25	Tier 1: coding
rs11571297	2	203880280	T>C	0.493	intergenic_variant	CTLA4 - ICOS	2e-23	Tier 4: intronic/intergenic
rs3756838	6	166957763	G>A,C,T	0.246	intergenic_variant	RNASET2 - MIR3939	3e-22	Tier 4: intronic/intergenic
rs7073236	10	6064589	T>A,C	0.434	intergenic_variant	IL2RA - RPL32P23	2e-19	Tier 4: intronic/intergenic
rs75143612	8	132837410	G>C,T	0.02	intron_variant	PHF20L1	2e-19	Tier 4: intronic/intergenic
rs114322847	8	132871426	C>T	0.022	missense_variant	TG	1e-18	Tier 1: coding
rs17020139	1	107826861	G>A	0.05	intron_variant	VAV3	3e-18	Tier 4: intronic/intergenic
rs71508903	10	62020112	C>T	0.186	intron_variant	ARID5B	7e-17	Tier 4: intronic/intergenic
rs201758905	12	9772381	CTTT>C,CT,CTT,CTTTT,CTTTTT,CTTTTTTTTTT,CTTTTTTTTTTT	0.288	intergenic_variant	CD69 - GCNAP1	1e-16	Tier 4: intronic/intergenic
rs72928038	6	90267049	G>A	0.144	intron_variant	BACH2	8e-16	Tier 4: intronic/intergenic
rs1993945	5	77222370	A>C,G,T	0.05	intron_variant	PDE8B	1e-15	Tier 4: intronic/intergenic
rs13098877	3	188415375	C>T	0.431	intron_variant	LPP	2e-15	Tier 4: intronic/intergenic
rs661713	6	90266280	G>A,C,T	0.393	intron_variant	BACH2	4e-15	Tier 4: intronic/intergenic
rs705704	12	56041628	G>A,C	0.295	regulatory_region_variant	RPS26	4e-15	Tier 3: regulatory
rs117295261	6	30934590	G>T	0.044	5_prime_UTR_variant	SFTA2	6e-15	Tier 2: splice/UTR
rs10168266	2	191071078	C>T	0.206	intron_variant	STAT4	9e-15	Tier 4: intronic/intergenic
rs706778	10	6056986	C>G,T	0.404	intron_variant	IL2RA	1e-14	Tier 4: intronic/intergenic
rs796395	1	218508629	G>A	0.4	intron_variant	LINC02869	1e-14	Tier 4: intronic/intergenic
rs34636506	2	203827493	A>G,T	0.05	intergenic_variant	RNU6-474P - CTLA4	2e-14	Tier 4: intronic/intergenic
rs12575636	11	95578096	T>G	0.171	intron_variant	LNCRNA-IUR - FAM76B	1e-13	Tier 4: intronic/intergenic

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 pathogenic, 2 conflicting classifications of pathogenicity, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
161109	NM_005214.5(CTLA4):c.151C>T (p.Arg51Ter)	CTLA4	Pathogenic	reviewed by expert panel
636389	NM_005214.5(CTLA4):c.457G>A (p.Asp153Asn)	CTLA4	Pathogenic	reviewed by expert panel
432079	NM_005214.5(CTLA4):c.410C>T (p.Pro137Leu)	CTLA4	Likely pathogenic	reviewed by expert panel
430906	NM_005214.5(CTLA4):c.118G>A (p.Val40Met)	CTLA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
574111	NM_005214.5(CTLA4):c.410C>A (p.Pro137Gln)	CTLA4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 21 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BACH2	Orphanet:714472	Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
MMEL1	Orphanet:186	Primary biliary cholangitis
CCR6	Orphanet:220393	Diffuse cutaneous systemic sclerosis
CCR6	Orphanet:220402	Limited cutaneous systemic sclerosis
PRICKLE1	Orphanet:308	Progressive myoclonic epilepsy type 1
CTLA4	Orphanet:2584	Classic mycosis fungoides
CTLA4	Orphanet:3162	Sézary syndrome
CTLA4	Orphanet:391490	Adult-onset myasthenia gravis
CTLA4	Orphanet:436159	Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency
CTLA4	Orphanet:536	Systemic lupus erythematosus
CTLA4	Orphanet:900	Granulomatosis with polyangiitis
IL2RA	Orphanet:169100	Immunodeficiency due to CD25 deficiency
IL2RA	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
IL2RA	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
ITGAM	Orphanet:536	Systemic lupus erythematosus
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

14 cohort genes, 14 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	13
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
VAV3	HGNC:12659	ENSG00000134215	Q9UKW4	Guanine nucleotide exchange factor VAV3	gwas
BACH2	HGNC:14078	ENSG00000112182	Q9BYV9	Transcription regulator protein BACH2	gwas
MMEL1	HGNC:14668	ENSG00000142606	Q495T6	Membrane metallo-endopeptidase-like 1	gwas
CCR6	HGNC:1607	ENSG00000112486	P51684	C-C chemokine receptor type 6	gwas
CEP43	HGNC:17012	ENSG00000213066	O95684	Centrosomal protein 43	gwas
PRICKLE1	HGNC:17019	ENSG00000139174	Q96MT3	Prickle-like protein 1	gwas
SDK2	HGNC:19308	ENSG00000069188	Q58EX2	Protein sidekick-2	gwas
SLC25A27	HGNC:21065	ENSG00000153291	O95847	Mitochondrial uncoupling protein 4	gwas
CTLA4	HGNC:2505	ENSG00000163599	P16410	Cytotoxic T-lymphocyte protein 4	clinvar
TRIB2	HGNC:30809	ENSG00000071575	Q92519	Tribbles homolog 2	gwas
IL2RA	HGNC:6008	ENSG00000134460	P01589	Interleukin-2 receptor subunit alpha	gwas
ITGAM	HGNC:6149	ENSG00000169896	P11215	Integrin alpha-M	gwas
LPP	HGNC:6679	ENSG00000145012	Q93052	Lipoma-preferred partner	gwas
PTPN22	HGNC:9652	ENSG00000134242	Q9Y2R2	Tyrosine-protein phosphatase non-receptor type 22	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
VAV3	Guanine nucleotide exchange factor VAV3	Exchange factor for GTP-binding proteins RhoA, RhoG and, to a lesser extent, Rac1.
BACH2	Transcription regulator protein BACH2	Transcriptional regulator that acts as a repressor or activator.
MMEL1	Membrane metallo-endopeptidase-like 1	Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development.
CCR6	C-C chemokine receptor type 6	Receptor for the C-C type chemokine CCL20.
CEP43	Centrosomal protein 43	Required for anchoring microtubules to the centrosomes.
PRICKLE1	Prickle-like protein 1	Involved in the planar cell polarity pathway that controls convergent extension during gastrulation and neural tube closure.
SDK2	Protein sidekick-2	Adhesion molecule that promotes lamina-specific synaptic connections in the retina and is specifically required for the formation of neuronal circuits that detect motion.
SLC25A27	Mitochondrial uncoupling protein 4	Facilitates proton transport across the inner mitochondrial membrane and may dissipate excessive proton gradient associated with oxidative and metabolic stress at neuronal synapses.
CTLA4	Cytotoxic T-lymphocyte protein 4	Inhibitory receptor acting as a major negative regulator of T-cell responses.
TRIB2	Tribbles homolog 2	Interacts with MAPK kinases and regulates activation of MAP kinases.
IL2RA	Interleukin-2 receptor subunit alpha	Receptor for interleukin-2.
ITGAM	Integrin alpha-M	Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens.
LPP	Lipoma-preferred partner	May play a structural role at sites of cell adhesion in maintaining cell shape and motility.
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: 9 · Difficult: 4 · Unknown: 1 · Druggable fraction: 0.64

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	3	6.3×	0.110
Complement	1	19.1×	0.255
Phosphatase	1	6.0×	0.414
Transporter	1	5.6×	0.414
Transcription factor	3	1.8×	0.472
Protease	1	2.6×	0.536
Kinase	1	2.0×	0.562
GPCR	1	1.7×	0.562
Scaffold/PPI	1	1.2×	0.629
Other/Unknown	1	0.1×	1.000

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
VAV3	Scaffold/PPI	no		DH_dom, SH2, GDS_CDC24_CS
BACH2	Transcription factor	no		BTB/POZ_dom, bZIP_Maf, bZIP
MMEL1	Protease	yes	3.4.24.B14	Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
CCR6	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR6
CEP43	Other/Unknown	no		LisH, FOP_dimerisation-dom_N
PRICKLE1	Transcription factor	no		Znf_LIM, PET_domain, PET_prickle
SDK2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
SLC25A27	Transporter	yes		MCP_transmembrane, MCP_dom_sf, Mito_Metabolite_Transporter
CTLA4	Antibody/Immunoglobulin	yes		Ig_sub, CTLA4, Ig_V-set
TRIB2	Kinase	yes		Prot_kinase_dom, Kinase-like_dom_sf, Tribbles/Ser_Thr_kinase_40
IL2RA	Complement	yes		Sushi_SCR_CCP_dom, IL-2_rcpt_alpha, Sushi/SCR/CCP_sf
ITGAM	Antibody/Immunoglobulin	yes		Integrin_alpha, VWF_A, FG-GAP
LPP	Transcription factor	no		Znf_LIM
PTPN22	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 0.

13 cohort genes 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)	14
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lymph node	3
vermiform appendix	3
tendon of biceps brachii	2
buccal mucosa cell	2
left ovary	2
monocyte	2
esophagus squamous epithelium	1
renal medulla	1
tongue squamous epithelium	1
cortical plate	1
epithelium of nasopharynx	1
sural nerve	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
spleen	1
secondary oocyte	1
sperm	1
lateral nuclear group of thalamus	1
cartilage tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
VAV3	258	ubiquitous	marker	tongue squamous epithelium, renal medulla, esophagus squamous epithelium
BACH2	237	ubiquitous	marker	cortical plate, sural nerve, epithelium of nasopharynx
MMEL1	131	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, left testis
CCR6	103	broad	marker	lymph node, vermiform appendix, spleen
CEP43	278	ubiquitous	marker	sperm, secondary oocyte, tendon of biceps brachii
PRICKLE1	243	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, lateral nuclear group of thalamus
SDK2	219	broad	marker	cartilage tissue, tibia, type B pancreatic cell
SLC25A27	243	ubiquitous	marker	mucosa of stomach, adenohypophysis, left ovary
CTLA4	164	tissue_specific	marker	lymph node, vermiform appendix, buccal mucosa cell
TRIB2	285	ubiquitous	marker	left ovary, ganglionic eminence, right ovary
IL2RA	153	broad	marker	lymph node, vermiform appendix, caecum
ITGAM	236	broad	marker	monocyte, mononuclear cell, leukocyte
LPP	292	ubiquitous	marker	saphenous vein, urethra, vena cava
PTPN22	190	broad	marker	bone marrow cell, bone marrow, monocyte

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITGAM	4,816
CTLA4	3,863
IL2RA	2,557
PTPN22	2,480
BACH2	1,917
CCR6	1,832
TRIB2	1,820
VAV3	1,575
PRICKLE1	1,485
SDK2	1,373

Intra-cohort edges

A	B	Sources
CCR6	CEP43	string_interaction
CTLA4	PTPN22	string_interaction

Structural data

PDB: 10 · AlphaFold-only: 4 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITGAM	P11215	31
CTLA4	P16410	22
PTPN22	Q9Y2R2	14
IL2RA	P01589	10
SDK2	Q58EX2	4
BACH2	Q9BYV9	2
VAV3	Q9UKW4	1
CCR6	P51684	1
CEP43	O95684	1
TRIB2	Q92519	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MMEL1	Q495T6	90.34
SLC25A27	O95847	80.95
LPP	Q93052	60.99
PRICKLE1	Q96MT3	55.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 76. Enrichment computed across 14 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	2	228.4×	0.002	CTLA4, IL2RA
SDK interactions	1	571.0×	0.067	SDK2
The fatty acid cycling model	1	228.4×	0.111	SLC25A27
FGFR1 mutant receptor activation	1	114.2×	0.126	CEP43
Interleukin-2 signaling	1	95.2×	0.126	IL2RA
Signaling by cytosolic FGFR1 fusion mutants	1	63.4×	0.126	CEP43
Translocation of ZAP-70 to Immunological synapse	1	63.4×	0.126	PTPN22
Phosphorylation of CD3 and TCR zeta chains	1	54.4×	0.126	PTPN22
Co-inhibition by CTLA4	1	51.9×	0.126	CTLA4
Azathioprine ADME	1	49.6×	0.126	VAV3
Signaling by FGFR in disease	1	42.3×	0.126	CEP43
VEGFR2 mediated vascular permeability	1	40.8×	0.126	VAV3
Interleukin receptor SHC signaling	1	40.8×	0.126	IL2RA
Co-stimulation by CD28	1	38.1×	0.126	CTLA4
DAP12 signaling	1	36.8×	0.126	VAV3
FCERI mediated Ca+2 mobilization	1	35.7×	0.126	VAV3
FCERI mediated MAPK activation	1	34.6×	0.126	VAV3
GPVI-mediated activation cascade	1	30.9×	0.126	VAV3
Signaling by FGFR1 in disease	1	29.3×	0.126	CEP43
Beta defensins	1	27.2×	0.126	CCR6
Centrosome maturation	1	25.4×	0.126	CEP43
Cell-cell junction organization	1	24.8×	0.126	SDK2
Defensins	1	23.8×	0.126	CCR6
Antimicrobial peptides	1	22.4×	0.126	CCR6
EPH-ephrin mediated repulsion of cells	1	22.0×	0.126	VAV3
Asymmetric localization of PCP proteins	1	20.4×	0.126	PRICKLE1
Chemokine receptors bind chemokines	1	18.7×	0.126	CCR6
Cell junction organization	1	18.7×	0.126	SDK2
FCGR3A-mediated phagocytosis	1	18.7×	0.126	VAV3
NRAGE signals death through JNK	1	18.4×	0.126	VAV3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of T cell tolerance induction	1	1203.7×	0.015	IL2RA
phosphoanandamide dephosphorylation	1	1203.7×	0.015	PTPN22
isotype switching to IgA isotypes	1	1203.7×	0.015	CCR6
primary adaptive immune response involving T cells and B cells	1	1203.7×	0.015	BACH2
DN3 thymocyte differentiation	1	1203.7×	0.015	CCR6
negative regulation of T cell activation	2	75.2×	0.015	CTLA4, PTPN22
B cell receptor signaling pathway	2	57.3×	0.015	VAV3, CTLA4
negative regulation of T cell receptor signaling pathway	2	52.3×	0.015	CTLA4, PTPN22
negative regulation of T cell proliferation	2	47.2×	0.015	CTLA4, IL2RA
cell-cell adhesion	3	21.8×	0.015	PRICKLE1, ITGAM, LPP
regulation of natural killer cell proliferation	1	601.9×	0.017	PTPN22
polarized secretion of basement membrane proteins in epithelium	1	601.9×	0.017	PRICKLE1
response to curcumin	1	601.9×	0.017	ITGAM
anterior visceral endoderm cell migration	1	601.9×	0.017	PRICKLE1
regulation of CD4-positive, alpha-beta T cell proliferation	1	601.9×	0.017	IL2RA
negative regulation of cardiac muscle cell myoblast differentiation	1	601.9×	0.017	PRICKLE1
positive regulation of neutrophil degranulation	1	401.2×	0.017	ITGAM
negative regulation of dopamine metabolic process	1	401.2×	0.017	ITGAM
regulation of T cell homeostatic proliferation	1	401.2×	0.017	IL2RA
positive regulation of flagellated sperm motility involved in capacitation	1	401.2×	0.017	CCR6
establishment of bipolar cell polarity involved in cell morphogenesis	1	401.2×	0.017	PRICKLE1
thymocyte migration	1	401.2×	0.017	CCR6
focal adhesion disassembly	1	401.2×	0.017	PRICKLE1
vertebrate eye-specific patterning	1	401.2×	0.017	ITGAM
ectodermal cell differentiation	1	300.9×	0.017	ITGAM
negative regulation of mitochondrial calcium ion concentration	1	300.9×	0.017	SLC25A27
renal tubule development	1	300.9×	0.017	PRICKLE1
tear secretion	1	300.9×	0.017	PRICKLE1
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	1	300.9×	0.017	PTPN22
maintenance of postsynaptic density structure	1	300.9×	0.017	PRICKLE1

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Selenomethionine	Phase 2

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 12

Druggability breadth: 9 of 14 evidence-associated genes (64%) 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
CCR6	TEGASEROD MALEATE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CCR6	3	4
TRIB2	1	1
VAV3	0	0
BACH2	0	0
MMEL1	0	0
CEP43	0	0
PRICKLE1	0	0
SDK2	0	0
SLC25A27	0	0
CTLA4	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TEGASEROD MALEATE	4	CCR6
NAVARIXIN ANHYDROUS	2	CCR6
PF-07054894	1	CCR6
5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1	TRIB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
PTPN22	137	Binding:122, Functional:10, ADMET:5
CCR6	60	Functional:33, Binding:27
TRIB2	40	Binding:40
ITGAM	14	Binding:12, Functional:2
BACH2	3	Binding:3
MMEL1	2	Binding:2
CEP43	2	Binding:2
IL2RA	2	Binding:2
CTLA4	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MMEL1	3.4.24.B14
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: 14; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

4 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)
TEGASEROD MALEATE	4	CCR6
NAVARIXIN ANHYDROUS	2	CCR6
PF-07054894	1	CCR6
5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1	TRIB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CCR6
B	Phased (≥1) drug, not yet approved	1	TRIB2
C	Druggable family + PDB, no drug	5	SDK2, CTLA4, IL2RA, ITGAM, PTPN22
D	Druggable family + AlphaFold only, no drug	2	MMEL1, SLC25A27
E	Difficult family or no structure, no drug	5	VAV3, BACH2, CEP43, PRICKLE1, LPP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CEP43	2	CCR6
PTPN22	137	—
VAV3	0	—
BACH2	3	—
MMEL1	2	—
PRICKLE1	0	—
SDK2	0	—
SLC25A27	0	—
CTLA4	1	—
IL2RA	2	—
ITGAM	14	—
LPP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 35.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	32
PHASE4	1
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05435547	PHASE4	RECRUITING	Preoperative Corticosteroids in Autoimmune Thyroid Disease
NCT07571681	PHASE2/PHASE3	NOT_YET_RECRUITING	Colchicine for Autoimmune and Subacute Thyroiditis
NCT05077865	PHASE1	COMPLETED	Single Ascending and Multiple Dose Study to Evaluate Safety, Tolerability, and PK of MYMD1 in Healthy Male and Female Adult Subjects
NCT04693936	Not specified	ACTIVE_NOT_RECRUITING	Metabolic Biomarkers in Hashimoto’s Thyroiditis and Psoriasis
NCT06419309	Not specified	NOT_YET_RECRUITING	Comparison of the Effect of Gluten-Free-Lactose-Free / Aronia Melanocarpa Supplemented Diet in Patients With Hashimoto’s Thyroiditis
NCT06521359	Not specified	NOT_YET_RECRUITING	Role of Follicular T Cells in Hashimoto’s Thyroiditis
NCT06603415	Not specified	RECRUITING	Hashimoto’s Thyroiditis in Upper Egypt
NCT07060118	Not specified	ACTIVE_NOT_RECRUITING	Gluten Free Diet in Hashimoto’s Hypothyroidism
NCT07413874	Not specified	NOT_YET_RECRUITING	Telehealth Music Therapy for Adults With Endocrine Disorder and Depression
NCT00552487	Not specified	COMPLETED	Isolated ACTH Deficiency in Patients With Hashimoto Thyroiditis
NCT00958113	Not specified	COMPLETED	Autoimmune Thyroid Disease Genetic Study
NCT01102205	Not specified	COMPLETED	Evaluation of Oxidative Stress and Effect of Levothyroxine Treatment on Oxidative Stress in Hashimoto Disease
NCT01270425	Not specified	COMPLETED	Sonographic and Laboratory Evaluation of the Thyroid Gland in Patients With Systemic Sclerosis
NCT01760421	Not specified	COMPLETED	The Effect of Hydroxychloroquine Treatment in Hashimoto’s Thyroiditis
NCT01884649	Not specified	COMPLETED	Fetuin A in Hashimoto Thyroiditis
NCT02126683	Not specified	UNKNOWN	The Effect of Plaquenil on Serum Inflammatory Markers and Goiter in Euthyroid Young Women With Hashimoto’s Thyroiditis
NCT02190214	Not specified	COMPLETED	Thyroid Disorders in Malaysia: A Nationwide Multicentre Study
NCT02319538	Not specified	COMPLETED	Hashimoto - a Surgical Disease. Total Thyroidectomy Makes Antibodies Disappear and Ameliorates Symptoms
NCT02491567	Not specified	COMPLETED	DNA Methylation and Autoimmune Thyroid Diseases
NCT02725879	Not specified	COMPLETED	FGF-21 Levels and RMR in Children and Adolescents With Hashimoto’s Thyroiditis (THYROMETABOL)
NCT03114267	Not specified	COMPLETED	Involvement of Viral Infections in the Pathogenesis of Chronic Lymphocytic Thyroiditis
NCT03941184	Not specified	COMPLETED	Spontaneous Coronary Artery Dissection (SCAD) and Autoimmunity
NCT04239521	Not specified	COMPLETED	The Epidemiology, Management, and the Associated Burden of Related Conditions in Alopecia Areata
NCT04613323	Not specified	UNKNOWN	Management of Thyroid Function in Hashimoto’s Thyroiditis During Pregnancy
NCT04682340	Not specified	COMPLETED	Analysis of BPA Concentration in Serum in Women of Reproductive Age With Autoimmune Thyroid Disease
NCT04752202	Not specified	COMPLETED	The Influence of Reducing Diets on Changes in Thyroid Parameters in Obese Women With Hashimoto’s Disease
NCT04754607	Not specified	COMPLETED	Effects of Low-Level Laser Therapy on Oxidative Stress Levels
NCT04778865	Not specified	UNKNOWN	Effect of Treatment for Vitamin D Deficiency on Thyroid Function and Autoimmunity in Hashimoto’s Thyroiditis.
NCT04789993	Not specified	UNKNOWN	Additional Autoimmune Diseases With Type 1 Diabetes in Pediatrics at Diabetes Diagnosis and During Follow-up
NCT05871957	Not specified	UNKNOWN	Adjuvant Therapeutic Effect of Vitamin D on Hashimoto’s Thyroiditis
NCT05949671	Not specified	COMPLETED	Evaluation of the Effect of Gluten-Free Diet and Mediterranean Diet
NCT05975866	Not specified	UNKNOWN	The Effects of an Anti-inflammatory Diet With or Without Curcumin Supplementation on Anthropometric Measurements, Concentrations of Thyroid Hormones, Anti-TPO, and Systemic Inflammation in Plasma and NFK-B in Peripheral Blood Mononuclear Cells in Patients With Hashimato
NCT06735040	Not specified	COMPLETED	Effect of Photobiomodulation Therapy in Patients With Hashimoto’s Thyroiditis
NCT07048821	Not specified	COMPLETED	The Impact of Change of Thyroid Antibodies on Hormone Level and Disease Burden in Patients With Hashimoto’s Thyroiditis
NCT07510750	Not specified	COMPLETED	rT3 and Inflammation in Hashimoto’s Thyroiditis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
COSYNTROPIN	4	1
DEXAMETHASONE	4	1