Temporal arteritis

Summary

Temporal arteritis (MONDO:0008538) is a disease with 9 cohort genes (18 GWAS associations across 7 studies) and 130 clinical trials. The dominant Reactome pathway is Translocation of ZAP-70 to Immunological synapse (5 cohort genes). Top therapeutic interventions include tocilizumab, abatacept, and bosentan.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Cohort genes: 9
• GWAS associations: 18
• Phenotypes (HPO): 69
• Clinical trials: 130

Clinical features

Epidemiology

Prevalence records

8 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000		Europe	Validated
Annual incidence	1-9 / 1 000 000	0.35	United States	Validated
Annual incidence	1-9 / 100 000	2.8	Italy	Validated
Annual incidence	1-9 / 100 000	7.7	Sweden	Validated
Annual incidence	1-5 / 10 000	11.2	United Kingdom	Validated
Annual incidence	1-5 / 10 000	16.8	Norway	Validated
Point prevalence	1-9 / 100 000	8.9	Germany	Validated
Point prevalence	1-5 / 10 000	30.4	Italy	Validated

Signs & symptoms

Clinical features (HPO)

69 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0001387	Joint stiffness	Very frequent (80-99%)
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002039	Anorexia	Very frequent (80-99%)
HP:0002315	Headache	Very frequent (80-99%)
HP:0002633	Vasculitis	Very frequent (80-99%)
HP:0002637	Cerebral ischemia	Very frequent (80-99%)
HP:0005216	Impaired mastication	Very frequent (80-99%)
HP:0011227	Elevated circulating C-reactive protein concentration	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0000505	Visual impairment	Frequent (30-79%)
HP:0000597	Ophthalmoparesis	Frequent (30-79%)
HP:0000716	Depression	Frequent (30-79%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0001596	Alopecia	Frequent (30-79%)
HP:0001903	Anemia	Frequent (30-79%)
HP:0003565	Elevated erythrocyte sedimentation rate	Frequent (30-79%)
HP:0005413	Increased alpha-globulin	Frequent (30-79%)
HP:0005764	Polyarticular arthritis	Frequent (30-79%)
HP:0011899	Hyperfibrinogenemia	Frequent (30-79%)
HP:0030164	Jaw claudication	Frequent (30-79%)
HP:0030783	Increased circulating interleukin 6 concentration	Frequent (30-79%)
HP:0033123	Elevated circulating osteopontin level	Frequent (30-79%)
HP:0033834	Malaise	Frequent (30-79%)
HP:6000502	Elevated circulating calprotectin concentration	Frequent (30-79%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000206	Glossitis	Occasional (5-29%)
HP:0000365	Hearing impairment	Occasional (5-29%)
HP:0000405	Conductive hearing impairment	Occasional (5-29%)
HP:0000421	Epistaxis	Occasional (5-29%)
HP:0000508	Ptosis	Occasional (5-29%)
HP:0000572	Visual loss	Occasional (5-29%)
HP:0000639	Nystagmus	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000651	Diplopia	Occasional (5-29%)
HP:0000790	Hematuria	Occasional (5-29%)
HP:0000873	Diabetes insipidus	Occasional (5-29%)
HP:0000975	Hyperhidrosis	Occasional (5-29%)
HP:0001123	Visual field defect	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001260	Dysarthria	Occasional (5-29%)
HP:0001287	Meningitis	Occasional (5-29%)
HP:0001324	Muscle weakness	Occasional (5-29%)
HP:0001399	Hepatic failure	Occasional (5-29%)
HP:0001645	Sudden cardiac death	Occasional (5-29%)
HP:0001701	Pericarditis	Occasional (5-29%)
HP:0001872	Abnormality of thrombocytes	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002103	Abnormality of the pleura	Occasional (5-29%)
HP:0002321	Vertigo	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	temporal arteritis
Mondo ID	MONDO:0008538
EFO	EFO:1001209
OMIM	187360
Orphanet	397
DOID	DOID:13375
ICD-11	1929970386
NCIT	C35065
SNOMED CT	400130008
UMLS	C1956391
MedGen	365495
GARD	0009615
MedDRA	10018250, 10043207
NORD	805
Is cancer (heuristic)	no

Also known as: arteritis cranialis · arteritis temporalis · GCA · Giant Cell Arteritis · giant cell arteritis · Horton disease · Horton’s arteritis · Horton’s giant cell arteritis · Horton’s temporal arteritis · Horton’s disease · Horton’s syndrome · inflammation of temporal artery · temporal arteritis · temporal artery inflammation

Data availability: 18 GWAS associations (7 studies) · 6 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › arteritis › granulomatous angiitis › temporal arteritis

Subtypes (1): arteritic anterior ischemic optic neuropathy

Genetics & variants

GWAS landscape

18 GWAS associations across 7 studies. Top hits map to 10 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs41269974	2e-87	HLA-DQA1 - HLA-DQB1	A	2.03
rs17882084	4e-87	HLA-DRB1	A	2.02
rs9268905	2e-54	HLA-DRB9	?	1.79
rs1049087	8e-44	HLA-DQB1	A	1.49
rs9275592	1e-40	MTCO3P1 - HLA-DQB3	?	2.08
rs477515	4e-40	HLA-DRB1 - HLA-DQA1	?	1.73
rs4252114	1e-13	PLG	C	1.25
rs4252134	1e-10	PLG	?	1.28
rs2596501	3e-10	LINC02571 - HLA-B	G	1.2
rs704	3e-09	VTN, SARM1	A	0.84
rs128738	5e-09	P4HA2	?	1.32
rs11782624	1e-08	CCDC25	T	1.18
rs8029053	5e-08	MFGE8	T	1.19
rs2856726	1e-07	HLA-DQB1 - MTCO3P1	A	1.17
HLA-DPB1*03	4e-07		?	0.77
rs6679677	1e-06	PHTF1 - RSBN1	A	1.39
rs10160518	4e-06	EMSY - LINC02757	A	1.2
rs2256175	8e-06	MICA	?	1.18

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90446467	Borrego-Yaniz G	2024	3,498	15,550	Risk loci involved in giant cell arteritis susceptibility: a genome-wide association study.
GCST90454278	Zeng Y	2023	3,391	373,480	Genetic Associations Between Stress-Related Disorders and Autoimmune Disease.
GCST003928	Carmona FD	2016	2,134	9,125	A Genome-wide Association Study Identifies Risk Alleles in Plasminogen and P4HA2 Associated with Giant Cell Arteritis.
GCST006198	Carmona FD	2015	1,651	15,306	A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility.
GCST90482043	Verma A	2024	876	449,995	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436168	Zhou W	2018	388	400,595	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90044019	Jiang L	2021	278	456,070	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	16

MAF distribution

Bucket	Variants
common (>=0.05)	18
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	8
intergenic_variant	6
stop_gained	1
synonymous_variant	1
missense_variant	1
unknown	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs41269974	6	32652425	G>A,T	0.05	intergenic_variant	HLA-DQA1 - HLA-DQB1	2e-87	Tier 4: intronic/intergenic
rs17882084	6	32581836	G>A,C,T	0.16	stop_gained	HLA-DRB1	4e-87	Tier 1: coding
rs9268905	6	32464300	G>A,C,T	0.37	intron_variant	HLA-DRB9	2e-54	Tier 4: intronic/intergenic
rs1049087	6	32662112	G>A,C,T	0.41	synonymous_variant	HLA-DQB1	8e-44	Tier 4: intronic/intergenic
rs9275592	6	32712843	G>A,T	0.11	intergenic_variant	MTCO3P1 - HLA-DQB3	1e-40	Tier 4: intronic/intergenic
rs477515	6	32601914	G>A,C,T	0.05	intergenic_variant	HLA-DRB1 - HLA-DQA1	4e-40	Tier 4: intronic/intergenic
rs4252114	6	160722158	T>C	0.05	intron_variant	PLG	1e-13	Tier 4: intronic/intergenic
rs4252134	6	160732495	T>C	0.28	intron_variant	PLG	1e-10	Tier 4: intronic/intergenic
rs2596501	6	31353434	C>A,G,T	0.48	intron_variant	LINC02571 - HLA-B	3e-10	Tier 4: intronic/intergenic
rs704	17	28367840	G>A	0.05	missense_variant	VTN, SARM1	3e-09	Tier 1: coding
rs128738	5	132205182	G>A,T	0.17	intron_variant	P4HA2	5e-09	Tier 4: intronic/intergenic
rs11782624	8	27755870	G>C,T	0.05	intron_variant	CCDC25	1e-08	Tier 4: intronic/intergenic
rs8029053	15	88906856	C>G,T	0.05	intron_variant	MFGE8	5e-08	Tier 4: intronic/intergenic
rs2856726	6	32698944	A>C,G,T	0.36	intergenic_variant	HLA-DQB1 - MTCO3P1	1e-07	Tier 4: intronic/intergenic
HLA-DPB1*03				0.11			4e-07	Tier 4: intronic/intergenic
rs6679677	1	113761186	C>A,T	0.095	intergenic_variant	PHTF1 - RSBN1	1e-06	Tier 4: intronic/intergenic
rs10160518	11	76585627	A>G	0.494	intergenic_variant	EMSY - LINC02757	4e-06	Tier 4: intronic/intergenic
rs2256175	6	31412672	C>G,T	0.05	intron_variant	MICA	8e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 32 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 4

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
HLA-B	HLA-B	GWAS, Orphanet
HLA-DRB1	HLA-DRB1	GWAS, Orphanet
P4HA2	P4HA2	GWAS, Orphanet
PTPN22	PTPN22	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome
HLA-B	Orphanet:397	Giant cell arteritis
HLA-DQA1	Orphanet:391490	Adult-onset myasthenia gravis
HLA-DQA1	Orphanet:930	Idiopathic achalasia
HLA-DRA	Orphanet:505	Graham Little-Piccardi-Lassueur syndrome
HLA-DRB1	Orphanet:2073	Narcolepsy type 1
HLA-DRB1	Orphanet:220393	Diffuse cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220402	Limited cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220407	Limited systemic sclerosis
HLA-DRB1	Orphanet:3437	Vogt-Koyanagi-Harada disease
HLA-DRB1	Orphanet:397	Giant cell arteritis
HLA-DRB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DRB1	Orphanet:536	Systemic lupus erythematosus
HLA-DRB1	Orphanet:545	Follicular lymphoma
HLA-DRB1	Orphanet:703	Bullous pemphigoid
HLA-DRB1	Orphanet:747	Autoimmune pulmonary alveolar proteinosis
HLA-DRB1	Orphanet:797	Sarcoidosis
HLA-DRB1	Orphanet:83465	Narcolepsy type 2
HLA-DRB1	Orphanet:85414	Systemic-onset juvenile idiopathic arthritis
P4HA2	Orphanet:397	Giant cell arteritis
PLG	Orphanet:537072	PLG-related hereditary angioedema with normal C1Inh
PLG	Orphanet:722	Hypoplasminogenemia
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

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	9

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LRRC32	HGNC:4161	ENSG00000137507	Q14392	Transforming growth factor beta activator LRRC32	gwas
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas
HLA-DQA1	HGNC:4942	ENSG00000196735	P01909	HLA class II histocompatibility antigen, DQ alpha 1 chain	gwas
HLA-DQA2	HGNC:4943	ENSG00000237541	P01906	HLA class II histocompatibility antigen, DQ alpha 2 chain	gwas
HLA-DRA	HGNC:4947	ENSG00000204287	P01903	HLA class II histocompatibility antigen, DR alpha chain	gwas
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas
P4HA2	HGNC:8547	ENSG00000072682	O15460	Prolyl 4-hydroxylase subunit alpha-2	gwas
PLG	HGNC:9071	ENSG00000122194	P00747	Plasminogen	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)
LRRC32	Transforming growth factor beta activator LRRC32	Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space.
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQA2	HLA class II histocompatibility antigen, DQ alpha 2 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
P4HA2	Prolyl 4-hydroxylase subunit alpha-2	Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
PLG	Plasminogen	Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation.
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: 8 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.89

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	5	16.2×	3e-05
Phosphatase	1	9.3×	0.256
Protease	1	4.1×	0.368
Enzyme (other)	1	1.3×	0.679
Other/Unknown	1	0.2×	0.999

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LRRC32	Other/Unknown	no		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HLA-DQA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQA2	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DRA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
P4HA2	Enzyme (other)	yes	1.14.11.2	Oxoglu/Fe-dep_dioxygenase_dom, Pro_4_hyd_alph, TPR-like_helical_dom_sf
PLG	Protease	yes	3.4.21.7	Kringle, Trypsin_dom, Peptidase_S1A
PTPN22	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

Expression context

Cohort genes with no expression data: 0.

9 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	3
monocyte	3
vermiform appendix	3
right lung	2
left coronary artery	1
right coronary artery	1
blood	1
spleen	1
gall bladder	1
rectum	1
male germ line stem cell (sensu Vertebrata) in testis	1
leukocyte	1
body of pancreas	1
stromal cell of endometrium	1
tibia	1
adult organism	1
liver	1
right lobe of liver	1
bone marrow	1
bone marrow cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LRRC32	220	ubiquitous	marker	right coronary artery, left coronary artery, right lung
HLA-B	134	ubiquitous	marker	blood, spleen, granulocyte
HLA-DQA1	244	broad	marker	gall bladder, rectum, monocyte
HLA-DQA2	127	broad	marker	granulocyte, vermiform appendix, male germ line stem cell (sensu Vertebrata) in testis
HLA-DRA	132	broad	marker	monocyte, leukocyte, vermiform appendix
HLA-DRB1	131	tissue_specific	marker	vermiform appendix, granulocyte, right lung
P4HA2	274	ubiquitous	marker	stromal cell of endometrium, tibia, body of pancreas
PLG	174	tissue_specific	marker	right lobe of liver, liver, adult organism
PTPN22	190	broad	marker	bone marrow cell, bone marrow, monocyte

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HLA-DRB1	3,448
PLG	3,441
HLA-DRA	3,244
HLA-B	3,209
PTPN22	2,480
P4HA2	2,423
HLA-DQA2	1,611
LRRC32	1,441
HLA-DQA1	196

Intra-cohort edges

A	B	Sources
HLA-B	HLA-DQA2	string_interaction
HLA-DQA1	HLA-DQA2	intact
HLA-DQA2	HLA-DRB1	string_interaction
HLA-DRA	HLA-DRB1	biogrid_interaction, intact, string_interaction
HLA-DRB1	PTPN22	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-B	P01889	237
HLA-DRA	P01903	140
HLA-DRB1	P01911	108
PLG	P00747	49
HLA-DQA1	P01909	28
PTPN22	Q9Y2R2	14
P4HA2	O15460	7
LRRC32	Q14392	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HLA-DQA2	P01906	89.29

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. Enrichment computed across 9 evidence-associated genes (8 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 8 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	5	396.5×	7e-12	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, PTPN22
Phosphorylation of CD3 and TCR zeta chains	5	339.9×	8e-12	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, PTPN22
Co-inhibition by PD-1	4	259.6×	6e-09	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
Interferon gamma signaling	5	78.4×	9e-09	HLA-B, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
Generation of second messenger molecules	4	173.0×	2e-08	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
Downstream TCR signaling	4	64.2×	9e-07	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
MHC class II antigen presentation	4	44.6×	3e-06	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
Endosomal/Vacuolar pathway	1	129.8×	0.022	HLA-B
Dissolution of Fibrin Clot	1	102.0×	0.025	PLG
DAP12 interactions	1	59.5×	0.038	HLA-B
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	1	49.2×	0.042	HLA-B
Activation of Matrix Metalloproteinases	1	38.6×	0.049	PLG
Signaling by PDGF	1	31.7×	0.055	PLG
Maturation of DENV proteins	1	26.4×	0.061	P4HA2
Collagen biosynthesis and modifying enzymes	1	21.3×	0.071	P4HA2
Interferon alpha/beta signaling	1	19.0×	0.074	HLA-B
ER-Phagosome pathway	1	16.2×	0.081	HLA-B
Degradation of the extracellular matrix	1	14.7×	0.084	PLG
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	11.2×	0.093	HLA-B
Platelet degranulation	1	11.0×	0.093	PLG
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	10.9×	0.093	HLA-B
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	10.8×	0.093	PLG
Neutrophil degranulation	1	2.9×	0.299	HLA-B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peptide antigen assembly with MHC class II protein complex	4	526.6×	4e-09	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
antigen processing and presentation of exogenous peptide antigen via MHC class II	4	271.8×	3e-08	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
positive regulation of immune response	4	240.7×	3e-08	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
positive regulation of T cell activation	4	221.7×	4e-08	HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class II	2	2106.5×	4e-06	HLA-DRA, HLA-DRB1
immune response	5	29.4×	4e-06	HLA-B, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1
positive regulation of T cell mediated cytotoxicity	3	191.5×	5e-06	HLA-B, HLA-DRA, HLA-DRB1
myeloid dendritic cell antigen processing and presentation	2	1404.3×	7e-06	HLA-DRA, HLA-DRB1
regulation of T-helper cell differentiation	2	1053.2×	1e-05	HLA-DRA, HLA-DRB1
positive regulation of CD4-positive, alpha-beta T cell activation	2	1053.2×	1e-05	HLA-DRA, HLA-DRB1
adaptive immune response	4	42.1×	1e-05	HLA-B, HLA-DQA1, HLA-DQA2, HLA-DRA
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	2	842.6×	2e-05	HLA-DRA, HLA-DRB1
positive regulation of memory T cell differentiation	2	468.1×	5e-05	HLA-DRA, HLA-DRB1
detection of bacterium	2	351.1×	9e-05	HLA-B, HLA-DRB1
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II	1	2106.5×	0.003	HLA-DRA
regulation of interleukin-4 production	1	2106.5×	0.003	HLA-DRB1
phosphoanandamide dephosphorylation	1	2106.5×	0.003	PTPN22
regulation of interleukin-10 production	1	1053.2×	0.005	HLA-DRB1
regulation of natural killer cell proliferation	1	1053.2×	0.005	PTPN22
establishment of protein localization to extracellular region	1	1053.2×	0.005	LRRC32
T cell receptor signaling pathway	2	38.0×	0.005	HLA-DRB1, PTPN22
trans-synaptic signaling by BDNF, modulating synaptic transmission	1	702.2×	0.006	PLG
regulation of dendritic cell differentiation	1	702.2×	0.006	HLA-B
regulation of T cell anergy	1	526.6×	0.007	HLA-B
regulation of interleukin-12 production	1	526.6×	0.007	HLA-B
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	1	526.6×	0.007	PTPN22
mononuclear cell migration	1	526.6×	0.007	PLG
positive regulation of fibrinolysis	1	421.3×	0.008	PLG
protection from natural killer cell mediated cytotoxicity	1	351.1×	0.009	HLA-B
regulation of B cell receptor signaling pathway	1	351.1×	0.009	PTPN22

Therapeutics

Drugs indicated for this disease

1 approved, 10 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Tocilizumab	Approved (phase 4)
Abatacept	Phase 3 (in late-stage trials)
Adalimumab	Phase 3 (in late-stage trials)
Anakinra	Phase 3 (in late-stage trials)
Hydroxychloroquine	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)
Sarilumab	Phase 3 (in late-stage trials)
Secukinumab	Phase 3 (in late-stage trials)
Sirukumab	Phase 3 (in late-stage trials)
Upadacitinib	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Baricitinib, Guselkumab, Infliximab, Prednisolone, Sodium Chloride, Ustekinumab.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 8

Druggability breadth: 6 of 9 evidence-associated genes (67%) 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
PLG	AMINOCAPROIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PLG	11	4
LRRC32	0	0
HLA-B	0	0
HLA-DQA1	0	0
HLA-DQA2	0	0
HLA-DRA	0	0
HLA-DRB1	0	0
P4HA2	0	0
PTPN22	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMINOCAPROIC ACID	4	PLG
TELAPREVIR	4	PLG
MELAGATRAN	4	PLG
BEROTRALSTAT	4	PLG
PENTAMIDINE	4	PLG
TRANEXAMIC ACID	4	PLG
NAFAMOSTAT	3	PLG
MILVEXIAN	3	PLG
DABIGATRAN	3	PLG
GABEXATE	3	PLG
EFEGATRAN	2	PLG

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
PLG	480	Binding:467, ADMET:7, Functional:6
PTPN22	137	Binding:122, Functional:10, ADMET:5
HLA-DRB1	17	Binding:17
HLA-DQA1	2	Binding:2
HLA-B	1	Binding:1
P4HA2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
P4HA2	1.14.11.2	procollagen-proline 4-dioxygenase
PLG	3.4.21.7	plasmin
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
PLG	480
PTPN22	137

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

Chemical tractability of cohort targets

11 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)
AMINOCAPROIC ACID	4	PLG
TELAPREVIR	4	PLG
MELAGATRAN	4	PLG
BEROTRALSTAT	4	PLG
PENTAMIDINE	4	PLG
TRANEXAMIC ACID	4	PLG
NAFAMOSTAT	3	PLG
MILVEXIAN	3	PLG
DABIGATRAN	3	PLG
GABEXATE	3	PLG
EFEGATRAN	2	PLG

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PLG
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	6	HLA-B, HLA-DQA1, HLA-DRA, HLA-DRB1, P4HA2, PTPN22
D	Druggable family + AlphaFold only, no drug	1	HLA-DQA2
E	Difficult family or no structure, no drug	1	LRRC32

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PTPN22	137	—
LRRC32	0	—
HLA-B	1	—
HLA-DQA1	2	—
HLA-DQA2	0	—
HLA-DRA	0	—
HLA-DRB1	17	—
P4HA2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 130.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	81
PHASE3	18
PHASE2	17
PHASE4	6
PHASE1	5
PHASE1/PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05193396	PHASE4	RECRUITING	Hydrocortisone and Placebo in Patients With Symptoms of Adrenal Insufficiency After Cessation of Glucocorticoid Treatment
NCT05435781	PHASE4	RECRUITING	Effect of Supplemental Hydrocortisone During Stress in Prednisolone-induced Adrenal Insufficiency
NCT06763783	PHASE4	ENROLLING_BY_INVITATION	Vaccination Against Herpes Zoster in Patients With Inflammatory Rheumatic Diseases
NCT01400464	PHASE4	UNKNOWN	Steroids Pharmacokinetics and the Response to Prednisone Therapy in Giant Cell Arteritis
NCT03244709	PHASE4	UNKNOWN	Tocilizumab Dose-tapering and Interruption in Patients With Giant Cell Arteritis Achieving the Clinical Remission.
NCT03726749	PHASE4	COMPLETED	Tocilizumab Plus a Short Prednisone Taper for GCA
NCT03892785	PHASE3	ACTIVE_NOT_RECRUITING	MEthotrexate Versus TOcilizumab for Treatment of GIant Cell Arteritis: a Multicenter, Randomized, Controlled Trial
NCT04012905	PHASE3	NOT_YET_RECRUITING	Giant Cell Arteritis: Comparison Between Two Standardized Corticosteroids Tapering
NCT04474847	PHASE3	RECRUITING	Abatacept for the Treatment of Giant Cell Arteritis
NCT04888221	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy of Tocilizumab in Association to Steroids in Giant Cell Arteritis With Cerebro-vascular Involvement
NCT06037460	PHASE3	ACTIVE_NOT_RECRUITING	TocilizuMab discontinuAtion in GIant Cell Arteritis
NCT06833411	PHASE3	NOT_YET_RECRUITING	Treatment for Giant Cell Arteritis With Tocilizumab and 8 as Compared to 26 Weeks of Prednisone
NCT00138983	PHASE3	COMPLETED	Prevention of Glucocorticoid-Induced Osteoporosis in Rheumatic Diseases: Alendronate Versus Alfacalcidol.
NCT00305539	PHASE3	COMPLETED	HECTHOR: Humira to Spare Steroids in Giant Cell Arteritis
NCT00430807	PHASE3	COMPLETED	Hydroxychloroquine in Giant Cell Arteritis
NCT01791153	PHASE3	COMPLETED	An Efficacy and Safety Study of Tocilizumab (RoActemra/Actemra) in Participants With Giant Cell Arteritis (GCA)
NCT02531633	PHASE3	TERMINATED	Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis
NCT02902731	PHASE3	TERMINATED	Giant Cell Arteritis and Anakinra Trial
NCT03192969	PHASE3	WITHDRAWN	A Study to Evaluate Efficacy and Safety of Subcutaneous Abatacept With Steroid Treatment Compared to Steroid Treatment Alone in Adults With Giant Cell Arteritis (GCA)
NCT03202368	PHASE3	COMPLETED	An Extension Study to Evaluate Long-Term Safety of Subcutaneous (SC) Tocilizumab in Participants With Giant Cell Arteritis (GCA)
NCT03600805	PHASE3	TERMINATED	Evaluation of Efficacy and Safety of Sarilumab in Patients With GCA
NCT03725202	PHASE3	COMPLETED	A Study to Evaluate the Safety and Efficacy of Upadacitinib in Participants With Giant Cell Arteritis
NCT04930094	PHASE3	COMPLETED	Phase III Study of Efficacy and Safety of Secukinumab Versus Placebo, in Combination With Glucocorticoid Taper Regimen, in Patients With Giant Cell Arteritis (GCA)
NCT05380453	PHASE3	COMPLETED	Efficacy and Safety of Secukinumab in Patients With New Onset of Giant Cell Arteritis Who Are in Clinical Remission
NCT06335888	PHASE2	RECRUITING	A Clinical Trial to Investigate 18F-AzaFol in the Diagnosis of Large Vessel Vasculitis
NCT06887062	PHASE2	RECRUITING	Dapagliflozin and Endothelin Receptor Antagonism in Large Vessel Vasculitis (DERAIL-LVV)
NCT06957002	PHASE2	NOT_YET_RECRUITING	Bosentan in the Treatment of Giant Cell Arteritis
NCT07108387	PHASE2	RECRUITING	Tocilizumab Discontinuation Versus Dose Reduction for Patients With Well-Controlled Giant Cell Arteritis
NCT00004686	PHASE2	COMPLETED	Phase II Randomized Study of Glucocorticoids With or Without Methotrexate for Treatment of Giant Cell Arteritis
NCT00076726	PHASE2	TERMINATED	A Study of the Safety and Effectiveness of Infliximab (Remicade) in Patients With Giant Cell Arteritis
NCT00556439	PHASE2	COMPLETED	Abatacept for Treating Adults With Giant Cell Arteritis and Takayasu’s Arteritis
NCT01450137	PHASE2	COMPLETED	Tocilizumab for Patients With Giant Cell Arteritis
NCT01910038	PHASE2	COMPLETED	Evaluation of Tocilizumab as an add-on Therapy to Corticoids in Giant Cell Arteritis: Proof of Concept Study.
NCT02955147	PHASE1/PHASE2	TERMINATED	Ustekinumab for the Treatment of Giant Cell Arteritis
NCT03482479	PHASE2	COMPLETED	Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis
NCT03745586	PHASE1/PHASE2	COMPLETED	Giant Cell Arteritis Treatment With Ultra-short Glucocorticoids and Tocilizumab
NCT03765788	PHASE2	COMPLETED	A Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis
NCT03812302	PHASE2	COMPLETED	Use of Gallium-68 HA-DOTATATE PET/CT in Giant Cell Arteritis (GCA)
NCT03827018	PHASE2	COMPLETED	KPL-301 for Subjects With Giant Cell Arteritis
NCT04239196	PHASE2	UNKNOWN	Efficacy of Tocilizumab for the Treatment of Acute AION Related to GCA

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TOCILIZUMAB	4	14
ABATACEPT	4	3
BOSENTAN	4	2
FLUORESCEIN	4	2
HYDROCORTISONE	4	2
ANAKINRA	4	1
GUSELKUMAB	4	1
HYDROXYCHLOROQUINE	4	1
PREDNISONE	4	1
SARILUMAB	4	1
UPADACITINIB	4	1
USTEKINUMAB	4	1
VARICELLA ZOSTER VIRUS ENVELOPE GLYCOPROTEIN E	4	1
SIRUKUMAB	3	1
MAVRILIMUMAB	2	1
CHEMBL177756	0	2
CHEMBL15720	0	1
CHEMBL5220618	0	1
CHEMBL4783966	0	1