Anterior uveitis

disease

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Also known as anterior uveitis (disease)iridocyclitis

Summary

Anterior uveitis (MONDO:0006651) is a disease with 24 cohort genes (32 GWAS associations across 5 studies) and 26 clinical trials. The dominant Reactome pathway is Antigen Presentation: Folding, assembly and peptide loading of class I MHC (3 cohort genes). Top therapeutic interventions include dexamethasone, ganciclovir, and certolizumab pegol.

At a glance

Prevalence: >1 / 1000 (Denmark) [Orphanet-validated]
Cohort genes: 24
GWAS associations: 32
Clinical trials: 26

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	>1 / 1000	185	Denmark	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	anterior uveitis
Mondo ID	MONDO:0006651
EFO	EFO:1000811
MeSH	D014606
Orphanet	280886
DOID	DOID:1407
ICD-11	908233081
NCIT	C35109
SNOMED CT	410692006
UMLS	C0042165
MedGen	22595
MedDRA	10002709
Is cancer (heuristic)	no

Also known as: anterior uveitis · anterior uveitis (disease) · iridocyclitis

Data availability: 32 GWAS associations (5 studies) · 1 HPO phenotype.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › uveal disorder › uveitis › anterior uveitis

Subtypes (3): iridocyclitis, idiopathic anterior uveitis, non-infectious anterior uveitis

Genetics & variants

GWAS landscape

32 GWAS associations across 5 studies. Top hits map to 17 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
HLA-B27	1e-300		?	59.7
rs116488202	1e-300	RNU6-283P - FGFR3P1	?	16.8
rs543685299	1e-196	HLA-B	?	3.37
HLA-B*27	2e-42		?	2.35
rs114102658	1e-41	MICA-AS1	?	17.4
rs115879499	5e-18	MICA-AS1	G	1.36
rs2032890	2e-16	ERAP1	A	1.51
rs4672507	2e-12	RN7SL51P - RN7SL18P	T	1.38
rs149567432	4e-09	HLA-B	?	9
rs79755370	1e-08	IL23R	C	1.8
rs3198304	1e-08	ERAP1, CAST	?	0.86
rs12132349	2e-07	INAVA	T	1.31
rs27529	2e-07	ERAP1	A	1.22
rs508063	6e-07	KIFAP3	A	1.2
rs2274894	8e-07	NOS2	?	1.2
rs6690230	1e-06	IL6R	C	1.23
rs17351243	1e-06	IL19	A	1.24
rs67412457	1e-06	CLCN7 - RPS3AP2	A	1.25
rs9947182	1e-06	SMUG1P1 - ACAA2	T	1.37
rs10197284	2e-06	IL18R1	G	1.25
rs76412624	2e-06	TBC1D5	?	1.49
rs10171979	3e-06	TMEM87B	C	1.2
rs114977878	4e-06	HLA-DQA2	?	1.4
rs665873	5e-06	EYS	A	2.03
rs7281081	5e-06	LINC01697	?	1.27
rs115711695	6e-06	HLA-DRB5	?	1.7
rs7784778	6e-06	EPS15P1 - MRPL42P4	?	1.19
rs10093384	7e-06	CNBD1 - SOX5P1	A	1.2
rs1580226	8e-06	LINC01643 - ACO2P1	?	1.22

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010481	Huang XF	2020	2,752	3,836	Genomewide Association Study of Acute Anterior Uveitis Identifies New Susceptibility Loci.
GCST007361	Robinson PC	2014	1,199	1,731	Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis.
GCST90295958	Gelfman S	2023	421	42,369	A large meta-analysis identifies genes associated with anterior uveitis.
GCST90295959	Gelfman S	2023	421	42,369	A large meta-analysis identifies genes associated with anterior uveitis.
GCST007362	Robinson PC	2014	238	9,564	Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	27

MAF distribution

Bucket	Variants
common (>=0.05)	22
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	5

Functional consequences

Consequence	Count
intron_variant	21
intergenic_variant	3
unknown	2
non_coding_transcript_exon_variant	1
3_prime_UTR_variant	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
HLA-B27							1e-300	Tier 4: intronic/intergenic
rs116488202	6	31377139	C>A,T	0.05	intron_variant	RNU6-283P - FGFR3P1	1e-300	Tier 4: intronic/intergenic
rs543685299	6	31360487	GAA>G,GA,GAAA	0.05	intron_variant	HLA-B	1e-196	Tier 4: intronic/intergenic
HLA-B*27							2e-42	Tier 4: intronic/intergenic
rs114102658	6	31383313			intron_variant	MICA-AS1	1e-41	Tier 4: intronic/intergenic
rs115879499	6	31392512		0.49	intron_variant	MICA-AS1	5e-18	Tier 4: intronic/intergenic
rs2032890	5	96785448	A>C,T	0.23	non_coding_transcript_exon_variant	ERAP1	2e-16	Tier 4: intronic/intergenic
rs4672507	2	62343438	T>A,C,G	0.43	intron_variant	RN7SL51P - RN7SL18P	2e-12	Tier 4: intronic/intergenic
rs149567432	6	31360821			intron_variant	HLA-B	4e-09	Tier 4: intronic/intergenic
rs79755370	1	67234232	C>A,T	0.04	intron_variant	IL23R	1e-08	Tier 4: intronic/intergenic
rs3198304	5	96775524	A>G,T	0.05	3_prime_UTR_variant	ERAP1, CAST	1e-08	Tier 2: splice/UTR
rs12132349	1	200906114	T>A	0.24	intron_variant	INAVA	2e-07	Tier 4: intronic/intergenic
rs27529	5	96790605	A>G,T	0.05	missense_variant	ERAP1	2e-07	Tier 1: coding
rs508063	1	169954535	A>C,G	0.05	intron_variant	KIFAP3	6e-07	Tier 4: intronic/intergenic
rs2274894	17	27772145	T>A,C,G	0.05	intron_variant	NOS2	8e-07	Tier 4: intronic/intergenic
rs6690230	1	154460401	C>A,G,T	0.41	intron_variant	IL6R	1e-06	Tier 4: intronic/intergenic
rs17351243	1	206786182	G>A,C,T	0.49	intron_variant	IL19	1e-06	Tier 4: intronic/intergenic
rs67412457	16	1475709	G>A,C,T	0.05	intergenic_variant	CLCN7 - RPS3AP2	1e-06	Tier 4: intronic/intergenic
rs9947182	18	49727534	C>T	0.05	intron_variant	SMUG1P1 - ACAA2	1e-06	Tier 4: intronic/intergenic
rs10197284	2	102366243	G>A	0.26	intron_variant	IL18R1	2e-06	Tier 4: intronic/intergenic
rs76412624	3	18145113	A>C,G	0.05	intergenic_variant	TBC1D5	2e-06	Tier 4: intronic/intergenic
rs10171979	2	112065743	C>A,G,T	0.05	intron_variant	TMEM87B	3e-06	Tier 4: intronic/intergenic
rs114977878	6	32744080			intron_variant	HLA-DQA2	4e-06	Tier 4: intronic/intergenic
rs665873	6	64588658	G>A,C	0.02	intron_variant	EYS	5e-06	Tier 4: intronic/intergenic
rs7281081	21	28099170	G>C,T	0.05	intron_variant	LINC01697	5e-06	Tier 4: intronic/intergenic
rs115711695	6	32528217	T>A,G	0.05	intron_variant	HLA-DRB5	6e-06	Tier 4: intronic/intergenic
rs7784778	7	46912235	C>T	0.05	intron_variant	EPS15P1 - MRPL42P4	6e-06	Tier 4: intronic/intergenic
rs10093384	8	87623714	G>A	0.05	intron_variant	CNBD1 - SOX5P1	7e-06	Tier 4: intronic/intergenic
rs1580226	22	34413463	C>T	0.05	intergenic_variant	LINC01643 - ACO2P1	8e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 18 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ERAP1	Orphanet:117	Behçet disease
IL23R	Orphanet:117	Behçet disease
CLCN7	Orphanet:210110	Intermediate osteopetrosis
CLCN7	Orphanet:53	Albers-Schönberg osteopetrosis
CLCN7	Orphanet:667	Autosomal recessive malignant osteopetrosis
EYS	Orphanet:791	Retinitis pigmentosa
TMEM87B	Orphanet:684742	2q13 microdeletion syndrome
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
IL10	Orphanet:117	Behçet disease
IL10	Orphanet:238569	Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome
IL10	Orphanet:536	Systemic lupus erythematosus
IL6R	Orphanet:656326	Autosomal recessive combined immunodeficiency due to IL6R deficiency
MERTK	Orphanet:791	Retinitis pigmentosa

Cohort genes → proteins

24 cohort genes, 24 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	24

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KIFAP3	HGNC:17060	ENSG00000075945	Q92845	Kinesin-associated protein 3	gwas
ERAP1	HGNC:18173	ENSG00000164307	Q9NZ08	Endoplasmic reticulum aminopeptidase 1	gwas
IL23R	HGNC:19100	ENSG00000162594	Q5VWK5	Interleukin-23 receptor	gwas
SCYL3	HGNC:19285	ENSG00000000457	Q8IZE3	Protein-associating with the carboxyl-terminal domain of ezrin	gwas
CLCN7	HGNC:2025	ENSG00000103249	P51798	H(+)/Cl(-) exchange transporter 7	gwas
EYS	HGNC:21555	ENSG00000188107	Q5T1H1	Protein eyes shut homolog	gwas
NANOS2	HGNC:23292	ENSG00000188425	P60321	Nanos homolog 2	gwas
FIRRM	HGNC:25565	ENSG00000000460	Q9NSG2	FIGNL1-interacting regulator of recombination and mitosis	gwas
INAVA	HGNC:25599	ENSG00000163362	Q3KP66	Innate immunity activator protein	gwas
TMEM87B	HGNC:25913	ENSG00000153214	Q96K49	Transmembrane protein 87B	gwas
KIF21B	HGNC:29442	ENSG00000116852	O75037	Kinesin-like protein KIF21B	gwas
ERAP2	HGNC:29499	ENSG00000164308	Q6P179	Endoplasmic reticulum aminopeptidase 2	gwas
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas
HLA-DQA2	HGNC:4943	ENSG00000237541	P01906	HLA class II histocompatibility antigen, DQ alpha 2 chain	gwas
HLA-DRB5	HGNC:4953	ENSG00000198502	Q30154	HLA class II histocompatibility antigen, DR beta 5 chain	gwas
IL10	HGNC:5962	ENSG00000136634	P22301	Interleukin-10	gwas
IL18R1	HGNC:5988	ENSG00000115604	Q13478	Interleukin-18 receptor 1	gwas
IL19	HGNC:5990	ENSG00000142224	Q9UHD0	Interleukin-19	gwas
IL1R1	HGNC:5993	ENSG00000115594	P14778	Interleukin-1 receptor type 1	gwas
IL6R	HGNC:6019	ENSG00000160712	P08887	Interleukin-6 receptor subunit alpha	gwas
LNPEP	HGNC:6656	ENSG00000113441	Q9UIQ6	Leucyl-cystinyl aminopeptidase	gwas
MERTK	HGNC:7027	ENSG00000153208	Q12866	Tyrosine-protein kinase Mer	gwas
MICA	HGNC:7090	ENSG00000204520	Q29983	MHC class I polypeptide-related sequence A	gwas
ACAA2	HGNC:83	ENSG00000167315	P42765	3-ketoacyl-CoA thiolase, mitochondrial	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KIFAP3	Kinesin-associated protein 3	Involved in tethering the chromosomes to the spindle pole and in chromosome movement.
ERAP1	Endoplasmic reticulum aminopeptidase 1	Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.
IL23R	Interleukin-23 receptor	Associates with IL12RB1 to form the interleukin-23 receptor.
SCYL3	Protein-associating with the carboxyl-terminal domain of ezrin	May play a role in regulating cell adhesion/migration complexes in migrating cells.
CLCN7	H(+)/Cl(-) exchange transporter 7	Slowly voltage-gated channel mediating the exchange of chloride ions against protons.
EYS	Protein eyes shut homolog	Required to maintain the integrity of photoreceptor cells.
NANOS2	Nanos homolog 2	Plays a key role in the sexual differentiation of germ cells by promoting the male fate but suppressing the female fate.
FIRRM	FIGNL1-interacting regulator of recombination and mitosis	Regulates PLK1 kinase activity at kinetochores and promotes faithful chromosome segregation in prometaphase by bridging kinase and phosphatase activities.
INAVA	Innate immunity activator protein	Expressed in peripheral macrophages and intestinal myeloid-derived cells, is required for optimal PRR (pattern recognition receptor)-induced signaling, cytokine secretion, and bacterial clearance.
TMEM87B	Transmembrane protein 87B	May be involved in retrograde transport from endosomes to the trans-Golgi network (TGN).
KIF21B	Kinesin-like protein KIF21B	Plus-end directed microtubule-dependent motor protein which displays processive activity.
ERAP2	Endoplasmic reticulum aminopeptidase 2	Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
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-DRB5	HLA class II histocompatibility antigen, DR beta 5 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.
IL10	Interleukin-10	Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.
IL18R1	Interleukin-18 receptor 1	Within the IL18 receptor complex, responsible for the binding of the pro-inflammatory cytokine IL18, but not IL1A nor IL1B.
IL19	Interleukin-19	Cytokine that functions as an anti-inflammatory and proangiogenic factor.
IL1R1	Interleukin-1 receptor type 1	Receptor for IL1A, IL1B and IL1RN.
IL6R	Interleukin-6 receptor subunit alpha	Part of the receptor for interleukin 6.
LNPEP	Leucyl-cystinyl aminopeptidase	Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids.
MERTK	Tyrosine-protein kinase Mer	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands including LGALS3, TUB, TULP1 or GAS6.
MICA	MHC class I polypeptide-related sequence A	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8 alphabeta T-cells.
ACAA2	3-ketoacyl-CoA thiolase, mitochondrial	In the production of energy from fats, this is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA.

Protein-family classification

Druggable: 14 · Difficult: 2 · Unknown: 8 · Druggable fraction: 0.58

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	8	9.7×	6e-06
Protease	3	4.6×	0.094
Kinase	2	2.3×	0.499
Scaffold/PPI	1	0.7×	0.992
Other/Unknown	8	0.6×	0.992
Enzyme (other)	1	0.5×	0.992
Transcription factor	1	0.3×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KIFAP3	Other/Unknown	no		Armadillo, KAP3, ARM-like
ERAP1	Protease	yes	3.4.11.1	Peptidase_M1, Peptidase_M1_dom, ERAP1-like_C_dom
IL23R	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
SCYL3	Kinase	yes		Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Kinase-like_dom_sf
CLCN7	Other/Unknown	no		CBS_dom, ClC, CIC-7
EYS	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
NANOS2	Transcription factor	no		Nanos/Xcar2, Znf_nanos-typ, Nanos_sf
FIRRM	Other/Unknown	no		DUF4487
INAVA	Other/Unknown	no		CUPID, CCDC120/INAVA
TMEM87B	Other/Unknown	no		GPR107/GPR108-like, GOST_TM, TMEM87A/B_GOLD
KIF21B	Scaffold/PPI	no		WD40_rpt, Kinesin_motor_dom, WD40/YVTN_repeat-like_dom_sf
ERAP2	Protease	yes	3.4.11.1	Peptidase_M1, Peptidase_M1_dom, ERAP1-like_C_dom
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HLA-DQA2	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB5	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
IL10	Other/Unknown	no		IL-10, 4_helix_cytokine-like_core, IL-10_CS
IL18R1	Antibody/Immunoglobulin	yes		TIR_dom, Ig_sub, IL-1_rcpt_I/II-typ
IL19	Other/Unknown	no		4_helix_cytokine-like_core, IL-19, IL-10_CS
IL1R1	Antibody/Immunoglobulin	yes		TIR_dom, Ig_sub, IL-1_rcpt_I/II-typ
IL6R	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_L_F3_CS, Ig_sub2, Ig_sub
LNPEP	Protease	yes	3.4.11.3	Peptidase_M1, Peptidase_M1_dom, ERAP1-like_C_dom
MERTK	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub
MICA	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
ACAA2	Enzyme (other)	yes	2.3.1.16	Thiolase, Thiolase-like, Thiolase_AS

Expression context

Cohort genes with no expression data: 0.

22 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)	24
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	4
granulocyte	4
primordial germ cell in gonad	3
vermiform appendix	3
cortical plate	2
jejunal mucosa	2
monocyte	2
rectum	2
oocyte	2
secondary oocyte	2
buccal mucosa cell	2
right adrenal gland cortex	2
nasal cavity epithelium	2
lymph node	2
blood	2
mucosa of stomach	2
tibia	2
orbitofrontal cortex	1
pons	1
adrenal tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KIFAP3	285	ubiquitous	marker	cortical plate, pons, orbitofrontal cortex
ERAP1	286	ubiquitous	marker	jejunal mucosa, rectum, monocyte
IL23R	39	tissue_specific	marker	secondary oocyte, oocyte, adrenal tissue
SCYL3	275	ubiquitous	marker	buccal mucosa cell, secondary oocyte, oocyte
CLCN7	296	ubiquitous	marker	metanephros cortex, right adrenal gland cortex, left adrenal gland cortex
EYS	153	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, islet of Langerhans
NANOS2	32	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, right testis
FIRRM	177	ubiquitous	yes	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, ventricular zone
INAVA	221	broad	marker	ileal mucosa, jejunal mucosa, nasal cavity epithelium
TMEM87B	243	ubiquitous	marker	mucosa of sigmoid colon, corpus epididymis, rectum
KIF21B	216	ubiquitous	marker	cortical plate, ganglionic eminence, Brodmann (1909) area 10
ERAP2	244	ubiquitous	marker	buccal mucosa cell, granulocyte, lymph node
HLA-B	134	ubiquitous	marker	blood, spleen, granulocyte
HLA-DQA2	127	broad	marker	granulocyte, vermiform appendix, male germ line stem cell (sensu Vertebrata) in testis
HLA-DRB5	130	tissue_specific	marker	granulocyte, lymph node, vermiform appendix
IL10	158	broad	marker	vermiform appendix, gall bladder, cartilage tissue
IL18R1	191	broad	marker	right lung, upper lobe of left lung, upper lobe of lung
IL19	111	broad	marker	nasal cavity epithelium, mucosa of stomach, nasal cavity mucosa
IL1R1	279	ubiquitous	marker	palpebral conjunctiva, tibia, pericardium
IL6R	271	ubiquitous	marker	blood, monocyte, leukocyte
LNPEP	275	ubiquitous	marker	visceral pleura, Brodmann (1909) area 23, tibia
MERTK	246	ubiquitous	marker	right adrenal gland cortex, mucosa of stomach, right adrenal gland
MICA	134	ubiquitous	marker	descending thoracic aorta, left ovary, popliteal artery
ACAA2	260	ubiquitous	marker	right lobe of liver, mucosa of transverse colon, apex of heart

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IL10	6,185
HLA-B	3,209
ACAA2	3,130
IL1R1	2,820
IL6R	2,805
MERTK	2,735
LNPEP	2,238
ERAP1	2,107
CLCN7	1,991
HLA-DRB5	1,897

Intra-cohort edges

A	B	Sources
ERAP1	ERAP2	intact, string_interaction
ERAP1	HLA-B	biogrid_interaction, intact, string_interaction
ERAP1	IL23R	string_interaction
ERAP1	IL6R	intact
ERAP1	KIF21B	string_interaction
ERAP2	HLA-B	string_interaction
FIRRM	HLA-B	intact
HLA-B	HLA-DQA2	string_interaction
IL10	IL19	string_interaction
IL10	IL23R	string_interaction
IL18R1	IL1R1	string_interaction
IL1R1	IL6R	string_interaction
IL23R	KIF21B	string_interaction
INAVA	KIF21B	string_interaction
MERTK	TMEM87B	string_interaction

Structural data

PDB: 15 · AlphaFold-only: 9 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-B	P01889	237
MERTK	Q12866	42
ERAP1	Q9NZ08	23
ERAP2	Q6P179	14
LNPEP	Q9UIQ6	11
IL6R	P08887	10
MICA	Q29983	10
CLCN7	P51798	9
IL10	P22301	9
IL1R1	P14778	5
IL23R	Q5VWK5	4
HLA-DRB5	Q30154	4
IL18R1	Q13478	3
ACAA2	P42765	2
IL19	Q9UHD0	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HLA-DQA2	P01906	89.29
FIRRM	Q9NSG2	86.78
KIFAP3	Q92845	83.66
NANOS2	P60321	76.58
TMEM87B	Q96K49	74.41
KIF21B	O75037	70.07
SCYL3	Q8IZE3	69.60
INAVA	Q3KP66	56.87
EYS	Q5T1H1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 59. Enrichment computed across 24 evidence-associated genes (18 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 18 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	3	65.6×	7e-04	ERAP1, ERAP2, HLA-B
Endosomal/Vacuolar pathway	2	115.3×	0.004	HLA-B, LNPEP
Translocation of ZAP-70 to Immunological synapse	2	70.5×	0.005	HLA-DQA2, HLA-DRB5
Phosphorylation of CD3 and TCR zeta chains	2	60.4×	0.005	HLA-DQA2, HLA-DRB5
Co-inhibition by PD-1	2	57.7×	0.005	HLA-DQA2, HLA-DRB5
Interferon gamma signaling	3	20.9×	0.005	HLA-B, HLA-DQA2, HLA-DRB5
Interleukin-4 and Interleukin-13 signaling	3	17.1×	0.006	IL23R, IL10, IL6R
MHC class II antigen presentation	3	14.9×	0.007	KIFAP3, HLA-DQA2, HLA-DRB5
Generation of second messenger molecules	2	38.5×	0.008	HLA-DQA2, HLA-DRB5
Interleukin-10 signaling	2	25.9×	0.016	IL10, IL1R1
Kinesins	2	19.8×	0.024	KIFAP3, KIF21B
Translocation of SLC2A4 (GLUT4) to the plasma membrane	2	17.1×	0.029	KIFAP3, LNPEP
Golgi-to-ER retrograde transport	2	14.8×	0.036	KIFAP3, KIF21B
Downstream TCR signaling	2	14.3×	0.036	HLA-DQA2, HLA-DRB5
Interleukin-18 signaling	1	79.3×	0.037	IL18R1
Potential therapeutics for SARS	2	12.7×	0.037	IL1R1, IL6R
COPI-dependent Golgi-to-ER retrograde traffic	2	12.3×	0.037	KIFAP3, KIF21B
Intra-Golgi and retrograde Golgi-to-ER traffic	2	11.6×	0.037	KIFAP3, KIF21B
Membrane Trafficking	3	6.2×	0.037	KIFAP3, KIF21B, LNPEP
Hemostasis	3	6.0×	0.037	KIFAP3, KIF21B, MERTK
Interleukin-23 signaling	1	70.5×	0.038	IL23R
Vesicle-mediated transport	3	5.8×	0.038	KIFAP3, KIF21B, LNPEP
MAPK1 (ERK2) activation	1	63.4×	0.038	IL6R
CD163 mediating an anti-inflammatory response	1	63.4×	0.038	IL10
MAPK3 (ERK1) activation	1	57.7×	0.041	IL6R
Interleukin-6 signaling	1	52.9×	0.043	IL6R
Factors involved in megakaryocyte development and platelet production	2	7.4×	0.064	KIFAP3, KIF21B
Interleukin-37 signaling	1	28.8×	0.072	IL18R1
DAP12 interactions	1	26.4×	0.076	HLA-B
Interleukin-20 family signaling	1	23.5×	0.082	IL19

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 24 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
adaptive immune response	6	21.1×	6e-05	ERAP1, ERAP2, HLA-B, HLA-DQA2, HLA-DRB5, IL18R1
immune response	7	13.7×	6e-05	HLA-B, HLA-DQA2, IL10, IL18R1, IL19, IL1R1, MICA
antigen processing and presentation of peptide antigen via MHC class I	2	280.9×	0.002	ERAP1, ERAP2
antigen processing and presentation of endogenous peptide antigen via MHC class I	2	175.5×	0.003	ERAP1, ERAP2
positive regulation of T-helper 1 cell cytokine production	2	175.5×	0.003	IL18R1, IL1R1
positive regulation of type II interferon production	3	28.1×	0.006	IL23R, IL18R1, IL1R1
regulation of blood pressure	3	27.7×	0.006	ERAP1, ERAP2, LNPEP
peptide antigen assembly with MHC class II protein complex	2	87.8×	0.006	HLA-DQA2, HLA-DRB5
peptide catabolic process	2	87.8×	0.006	ERAP1, ERAP2
negative regulation of interleukin-8 production	2	82.6×	0.006	IL10, IL6R
antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent	1	702.2×	0.016	LNPEP
negative regulation of chronic inflammatory response to antigenic stimulus	1	702.2×	0.016	IL10
positive regulation of calcium-dependent cell-cell adhesion	1	702.2×	0.016	KIFAP3
negative regulation of cytokine activity	1	702.2×	0.016	IL10
regulation of response to wounding	1	702.2×	0.016	IL10
positive regulation of interleukin-1-mediated signaling pathway	1	702.2×	0.016	IL1R1
cell surface receptor signaling pathway via STAT	2	46.8×	0.016	IL23R, IL6R
antigen processing and presentation of exogenous peptide antigen via MHC class II	2	45.3×	0.016	HLA-DQA2, HLA-DRB5
negative regulation of cytokine production	2	42.6×	0.016	IL10, MERTK
positive regulation of T cell mediated cytotoxicity	2	42.6×	0.016	IL23R, HLA-B
positive regulation of immune response	2	40.1×	0.016	HLA-DQA2, HLA-DRB5
positive regulation of T cell activation	2	37.0×	0.016	HLA-DQA2, HLA-DRB5
negative regulation of cold-induced thermogenesis	2	28.7×	0.023	IL18R1, LNPEP
chronic inflammatory response to antigenic stimulus	1	351.1×	0.026	IL10
neuropeptide catabolic process	1	351.1×	0.026	LNPEP
negative regulation of interleukin-18 production	1	351.1×	0.026	IL10
negative regulation of leukocyte apoptotic process	1	351.1×	0.026	MERTK
microtubule-based movement	2	24.6×	0.026	KIFAP3, KIF21B
inflammatory response	4	6.3×	0.029	IL23R, SCYL3, IL18R1, IL1R1
hepatic immune response	1	234.1×	0.030	IL6R

Therapeutics

Drugs indicated for this disease

2 approved, 7 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Difluprednate	Approved (phase 4)
Loteprednol Etabonate	Approved (phase 4)
Dexamethasone	Phase 3 (in late-stage trials)
Dexamethasone Phosphoric Acid	Phase 3 (in late-stage trials)
Ethambutol	Phase 3 (in late-stage trials)
Fluocinolone Acetonide	Phase 3 (in late-stage trials)
Prednisolone Acetate	Phase 3 (in late-stage trials)
Sodium Citrate	Phase 3 (in late-stage trials)
Voclosporin	Phase 3 (in late-stage trials)

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 3 · Undrugged: 21

Druggability breadth: 12 of 24 evidence-associated genes (50%) 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
MERTK	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MERTK	48	4
ERAP1	2	2
ERAP2	1	2
KIFAP3	0	0
IL23R	0	0
SCYL3	0	0
CLCN7	0	0
EYS	0	0
NANOS2	0	0
FIRRM	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	MERTK
AXITINIB	4	MERTK
SORAFENIB	4	MERTK
NERATINIB	4	MERTK
CABOZANTINIB	4	MERTK
VANDETANIB	4	MERTK
BOSUTINIB	4	MERTK
FILGOTINIB	4	MERTK
PACLITAXEL	4	MERTK
PAZOPANIB	4	MERTK
NINTEDANIB	4	MERTK
SUNITINIB	4	MERTK
ERLOTINIB	4	MERTK
QUIZARTINIB	4	MERTK
CRIZOTINIB	4	MERTK
MIDOSTAURIN	4	MERTK
LINIFANIB	3	MERTK
ITACITINIB	3	MERTK
ALVOCIDIB	3	MERTK
SURUFATINIB	3	MERTK
CEDIRANIB	3	MERTK
POVORCITINIB	3	MERTK
DOVITINIB	3	MERTK
LESTAURTINIB	3	MERTK
TOSEDOSTAT	2	ERAP1, ERAP2
UBENIMEX	2	ERAP1
DORAMAPIMOD	2	MERTK
FORETINIB	2	MERTK
TANDUTINIB	2	MERTK
SU-014813	2	MERTK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 5.

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

Symbol	Assays	Type breakdown
MERTK	443	Binding:442, Functional:1
ERAP1	88	Binding:85, Functional:2, ADMET:1
ERAP2	46	Binding:40, ADMET:4, Functional:2
LNPEP	34	Binding:33, ADMET:1
IL23R	13	Binding:13
IL1R1	11	Binding:11
IL6R	5	Binding:5
HLA-B	1	Binding:1
MICA	1	Binding:1
ACAA2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ERAP1	3.4.11.1, 3.4.11.22	leucyl aminopeptidase, aminopeptidase I
ERAP2	3.4.11.1, 3.4.11.6	leucyl aminopeptidase, aminopeptidase B
LNPEP	3.4.11.3	cystinyl aminopeptidase
MERTK	2.7.10.1	receptor protein-tyrosine kinase
ACAA2	2.3.1.16	acetyl-CoA C-acyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MERTK	443

Pharmacogenomics

Cohort genes with a PharmGKB record: 24; 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

30 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)
FEDRATINIB	4	MERTK
AXITINIB	4	MERTK
SORAFENIB	4	MERTK
NERATINIB	4	MERTK
CABOZANTINIB	4	MERTK
VANDETANIB	4	MERTK
BOSUTINIB	4	MERTK
FILGOTINIB	4	MERTK
PACLITAXEL	4	MERTK
PAZOPANIB	4	MERTK
NINTEDANIB	4	MERTK
SUNITINIB	4	MERTK
ERLOTINIB	4	MERTK
QUIZARTINIB	4	MERTK
CRIZOTINIB	4	MERTK
MIDOSTAURIN	4	MERTK
LINIFANIB	3	MERTK
ITACITINIB	3	MERTK
ALVOCIDIB	3	MERTK
SURUFATINIB	3	MERTK
CEDIRANIB	3	MERTK
POVORCITINIB	3	MERTK
DOVITINIB	3	MERTK
LESTAURTINIB	3	MERTK
TOSEDOSTAT	2	ERAP1, ERAP2
UBENIMEX	2	ERAP1
DORAMAPIMOD	2	MERTK
FORETINIB	2	MERTK
TANDUTINIB	2	MERTK
SU-014813	2	MERTK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MERTK
B	Phased (≥1) drug, not yet approved	2	ERAP1, ERAP2
C	Druggable family + PDB, no drug	9	IL23R, HLA-B, HLA-DRB5, IL18R1, IL1R1, IL6R, LNPEP, MICA, ACAA2
D	Druggable family + AlphaFold only, no drug	2	SCYL3, HLA-DQA2
E	Difficult family or no structure, no drug	10	KIFAP3, CLCN7, EYS, NANOS2, FIRRM, INAVA, TMEM87B, KIF21B, IL10, IL19

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KIF21B	0	ERAP1
KIFAP3	0	—
IL23R	13	—
SCYL3	0	—
CLCN7	0	—
EYS	0	—
NANOS2	0	—
FIRRM	0	—
INAVA	0	—
TMEM87B	0	—
HLA-B	1	—
HLA-DQA2	0	—
HLA-DRB5	0	—
IL10	0	—
IL18R1	0	—
IL19	0	—
IL1R1	11	—
IL6R	5	—
LNPEP	34	—
MICA	1	—
ACAA2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 26.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	12
PHASE2	6
PHASE3	3
PHASE4	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02764697	PHASE4	COMPLETED	Study of H.P. ACTHAR Subcutaneous Gelatin (Gel)(Highly Purified Gel Injection) in Uveitis Patients
NCT03020992	PHASE4	COMPLETED	A Study to Assess the Effects of Certolizumab Pegol on the Reduction of Anterior Uveitis (AU) Flares in Axial Spondyloarthritis Subjects With a Documented History of AU
NCT00333996	PHASE2/PHASE3	TERMINATED	A Study of the Safety and Efficacy of a New Treatment for Non-Infectious Anterior Uveitis
NCT00406887	PHASE3	COMPLETED	Study of Difluprednate Ophthalmic Emulsion in the Treatment of Uveitis
NCT01505088	PHASE3	COMPLETED	Safety and Efficacy Study of Iontophoretic Dexamethasone Phosphate Ophthalmic Solution to Treat Non-Infectious Anterior Segment Uveitis
NCT02517619	PHASE3	COMPLETED	Safety and Efficacy of Iontophoretic Dexamethasone Phosphate Ophthalmic Solution in Non-Infectious Anterior Uveitis
NCT07513623	PHASE2	NOT_YET_RECRUITING	Systemic and Topical Antiviral Control of Cytomegalovirus Anterior Uveitis: Treatment Outcomes - Trials I and II
NCT00130637	PHASE2	COMPLETED	Human Anti-Tac (Daclizumab) to Treat Juvenile Idiopathic Arthritis (JIA)-Associated Uveitis
NCT00405496	PHASE2	COMPLETED	Study of Difluprednate Ophthalmic Emulsion in the Treatment of Uveitis
NCT00823173	PHASE2	COMPLETED	Exploratory Study on Topical ESBA105 in Acute Anterior Uveitis
NCT01376362	PHASE1/PHASE2	COMPLETED	Topical Interferon Gamma for Macular Edema Secondary to Uveitis
NCT02482129	PHASE2	COMPLETED	Proof of Concept Study to Evaluate Safety and Efficacy of LME636 in the Treatment of Acute Anterior Uveitis
NCT06679153	PHASE2	COMPLETED	A Phase 2 Study of VVN461 Ophthalmic Solution for Noninfectious Anterior Uveitis
NCT00876434	PHASE1	COMPLETED	Subconjunctival Sirolimus for the Treatment of Autoimmune Active Anterior Uveiti
NCT07065747	Not specified	RECRUITING	Quantification & Classification of Inflammatory Cells in Uveitis Using OCT
NCT00006188	Not specified	COMPLETED	Evaluation and Treatment of Patients With Inflammatory Eye Diseases
NCT00407316	Not specified	UNKNOWN	Quality of Life and Visual Function in Uveitis Patients
NCT00476593	Not specified	COMPLETED	Retinal OCT and (mfERG) Related to Age, Sex, and the Use of Anti-inflammatory Medications
NCT01154010	Not specified	COMPLETED	PEMF: an Adjunct Therapy for Anterior Uveitis
NCT01156285	Not specified	UNKNOWN	Acute Anterior Uveitis: Psychic Burden and Pain
NCT01486693	Not specified	UNKNOWN	Clinical Outcomes of Topical Ganciclovir Treatment in Cytomegalovirus Anterior Uveitis
NCT01647529	Not specified	COMPLETED	Topical Administration of 0.15% Ganciclovir Gel for CMV Anterior Uveitis / Endotheliitis
NCT02725177	Not specified	COMPLETED	Ocular Sarcoidosis Open Label Trial of ACTHAR Gel
NCT02765308	Not specified	COMPLETED	Aqueous Humor Dynamics and Hypertensive Uveitis
NCT02879084	Not specified	COMPLETED	Variations in Retinal Nerve Fiber Layer Thickness During Uncomplicated Anterior and Intermediate Uveitis
NCT03753893	Not specified	COMPLETED	Ocular Manifestations in Rheumatic Diseases

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEXAMETHASONE	4	4
GANCICLOVIR	4	2
CERTOLIZUMAB PEGOL	4	1
DACLIZUMAB	4	1
INTERFERON GAMMA-1B	4	1
PREDNISOLONE ACETATE	4	1
VALGANCICLOVIR	4	1
LICAMINLIMAB	2	1

Cohort genes: KIFAP3, ERAP1, IL23R, SCYL3, CLCN7, EYS, NANOS2, FIRRM, INAVA, TMEM87B, KIF21B, ERAP2, HLA-B, HLA-DQA2, HLA-DRB5, IL10, IL18R1, IL19, IL1R1, IL6R, LNPEP, MERTK, MICA, ACAA2
Drugs: Dexamethasone, Ganciclovir, Certolizumab Pegol, Daclizumab, INTERFERON GAMMA-1B, Prednisolone Acetate, Valganciclovir