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Sjogren syndrome

disease
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Also known as primary Sjogren-Gougerot syndromeprimary Sjögren-Gougerot syndromesicca syndromeSjögren syndromeSjögren-Gougerot syndromesyndrome, Sjogren's

Summary

Sjogren syndrome (MONDO:0010030) is a disease with 49 cohort genes (74 GWAS associations across 26 studies) and 73 clinical trials. The dominant Reactome pathway is Translocation of ZAP-70 to Immunological synapse (7 cohort genes). Top therapeutic interventions include tacrolimus anhydrous, cyclosporine, and hydroxychloroquine.

At a glance

  • Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
  • Cohort genes: 49
  • GWAS associations: 74
  • Phenotypes (HPO): 82
  • Clinical trials: 73

Clinical features

Epidemiology

Prevalence records

14 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Annual incidence1-9 / 100 0006.92WorldwideValidated
Point prevalence1-5 / 10 00048.99EuropeValidated
Annual incidence1-9 / 100 0003.95United StatesValidated
Annual incidence1-9 / 100 0009.5Taiwan, Province of ChinaValidated
Annual incidence1-9 / 100 0005.3GreeceValidated
Annual incidence1-9 / 100 0003.9SloveniaValidated
Point prevalence1-5 / 10 00011.343FranceValidated
Point prevalence6-9 / 10 00086.398GreeceValidated
Point prevalence1-5 / 10 00049.745NorwayValidated
Point prevalence1-5 / 10 00045.47DenmarkValidated
Point prevalence1-5 / 10 00037.15Taiwan, Province of ChinaValidated
Point prevalence>1 / 1000207.83TurkeyValidated
Point prevalence1-5 / 10 00030.91ItalyValidated
Point prevalence>1 / 1000165.98BrazilValidated

Signs & symptoms

Clinical features (HPO)

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

HPO IDTermFrequency
HP:0000217XerostomiaVery frequent (80-99%)
HP:0001097Keratoconjunctivitis siccaVery frequent (80-99%)
HP:0000077Abnormality of the kidneyFrequent (30-79%)
HP:0000707Abnormality of the nervous systemFrequent (30-79%)
HP:0000739AnxietyFrequent (30-79%)
HP:0000951Abnormality of the skinFrequent (30-79%)
HP:0001970Tubulointerstitial nephritisFrequent (30-79%)
HP:0002829ArthralgiaFrequent (30-79%)
HP:0003011Abnormality of the musculatureFrequent (30-79%)
HP:0004431Complement deficiencyFrequent (30-79%)
HP:0005195Polyarticular arthropathyFrequent (30-79%)
HP:0011850ParotitisFrequent (30-79%)
HP:0012378FatigueFrequent (30-79%)
HP:0012532Chronic painFrequent (30-79%)
HP:0031950Usual interstitial pneumoniaFrequent (30-79%)
HP:0033555Anti-Ro/SS-A antibody positivityFrequent (30-79%)
HP:0034064Anti-salivary protein antibody positivityFrequent (30-79%)
HP:0034066Anti-carbonic anhydrase VI antibody positivityFrequent (30-79%)
HP:0034069Anti-parotid secretory protein antibody positivityFrequent (30-79%)
HP:0000083Renal insufficiencyOccasional (5-29%)
HP:0000099GlomerulonephritisOccasional (5-29%)
HP:0000708Atypical behaviorOccasional (5-29%)
HP:0000716DepressionOccasional (5-29%)
HP:0000958Dry skinOccasional (5-29%)
HP:0000965Cutis marmorataOccasional (5-29%)
HP:0000979PurpuraOccasional (5-29%)
HP:0001045VitiligoOccasional (5-29%)
HP:0001250SeizureOccasional (5-29%)
HP:0001287MeningitisOccasional (5-29%)
HP:0001317Abnormal cerebellum morphologyOccasional (5-29%)
HP:0001324Muscle weaknessOccasional (5-29%)
HP:0001369ArthritisOccasional (5-29%)
HP:0001871Abnormality of blood and blood-forming tissuesOccasional (5-29%)
HP:0001873ThrombocytopeniaOccasional (5-29%)
HP:0001882LeukopeniaOccasional (5-29%)
HP:0001888LymphopeniaOccasional (5-29%)
HP:0001895Normochromic anemiaOccasional (5-29%)
HP:0001897Normocytic anemiaOccasional (5-29%)
HP:0002011Morphological central nervous system abnormalityOccasional (5-29%)
HP:0002613Biliary cirrhosisOccasional (5-29%)
HP:0002633VasculitisOccasional (5-29%)
HP:0002665LymphomaOccasional (5-29%)
HP:0002716LymphadenopathyOccasional (5-29%)
HP:0003326MyalgiaOccasional (5-29%)
HP:0003474Somatic sensory dysfunctionOccasional (5-29%)
HP:0004302Functional motor deficitOccasional (5-29%)
HP:0004313Decreased circulating antibody levelOccasional (5-29%)
HP:0005421Decreased circulating complement C3 concentrationOccasional (5-29%)
HP:0005523Lymphoproliferative disorderOccasional (5-29%)
HP:0006527Lymphoid interstitial pneumoniaOccasional (5-29%)

Identifiers

Disease identifiers

FieldValue
Canonical nameSjogren syndrome
Mondo IDMONDO:0010030
EFOEFO:0000699
MeSHD012859
OMIM270150
Orphanet289390, 378
DOIDDOID:12894
ICD-10-CMM35.0
ICD-11899463360
NCITC26883
SNOMED CT83901003
UMLSC1527336
MedGen282890
Is cancer (heuristic)no

Also known as: primary Sjogren-Gougerot syndrome · primary Sjögren-Gougerot syndrome · sicca syndrome · Sjogren syndrome · Sjögren syndrome · Sjögren-Gougerot syndrome · syndrome, Sjogren’s

Data availability: 74 GWAS associations (26 studies) · 5 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › autoimmune disease › autoimmune disorder of exocrine system › Sjogren syndrome

Related subtypes (2): benign lymphoepithelial lesion of salivary gland, autoimmune hepatitis

Genetics & variants

GWAS landscape

74 GWAS associations across 26 studies. Top hits map to 29 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs1155758578e-114HLA-DQB1 - MTCO3P1G3.53
rs31353945e-113HLA-DRAG3.52
rs1162328571e-96HLA-DQA1G2.53
rs1170263261e-53GTF2I-AS1, GTF2IT2.2
rs92715733e-42HLA-DRB1 - HLA-DQA1?2.02
rs92715889e-37HLA-DRB1 - HLA-DQA1T1.75
rs25235716e-28HLA-BA0.71
rs42824389e-25COL11A2P1G1.58
rs37573873e-19IRF5C1.44
rs101682662e-17STAT4T1.44
rs173398362e-16TNPO3T1.58
rs105535777e-15STAT4T1.43
rs38235363e-14IRF5?1.49
rs118893417e-12STAT4T0.29
rs3723498702e-11DIPK1CT2.66
rs14870702923e-11LINC02008 - CYP51A1P1G1.68
rs1855884025e-11FKBP1A - NSFL1CT2.79
rs4854971e-10IL12A-AS1A1.3
rs27363455e-10BLKG1.3
rs560363026e-10TSBP1-AS1, TSBP1T0.67
rs47315321e-09KCP - IRF5A0.23
rs50299398e-09TNFAIP3G1.67
rs71190381e-08Y_RNA - CXCR5A1.35
rs75748652e-08STAT4?1.51
rs65798373e-08TNIP1T1.43
rs170744926e-08HIGD1AP2 - PTMAP5?1.53
rs69334047e-08BTF3L4P3 - LINC03004C1.29
rs24310982e-07MIR3142HGG1.23
rs73414753e-07RELN?1.39
rs92775543e-07HLA-DPB1?1.65

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90651182Liu TY20254,862210,768Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST005532Lessard CJ20131,5412,634Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome.
GCST90018920Sakaue S20211,296482,717A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90478853Verma A20241,080448,272Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90080468Backman JD2021711387,080Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90084454Backman JD2021711387,080Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90014460Glanville KP2021647324,074Investigating Pleiotropy Between Depression and Autoimmune Diseases Using the UK Biobank.
GCST004061Taylor KE20175851,546Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren’s Syndrome According to Ancestry.
GCST012796Taylor KE20175851,546Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren’s Syndrome According to Ancestry.
GCST002217Li Y20135421,050A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren’s syndrome at 7q11.23.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR2
Tier 3: regulatory2
Tier 4: intronic/intergenic46

MAF distribution

BucketVariants
common (>=0.05)45
low_freq (0.01-0.05)2
rare (<0.01)3
unknown0

Functional consequences

ConsequenceCount
intron_variant30
intergenic_variant12
unknown3
regulatory_region_variant2
3_prime_UTR_variant2
non_coding_transcript_exon_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs1155758576326918680.12intergenic_variantHLA-DQB1 - MTCO3P18e-114Tier 4: intronic/intergenic
rs3135394632440720A>G,T0.11intron_variantHLA-DRA5e-113Tier 4: intronic/intergenic
rs1162328576326292870.42intergenic_variantHLA-DQA11e-96Tier 4: intronic/intergenic
rs117026326774711703C>T0.15intron_variantGTF2I-AS1, GTF2I1e-53Tier 4: intronic/intergenic
rs9271573632622724A>C0.05regulatory_region_variantHLA-DRB1 - HLA-DQA13e-42Tier 3: regulatory
rs9271588632623176T>C0.468regulatory_region_variantHLA-DRB1 - HLA-DQA19e-37Tier 3: regulatory
rs2523571631361914T>A0.05non_coding_transcript_exon_variantHLA-B6e-28Tier 4: intronic/intergenic
rs4282438633104395T>G0.355intron_variantCOL11A2P19e-25Tier 4: intronic/intergenic
rs37573877128936032T>C0.45intergenic_variantIRF53e-19Tier 4: intronic/intergenic
rs101682662191071078C>T0.336intron_variantSTAT42e-17Tier 4: intronic/intergenic
rs173398367129041008C>T0.12intron_variantTNPO32e-16Tier 4: intronic/intergenic
rs105535772191090464TATAATA>T,TATA,TATAATAATA0.23intron_variantSTAT47e-15Tier 4: intronic/intergenic
rs38235367128939612G>A0.05intron_variantIRF53e-14Tier 4: intronic/intergenic
rs118893412191079016C>T0.05intron_variantSTAT47e-12Tier 4: intronic/intergenic
rs3723498701874442441T>G0.001intron_variantDIPK1C2e-11Tier 4: intronic/intergenic
rs1487070292382571454G>A0.002intergenic_variantLINC02008 - CYP51A1P13e-11Tier 4: intronic/intergenic
rs185588402201412485T>C0.001intron_variantFKBP1A - NSFL1C5e-11Tier 4: intronic/intergenic
rs4854973160001345A>C,G0.48intron_variantIL12A-AS11e-10Tier 4: intronic/intergenic
rs2736345811494976A>G,T0.29intron_variantBLK5e-10Tier 4: intronic/intergenic
rs56036302632304379A>T0.201intron_variantTSBP1-AS1, TSBP16e-10Tier 4: intronic/intergenic
rs47315327128932712G>A0.05intergenic_variantKCP - IRF51e-09Tier 4: intronic/intergenic
rs50299396137874586C>G0.044intron_variantTNFAIP38e-09Tier 4: intronic/intergenic
rs711903811118867572G>A,C,T0.23intron_variantY_RNA - CXCR51e-08Tier 4: intronic/intergenic
rs75748652191099907T>A,G0.05intron_variantSTAT42e-08Tier 4: intronic/intergenic
rs65798375151055333G>T0.09intron_variantTNIP13e-08Tier 4: intronic/intergenic
rs170744921381587764C>A,T0.05intergenic_variantHIGD1AP2 - PTMAP56e-08Tier 4: intronic/intergenic
rs69334046137638098T>C0.21intergenic_variantBTF3L4P3 - LINC030047e-08Tier 4: intronic/intergenic
rs24310985160460329A>G,T0.49intergenic_variantMIR3142HG2e-07Tier 4: intronic/intergenic
rs73414757103764368G>A0.05intron_variantRELN3e-07Tier 4: intronic/intergenic
rs9277554633087761C>G,T0.053_prime_UTR_variantHLA-DPB13e-07Tier 2: splice/UTR

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 62 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SATB1Orphanet:684232Intellectual disability-epilepsy-dental anomalies-facial dysmorphism syndrome
ATXN2Orphanet:803Amyotrophic lateral sclerosis
ATXN2Orphanet:98756Spinocerebellar ataxia type 2
BLKOrphanet:536Systemic lupus erythematosus
BLKOrphanet:552MODY
STAT4Orphanet:117Behçet disease
STAT4Orphanet:536Systemic lupus erythematosus
STAT4Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
STAT4Orphanet:85410Oligoarticular juvenile idiopathic arthritis
STAT4Orphanet:93552Pediatric systemic lupus erythematosus
BTNL2Orphanet:797Sarcoidosis
TNFAIP3Orphanet:536Systemic lupus erythematosus
TNFAIP3Orphanet:674762Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
PHIPOrphanet:589905PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome
TNIP1Orphanet:536Systemic lupus erythematosus
TNPO3Orphanet:186Primary biliary cholangitis
TNPO3Orphanet:55595TNP03-related limb-girdle muscular dystrophy D2
COL11A2Orphanet:1427Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2Orphanet:166100Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2Orphanet:2021Fibrochondrogenesis
COL11A2Orphanet:90635Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2Orphanet:90636Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CCDC174Orphanet:467176Severe hypotonia-psychomotor developmental delay-strabismus-cardiac septal defect syndrome
GTF2IOrphanet:904Williams syndrome
GTF2IRD1Orphanet:904Williams syndrome
HLA-DPA1Orphanet:900Granulomatosis with polyangiitis
HLA-DPB1Orphanet:133Chronic beryllium disease
HLA-DPB1Orphanet:900Granulomatosis with polyangiitis
HLA-DQA1Orphanet:391490Adult-onset myasthenia gravis
HLA-DQA1Orphanet:930Idiopathic achalasia
HLA-DQB1Orphanet:2073Narcolepsy type 1
HLA-DQB1Orphanet:477738Pediatric multiple sclerosis
HLA-DQB1Orphanet:703Bullous pemphigoid
HLA-DQB1Orphanet:83465Narcolepsy type 2
HLA-DQB1Orphanet:930Idiopathic achalasia
HLA-DRAOrphanet:505Graham Little-Piccardi-Lassueur syndrome
HLA-DRB1Orphanet:2073Narcolepsy type 1
HLA-DRB1Orphanet:220393Diffuse cutaneous systemic sclerosis
HLA-DRB1Orphanet:220402Limited cutaneous systemic sclerosis
HLA-DRB1Orphanet:220407Limited systemic sclerosis
HLA-DRB1Orphanet:3437Vogt-Koyanagi-Harada disease
HLA-DRB1Orphanet:397Giant cell arteritis
HLA-DRB1Orphanet:477738Pediatric multiple sclerosis
HLA-DRB1Orphanet:536Systemic lupus erythematosus
HLA-DRB1Orphanet:545Follicular lymphoma
HLA-DRB1Orphanet:703Bullous pemphigoid
HLA-DRB1Orphanet:747Autoimmune pulmonary alveolar proteinosis
HLA-DRB1Orphanet:797Sarcoidosis
HLA-DRB1Orphanet:83465Narcolepsy type 2
HLA-DRB1Orphanet:85414Systemic-onset juvenile idiopathic arthritis

Cohort genes → proteins

49 cohort genes, 45 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only49

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SATB1HGNC:10541ENSG00000182568Q01826DNA-binding protein SATB1gwas
ATXN2HGNC:10555ENSG00000204842Q99700Ataxin-2gwas
BLKHGNC:1057ENSG00000136573P51451Tyrosine-protein kinase Blkgwas
CXCR5HGNC:1060ENSG00000160683P32302C-X-C chemokine receptor type 5gwas
SH2D2AHGNC:10821ENSG00000027869Q9NP31SH2 domain-containing protein 2Agwas
STAT4HGNC:11365ENSG00000138378Q14765Signal transducer and activator of transcription 4gwas
BTNL2HGNC:1142ENSG00000204290Q9UIR0Butyrophilin-like protein 2gwas
TNFAIP3HGNC:11896ENSG00000118503P21580Tumor necrosis factor alpha-induced protein 3gwas
VCAM1HGNC:12663ENSG00000162692P19320Vascular cell adhesion protein 1gwas
TSBP1HGNC:13922ENSG00000204296Q5SRN2Testis-expressed basic protein 1gwas
RASGRP3HGNC:14545ENSG00000152689Q8IV61Ras guanyl-releasing protein 3gwas
PHIPHGNC:15673ENSG00000146247Q8WWQ0PH-interacting proteingwas
TNIP1HGNC:16903ENSG00000145901Q15025TNFAIP3-interacting protein 1gwas
TNPO3HGNC:17103ENSG00000064419Q9Y5L0Transportin-3gwas
IRAK1BP1HGNC:17368ENSG00000146243Q5VVH5Interleukin-1 receptor-associated kinase 1-binding protein 1gwas
MIS18BP1HGNC:20190ENSG00000129534Q6P0N0Mis18-binding protein 1gwas
CPEB4HGNC:21747ENSG00000113742Q17RY0Cytoplasmic polyadenylation element-binding protein 4gwas
COL11A2HGNC:2187ENSG00000204248P13942Collagen alpha-2(XI) chaingwas
GRIP2HGNC:23841ENSG00000144596Q9C0E4Glutamate receptor-interacting protein 2gwas
NACC2HGNC:23846ENSG00000148411Q96BF6Nucleus accumbens-associated protein 2gwas
CCDC174HGNC:28033ENSG00000154781Q6PII3Coiled-coil domain-containing protein 174gwas
DGKQHGNC:2856ENSG00000145214P52824Diacylglycerol kinase thetagwas
SHISA9HGNC:37231ENSG00000237515B4DS77Protein shisa-9gwas
LINC00562HGNC:43706ENSG00000260388long intergenic non-protein coding RNA 562gwas
GTF2IHGNC:4659ENSG00000263001P78347General transcription factor II-Igwas
GTF2IRD1HGNC:4661ENSG00000006704Q9UHL9General transcription factor II-I repeat domain-containing protein 1gwas
LINC00871HGNC:47038ENSG00000258700long intergenic non-protein coding RNA 871gwas
HLA-DPA1HGNC:4938ENSG00000231389P20036HLA class II histocompatibility antigen, DP alpha 1 chaingwas
HLA-DPB1HGNC:4940ENSG00000223865P04440HLA class II histocompatibility antigen, DP beta 1 chaingwas
HLA-DQA1HGNC:4942ENSG00000196735P01909HLA class II histocompatibility antigen, DQ alpha 1 chaingwas
HLA-DQA2HGNC:4943ENSG00000237541P01906HLA class II histocompatibility antigen, DQ alpha 2 chaingwas
HLA-DQB1HGNC:4944ENSG00000179344P01920HLA class II histocompatibility antigen, DQ beta 1 chaingwas
HLA-DRAHGNC:4947ENSG00000204287P01903HLA class II histocompatibility antigen, DR alpha chaingwas
HLA-DRB1HGNC:4948ENSG00000196126P01911HLA class II histocompatibility antigen, DRB1 beta chaingwas
HLA-DRB5HGNC:4953ENSG00000198502Q30154HLA class II histocompatibility antigen, DR beta 5 chaingwas
HLA-DRB6HGNC:4954ENSG00000229391major histocompatibility complex, class II, DR beta 6 (pseudogene)gwas
HTR2AHGNC:5293ENSG00000102468P282235-hydroxytryptamine receptor 2Agwas
IL12AHGNC:5969ENSG00000168811P29459Interleukin-12 subunit alphagwas
IRF5HGNC:6120ENSG00000128604Q13568Interferon regulatory factor 5gwas
ITSN2HGNC:6184ENSG00000198399Q9NZM3Intersectin-2gwas
KLRG1HGNC:6380ENSG00000139187Q96E93Killer cell lectin-like receptor subfamily G member 1gwas
M6PRHGNC:6752ENSG00000003056P20645Cation-dependent mannose-6-phosphate receptorgwas
NFAT5HGNC:7774ENSG00000102908O94916Nuclear factor of activated T-cells 5gwas
PDE8BHGNC:8794ENSG00000113231O95263High affinity cAMP-specific and IBMX-insensitive 3’,5’-cyclic phosphodiesterase 8Bgwas
PRCCHGNC:9343ENSG00000143294Q92733Proline-rich protein PRCCgwas
PRDM1HGNC:9346ENSG00000057657O75626PR domain zinc finger protein 1gwas
PTMAP5HGNC:9628ENSG00000214182prothymosin alpha pseudogene 5gwas
PTTG1HGNC:9690ENSG00000164611O95997Securingwas
RELNHGNC:9957ENSG00000189056P78509Reelingwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SATB1DNA-binding protein SATB1Crucial silencing factor contributing to the initiation of X inactivation mediated by Xist RNA that occurs during embryogenesis and in lymphoma.
ATXN2Ataxin-2Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
BLKTyrosine-protein kinase BlkNon-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
CXCR5C-X-C chemokine receptor type 5Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC).
SH2D2ASH2 domain-containing protein 2ACould be a T-cell-specific adapter protein involved in the control of T-cell activation.
STAT4Signal transducer and activator of transcription 4Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response.
BTNL2Butyrophilin-like protein 2Negative regulator of T-cell proliferation.
TNFAIP3Tumor necrosis factor alpha-induced protein 3Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
VCAM1Vascular cell adhesion protein 1Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation.
RASGRP3Ras guanyl-releasing protein 3Guanine nucleotide exchange factor (GEF) for Ras and Rap1.
PHIPPH-interacting proteinProbable regulator of the insulin and insulin-like growth factor signaling pathways.
TNIP1TNFAIP3-interacting protein 1Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating TAX1BP1 and A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG.
TNPO3Transportin-3Importin, which transports target proteins into the nucleus.
IRAK1BP1Interleukin-1 receptor-associated kinase 1-binding protein 1Component of the IRAK1-dependent TNFRSF1A signaling pathway that leads to NF-kappa-B activation and is required for cell survival.
MIS18BP1Mis18-binding protein 1Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.
CPEB4Cytoplasmic polyadenylation element-binding protein 4Sequence-specific RNA-binding protein that binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5’-UUUUUAU-3’) within the mRNA 3’-UTR.
COL11A2Collagen alpha-2(XI) chainMay play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
GRIP2Glutamate receptor-interacting protein 2May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons.
NACC2Nucleus accumbens-associated protein 2Functions as a transcriptional repressor through its association with the NuRD complex.
CCDC174Coiled-coil domain-containing protein 174Probably involved in neuronal development.
DGKQDiacylglycerol kinase thetaDiacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
SHISA9Protein shisa-9Regulator of short-term neuronal synaptic plasticity in the dentate gyrus.
GTF2IGeneral transcription factor II-IInteracts with the basal transcription machinery by coordinating the formation of a multiprotein complex at the C-FOS promoter, and linking specific signal responsive activator complexes.
GTF2IRD1General transcription factor II-I repeat domain-containing protein 1May be a transcription regulator involved in cell-cycle progression and skeletal muscle differentiation.
HLA-DPA1HLA class II histocompatibility antigen, DP alpha 1 chainBinds 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-DPB1HLA class II histocompatibility antigen, DP beta 1 chainBinds 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-DQA1HLA class II histocompatibility antigen, DQ alpha 1 chainBinds 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-DQA2HLA class II histocompatibility antigen, DQ alpha 2 chainBinds 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-DQB1HLA class II histocompatibility antigen, DQ beta 1 chainBinds 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-DRAHLA class II histocompatibility antigen, DR alpha chainAn alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB1HLA class II histocompatibility antigen, DRB1 beta chainA beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB5HLA class II histocompatibility antigen, DR beta 5 chainBinds 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.
HTR2A5-hydroxytryptamine receptor 2AG-protein coupled receptor for 5-hydroxytryptamine (serotonin).
IL12AInterleukin-12 subunit alphaHeterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine.
IRF5Interferon regulatory factor 5Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9.
ITSN2Intersectin-2Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery.
KLRG1Killer cell lectin-like receptor subfamily G member 1Plays an inhibitory role on natural killer (NK) cells and T-cell functions upon binding to their non-MHC ligands.
M6PRCation-dependent mannose-6-phosphate receptorTransport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes.
NFAT5Nuclear factor of activated T-cells 5Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes.
PDE8BHigh affinity cAMP-specific and IBMX-insensitive 3’,5’-cyclic phosphodiesterase 8BHydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
PRCCProline-rich protein PRCCMay regulate cell cycle progression through interaction with MAD2L2.
PRDM1PR domain zinc finger protein 1Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and n…
PTTG1SecurinRegulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair.
RELNReelinExtracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment.

Protein-family classification

Druggable: 14 · Difficult: 13 · Unknown: 22 · Druggable fraction: 0.29

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.

FamilyGenesFoldFDR
Antibody/Immunoglobulin106.0×3e-05
Transcription factor91.5×0.396
Scaffold/PPI41.4×0.629
Kinase21.1×0.735
GPCR21.0×0.735
Other/Unknown220.8×0.954

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SATB1Transcription factornoHD, CUT_dom, Homeodomain-like_sf
ATXN2Other/UnknownnoLsmAD_domain, PAM2_motif, LSM_dom_sf
BLKKinaseyes2.7.10.2Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
CXCR5GPCRyesGPCR_Rhodpsn, Chemokine_CXCR5, GPCR_Rhodpsn_7TM
SH2D2AScaffold/PPInoSH2, SH2D2A_SH2, SH2_dom_sf
STAT4Transcription factornoSH2, STAT, p53-like_TF_DNA-bd_sf
BTNL2Antibody/ImmunoglobulinyesIg_C1-set, Ig_sub, Ig-like_dom
TNFAIP3Transcription factornoZnf_A20, OTU_dom, OTU_Deubiquitinase
VCAM1Antibody/ImmunoglobulinyesIg_sub2, Ig_sub, ICAM_VCAM_N
TSBP1Other/UnknownnoTSBP1
RASGRP3Other/UnknownnoRas-like_Gua-exchang_fac_N, RASGEF_cat_dom, EF_hand_dom
PHIPScaffold/PPInoBromodomain, WD40_rpt, WD40/YVTN_repeat-like_dom_sf
TNIP1Other/Unknownno
TNPO3Other/UnknownnoARM-like, Exportin-1/Importin-b-like, ARM-type_fold
IRAK1BP1Other/UnknownnoSIMPL/DUF541, IRAK1BP1
MIS18BP1Transcription factornoSANT/Myb, Homeodomain-like_sf, SANTA
CPEB4Other/UnknownnoRRM_dom, Nucleotide-bd_a/b_plait_sf, CEBP_ZZ
COL11A2Other/UnknownnoFib_collagen_C, Laminin_G, Collagen
GRIP2Scaffold/PPInoPDZ, PDZ_sf, PDZ_6
NACC2Other/UnknownnoBTB/POZ_dom, SKP1/BTB/POZ_sf, BEN_domain
CCDC174Other/UnknownnoCCDC174-like, CCDC174_GRSR
DGKQKinaseyes2.7.1.107RA_dom, Diacylglycerol_kin_accessory, Diacylglycerol_kinase_cat_dom
SHISA9Other/UnknownnoShisa, Shisa_N
LINC00562Other/Unknownno
GTF2ITranscription factornoGTF2I, TF_II-I, GTF2I-like_rpt_sf
GTF2IRD1Transcription factornoGTF2I, TF_II-I, GTF2I-like_rpt_sf
LINC00871Other/Unknownno
HLA-DPA1Antibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DPB1Antibody/ImmunoglobulinyesMHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQA1Antibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQA2Antibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1Antibody/ImmunoglobulinyesMHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRAAntibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB1Antibody/ImmunoglobulinyesMHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB5Antibody/ImmunoglobulinyesMHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB6Other/Unknownno
HTR2AGPCRyesGPCR_Rhodpsn, 5HT2A_rcpt, 5HT_rcpt
IL12AOther/UnknownnoIL-12_alpha, 4_helix_cytokine-like_core, IL-12
IRF5Other/UnknownnoInterferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
ITSN2Scaffold/PPInoC2_dom, DH_dom, EH_dom
KLRG1Other/UnknownnoC-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
M6PROther/UnknownnoMan-6-P_rcpt_cation_dep, Man6P_isomerase_rcpt-bd_dom_sf, Man-6-P_rcpt
NFAT5Transcription factornoIPT_dom, NFAT, p53-like_TF_DNA-bd_sf
PDE8BTranscription factorno3.1.4.53PAS, PDEase_catalytic_dom, HD/PDEase_dom
PRCCOther/UnknownnoPRCC
PRDM1Transcription factornoSET_dom, Znf_C2H2_type, PRDM1
PTMAP5Other/Unknownno
PTTG1Other/UnknownnoSecurin_separation_inhibitor
RELNOther/UnknownnoEGF, Reeler_dom, EGF_extracell

Expression context

Cohort genes with no expression data: 0.

42 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)49
unknown0

Top tissues across cohort

TissueCohort genes
granulocyte12
male germ line stem cell (sensu Vertebrata) in testis9
vermiform appendix7
monocyte6
primordial germ cell in gonad5
ventricular zone5
lymph node4
sural nerve4
lower esophagus mucosa4
secondary oocyte4
buccal mucosa cell3
colonic epithelium3
spleen3
blood3
hindlimb stylopod muscle3
mononuclear cell3
leukocyte3
frontal pole2
olfactory bulb2
middle temporal gyrus2

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SATB1294ubiquitousmarkerorbitofrontal cortex, frontal pole, thymus
ATXN2286ubiquitousmarkerbuccal mucosa cell, colonic epithelium, olfactory bulb
BLK145tissue_specificmarkerspleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
CXCR5172tissue_specificmarkergranulocyte, spleen, lymph node
SH2D2A166broadmarkergranulocyte, male germ line stem cell (sensu Vertebrata) in testis, blood
STAT4201broadmarkergranulocyte, sperm, middle temporal gyrus
BTNL2106yessural nerve, ventricular zone, primordial germ cell in gonad
TNFAIP3274ubiquitousmarkervena cava, mucosa of paranasal sinus, vermiform appendix
VCAM1257ubiquitousmarkercartilage tissue, trabecular bone tissue, parietal pleura
TSBP158tissue_specificyesleft testis, testis, right testis
RASGRP3255ubiquitousmarkercorpus callosum, inferior vagus X ganglion, C1 segment of cervical spinal cord
PHIP302ubiquitousmarkerbronchial epithelial cell, epithelium of bronchus, ventricular zone
TNIP1298ubiquitousmarkerlower esophagus mucosa, blood, hindlimb stylopod muscle
TNPO3299ubiquitousmarkersecondary oocyte, tendon of biceps brachii, medial globus pallidus
IRAK1BP1211ubiquitousmarkeroocyte, secondary oocyte, caput epididymis
MIS18BP1239ubiquitousmarkermonocyte, mononuclear cell, ventricular zone
CPEB4261ubiquitousmarkeradrenal tissue, left ventricle myocardium, secondary oocyte
COL11A2134broadyespituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis
GRIP2202tissue_specificmarkerapex of heart, lateral nuclear group of thalamus, hindlimb stylopod muscle
NACC2289ubiquitousmarkerdorsal motor nucleus of vagus nerve, inferior olivary complex, medial globus pallidus
CCDC174243ubiquitousmarkercalcaneal tendon, sural nerve, kidney epithelium
DGKQ235ubiquitousyesileal mucosa, pancreatic ductal cell, granulocyte
SHISA9151broadmarkercortical plate, lateral nuclear group of thalamus, prefrontal cortex
LINC00562128yesprimordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, sural nerve
GTF2I237ubiquitousmarkerganglionic eminence, colonic epithelium, sural nerve
GTF2IRD1270ubiquitousmarkerlower esophagus mucosa, hindlimb stylopod muscle, tibialis anterior
LINC00871113tissue_specificmarkermale germ line stem cell (sensu Vertebrata) in testis, cortex of kidney, primordial germ cell in gonad
HLA-DPA1133ubiquitousmarkermonocyte, leukocyte, granulocyte
HLA-DPB1135ubiquitousmarkergranulocyte, lymph node, vermiform appendix
HLA-DQA1244broadmarkergall bladder, rectum, monocyte

Protein interactions among cohort

Intra-cohort edges: 30.

Hub genes (top 10 by interactor count)

SymbolInteractor count
VCAM15,031
ITSN23,717
TNFAIP33,716
HLA-DRB13,448
ATXN23,360
TNIP13,304
HLA-DRA3,244
PHIP3,057
TNPO32,970
BLK2,967

Intra-cohort edges

ABSources
ATXN2CPEB4biogrid_interaction
BLKIRF5string_interaction
BLKSTAT4string_interaction
BLKTNFAIP3string_interaction
BTNL2HLA-DQA2string_interaction
BTNL2HLA-DQB1intact
BTNL2HLA-DRAstring_interaction
BTNL2HLA-DRB1string_interaction
BTNL2HLA-DRB5string_interaction
BTNL2TSBP1string_interaction
COL11A2TSBP1string_interaction
GTF2IPRDM1biogrid_interaction
HLA-DPA1HLA-DPB1intact
HLA-DPA1HLA-DQB1intact
HLA-DQA1HLA-DQA2intact
HLA-DQA1HLA-DQB1biogrid_interaction, intact
HLA-DQA1HLA-DRB5intact
HLA-DQA2HLA-DRB1string_interaction
HLA-DRAHLA-DRB1biogrid_interaction, intact, string_interaction
HLA-DRAHLA-DRB5biogrid_interaction, intact, string_interaction
HLA-DRATSBP1string_interaction
HLA-DRB1HLA-DRB5biogrid_interaction, intact
HLA-DRB1IRF5string_interaction
HLA-DRB1TSBP1string_interaction
IRAK1BP1PHIPstring_interaction
IRF5STAT4string_interaction
IRF5TNFAIP3string_interaction
IRF5TNIP1string_interaction
IRF5TNPO3string_interaction
TNFAIP3TNIP1biogrid_interaction, intact, string_interaction

Structural data

PDB: 29 · AlphaFold-only: 16 · No structure: 4

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
PHIPQ8WWQ0146
HLA-DRAP01903140
HLA-DRB1P01911108
HTR2AP2822339
HLA-DQA1P0190928
TNFAIP3P2158017
HLA-DPA1P2003610
HLA-DPB1P0444010
HLA-DQB1P0192010
SATB1Q018268
TNIP1Q150258
ITSN2Q9NZM38
TNPO3Q9Y5L06
MIS18BP1Q6P0N04
GTF2IP783474
GTF2IRD1Q9UHL94
HLA-DRB5Q301544
IL12AP294594
VCAM1P193203
CPEB4Q17RY03
PRDM1O756263
GRIP2Q9C0E42
PTTG1O959972
ATXN2Q997001
IRF5Q135681
KLRG1Q96E931
M6PRP206451
NFAT5O949161
RELNP785091

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
HLA-DQA2P0190689.29
STAT4Q1476586.87
BTNL2Q9UIR085.97
DGKQP5282482.56
IRAK1BP1Q5VVH582.40
BLKP5145181.89
CXCR5P3230280.85
PDE8BO9526374.88
CCDC174Q6PII372.79
RASGRP3Q8IV6170.51
SH2D2AQ9NP3161.87
NACC2Q96BF661.41
PRCCQ9273359.89
SHISA9B4DS7757.01
COL11A2P1394250.18
TSBP1Q5SRN245.58

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 112. Enrichment computed across 49 evidence-associated genes (34 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 34 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Translocation of ZAP-70 to Immunological synapse7130.6×4e-12HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, HLA-DRB5
Interferon gamma signaling1036.9×4e-12VCAM1, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB1 (+2 more)
Phosphorylation of CD3 and TCR zeta chains7112.0×5e-12HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, HLA-DRB5
Co-inhibition by PD-17106.9×5e-12HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, HLA-DRB5
Generation of second messenger molecules771.2×1e-10HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, HLA-DRB5
Downstream TCR signaling726.4×1e-07HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, HLA-DRB5
MHC class II antigen presentation718.4×1e-06HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB1, HLA-DRB5
Interleukin-35 Signalling256.0×0.008STAT4, IL12A
Interleukin-12 signaling224.0×0.039STAT4, IL12A
Regulation of TP53 Expression1167.9×0.067PRDM1
Ovarian tumor domain proteases216.4×0.067TNFAIP3, TNIP1
Activation of RAS in B cells167.2×0.132RASGRP3
Reelin signalling pathway156.0×0.132RELN
RUNX1 regulates transcription of genes involved in BCR signaling156.0×0.132BLK
SLC15A4:TASL-dependent IRF5 activation156.0×0.132IRF5
Interleukin-23 signaling137.3×0.185STAT4
Interleukin-21 signaling133.6×0.194STAT4
STAT3 nuclear events downstream of ALK signaling130.5×0.194PRDM1
Serotonin receptors128.0×0.194HTR2A
Butyrophilin (BTN) family interactions125.8×0.194BTNL2
Specification of primordial germ cells125.8×0.194PRDM1
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)125.8×0.194STAT4
Cargo recognition for clathrin-mediated endocytosis26.2×0.200ITSN2, M6PR
Interleukin-4 and Interleukin-13 signaling26.0×0.200VCAM1, IL12A
Trafficking of GluR2-containing AMPA receptors119.8×0.222GRIP2
Interleukin-2 family signaling118.7×0.225STAT4
Apoptotic cleavage of cellular proteins114.0×0.235SATB1
Interleukin-12 family signaling114.0×0.235STAT4
Apoptotic execution phase114.0×0.235SATB1
Nucleosome assembly114.0×0.235MIS18BP1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 43 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
peptide antigen assembly with MHC class II protein complex8195.9×4e-15HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
antigen processing and presentation of exogenous peptide antigen via MHC class II8101.1×1e-12HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
positive regulation of immune response889.6×3e-12HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
positive regulation of T cell activation882.5×4e-12HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
adaptive immune response815.7×3e-06HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB5, PRDM1
immune response99.8×1e-05CXCR5, IRAK1BP1, HLA-DPA1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA, HLA-DRB1 (+1 more)
antigen processing and presentation of endogenous peptide antigen via MHC class II2391.9×3e-04HLA-DRA, HLA-DRB1
myeloid dendritic cell antigen processing and presentation2261.3×9e-04HLA-DRA, HLA-DRB1
positive regulation of T cell proliferation424.1×9e-04BTNL2, VCAM1, HLA-DPA1, HLA-DPB1
regulation of T-helper cell differentiation2195.9×0.001HLA-DRA, HLA-DRB1
positive regulation of CD4-positive, alpha-beta T cell activation2195.9×0.001HLA-DRA, HLA-DRB1
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation2156.8×0.002HLA-DRA, HLA-DRB1
positive regulation of T cell mediated cytotoxicity335.6×0.002HLA-DRA, HLA-DRB1, IL12A
T cell receptor signaling pathway414.1×0.005BTNL2, HLA-DPB1, HLA-DQB1, HLA-DRB1
artery smooth muscle contraction287.1×0.005GRIP2, HTR2A
interleukin-12-mediated signaling pathway287.1×0.005STAT4, IL12A
positive regulation of memory T cell differentiation287.1×0.005HLA-DRA, HLA-DRB1
positive regulation of cytokine production involved in immune response246.1×0.017HTR2A, IRF5
positive regulation of type II interferon production315.7×0.018HLA-DPA1, HLA-DPB1, IL12A
antigen processing and presentation of peptide or polysaccharide antigen via MHC class II1391.9×0.030HLA-DRA
transition between slow and fast fiber1391.9×0.030GTF2IRD1
spinal cord patterning1391.9×0.030RELN
regulation of interleukin-4 production1391.9×0.030HLA-DRB1
negative regulation of toll-like receptor 5 signaling pathway1391.9×0.030TNFAIP3
cardiac neuron differentiation1391.9×0.030VCAM1
regulation of vascular wound healing1391.9×0.030TNFAIP3
negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway1391.9×0.030TNFAIP3
establishment of protein localization to vacuole1391.9×0.030TNFAIP3
negative regulation of steroid hormone biosynthetic process1391.9×0.030PDE8B
positive regulation of lateral motor column neuron migration1391.9×0.030RELN

Therapeutics

Drugs indicated for this disease

1 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

DrugDevelopment status
PilocarpineApproved (phase 4)
AbataceptPhase 3 (in late-stage trials)
DazodalibepPhase 3 (in late-stage trials)
HydroxychloroquinePhase 3 (in late-stage trials)
IanalumabPhase 3 (in late-stage trials)
Sodium ChloridePhase 3 (in late-stage trials)
TelitaciceptPhase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Anifrolumab, Baricitinib, Belimumab, Efalizumab, Efgartigimod Alfa, Etanercept, Filgotinib, Frexalimab, Iguratimod, Leflunomide, Mycophenolate Mofetil, Nipocalimab, OMEGA-3 FATTY ACIDS, Parsaclisib, Prednisolone, Remibrutinib, Rituximab, Tacrolimus Anhydrous, Tirabrutinib, Tofacitinib.

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 3 · Phased (≥1): 5 · Undrugged: 44

Druggability breadth: 20 of 49 evidence-associated genes (41%) 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.

SymbolExample approved molecule
BLKAFATINIB
HTR2APIMOZIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
HTR2A3854
BLK624
VCAM113
RASGRP312
GTF2I12
SATB100
ATXN200
CXCR500
SH2D2A00
STAT400

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
AFATINIB4BLK
FEDRATINIB4BLK, HTR2A
AXITINIB4BLK
SORAFENIB4BLK, HTR2A
NERATINIB4BLK, HTR2A
IBRUTINIB4BLK
ENTRECTINIB4BLK
BELUMOSUDIL4BLK
AFATINIB DIMALEATE4BLK
VANDETANIB4BLK, HTR2A
NILOTINIB4BLK
BOSUTINIB4BLK, HTR2A
BRIGATINIB4BLK
ACALABRUTINIB4BLK
ZANUBRUTINIB4BLK
TIRABRUTINIB4BLK
RITLECITINIB4BLK
PAZOPANIB4BLK
NINTEDANIB4BLK
SUNITINIB4BLK, HTR2A
DASATINIB4BLK, HTR2A
ERLOTINIB4BLK
QUIZARTINIB4BLK
CRIZOTINIB4BLK, HTR2A
MIDOSTAURIN4BLK
GEFITINIB4BLK
IMATINIB4BLK, HTR2A
PIMOZIDE4HTR2A
CISAPRIDE4HTR2A
CLOZAPINE4HTR2A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

SymbolAssaysType breakdown
HTR2A1,639Binding:1250, Functional:345, ADMET:41, Toxicity:2, Unclassified:1
BLK483Binding:477, ADMET:4, Functional:2
PDE8B35Binding:33, ADMET:1, Functional:1
CXCR533Binding:21, Functional:12
STAT420Binding:20
RASGRP320Binding:20
PHIP17Binding:17
HLA-DRB117Binding:17
VCAM116Binding:15, Functional:1
GTF2I8Binding:8
ATXN25Binding:3, Functional:2
HLA-DQA12Binding:2
M6PR2Binding:2
SH2D2A1Binding:1
TNFAIP31Binding:1
TNPO31Binding:1
PRDM11Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
BLK2.7.10.2non-specific protein-tyrosine kinase
DGKQ2.7.1.107diacylglycerol kinase (ATP)
PDE8B3.1.4.533’,5’-cyclic-AMP phosphodiesterase

Cohort genes with high screening signal

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

SymbolChEMBL assays
BLK483
HTR2A1,639

Pharmacogenomics

Cohort genes with a PharmGKB record: 47; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
HTR2A1

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.

CompoundMax phaseCohort target (bioactivity)
AFATINIB4BLK
FEDRATINIB4BLK, HTR2A
AXITINIB4BLK
SORAFENIB4BLK, HTR2A
NERATINIB4BLK, HTR2A
IBRUTINIB4BLK
ENTRECTINIB4BLK
BELUMOSUDIL4BLK
AFATINIB DIMALEATE4BLK
VANDETANIB4BLK, HTR2A
NILOTINIB4BLK
BOSUTINIB4BLK, HTR2A
BRIGATINIB4BLK
ACALABRUTINIB4BLK
ZANUBRUTINIB4BLK
TIRABRUTINIB4BLK
RITLECITINIB4BLK
PAZOPANIB4BLK
NINTEDANIB4BLK
SUNITINIB4BLK, HTR2A
DASATINIB4BLK, HTR2A
ERLOTINIB4BLK
QUIZARTINIB4BLK
CRIZOTINIB4BLK, HTR2A
MIDOSTAURIN4BLK
GEFITINIB4BLK
IMATINIB4BLK, HTR2A
PIMOZIDE4HTR2A
CISAPRIDE4HTR2A
CLOZAPINE4HTR2A

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)2BLK, HTR2A
BPhased (≥1) drug, not yet approved3VCAM1, RASGRP3, GTF2I
CDruggable family + PDB, no drug7HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5
DDruggable family + AlphaFold only, no drug4CXCR5, BTNL2, DGKQ, HLA-DQA2
EDifficult family or no structure, no drug33SATB1, ATXN2, SH2D2A, STAT4, TNFAIP3, TSBP1, PHIP, TNIP1, TNPO3, IRAK1BP1 (+23 more)

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
SATB10—
ATXN25—
CXCR533—
SH2D2A1—
STAT420—
BTNL20—
TNFAIP31—
TSBP10—
PHIP17—
TNIP10—
TNPO31—
IRAK1BP10—
MIS18BP10—
CPEB40—
COL11A20—
GRIP20—
NACC20—
CCDC1740—
DGKQ0—
SHISA90—
LINC005620—
GTF2IRD10—
LINC008710—
HLA-DPA10—
HLA-DPB10—
HLA-DQA12—
HLA-DQA20—
HLA-DQB10—
HLA-DRA0—
HLA-DRB117—

Clinical trials & evidence

Clinical trials

Clinical trials: 73.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified39
PHASE212
PHASE46
PHASE36
PHASE1/PHASE25
EARLY_PHASE13
PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT07153276PHASE4RECRUITINGTREATMENT OF VAGINAL DRYNESS IN SJÖGREN’S DISEASE WITH CO2-LASER VERSUS TOPICAL PROMESTRIENE
NCT01850979PHASE4COMPLETEDTreatment of Dry Eye Using 0.03% Tacrolimus Eye Drops
NCT02004067PHASE4COMPLETEDSafety Study of the Use of Topical Cyclosporine in the Treatment of Dry Eye Disease
NCT02049112PHASE4COMPLETEDA New Oral salIvary equivAlent Compared to Two moisturizinG Mouth sprAys in Patients With xeRostomiA: NIAGARA Study
NCT03608761PHASE4COMPLETEDComparison Between Rebamipide 2% Versus Autologous Serum
NCT03762824PHASE4COMPLETEDCombined Pneumococcal Conjugate and Polysaccharide Vaccination in Inflammatory Rheumatic Disease
NCT05349214PHASE3ACTIVE_NOT_RECRUITINGThree-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren’s Syndrome
NCT05350072PHASE3ACTIVE_NOT_RECRUITINGTwo-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren’s Syndrome
NCT06931041PHASE3ACTIVE_NOT_RECRUITINGComparing Efficacy of Autologous Serum Eye Drops With and Without Insulin in Autoimmune Dry Eye: A Randomized Clinical Trial
NCT02257957PHASE3COMPLETEDPlatelet -Rich Plasma (PRP) Injection for the Treatment of Severe Dry Eye
NCT03865888PHASE3COMPLETEDComparing Effect of Topical Tacrolimus 0.03% Versus Cyclosporine 0.05% in Dry Eyes of Secondary Sjogren Syndrome
NCT04819269PHASE3COMPLETEDTivanisiran for Dry Eye in Subjects With Sjögren’s Syndrome
NCT06440525PHASE2RECRUITINGA Study of RSLV-132 in Females With Sjögren’s Disease
NCT06519617PHASE2ENROLLING_BY_INVITATIONStudy on Optimization and Evaluation of Integrated Chinese and Western Medicine for pSS Glandular Damage
NCT06794008PHASE2RECRUITINGBCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT06821659PHASE1/PHASE2NOT_YET_RECRUITINGSafety and Efficacy of Universal CAR-T Cells (UWD-CD19) Combined with Immunosuppressants in the Treatment of Refractory Autoimmune Diseases
NCT06828042PHASE1/PHASE2RECRUITINGSafety and Efficacy of Universal CD19-targeting CAR-γδT Cells in Refractory Autoimmune Diseases
NCT06991114PHASE2RECRUITINGAlloNK®, an Allogeneic Non-genetically Modified, Cord Blood-derived NK Cell Therapy, in Combination With Rituximab, Studied in Relapsing Forms of B-cell Dependent Rheumatologic Diseases.
NCT07375524PHASE2NOT_YET_RECRUITINGA Phase 2 Study on the Safety and Efficacy of the Anti-BAFF-R Monoclonal Antibody, ESG206, in Patients With Primary Sjogren Syndrome
NCT01647737PHASE1/PHASE2COMPLETEDGreen Tea Lozenges for the Management of Dry Mouth
NCT02962895PHASE2COMPLETEDSafety and Efficacy of VAY736 in Patients With Primary Sjogren’s Syndrome (pSS)
NCT03226444PHASE1/PHASE2COMPLETEDLacripep™ in Subjects With Dry Eye Associated With Primary Sjögren’s Syndrome
NCT03905525PHASE2COMPLETEDStudy of Safety and Efficacy of Multiple Doses of CFZ533 in Two Distinct Populations of Patients With Sjogren’s Syndrome
NCT04035668PHASE2TERMINATEDA Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren’s Syndrome
NCT04700280PHASE2TERMINATEDA Study Evaluating the Effects of GLPG3970 Given as an Oral Treatment for 12 Weeks in Adults With Active Primary Sjögren’s Syndrome (pSS)
NCT04830644PHASE2UNKNOWNA Study to Evaluate the Efficacy and Safety of Iguratimod Compared to Placebo in Patients With Active Primary Sjogren’s Syndrome.
NCT04988087PHASE2TERMINATEDA Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren’s Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD)
NCT05124925PHASE2COMPLETEDBiopsy Based Study to Understand Mechanism of Action of Ianalumab in Salivary Glands and Explore Relationships With Clinical Assessments.
NCT06049368PHASE1/PHASE2UNKNOWN68Ga-P16-093 PET/CT Imaging in the Salivary Gland
NCT03816345PHASE1RECRUITINGTesting an Immunotherapy Anti-cancer Drug, Nivolumab, for Advanced Cancers in Patients With Autoimmune Disorders, AIM-NIVO
NCT04093531PHASE1COMPLETEDPilot Trial of Ustekinumab for Primary Sjögren’s Syndrome
NCT07246096EARLY_PHASE1RECRUITINGExploratory Clinical Study on the Safety and Efficacy of Anti- CD19/BCMA U CAR-T Cell Injection for the Treatment of Relapsed/Refractory Autoimmune Diseases
NCT07301164EARLY_PHASE1NOT_YET_RECRUITINGClinical Study of BCT301 Cell Injection Therapy for Refractory Autoimmune Diseases
NCT07596680EARLY_PHASE1NOT_YET_RECRUITINGCD19/BCMA-Targeted Universal CAR-T Cell Injection for the Treatment of Autoimmune Diseases
NCT03509064Not specifiedRECRUITINGMedico-economic and Quality of Life Impact of Sjogren-associated Small Fiber Neuropathy
NCT04848870Not specifiedRECRUITINGDental and Periodontal Status of Patients With Sjögren’s Syndrome.
NCT05715463Not specifiedACTIVE_NOT_RECRUITINGRheumatology-based Adaptive Intervention for Social Determinants and Health Equity
NCT06528197Not specifiedRECRUITINGConstruction of Clinical Model of Primary Sjogren’s Syndrome Combined Traditional Chinese and Western Medicine
NCT06642870Not specifiedRECRUITINGRare AutoImmune SElf-management Programme Development
NCT06680310Not specifiedNOT_YET_RECRUITINGUltrasonic COmparison of Salivary Glands in Autoimmune Diseases (COUGAR)

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
TACROLIMUS ANHYDROUS42
CYCLOSPORINE41
HYDROXYCHLOROQUINE41
INSULIN LISPRO41
OLIVE OIL41
IANALUMAB34
IGURATIMOD31
PLATINUM31
PROMESTRIENE31
REBAMIPIDE31
REMIBRUTINIB31
SYRUP31
TIVANISIRAN31
XYLITOL31
GLPG-397021
ISCALIMAB21
MHV-37021
RSLV-13221
CHEMBL170333601
CHEMBL539377101
BOSCALID-11

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 73

This page pulls from 73 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similaritydoidefoensemblentrezesm2_similarityfantom5_genefantom5_promotergenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncicd10cmicd11intactinterpromedgenmeshmimmondomondochildmondoparentncitorphanetpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralsctidscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot