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Atlas / Disease / Adult-onset myasthenia gravis

Adult-onset myasthenia gravis

disease
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Also known as adult-onset acquired myastheniaadult-onset autoimmune myasthenia gravis

Summary

Adult-onset myasthenia gravis (MONDO:0018324) is a disease with 12 cohort genes (28 GWAS associations across 3 studies). The dominant Reactome pathway is Translocation of ZAP-70 to Immunological synapse (3 cohort genes).

At a glance

  • Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
  • Cohort genes: 12
  • GWAS associations: 28

Clinical features

Epidemiology

Prevalence records

5 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Point prevalence1-5 / 10 000EuropeValidated
Annual incidence1-9 / 100 0001.33SerbiaValidated
Point prevalence1-5 / 10 00031.8SerbiaValidated
Point prevalence1-5 / 10 00017United StatesValidated
Point prevalence1-5 / 10 00028United KingdomValidated

Identifiers

Disease identifiers

FieldValue
Canonical nameadult-onset myasthenia gravis
Mondo IDMONDO:0018324
EFOEFO:1001490
Orphanet391490
UMLSC5680024
MedGen1843050
GARD0021623
Is cancer (heuristic)no

Also known as: adult-onset acquired myasthenia · adult-onset autoimmune myasthenia gravis

Data availability: 28 GWAS associations (3 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › autoimmune disorder of the nervous system › autoimmune disorder of peripheral nervous system › myasthenia gravis › adult-onset myasthenia gravis

Related subtypes (5): neonatal myasthenia gravis, myasthenia, limb-girdle, autoimmune, myasthenia gravis with thymus hyperplasia, juvenile myasthenia gravis, transient neonatal myasthenia gravis

Genetics & variants

GWAS landscape

28 GWAS associations across 3 studies. Top hits map to 12 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs24766015e-27AP4B1-AS1, PTPN22A1.36
rs92713752e-19HLA-DRB1 - HLA-DQA1A0.66
rs43697746e-19TNFRSF11AA1.45
rs1119457673e-17HLA-DRB5 - RNU1-61PG1.92
rs352743881e-12CHRNA1A1.86
rs72392612e-12TNFRSF11AA1.14
rs20715914e-12NFKBIL1, ATP6V1G2?
HLA-DQA1*05:016e-12?1.85
rs1508811761e-11POLR1HASP, POLR1HASP?
rs728482041e-11HLA-DRB1 - HLA-DQA1G1.15
HLA-DQA1*052e-10?1.85
rs69989679e-10RNU6-1213P - Y_RNAG1.89
rs2317795e-09CTLA4C0.89
HLA-DRB1*03:017e-08?2
HLA-DQB1*02:011e-07?1.92
HLA-DRB1*13:012e-07?2.56
HLA-DRB1*033e-07?2.04
rs45740254e-07TNFRSF11AC1.42
rs99638624e-07RBBP8G1.44
rs126531175e-07SEMA5AT1.76
rs69147042e-06GMDSC1.39
HLA-DRB1*132e-06?1.89
rs41285274e-06EYA1 - U8C1.61
chr5:31213962:D4e-06TC1.84
rs45184674e-06MAP3K7 - MIR4643A1.77
HLA-DQA1*01:034e-06?2.08
HLA-DQB1*02:029e-06?1.66

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90432158Braun A20242,40464,103Genome-wide meta-analysis of myasthenia gravis uncovers new loci and provides insights into polygenic prediction.
GCST90093466Chia R20221,27833,652Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study.
GCST003251Seldin MF20155322,128Genome-wide Association Study of Late-Onset Myasthenia Gravis: Confirmation of TNFRSF11A, and Identification of ZBTB10 and Three Distinct HLA Associations.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding1
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic26

MAF distribution

BucketVariants
common (>=0.05)16
low_freq (0.01-0.05)1
rare (<0.01)0
unknown10

Functional consequences

ConsequenceCount
intron_variant12
unknown10
intergenic_variant4
missense_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs24766011113834946A>G,T0.132missense_variantAP4B1-AS1, PTPN225e-27Tier 1: coding
rs9271375632619290G>A,C,T0.481intergenic_variantHLA-DRB1 - HLA-DQA12e-19Tier 4: intronic/intergenic
rs43697741862343215A>C,G,T0.461intron_variantTNFRSF11A6e-19Tier 4: intronic/intergenic
rs111945767632549268G>C0.38intergenic_variantHLA-DRB5 - RNU1-61P3e-17Tier 4: intronic/intergenic
rs352743882174764492G>A,T0.036intron_variantCHRNA11e-12Tier 4: intronic/intergenic
rs72392611862337813A>C,T0.368intron_variantTNFRSF11A2e-12Tier 4: intronic/intergenic
rs2071591631548022G>A,C0.05intron_variantNFKBIL1, ATP6V1G24e-12Tier 4: intronic/intergenic
HLA-DQA1*05:016e-12Tier 4: intronic/intergenic
rs150881176629979963intron_variantPOLR1HASP, POLR1HASP1e-11Tier 4: intronic/intergenic
rs72848204632626296G>A,T0.303intergenic_variantHLA-DRB1 - HLA-DQA11e-11Tier 4: intronic/intergenic
HLA-DQA1*052e-10Tier 4: intronic/intergenic
rs6998967880451970G>A,C0.17intron_variantRNU6-1213P - Y_RNA9e-10Tier 4: intronic/intergenic
rs2317792203869764C>T0.485intron_variantCTLA45e-09Tier 4: intronic/intergenic
HLA-DRB1*03:017e-08Tier 4: intronic/intergenic
HLA-DQB1*02:011e-07Tier 4: intronic/intergenic
HLA-DRB1*13:012e-07Tier 4: intronic/intergenic
HLA-DRB1*033e-07Tier 4: intronic/intergenic
rs45740251862342581C>A,G,T0.47intron_variantTNFRSF11A4e-07Tier 4: intronic/intergenic
rs99638621823007948G>A,C0.34intron_variantRBBP84e-07Tier 4: intronic/intergenic
rs1265311759386473C>T0.08intron_variantSEMA5A5e-07Tier 4: intronic/intergenic
rs691470461759646G>A,C,T0.49intron_variantGMDS2e-06Tier 4: intronic/intergenic
HLA-DRB1*132e-06Tier 4: intronic/intergenic
rs4128527871770458C>A,T0.19intron_variantEYA1 - U84e-06Tier 4: intronic/intergenic
chr5:31213962:D0.054e-06Tier 4: intronic/intergenic
rs4518467691486680G>A0.07intergenic_variantMAP3K7 - MIR46434e-06Tier 4: intronic/intergenic
HLA-DQA1*01:034e-06Tier 4: intronic/intergenic
HLA-DQB1*02:029e-06Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 31 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

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

GeneHGNCEvidence routes
HLA-DQA1HLA-DQA1GWAS, Orphanet
HLA-DRB1HLA-DRB1GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
SEMA5AOrphanet:281Monosomy 5p syndrome
HLA-AOrphanet:179Birdshot chorioretinopathy
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-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
PTPN22Orphanet:3437Vogt-Koyanagi-Harada disease
PTPN22Orphanet:397Giant cell arteritis
PTPN22Orphanet:536Systemic lupus erythematosus
PTPN22Orphanet:85408Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
PTPN22Orphanet:85410Oligoarticular juvenile idiopathic arthritis
PTPN22Orphanet:900Granulomatosis with polyangiitis
RBBP8Orphanet:313795Jawad syndrome
RBBP8Orphanet:808Seckel syndrome

Cohort genes → proteins

12 cohort genes, 11 distinct canonical proteins.

Evidence partition

SubsetGenes
gwas_only12

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
SEMA5AHGNC:10736ENSG00000112902Q13591Semaphorin-5Agwas
CDH6HGNC:1765ENSG00000113361P55285Cadherin-6gwas
ZBTB10HGNC:30953ENSG00000205189Q96DT7Zinc finger and BTB domain-containing protein 10gwas
MIR4643HGNC:41814ENSG00000263734microRNA 4643gwas
GMDSHGNC:4369ENSG00000112699O60547GDP-mannose 4,6 dehydratasegwas
HLA-AHGNC:4931ENSG00000206503P04439HLA class I histocompatibility antigen, A alpha chaingwas
HLA-DQA1HGNC:4942ENSG00000196735P01909HLA class II histocompatibility antigen, DQ alpha 1 chaingwas
HLA-DQB1HGNC:4944ENSG00000179344P01920HLA class II histocompatibility antigen, DQ beta 1 chaingwas
HLA-DRB1HGNC:4948ENSG00000196126P01911HLA class II histocompatibility antigen, DRB1 beta chaingwas
MSCHGNC:7321ENSG00000178860O60682Musculingwas
PTPN22HGNC:9652ENSG00000134242Q9Y2R2Tyrosine-protein phosphatase non-receptor type 22gwas
RBBP8HGNC:9891ENSG00000101773Q99708DNA endonuclease RBBP8gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
SEMA5ASemaphorin-5ABifunctional axonal guidance cue regulated by sulfated proteoglycans; attractive effects result from interactions with heparan sulfate proteoglycans (HSPGs), while the inhibitory effects depend on interactions with chondroitin sulfate prot…
CDH6Cadherin-6Cadherins are calcium-dependent cell adhesion proteins.
ZBTB10Zinc finger and BTB domain-containing protein 10May be involved in transcriptional regulation.
GMDSGDP-mannose 4,6 dehydrataseCatalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose.
HLA-AHLA class I histocompatibility antigen, A alpha chainAntigen-presenting major histocompatibility complex class I (MHCI) molecule.
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-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-DRB1HLA class II histocompatibility antigen, DRB1 beta chainA beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
MSCMusculinTranscription repressor capable of inhibiting the transactivation capability of TCF3/E47.
PTPN22Tyrosine-protein phosphatase non-receptor type 22Acts 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.
RBBP8DNA endonuclease RBBP8Endonuclease that cooperates with the MRE11-RAD50-NBN (MRN) complex in DNA-end resection, the first step of double-strand break (DSB) repair through the homologous recombination (HR) pathway.

Protein-family classification

Druggable: 6 · Difficult: 3 · Unknown: 3 · Druggable fraction: 0.5

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/Immunoglobulin49.7×0.003
Phosphatase17.0×0.402
Scaffold/PPI11.4×0.766
Transcription factor21.4×0.766
Enzyme (other)11.0×0.778
Other/Unknown30.5×0.993

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
SEMA5AScaffold/PPInoTSP1_rpt, Semap_dom, Plexin_repeat
CDH6Other/UnknownnoCadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
ZBTB10Transcription factornoBTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
MIR4643Other/Unknownno
GMDSEnzyme (other)yes4.2.1.47GDP_Man_deHydtase, NAD(P)-bd_dom, NAD(P)-bd_dom_sf
HLA-AAntibody/ImmunoglobulinyesMHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HLA-DQA1Antibody/ImmunoglobulinyesMHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1Antibody/ImmunoglobulinyesMHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB1Antibody/ImmunoglobulinyesMHC_II_b_N, Ig/MHC_CS, Ig_C1-set
MSCTranscription factornobHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
PTPN22Phosphataseyes3.1.3.48PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
RBBP8Other/UnknownnoCtp1_C, CtIP_N, RBBP8-like

Expression context

Cohort genes with no expression data: 0.

11 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)12
unknown0

Top tissues across cohort

TissueCohort genes
stromal cell of endometrium2
granulocyte2
monocyte2
right lung2
metanephric glomerulus1
renal glomerulus1
olfactory bulb1
tongue squamous epithelium1
type B pancreatic cell1
cauda epididymis1
mucosa of paranasal sinus1
secondary oocyte1
heart1
kidney1
right frontal lobe1
lower esophagus mucosa1
mucosa of transverse colon1
parotid gland1
blood1
gall bladder1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
SEMA5A262ubiquitousmarkermetanephric glomerulus, renal glomerulus, stromal cell of endometrium
CDH6228broadmarkerolfactory bulb, type B pancreatic cell, tongue squamous epithelium
ZBTB10264ubiquitousmarkersecondary oocyte, cauda epididymis, mucosa of paranasal sinus
MIR464322yeskidney, heart, right frontal lobe
GMDS264ubiquitousmarkerparotid gland, mucosa of transverse colon, lower esophagus mucosa
HLA-A134ubiquitousmarkerblood, granulocyte, stromal cell of endometrium
HLA-DQA1244broadmarkergall bladder, rectum, monocyte
HLA-DQB1268broadmarkerright lung, spleen, upper lobe of left lung
HLA-DRB1131tissue_specificmarkervermiform appendix, granulocyte, right lung
MSC165ubiquitousmarkerright coronary artery, left coronary artery, thoracic aorta
PTPN22190broadmarkerbone marrow cell, bone marrow, monocyte
RBBP8273ubiquitousmarkerchoroid plexus epithelium, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

SymbolInteractor count
HLA-DRB13,448
RBBP83,235
PTPN222,480
GMDS1,450
ZBTB101,255
SEMA5A1,189
CDH61,169
HLA-A688
MSC473
HLA-DQA1196

Intra-cohort edges

ABSources
HLA-AHLA-DQA1biogrid_interaction
HLA-AHLA-DQB1biogrid_interaction
HLA-DQA1HLA-DQB1biogrid_interaction, intact
HLA-DRB1PTPN22string_interaction

Structural data

PDB: 10 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
HLA-AP04439403
HLA-DRB1P01911108
HLA-DQA1P0190928
PTPN22Q9Y2R214
HLA-DQB1P0192010
GMDSO605477
SEMA5AQ135914
RBBP8Q997084
ZBTB10Q96DT72
CDH6P552851

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
MSCO6068265.61

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 51. Enrichment computed across 12 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Translocation of ZAP-70 to Immunological synapse3211.5×8e-06HLA-DQA1, HLA-DRB1, PTPN22
Phosphorylation of CD3 and TCR zeta chains3181.3×8e-06HLA-DQA1, HLA-DRB1, PTPN22
Interferon gamma signaling455.8×8e-06HLA-A, HLA-DQA1, HLA-DQB1, HLA-DRB1
Co-inhibition by PD-12115.3×0.002HLA-DQA1, HLA-DRB1
Generation of second messenger molecules276.9×0.003HLA-DQA1, HLA-DRB1
Downstream TCR signaling228.5×0.018HLA-DQA1, HLA-DRB1
GDP-fucose biosynthesis1211.5×0.030GMDS
MHC class II antigen presentation219.8×0.030HLA-DQA1, HLA-DRB1
Nef mediated downregulation of MHC class I complex cell surface expression1126.9×0.044HLA-A
Endosomal/Vacuolar pathway1115.3×0.044HLA-A
HDR through MMEJ (alt-NHEJ)197.6×0.047RBBP8
Other semaphorin interactions166.8×0.059SEMA5A
Impaired BRCA2 binding to PALB2150.8×0.059RBBP8
Defective homologous recombination repair (HRR) due to BRCA1 loss of function147.0×0.059RBBP8
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function147.0×0.059RBBP8
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function147.0×0.059RBBP8
Semaphorin interactions143.8×0.059SEMA5A
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)143.8×0.059RBBP8
Antigen Presentation: Folding, assembly and peptide loading of class I MHC143.8×0.059HLA-A
Homologous DNA Pairing and Strand Exchange142.3×0.059RBBP8
Defective B3GALTL causes PpS134.3×0.059SEMA5A
Impaired BRCA2 binding to RAD51134.3×0.059RBBP8
O-glycosylation of TSR domain-containing proteins133.4×0.059SEMA5A
Resolution of D-loop Structures through Holliday Junction Intermediates133.4×0.059RBBP8
HDR through Single Strand Annealing (SSA)132.5×0.059RBBP8
Transcriptional Regulation by E2F6132.5×0.059RBBP8
Presynaptic phase of homologous DNA pairing and strand exchange130.2×0.062RBBP8
Adherens junctions interactions127.6×0.063CDH6
Cell-cell junction organization127.6×0.063CDH6
Diseases associated with O-glycosylation of proteins123.9×0.070SEMA5A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 11 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 complex3287.2×1e-05HLA-DQA1, HLA-DQB1, HLA-DRB1
T cell receptor signaling pathway455.2×4e-05HLA-A, HLA-DQB1, HLA-DRB1, PTPN22
antigen processing and presentation of exogenous peptide antigen via MHC class II3148.3×4e-05HLA-DQA1, HLA-DQB1, HLA-DRB1
positive regulation of immune response3131.3×4e-05HLA-DQA1, HLA-DQB1, HLA-DRB1
positive regulation of T cell activation3121.0×4e-05HLA-DQA1, HLA-DQB1, HLA-DRB1
detection of bacterium2255.3×6e-04HLA-A, HLA-DRB1
immune response417.1×0.001HLA-A, HLA-DQA1, HLA-DQB1, HLA-DRB1
positive regulation of T cell mediated cytotoxicity292.8×0.003HLA-A, HLA-DRB1
regulation of interleukin-4 production11532.0×0.007HLA-DRB1
phosphoanandamide dephosphorylation11532.0×0.007PTPN22
signal clustering11532.0×0.007SEMA5A
humoral immune response251.1×0.007HLA-DQB1, HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-dependent1766.0×0.008HLA-A
antigen processing and presentation of endogenous peptide antigen via MHC class II1766.0×0.008HLA-DRB1
diencephalon development1766.0×0.008SEMA5A
regulation of interleukin-10 production1766.0×0.008HLA-DRB1
regulation of natural killer cell proliferation1766.0×0.008PTPN22
positive regulation of memory T cell activation1766.0×0.008HLA-A
positive regulation of CD8-positive, alpha-beta T cell activation1766.0×0.008HLA-A
positive regulation of type II interferon production240.9×0.008HLA-A, PTPN22
T cell mediated cytotoxicity directed against tumor cell target1510.7×0.010HLA-A
myeloid dendritic cell antigen processing and presentation1510.7×0.010HLA-DRB1
branchiomeric skeletal muscle development1510.7×0.010MSC
‘de novo’ GDP-L-fucose biosynthetic process1510.7×0.010GMDS
positive regulation of CD8-positive, alpha-beta T cell proliferation1510.7×0.010HLA-A
CD8-positive, alpha-beta T cell activation1383.0×0.011HLA-A
GDP-L-fucose biosynthetic process1383.0×0.011GMDS
regulation of T-helper cell differentiation1383.0×0.011HLA-DRB1
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway1383.0×0.011PTPN22
positive regulation of CD4-positive, alpha-beta T cell activation1383.0×0.011HLA-DRB1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 10

Druggability breadth: 6 of 12 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.

SymbolExample approved molecule
HLA-ARALOXIFENE HYDROCHLORIDE

Top cohort targets by molecule count

SymbolMoleculesMax phase
HLA-A84
GMDS12
SEMA5A00
CDH600
ZBTB1000
MIR464300
HLA-DQA100
HLA-DQB100
HLA-DRB100
MSC00

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
RALOXIFENE HYDROCHLORIDE4HLA-A
DOXAZOSIN MESYLATE4HLA-A
TRAZODONE HYDROCHLORIDE4HLA-A
ASTEMIZOLE4HLA-A
VATALANIB3HLA-A
MOLIBRESIB2GMDS
DISOMOTIDE2HLA-A
OVEMOTIDE2HLA-A
SPIPERONE2HLA-A

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
PTPN22137Binding:122, Functional:10, ADMET:5
HLA-DRB117Binding:17
GMDS8Binding:8
HLA-A4Binding:4
ZBTB103Binding:3
HLA-DQA12Binding:2

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
GMDS4.2.1.47GDP-mannose 4,6-dehydratase
PTPN223.1.3.48protein-tyrosine-phosphatase

Cohort genes with high screening signal

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

SymbolChEMBL assays
PTPN22137

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
HLA-A1

Chemical tractability of cohort targets

9 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)
RALOXIFENE HYDROCHLORIDE4HLA-A
DOXAZOSIN MESYLATE4HLA-A
TRAZODONE HYDROCHLORIDE4HLA-A
ASTEMIZOLE4HLA-A
VATALANIB3HLA-A
MOLIBRESIB2GMDS
DISOMOTIDE2HLA-A
OVEMOTIDE2HLA-A
SPIPERONE2HLA-A

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)1HLA-A
BPhased (≥1) drug, not yet approved1GMDS
CDruggable family + PDB, no drug4HLA-DQA1, HLA-DQB1, HLA-DRB1, PTPN22
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug6SEMA5A, CDH6, ZBTB10, MIR4643, MSC, RBBP8

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
PTPN22137—
SEMA5A0—
CDH60—
ZBTB103—
MIR46430—
HLA-DQA12—
HLA-DQB10—
HLA-DRB117—
MSC0—
RBBP80—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

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 68

This page pulls from 68 datasets indexed by BioBTree:

alphafoldantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsclinvarctd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityfantom5_genefantom5_promotergardgenccgenerifgogtopdbgtopdb_interactiongwasgwas_studyhgncintactinterpromedgenmeshmimmondomondochildmondoparentorphanetpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assayreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorstring_interactiontranscriptufeatureumlsuniprot