Neuromyelitis optica
diseaseOn this page
Also known as Devic diseaseDevic syndromeDevic's neuromyelitis opticaNeuromyelitis Optica Spectrum DisorderNMO
Summary
Neuromyelitis optica (MONDO:0019100) is a disease with 10 cohort genes (8 GWAS associations across 3 studies) and 117 clinical trials. The dominant Reactome pathway is Interferon gamma signaling (5 cohort genes). Top therapeutic interventions include inebilizumab, eculizumab, and ravulizumab.
At a glance
- Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
- Cohort genes: 10
- GWAS associations: 8
- Phenotypes (HPO): 17
- Clinical trials: 117
Clinical features
Epidemiology
Prevalence records
31 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Annual incidence | 1-9 / 1 000 000 | 0.1877 | Worldwide | Validated |
| Point prevalence | 1-9 / 100 000 | 2.071 | Worldwide | Validated |
| Annual incidence | 1-9 / 1 000 000 | 0.73 | Martinique | Validated |
| Annual incidence | <1 / 1 000 000 | 0.054 | Austria | Validated |
| Annual incidence | <1 / 1 000 000 | 0.08 | United Kingdom | Validated |
| Annual incidence | <1 / 1 000 000 | 0.09 | Netherlands | Validated |
| Annual incidence | <1 / 1 000 000 | 0.063 | Spain | Validated |
| Annual incidence | <1 / 1 000 000 | 0.07 | Denmark | Validated |
| Annual incidence | <1 / 1 000 000 | 0.079 | Sweden | Validated |
| Annual incidence | 1-9 / 1 000 000 | 0.132 | Hungary | Validated |
| Annual incidence | <1 / 1 000 000 | 0.037 | Australia | Validated |
| Annual incidence | <1 / 1 000 000 | 0.07 | United States | Validated |
| Annual incidence | 1-9 / 1 000 000 | 0.495 | India | Validated |
| Annual incidence | 1-9 / 1 000 000 | 0.495 | Canada | Validated |
| Annual incidence | 1-9 / 1 000 000 | 0.39 | Malaysia | Validated |
| Annual incidence | <1 / 1 000 000 | 0.053 | Cuba | Validated |
| Annual incidence | 1-9 / 1 000 000 | 0.285 | Costa rica | Validated |
| Point prevalence | 1-9 / 1 000 000 | 0.7 | Austria | Validated |
| Point prevalence | 1-9 / 100 000 | 1.43 | United Kingdom | Validated |
| Point prevalence | 1-9 / 1 000 000 | 0.89 | Spain | Validated |
Signs & symptoms
Clinical features (HPO)
17 HPO clinical features (Orphanet curated; top 17 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000009 | Functional abnormality of the bladder | Very frequent (80-99%) |
| HP:0000572 | Visual loss | Very frequent (80-99%) |
| HP:0002529 | Neuronal loss in central nervous system | Very frequent (80-99%) |
| HP:0003474 | Somatic sensory dysfunction | Very frequent (80-99%) |
| HP:0010550 | Paraplegia | Very frequent (80-99%) |
| HP:0011096 | Peripheral demyelination | Very frequent (80-99%) |
| HP:0012486 | Myelitis | Very frequent (80-99%) |
| HP:0030057 | Autoimmune antibody positivity | Very frequent (80-99%) |
| HP:0100653 | Optic neuritis | Very frequent (80-99%) |
| HP:0200026 | Ocular pain | Very frequent (80-99%) |
| HP:0012443 | Abnormality of brain morphology | Frequent (30-79%) |
| HP:0033342 | Anti-aquaporin 4 antibody positivity | Frequent (30-79%) |
| HP:0002018 | Nausea | Occasional (5-29%) |
| HP:0002878 | Respiratory failure | Occasional (5-29%) |
| HP:0012229 | CSF pleocytosis | Occasional (5-29%) |
| HP:0032492 | Anti-myelin oligodendrocyte glycoprotein antibody positivity | Occasional (5-29%) |
| HP:0100247 | Recurrent singultus | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | neuromyelitis optica |
| Mondo ID | MONDO:0019100 |
| EFO | EFO:0004256 |
| MeSH | D009471 |
| Orphanet | 71211 |
| DOID | DOID:8869 |
| ICD-10-CM | G36.0 |
| ICD-11 | 744293382 |
| NCIT | C84934 |
| SNOMED CT | 25044007 |
| UMLS | C0027873 |
| MedGen | 45063 |
| GARD | 0006267 |
| MedDRA | 10029322 |
| NORD | 1505 |
| Is cancer (heuristic) | no |
Also known as: Devic disease · Devic syndrome · Devic’s neuromyelitis optica · Neuromyelitis Optica Spectrum Disorder · NMO
Data availability: 8 GWAS associations (3 studies) · 4 GenCC gene-disease records · 24 cell lines.
Disease family
An umbrella term covering 3 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › neuromyelitis optica
Related subtypes (71): congenital nervous system disorder, central nervous system disorder, autoimmune disorder of the nervous system, cranial nerve neuropathy, peripheral nervous system disorder, neuronitis, diplegia of upper limb, retinal disorder, developmental disability, restless legs syndrome, movement disorder, toxic encephalopathy, Barre-Lieou syndrome, Gerstmann syndrome, drug-induced akathisia, drug-induced dyskinesia, stiff-person syndrome, Worster-Drought syndrome, corneal-cerebellar syndrome, pachygyria-intellectual disability-epilepsy syndrome, porencephaly-cerebellar hypoplasia-internal malformations syndrome, symmetrical thalamic calcifications, neonatal brainstem dysfunction, primary orthostatic hypotension, rippling muscle disease with myasthenia gravis, periodic paralysis, qualitative or quantitative protein defects in neuromuscular diseases, specific learning disability, cerebellar hypoplasia-tapetoretinal degeneration syndrome, locked-in syndrome, dopa-responsive dystonia, idiopathic recurrent stupor, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, spontaneous periodic hypothermia, Sydenham chorea, duplication of the pituitary gland, Balint syndrome, paraneoplastic neurologic syndrome, persistent idiopathic facial pain, serotonin syndrome, hypothalamic adipsic hypernatraemia syndrome, exercise-induced malignant hyperthermia, perineural cyst, neuromuscular disease, AL amyloidosis, AA amyloidosis, neuroleptic malignant syndrome, infectious disorder of the nervous system, central nervous system malformation, synaptopathy, nervous system neoplasm, sensory ganglionopathy, radiculitis, wet beriberi, perceptual disorders, prepubertal anorexia nervosa, neurocutaneous syndrome, neurovascular disorder, Wallerian degeneration, nervous system injury, neurosarcoidosis, neuroendocrine disorder, tubulinopathy, atactic disorder, hereditary neurological disease, meningitis-retention syndrome, KIF1A related neurological disorder, neurological pain disorder, neurodevelopmental disorder, post 5-alpha-reductase inhibitors treatment syndrome, post-selective serotonin reuptake inhibitor sexual dysfunction
Subtypes (3): neuromyelitis optica spectrum disorder with anti-AQP4 antibodies, neuromyelitis optica spectrum disorder with anti-MOG antibodies, neuromyelitis optica spectrum disorder without anti-MOG and without anti-AQP4 antibodies
Genetics & variants
GWAS landscape
8 GWAS associations across 3 studies. Top hits map to 2 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| HLA-DRB1*03:01 | 2e-12 | ? | 2.71 | |
| rs28383224 | 6e-12 | HLA-DRB1 - HLA-DQA1 | A | 2.24 |
| HLA-B*08:01 | 6e-12 | ? | 2.72 | |
| rs1150757 | 7e-12 | TNXB | A | 2.86 |
| HLA-DQB1*02:01 | 1e-11 | ? | 2.58 | |
| HLA-C*07:01 | 1e-10 | ? | 2.38 | |
| HLA-DQA1*05:01 | 5e-10 | ? | 2.2 | |
| rs9272219 | 8e-10 | HLA-DQA1 | A | 2.48 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST011432 | Romero-Hidalgo S | 2020 | 164 | 1,208 | Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population. |
| GCST005964 | Estrada K | 2018 | 66 | 0 | A whole-genome sequence study identifies genetic risk factors for neuromyelitis optica. |
| GCST000508 | Kim HJ | 2009 | 53 | 0 | Common CYP7A1 promoter polymorphism associated with risk of neuromyelitis optica. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 0 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 8 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 8 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| unknown | 5 |
| intergenic_variant | 2 |
| synonymous_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| HLA-DRB1*03:01 | 0.12 | 2e-12 | Tier 4: intronic/intergenic | |||||
| rs28383224 | 6 | 32615876 | A>G,T | 0.42 | intergenic_variant | HLA-DRB1 - HLA-DQA1 | 6e-12 | Tier 4: intronic/intergenic |
| HLA-B*08:01 | 0.11 | 6e-12 | Tier 4: intronic/intergenic | |||||
| rs1150757 | 6 | 32061428 | G>A,C | 0.1 | synonymous_variant | TNXB | 7e-12 | Tier 4: intronic/intergenic |
| HLA-DQB1*02:01 | 0.13 | 1e-11 | Tier 4: intronic/intergenic | |||||
| HLA-C*07:01 | 0.15 | 1e-10 | Tier 4: intronic/intergenic | |||||
| HLA-DQA1*05:01 | 0.23 | 5e-10 | Tier 4: intronic/intergenic | |||||
| rs9272219 | 6 | 32634492 | G>A,T | 0.42 | intergenic_variant | HLA-DQA1 | 8e-10 | Tier 4: intronic/intergenic |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · Orphanet: 32 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| AQP4 | Limited | Unknown | neuromyelitis optica | 4 |
| C5orf47 | Limited | Autosomal dominant | neuromyelitis optica | |
| FAM194C | Limited | Autosomal dominant | neuromyelitis optica | |
| ZNF606 | Limited | Autosomal dominant | neuromyelitis optica |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| C4A | Orphanet:117 | Behçet disease |
| C4A | Orphanet:169147 | Immunodeficiency due to a classical component pathway complement deficiency |
| C4A | Orphanet:300345 | Autosomal systemic lupus erythematosus |
| C4A | Orphanet:536 | Systemic lupus erythematosus |
| HLA-B | Orphanet:117 | Behçet disease |
| HLA-B | Orphanet:275798 | Pulmonary arterial hypertension associated with connective tissue disease |
| HLA-B | Orphanet:29207 | Reactive arthritis |
| HLA-B | Orphanet:3287 | Takayasu arteritis |
| HLA-B | Orphanet:36426 | Stevens-Johnson syndrome |
| HLA-B | Orphanet:397 | Giant cell arteritis |
| HLA-C | Orphanet:585909 | B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2) |
| HLA-DQA1 | Orphanet:391490 | Adult-onset myasthenia gravis |
| HLA-DQA1 | Orphanet:930 | Idiopathic achalasia |
| HLA-DQB1 | Orphanet:2073 | Narcolepsy type 1 |
| HLA-DQB1 | Orphanet:477738 | Pediatric multiple sclerosis |
| HLA-DQB1 | Orphanet:703 | Bullous pemphigoid |
| HLA-DQB1 | Orphanet:83465 | Narcolepsy type 2 |
| HLA-DQB1 | Orphanet:930 | Idiopathic achalasia |
| HLA-DRB1 | Orphanet:2073 | Narcolepsy type 1 |
| HLA-DRB1 | Orphanet:220393 | Diffuse cutaneous systemic sclerosis |
| HLA-DRB1 | Orphanet:220402 | Limited cutaneous systemic sclerosis |
| HLA-DRB1 | Orphanet:220407 | Limited systemic sclerosis |
| HLA-DRB1 | Orphanet:3437 | Vogt-Koyanagi-Harada disease |
| HLA-DRB1 | Orphanet:397 | Giant cell arteritis |
| HLA-DRB1 | Orphanet:477738 | Pediatric multiple sclerosis |
| HLA-DRB1 | Orphanet:536 | Systemic lupus erythematosus |
| HLA-DRB1 | Orphanet:545 | Follicular lymphoma |
| HLA-DRB1 | Orphanet:703 | Bullous pemphigoid |
| HLA-DRB1 | Orphanet:747 | Autoimmune pulmonary alveolar proteinosis |
| HLA-DRB1 | Orphanet:797 | Sarcoidosis |
| HLA-DRB1 | Orphanet:83465 | Narcolepsy type 2 |
| HLA-DRB1 | Orphanet:85414 | Systemic-onset juvenile idiopathic arthritis |
Cohort genes → proteins
10 cohort genes, 10 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| gwas_only | 6 |
| multi_evidence | 4 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| FAM194C | HGNC:25320 | ENSG00000131379 | Q8ND61 | Uncharacterized protein C3orf20 | gencc |
| ZNF606 | HGNC:25879 | ENSG00000166704 | Q8WXB4 | Zinc finger protein 606 | gencc |
| C5orf47 | HGNC:27026 | ENSG00000185056 | Q569G3 | Uncharacterized protein C5orf47 | gencc |
| AQP4 | HGNC:637 | ENSG00000171885 | P55087 | Aquaporin-4 | gencc |
| C4A | HGNC:1323 | ENSG00000244731 | P0C0L4 | Complement C4-A | gwas |
| HLA-B | HGNC:4932 | ENSG00000234745 | P01889 | HLA class I histocompatibility antigen, B alpha chain | gwas |
| HLA-C | HGNC:4933 | ENSG00000204525 | P10321 | HLA class I histocompatibility antigen, C alpha chain | gwas |
| HLA-DQA1 | HGNC:4942 | ENSG00000196735 | P01909 | HLA class II histocompatibility antigen, DQ alpha 1 chain | gwas |
| HLA-DQB1 | HGNC:4944 | ENSG00000179344 | P01920 | HLA class II histocompatibility antigen, DQ beta 1 chain | gwas |
| HLA-DRB1 | HGNC:4948 | ENSG00000196126 | P01911 | HLA class II histocompatibility antigen, DRB1 beta chain | gwas |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| ZNF606 | Zinc finger protein 606 | May act as a transcriptional repressor. |
| AQP4 | Aquaporin-4 | Forms a water-specific channel. |
| C4A | Complement C4-A | Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune sy… |
| HLA-B | HLA class I histocompatibility antigen, B alpha chain | Antigen-presenting major histocompatibility complex class I (MHCI) molecule. |
| HLA-C | HLA class I histocompatibility antigen, C alpha chain | Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity. |
| HLA-DQA1 | HLA class II histocompatibility antigen, DQ alpha 1 chain | Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. |
| HLA-DQB1 | HLA class II histocompatibility antigen, DQ beta 1 chain | Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. |
| HLA-DRB1 | HLA class II histocompatibility antigen, DRB1 beta chain | A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. |
Protein-family classification
Druggable: 6 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.6
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Antibody/Immunoglobulin | 5 | 14.6× | 4e-05 |
| Complement | 1 | 26.8× | 0.073 |
| Transcription factor | 1 | 0.8× | 0.967 |
| Other/Unknown | 3 | 0.5× | 0.976 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| FAM194C | Other/Unknown | no | FAM194_C | |
| ZNF606 | Transcription factor | no | KRAB, Znf_C2H2_type, KRAB_dom_sf | |
| C5orf47 | Other/Unknown | no | DUF4680 | |
| AQP4 | Other/Unknown | no | MIP, MIP_CS, Aquaporin-like | |
| C4A | Complement | yes | Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2 | |
| HLA-B | Antibody/Immunoglobulin | yes | MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set | |
| HLA-C | Antibody/Immunoglobulin | yes | MHC_I_a_a1/a2, Ig_C1-set, Ig-like_dom | |
| HLA-DQA1 | Antibody/Immunoglobulin | yes | MHC_II_a_N, Ig/MHC_CS, Ig_C1-set | |
| HLA-DQB1 | Antibody/Immunoglobulin | yes | MHC_II_b_N, Ig/MHC_CS, Ig_C1-set | |
| HLA-DRB1 | Antibody/Immunoglobulin | yes | MHC_II_b_N, Ig/MHC_CS, Ig_C1-set |
Expression context
Cohort genes with no expression data: 0.
10 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) | 10 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| spleen | 3 |
| right lung | 3 |
| blood | 2 |
| granulocyte | 2 |
| cardiac muscle of right atrium | 1 |
| left ventricle myocardium | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| bronchial epithelial cell | 1 |
| right uterine tube | 1 |
| secondary oocyte | 1 |
| left testis | 1 |
| primordial germ cell in gonad | 1 |
| right testis | 1 |
| lateral globus pallidus | 1 |
| substantia nigra pars compacta | 1 |
| substantia nigra pars reticulata | 1 |
| liver | 1 |
| right adrenal gland cortex | 1 |
| right lobe of liver | 1 |
| gall bladder | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FAM194C | 48 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, cardiac muscle of right atrium, left ventricle myocardium |
| ZNF606 | 241 | ubiquitous | marker | secondary oocyte, right uterine tube, bronchial epithelial cell |
| C5orf47 | 56 | tissue_specific | marker | primordial germ cell in gonad, right testis, left testis |
| AQP4 | 218 | tissue_specific | marker | lateral globus pallidus, substantia nigra pars reticulata, substantia nigra pars compacta |
| C4A | 134 | marker | right lobe of liver, liver, right adrenal gland cortex | |
| HLA-B | 134 | ubiquitous | marker | blood, spleen, granulocyte |
| HLA-C | 134 | ubiquitous | marker | blood, right lung, spleen |
| HLA-DQA1 | 244 | broad | marker | gall bladder, rectum, monocyte |
| HLA-DQB1 | 268 | broad | marker | right lung, spleen, upper lobe of left lung |
| HLA-DRB1 | 131 | tissue_specific | marker | vermiform appendix, granulocyte, right lung |
Protein interactions among cohort
Intra-cohort edges: 6.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| HLA-DRB1 | 3,448 |
| HLA-B | 3,209 |
| HLA-C | 836 |
| FAM194C | 684 |
| ZNF606 | 580 |
| C4A | 222 |
| HLA-DQA1 | 196 |
| C5orf47 | 130 |
| HLA-DQB1 | 128 |
| AQP4 | 27 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| C5orf47 | FAM194C | string_interaction |
| C5orf47 | ZNF606 | string_interaction |
| FAM194C | ZNF606 | string_interaction |
| HLA-B | HLA-C | biogrid_interaction, intact |
| HLA-C | HLA-DQB1 | intact |
| HLA-DQA1 | HLA-DQB1 | biogrid_interaction, intact |
Structural data
PDB: 7 · AlphaFold-only: 3 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| HLA-B | P01889 | 237 |
| HLA-DRB1 | P01911 | 108 |
| HLA-DQA1 | P01909 | 28 |
| HLA-C | P10321 | 13 |
| C4A | P0C0L4 | 12 |
| HLA-DQB1 | P01920 | 10 |
| AQP4 | P55087 | 4 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| C5orf47 | Q569G3 | 62.69 |
| ZNF606 | Q8WXB4 | 59.56 |
| FAM194C | Q8ND61 | 59.33 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 10 evidence-associated genes (8 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Interferon gamma signaling | 5 | 78.4× | 4e-08 | HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1 |
| Endosomal/Vacuolar pathway | 2 | 259.6× | 3e-04 | HLA-B, HLA-C |
| Translocation of ZAP-70 to Immunological synapse | 2 | 158.6× | 5e-04 | HLA-DQA1, HLA-DRB1 |
| Phosphorylation of CD3 and TCR zeta chains | 2 | 135.9× | 5e-04 | HLA-DQA1, HLA-DRB1 |
| Co-inhibition by PD-1 | 2 | 129.8× | 5e-04 | HLA-DQA1, HLA-DRB1 |
| DAP12 interactions | 2 | 119.0× | 5e-04 | HLA-B, HLA-C |
| Antigen Presentation: Folding, assembly and peptide loading of class I MHC | 2 | 98.5× | 6e-04 | HLA-B, HLA-C |
| Generation of second messenger molecules | 2 | 86.5× | 7e-04 | HLA-DQA1, HLA-DRB1 |
| Interferon alpha/beta signaling | 2 | 38.1× | 0.003 | HLA-B, HLA-C |
| ER-Phagosome pathway | 2 | 32.4× | 0.004 | HLA-B, HLA-C |
| Downstream TCR signaling | 2 | 32.1× | 0.004 | HLA-DQA1, HLA-DRB1 |
| MHC class II antigen presentation | 2 | 22.3× | 0.006 | HLA-DQA1, HLA-DRB1 |
| SARS-CoV-2 activates/modulates innate and adaptive immune responses | 2 | 22.3× | 0.006 | HLA-B, HLA-C |
| Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | 2 | 21.8× | 0.006 | HLA-B, HLA-C |
| Activation of C3 and C5 | 1 | 158.6× | 0.011 | C4A |
| Passive transport by Aquaporins | 1 | 109.8× | 0.015 | AQP4 |
| Initial triggering of complement | 1 | 75.1× | 0.020 | C4A |
| Aquaporin-mediated transport | 1 | 46.0× | 0.031 | AQP4 |
| Dengue virus activates/modulates innate and adaptive immune responses | 1 | 42.0× | 0.032 | C4A |
| Vasopressin regulates renal water homeostasis via Aquaporins | 1 | 33.2× | 0.039 | AQP4 |
| Regulation of Complement cascade | 1 | 29.1× | 0.042 | C4A |
| Neutrophil degranulation | 2 | 5.8× | 0.052 | HLA-B, HLA-C |
| Post-translational protein phosphorylation | 1 | 12.5× | 0.087 | C4A |
| Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | 1 | 10.8× | 0.096 | C4A |
| Transport of small molecules | 1 | 3.1× | 0.288 | AQP4 |
| Generic Transcription Pathway | 1 | 1.9× | 0.422 | ZNF606 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| peptide antigen assembly with MHC class II protein complex | 3 | 395.0× | 2e-06 | HLA-DQA1, HLA-DQB1, HLA-DRB1 |
| antigen processing and presentation of exogenous peptide antigen via MHC class II | 3 | 203.8× | 5e-06 | HLA-DQA1, HLA-DQB1, HLA-DRB1 |
| positive regulation of T cell mediated cytotoxicity | 3 | 191.5× | 5e-06 | HLA-B, HLA-C, HLA-DRB1 |
| positive regulation of immune response | 3 | 180.6× | 5e-06 | HLA-DQA1, HLA-DQB1, HLA-DRB1 |
| immune response | 5 | 29.4× | 5e-06 | HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1 |
| positive regulation of T cell activation | 3 | 166.3× | 5e-06 | HLA-DQA1, HLA-DQB1, HLA-DRB1 |
| adaptive immune response | 4 | 42.1× | 1e-05 | HLA-B, HLA-C, HLA-DQA1, HLA-DQB1 |
| detection of bacterium | 2 | 351.1× | 8e-05 | HLA-B, HLA-DRB1 |
| antigen processing and presentation of endogenous peptide antigen via MHC class Ib | 2 | 324.1× | 8e-05 | HLA-B, HLA-C |
| antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent | 2 | 324.1× | 8e-05 | HLA-B, HLA-C |
| humoral immune response | 2 | 70.2× | 0.002 | HLA-DQB1, HLA-DRB1 |
| regulation of interleukin-4 production | 1 | 2106.5× | 0.002 | HLA-DRB1 |
| antigen processing and presentation of endogenous peptide antigen via MHC class II | 1 | 1053.2× | 0.004 | HLA-DRB1 |
| regulation of interleukin-10 production | 1 | 1053.2× | 0.004 | HLA-DRB1 |
| T cell receptor signaling pathway | 2 | 38.0× | 0.004 | HLA-DQB1, HLA-DRB1 |
| myeloid dendritic cell antigen processing and presentation | 1 | 702.2× | 0.004 | HLA-DRB1 |
| regulation of dendritic cell differentiation | 1 | 702.2× | 0.004 | HLA-B |
| regulation of T cell anergy | 1 | 526.6× | 0.005 | HLA-B |
| regulation of interleukin-12 production | 1 | 526.6× | 0.005 | HLA-B |
| regulation of T-helper cell differentiation | 1 | 526.6× | 0.005 | HLA-DRB1 |
| positive regulation of CD4-positive, alpha-beta T cell activation | 1 | 526.6× | 0.005 | HLA-DRB1 |
| positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation | 1 | 421.3× | 0.006 | HLA-DRB1 |
| protection from natural killer cell mediated cytotoxicity | 1 | 351.1× | 0.007 | HLA-B |
| positive regulation of T cell mediated immune response to tumor cell | 1 | 300.9× | 0.007 | HLA-DRB1 |
| intracellular water homeostasis | 1 | 300.9× | 0.007 | AQP4 |
| positive regulation of apoptotic cell clearance | 1 | 300.9× | 0.007 | C4A |
| T-helper 1 type immune response | 1 | 234.1× | 0.008 | HLA-DRB1 |
| positive regulation of memory T cell differentiation | 1 | 234.1× | 0.008 | HLA-DRB1 |
| regulation of interleukin-6 production | 1 | 210.7× | 0.008 | HLA-B |
| multicellular organismal-level water homeostasis | 1 | 210.7× | 0.008 | AQP4 |
Therapeutics
Drugs indicated for this disease
2 approved, 5 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.
| Drug | Development status |
|---|---|
| Inebilizumab | Approved (phase 4) |
| Satralizumab | Approved (phase 4) |
| Azathioprine | Phase 3 (in late-stage trials) |
| Divozilimab | Phase 3 (in late-stage trials) |
| Eculizumab | Phase 3 (in late-stage trials) |
| Mycophenolate Mofetil | Phase 3 (in late-stage trials) |
| Ravulizumab | Phase 3 (in late-stage trials) |
Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Bortezomib, Carmustine, Cytarabine, Daratumumab, Etoposide, Filgrastim, Human Immunoglobulin G, Melphalan, Methylprednisolone, Prednisone, Rituximab, Tocilizumab, Zanubrutinib.
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 10
Druggability breadth: 5 of 10 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| FAM194C | 0 | 0 |
| ZNF606 | 0 | 0 |
| C5orf47 | 0 | 0 |
| AQP4 | 0 | 0 |
| C4A | 0 | 0 |
| HLA-B | 0 | 0 |
| HLA-C | 0 | 0 |
| HLA-DQA1 | 0 | 0 |
| HLA-DQB1 | 0 | 0 |
| HLA-DRB1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| HLA-DRB1 | 17 | Binding:17 |
| AQP4 | 8 | Binding:8 |
| HLA-DQA1 | 2 | Binding:2 |
| HLA-B | 1 | Binding:1 |
| HLA-C | 1 | Binding:1 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 10; 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
0 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.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 6 | C4A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 4 | FAM194C, ZNF606, C5orf47, AQP4 |
Undrugged target profiles
10 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| FAM194C | 0 | — |
| ZNF606 | 0 | — |
| C5orf47 | 0 | — |
| AQP4 | 8 | — |
| C4A | 0 | — |
| HLA-B | 1 | — |
| HLA-C | 1 | — |
| HLA-DQA1 | 2 | — |
| HLA-DQB1 | 0 | — |
| HLA-DRB1 | 17 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 117.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 52 |
| PHASE3 | 14 |
| PHASE2 | 13 |
| PHASE1 | 13 |
| PHASE4 | 7 |
| PHASE2/PHASE3 | 7 |
| PHASE1/PHASE2 | 7 |
| EARLY_PHASE1 | 4 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06180278 | PHASE4 | ACTIVE_NOT_RECRUITING | Long-term, Open-label, Safety Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorder (NMOSD) |
| NCT00304291 | PHASE4 | COMPLETED | A Pilot Study of Mitoxantrone for the Treatment of Recurrent Neuromyelitis Optica (Devic’s Disease) |
| NCT02021825 | PHASE4 | UNKNOWN | Efficacy and Safety of Mitoxantrone in Patients With Refractory Neuromyelitis Optica and Spectrum Disorders |
| NCT02809079 | PHASE4 | UNKNOWN | Mycophenolate Mofetil Treatment With Neuromyelitis Optica Spectrum Disorders in Chinese Patients |
| NCT04256252 | PHASE4 | COMPLETED | Rituximab at Low dosE for neuromyelitiS optiCa spectrUm disordEr (RESCUE) |
| NCT05269667 | PHASE4 | TERMINATED | A Study In Neuromyelitis Optica Spectrum Disorder (NMOSD) With Satralizumab As An Intervention |
| NCT06212245 | PHASE4 | UNKNOWN | A Clinical Research Study of Inebilizumab in Neuromyelitis Optica Spectrum Disorders |
| NCT05199688 | PHASE3 | RECRUITING | A Study To Evaluate Pharmacokinetics, Efficacy, Safety, Tolerability, And Pharmacodynamics Of Satralizumab In Pediatric Patients With Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorder (NMOSD) |
| NCT05314010 | PHASE3 | ACTIVE_NOT_RECRUITING | A Study of MIL62 in Patients With Neuromyelitis Optica Spectrum Disorder (NMOSD) |
| NCT05346354 | PHASE2/PHASE3 | RECRUITING | Efficacy and Safety Study of Ravulizumab IV in Pediatric Participants With NMOSD |
| NCT05403138 | PHASE2/PHASE3 | ACTIVE_NOT_RECRUITING | Safety and Efficacy of Daratumumab in Patients With Anti-Aquaporin 4 Antibody Positive Neuromyelitis Optica Spectrum Disorders |
| NCT05730699 | PHASE3 | ACTIVE_NOT_RECRUITING | Efficacy and Safety of Divozilimab in Patients With Neuromyelitis Optica Spectrum Disorders (AQUARELLE) |
| NCT06413654 | PHASE2/PHASE3 | RECRUITING | A Clinical Study of B001 Injection in the Treatment of Neuromyelitis Optica Spectrum Disorders(NMOSD) |
| NCT06724809 | PHASE3 | ACTIVE_NOT_RECRUITING | Efficacy, Safety, PK, PD, and ADA of Eculizumab in Chinese Adults With NMOSD |
| NCT07132398 | PHASE3 | NOT_YET_RECRUITING | Slow vs. Rapid Glucocorticoids Tapering With Inebilizumab in NMOSD |
| NCT07557420 | PHASE3 | NOT_YET_RECRUITING | Efficacy, Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity Study of Ravulizumab in Chinese Adults With Neuromyelitis Optica Spectrum Disorder (NMOSD) |
| NCT01892345 | PHASE3 | TERMINATED | A Randomized Controlled Trial of Eculizumab in AQP4 Antibody-positive Participants With NMO (PREVENT Study) |
| NCT02003144 | PHASE3 | COMPLETED | An Open Label Extension Trial of Eculizumab in Relapsing NMO Patients |
| NCT02028884 | PHASE3 | COMPLETED | Efficacy and Safety Study of Satralizumab (SA237) as Add-on Therapy to Treat Participants With Neuromyelitis Optica (NMO) and NMO Spectrum Disorder (NMOSD) |
| NCT02073279 | PHASE3 | COMPLETED | Efficacy and Safety Study of Satralizumab (SA237) as Monotherapy to Treat Participants With Neuromyelitis Optica (NMO) and Neuromyelitis Optica Spectrum Disorder (NMOSD) |
| NCT02398994 | PHASE3 | TERMINATED | A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis |
| NCT03002038 | PHASE2/PHASE3 | COMPLETED | Comparison of Clinical Effects of Azathioprine and Rituximab NMO-SD Patients |
| NCT03330418 | PHASE3 | TERMINATED | A Phase III Study of TACI-antibody Fusion Protein Injection (RC18) in Subjects With Neuromyelitis Optica Spectrum Disorders |
| NCT03350633 | PHASE2/PHASE3 | COMPLETED | Tocilizumab vs Azathioprine in Neuromyelitis Optica Spectrum Disorders |
| NCT03829566 | PHASE2/PHASE3 | WITHDRAWN | Autologous Transplant To End NMO Spectrum Disorder |
| NCT04155424 | PHASE2/PHASE3 | TERMINATED | A Study of the Safety and Activity of Eculizumab in Pediatric Participants With Relapsing Neuromyelitis Optica Spectrum Disorder |
| NCT04201262 | PHASE3 | COMPLETED | An Efficacy and Safety Study of Ravulizumab in Adult Participants With NMOSD |
| NCT04660539 | PHASE3 | COMPLETED | A Study to Evaluate the Safety and Efficacy of Satralizumab in Participants With Neuromyelitis Optica Spectrum Disorder (NMOSD) |
| NCT00716066 | PHASE2 | ACTIVE_NOT_RECRUITING | Autologous Stem Cell Transplant for Neurologic Autoimmune Diseases |
| NCT05504694 | PHASE1/PHASE2 | RECRUITING | Ofatumumab in AQP4-IgG Seropositive NMOSD |
| NCT05549258 | PHASE2 | RECRUITING | Study of Inebilizumab in Pediatric Subjects With Neuromyelitis Optica Spectrum Disorder |
| NCT06497374 | PHASE2 | NOT_YET_RECRUITING | FcRn Antagonists (Efgartigimod) for Acute NMOSD Attack |
| NCT06557174 | PHASE1/PHASE2 | NOT_YET_RECRUITING | A Study to Evaluate IMC-002 in Neuromyelitis Optica Spectrum Disorder (NMOSD) Patients |
| NCT06561009 | PHASE1/PHASE2 | NOT_YET_RECRUITING | Safety and Efficacy of BAFFR CART for Relapsed/ Refractory Neuromyelitis Optica Spectrum Disorder |
| NCT06697535 | PHASE2 | RECRUITING | A Study to Evaluate the Efficacy and Safety of JYP0061 in Patients With Acute Neuromyelitis Spectrum Disease (NMOSD) |
| NCT00904826 | PHASE1/PHASE2 | COMPLETED | An Open Label Study of the Effects of Eculizumab in Neuromyelitis Optica |
| NCT01339455 | PHASE1/PHASE2 | TERMINATED | Autologous Hematopoietic Stem Cell Transplant in Neuromyelitis Optica |
| NCT01845584 | PHASE2 | COMPLETED | Phase II Clinical Trial of NPB-01 in Patients With Anti-aquaporin 4 Antibody Positive Neuromyelitis Optica Spectrum Disorder Not Provided Adequate Effect of Therapy to Steroids Plus Therapy. |
| NCT02166346 | PHASE2 | COMPLETED | Safety and Efficacy of Sustained Release Dalfampridine in Transverse Myelitis (Re-Launch) |
| NCT02249676 | PHASE2 | COMPLETED | Autologous Mesenchymal Stem Cells for the Treatment of Neuromyelitis Optica Spectrum Disorders |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| INEBILIZUMAB | 4 | 8 |
| ECULIZUMAB | 4 | 5 |
| RAVULIZUMAB | 4 | 5 |
| SATRALIZUMAB | 4 | 5 |
| AZATHIOPRINE | 4 | 3 |
| MITOXANTRONE | 4 | 3 |
| 2-MERCAPTOETHANESULFONIC ACID | 4 | 2 |
| CETIRIZINE | 4 | 1 |
| DALFAMPRIDINE | 4 | 1 |
| DARATUMUMAB | 4 | 1 |
| EFGARTIGIMOD ALFA | 4 | 1 |
| HUMAN IMMUNOGLOBULIN G | 4 | 1 |
| MYCOPHENOLATE MOFETIL | 4 | 1 |
| PREDNISONE | 4 | 1 |
| RITUXIMAB | 4 | 1 |
| TOCILIZUMAB | 4 | 1 |
| UBLITUXIMAB | 4 | 1 |
| ZANUBRUTINIB | 4 | 1 |
| DIVOZILIMAB | 3 | 1 |
| ORELABRUTINIB | 3 | 1 |
| ELCUBRAGISTAT | 2 | 1 |
| CHEMBL15720 | 0 | 1 |
| CHEMBL5193128 | 0 | 1 |
Related Atlas pages
- Cohort genes: FAM194C, ZNF606, C5orf47, AQP4, C4A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1
- Drugs: Inebilizumab, Eculizumab, Ravulizumab, Satralizumab, Azathioprine, Mitoxantrone, 2-MERCAPTOETHANESULFONIC ACID, Cetirizine, Dalfampridine, Daratumumab, Efgartigimod Alfa, Human Immunoglobulin G, Mycophenolate Mofetil, Prednisone, Rituximab, Tocilizumab, Ublituximab, Zanubrutinib, Divozilimab, Orelabrutinib