anti-NMDA receptor encephalitis
diseaseOn this page
Also known as limbic encephalitis with N-methyl-D-aspartate receptor antibodieslimbic encephalitis with NMDA receptor antibodies
Summary
anti-NMDA receptor encephalitis (MONDO:0021081) is a disease with 9 GWAS associations across 2 studies and 8 clinical trials. Top therapeutic interventions include rituximab. A subtype of encephalitis — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- Prevalence: Unknown (Worldwide)
- GWAS associations: 9
- Phenotypes (HPO): 53
- Clinical trials: 8
Clinical features
Signs & symptoms
Clinical features (HPO)
53 HPO clinical features (Orphanet curated; top 50 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000708 | Atypical behavior | Very frequent (80-99%) |
| HP:0000736 | Short attention span | Very frequent (80-99%) |
| HP:0001250 | Seizure | Very frequent (80-99%) |
| HP:0001289 | Confusion | Very frequent (80-99%) |
| HP:0002354 | Memory impairment | Very frequent (80-99%) |
| HP:0012229 | CSF pleocytosis | Very frequent (80-99%) |
| HP:0032264 | Anti-NMDA receptor antibody positivity | Very frequent (80-99%) |
| HP:0032266 | CSF anti-NMDA receptor antibody positivity | Very frequent (80-99%) |
| HP:0000738 | Hallucinations | Frequent (30-79%) |
| HP:0000739 | Anxiety | Frequent (30-79%) |
| HP:0000746 | Delusion | Frequent (30-79%) |
| HP:0001945 | Fever | Frequent (30-79%) |
| HP:0002013 | Vomiting | Frequent (30-79%) |
| HP:0002014 | Diarrhea | Frequent (30-79%) |
| HP:0002315 | Headache | Frequent (30-79%) |
| HP:0004305 | Involuntary movements | Frequent (30-79%) |
| HP:0011289 | EEG with temporal sharp slow waves | Frequent (30-79%) |
| HP:0012226 | Ovarian teratoma | Frequent (30-79%) |
| HP:0012332 | Abnormal autonomic nervous system physiology | Frequent (30-79%) |
| HP:0100660 | Dyskinesia | Frequent (30-79%) |
| HP:0100754 | Mania | Frequent (30-79%) |
| HP:0100785 | Insomnia | Frequent (30-79%) |
| HP:0000709 | Psychosis | Occasional (5-29%) |
| HP:0000713 | Agitation | Occasional (5-29%) |
| HP:0000716 | Depression | Occasional (5-29%) |
| HP:0000733 | Abnormal repetitive mannerisms | Occasional (5-29%) |
| HP:0001266 | Choreoathetosis | Occasional (5-29%) |
| HP:0001278 | Orthostatic hypotension | Occasional (5-29%) |
| HP:0001332 | Dystonia | Occasional (5-29%) |
| HP:0001336 | Myoclonus | Occasional (5-29%) |
| HP:0002063 | Rigidity | Occasional (5-29%) |
| HP:0002072 | Chorea | Occasional (5-29%) |
| HP:0002133 | Status epilepticus | Occasional (5-29%) |
| HP:0002179 | Opisthotonus | Occasional (5-29%) |
| HP:0002197 | Generalized-onset seizure | Occasional (5-29%) |
| HP:0002300 | Mutism | Occasional (5-29%) |
| HP:0002310 | Orofacial dyskinesia | Occasional (5-29%) |
| HP:0002371 | Loss of speech | Occasional (5-29%) |
| HP:0002463 | Language impairment | Occasional (5-29%) |
| HP:0003781 | Excessive salivation | Occasional (5-29%) |
| HP:0007359 | Focal-onset seizure | Occasional (5-29%) |
| HP:0008763 | No social interaction | Occasional (5-29%) |
| HP:0010553 | Oculogyric crisis | Occasional (5-29%) |
| HP:0012173 | Orthostatic tachycardia | Occasional (5-29%) |
| HP:0012333 | Abnormal sudomotor regulation | Occasional (5-29%) |
| HP:0031258 | Delirium | Occasional (5-29%) |
| HP:5200321 | Amplification of sexual behavior | Occasional (5-29%) |
| HP:0003006 | Neuroblastoma | Very rare (<1-4%) |
| HP:0012189 | Hodgkin lymphoma | Very rare (<1-4%) |
| HP:0100013 | Neoplasm of the breast | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | anti-NMDA receptor encephalitis |
| Mondo ID | MONDO:0021081 |
| MeSH | D060426 |
| Orphanet | 217253 |
| ICD-11 | 1568915618 |
| NCIT | C94853 |
| SNOMED CT | 716684004 |
| UMLS | C2986717 |
| MedGen | 458943 |
| GARD | 0020513 |
| Is cancer (heuristic) | no |
Also known as: anti-NMDA receptor encephalitis · limbic encephalitis with N-methyl-D-aspartate receptor antibodies · limbic encephalitis with NMDA receptor antibodies
Data availability: 9 GWAS associations (2 studies).
Disease family
This is a subtype of encephalitis. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › encephalomyelitis › encephalitis › anti-NMDA receptor encephalitis
Related subtypes (6): post-vaccinal encephalitis, meningoencephalitis, limbic encephalitis, infectious encephalitis, autoimmune encephalitis, paraneoplastic isolated brainstem encephalitis
Genetics & variants
GWAS landscape
9 GWAS associations across 2 studies. Top hits map to 5 distinct genes (as reported by GWAS).
Top associations by p-value
| rsID | p-value | Gene | Risk allele | Odds ratio |
|---|---|---|---|---|
| HLA-DQB1*05:02 | 1e-12 | ? | 2.1 | |
| rs10902588 | 1e-08 | LRRK1 | ? | 2.24 |
| rs3747517 | 1e-08 | IFIH1 | C | 1.55 |
| rs75393320 | 4e-08 | ACP2 | ? | 2.2 |
| HLA-A*11:01 | 7e-08 | ? | 1.56 | |
| rs2508008 | 1e-07 | LINC02571 - HLA-B | C | 1.73 |
| HLA-A*02:07 | 1e-07 | ? | 1.73 | |
| rs9468731 | 2e-07 | MICC - TMPOP1 | T | 0.36 |
| rs139999228 | 4e-06 | HLA-DRB6, HLA-DRB6 | A | 0.7 |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|---|---|---|---|---|
| GCST90429007 | Liu X | 2024 | 378 | 6,576 | Genome-Wide Association Study Identifies IFIH1 and HLA-DQB1*05:02 Loci Associated With Anti-NMDAR Encephalitis. |
| GCST90058029 | Tietz AK | 2021 | 178 | 0 | Genome-wide Association Study Identifies 2 New Loci Associated With Anti-NMDAR Encephalitis. |
Variant details and genetic-evidence tiers
Tier distribution (top 50 variants)
| Tier | Variants |
|---|---|
| Tier 1: coding | 1 |
| Tier 2: splice/UTR | 0 |
| Tier 3: regulatory | 0 |
| Tier 4: intronic/intergenic | 8 |
MAF distribution
| Bucket | Variants |
|---|---|
| common (>=0.05) | 9 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|---|
| intron_variant | 4 |
| unknown | 3 |
| missense_variant | 1 |
| intergenic_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|---|---|---|---|---|---|---|---|
| HLA-DQB1*05:02 | 0.08 | 1e-12 | Tier 4: intronic/intergenic | |||||
| rs10902588 | 15 | 100978492 | T>C,G | 0.05 | intron_variant | LRRK1 | 1e-08 | Tier 4: intronic/intergenic |
| rs3747517 | 2 | 162272314 | T>A,C,G | 0.32 | missense_variant | IFIH1 | 1e-08 | Tier 1: coding |
| rs75393320 | 11 | 47244920 | G>C | 0.05 | intron_variant | ACP2 | 4e-08 | Tier 4: intronic/intergenic |
| HLA-A*11:01 | 0.2 | 7e-08 | Tier 4: intronic/intergenic | |||||
| rs2508008 | 6 | 31305720 | A>G,T | 0.11 | intron_variant | LINC02571 - HLA-B | 1e-07 | Tier 4: intronic/intergenic |
| HLA-A*02:07 | 0.09 | 1e-07 | Tier 4: intronic/intergenic | |||||
| rs9468731 | 6 | 30429437 | A>G | 0.14 | intergenic_variant | MICC - TMPOP1 | 2e-07 | Tier 4: intronic/intergenic |
| rs139999228 | 6 | 32556934 | T>C | 0.4 | intron_variant | HLA-DRB6, HLA-DRB6 | 4e-06 | Tier 4: intronic/intergenic |
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
No druggable-target or therapeutic data for this disease’s cohort.
Clinical trials & evidence
Clinical trials
Clinical trials: 8.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 7 |
| PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT03274375 | PHASE2 | RECRUITING | Immunoadsorption Therapy in Managing NMDAR Antibodies Encephalitis |
| NCT05017142 | Not specified | RECRUITING | Swiss Pediatric Inflammatory Brain Disease Registry (Swiss-Ped-IBrainD) |
| NCT06183788 | Not specified | RECRUITING | Antibody-mediated NMDA Receptor Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Prolonged Recovery Stage |
| NCT01865578 | Not specified | COMPLETED | Transcranial Direct Current Stimulation on Cortical Plasticity in Patients With Anti-NMDA Receptor Encephalitis |
| NCT04339127 | Not specified | UNKNOWN | Autoimmune Encephalitis With Anti-NMDA Receptor Antibodies Following Herpetic Encephalitis |
| NCT05738668 | Not specified | UNKNOWN | Clinical-immunological Features of Anti-NMDAR Encephalitis |
| NCT06023160 | Not specified | COMPLETED | Predicting Functional Outcome and Response to Therapy of Anti-NMDAR Encephalitis at Diagnosis |
| NCT06915103 | Not specified | COMPLETED | A Case Report of NMDAR Encephalopathy |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| RITUXIMAB | 4 | 1 |
Related Atlas pages
- Drugs: Rituximab