Summary
Autism spectrum disorder 1 (MONDO:0100610) is a disease with 6 cohort genes (5 GWAS associations across 2 studies) and 29 clinical trials. Top therapeutic interventions include milnacipran and risperidone.
At a glance
- Cohort genes: 6
- GWAS associations: 5
- Clinical trials: 29
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|
| Canonical name | autism spectrum disorder 1 |
| Mondo ID | MONDO:0100610 |
| MeSH | D020817 |
| Orphanet | 1162 |
| DOID | DOID:0050432 |
| ICD-11 | 366940030 |
| NCIT | C97159 |
| SNOMED CT | 23560001 |
| GARD | 0028001 |
| Is cancer (heuristic) | no |
Also known as: Asperger syndrome · autism spectrum disorder without disorder of intellectual development and with mild or no impairment of functional language
Data availability: 5 GWAS associations (2 studies).
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › psychiatric disorder › mental disorder › developmental disorder of mental health › pervasive developmental disorder › autism spectrum disorder › autism spectrum disorder 1
Related subtypes (4): autism, PAX5-related B lymphopenia and autism spectrum disorder, autism spectrum disorder 2, autism spectrum disorder 3
Genetics & variants
GWAS landscape
5 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 |
|---|
| rs4703129 | 1e-06 | MTCO1P24 - CTBP2P4 | ? | |
| rs1550976 | 2e-06 | NTM | ? | |
| rs10510837 | 4e-06 | FHIT | ? | |
| rs892055 | 5e-06 | RASGRP4 | ? | |
| rs7179456 | 7e-06 | RNF111, SLTM | ? | |
Top studies (by case count)
| Study | Lead author | Year | Cases | Controls | Title |
|---|
| GCST003029 | Warrier V | 2015 | 294 | 0 | A Pooled Genome-Wide Association Study of Asperger Syndrome. |
| GCST000904 | Salyakina D | 2010 | 0 | 0 | Variants in several genomic regions associated with asperger disorder. |
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 | 4 |
MAF distribution
| Bucket | Variants |
|---|
| common (>=0.05) | 5 |
| low_freq (0.01-0.05) | 0 |
| rare (<0.01) | 0 |
| unknown | 0 |
Functional consequences
| Consequence | Count |
|---|
| intron_variant | 3 |
| intergenic_variant | 1 |
| missense_variant | 1 |
Top variants
| rsID | Chr | Pos | Alleles | MAF | Consequence | Gene | p-value | Tier |
|---|
| rs4703129 | 5 | 98553032 | C>A,G,T | 0.41 | intergenic_variant | MTCO1P24 - CTBP2P4 | 1e-06 | Tier 4: intronic/intergenic |
| rs1550976 | 11 | 131450176 | T>A,C | 0.33 | intron_variant | NTM | 2e-06 | Tier 4: intronic/intergenic |
| rs10510837 | 3 | 60304113 | G>A | 0.12 | intron_variant | FHIT | 4e-06 | Tier 4: intronic/intergenic |
| rs892055 | 19 | 38422124 | A>C,G | 0.33 | missense_variant | RASGRP4 | 5e-06 | Tier 1: coding |
| rs7179456 | 15 | 58882340 | G>C,T | 0.39 | intron_variant | RNF111, SLTM | 7e-06 | Tier 4: intronic/intergenic |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|
| FHIT | Orphanet:422526 | Hereditary clear cell renal cell carcinoma |
Cohort genes → proteins
6 cohort genes, 6 distinct canonical proteins.
Evidence partition
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|
| RNF111 | HGNC:17384 | ENSG00000157450 | Q6ZNA4 | E3 ubiquitin-protein ligase Arkadia | gwas |
| NTM | HGNC:17941 | ENSG00000182667 | Q9P121 | Neurotrimin | gwas |
| SLTM | HGNC:20709 | ENSG00000137776 | Q9NWH9 | SAFB-like transcription modulator | gwas |
| CIMAP1D | HGNC:26841 | ENSG00000181781 | Q3SX64 | Protein CIMAP1D | gwas |
| RGMB | HGNC:26896 | ENSG00000174136 | Q6NW40 | Repulsive guidance molecule B | gwas |
| FHIT | HGNC:3701 | ENSG00000189283 | P49789 | Bis(5’-adenosyl)-triphosphatase | gwas |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|
| RNF111 | E3 ubiquitin-protein ligase Arkadia | E3 ubiquitin-protein ligase. |
| NTM | Neurotrimin | Neural cell adhesion molecule. |
| SLTM | SAFB-like transcription modulator | When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis. |
| RGMB | Repulsive guidance molecule B | Member of the repulsive guidance molecule (RGM) family that contributes to the patterning of the developing nervous system. |
| FHIT | Bis(5’-adenosyl)-triphosphatase | Possesses dinucleoside triphosphate hydrolase activity. |
Protein-family classification
Druggable: 2 · Difficult: 1 · Unknown: 3 · Druggable fraction: 0.33
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 | 1 | 4.9× | 0.719 |
| Enzyme (other) | 1 | 2.0× | 0.719 |
| Transcription factor | 1 | 1.4× | 0.719 |
| Other/Unknown | 3 | 0.9× | 0.758 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|
| RNF111 | Transcription factor | no | 2.3.2.27 | Znf_RING, Znf_RING/FYVE/PHD, RNF111_N |
| NTM | Antibody/Immunoglobulin | yes | | Ig_sub2, Ig_sub, Ig-like_dom |
| SLTM | Other/Unknown | no | | RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf |
| CIMAP1D | Other/Unknown | no | | SHIPPO-rpt, CIMAP |
| RGMB | Other/Unknown | no | | RGM_C, RGM_N, RGM |
| FHIT | Enzyme (other) | yes | 3.6.1.29 | HIT-like, Histidine_triad_CS, HIT-like_sf |
Expression context
Cohort genes with no expression data: 0.
5 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) | 6 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|
| endothelial cell | 1 |
| oocyte | 1 |
| secondary oocyte | 1 |
| cerebellar cortex | 1 |
| cerebellar hemisphere | 1 |
| right hemisphere of cerebellum | 1 |
| calcaneal tendon | 1 |
| sural nerve | 1 |
| tibia | 1 |
| left testis | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| right testis | 1 |
| ileal mucosa | 1 |
| pylorus | 1 |
| upper arm skin | 1 |
| left adrenal gland cortex | 1 |
| right adrenal gland | 1 |
| right adrenal gland cortex | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|
| RNF111 | 283 | ubiquitous | marker | secondary oocyte, oocyte, endothelial cell |
| NTM | 231 | ubiquitous | marker | right hemisphere of cerebellum, cerebellar cortex, cerebellar hemisphere |
| SLTM | 291 | ubiquitous | marker | calcaneal tendon, sural nerve, tibia |
| CIMAP1D | 134 | tissue_specific | yes | right testis, left testis, male germ line stem cell (sensu Vertebrata) in testis |
| RGMB | 254 | ubiquitous | marker | ileal mucosa, pylorus, upper arm skin |
| FHIT | 188 | ubiquitous | marker | right adrenal gland, right adrenal gland cortex, left adrenal gland cortex |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|
| SLTM | 2,598 |
| RNF111 | 2,198 |
| NTM | 1,777 |
| FHIT | 1,690 |
| RGMB | 531 |
| CIMAP1D | 501 |
Structural data
PDB: 4 · AlphaFold-only: 2 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|
| RGMB | Q6NW40 | 11 |
| FHIT | P49789 | 9 |
| RNF111 | Q6ZNA4 | 4 |
| NTM | Q9P121 | 2 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|
| CIMAP1D | Q3SX64 | 67.70 |
| SLTM | Q9NWH9 | 52.38 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 6 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|
| Global Genome Nucleotide Excision Repair (GG-NER) | 1 | 152.3× | 0.032 | RNF111 |
| Netrin-1 signaling | 1 | 146.4× | 0.032 | RGMB |
| Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer | 1 | 122.8× | 0.032 | RNF111 |
| Downregulation of SMAD2/3:SMAD4 transcriptional activity | 1 | 122.8× | 0.032 | RNF111 |
| SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription | 1 | 102.9× | 0.032 | RNF111 |
| Nucleotide Excision Repair | 1 | 95.2× | 0.032 | RNF111 |
| Formation of Incision Complex in GG-NER | 1 | 84.6× | 0.032 | RNF111 |
| Signaling by TGF-beta Receptor Complex | 1 | 66.8× | 0.035 | RNF111 |
| Post-translational modification: synthesis of GPI-anchored proteins | 1 | 56.0× | 0.037 | NTM |
| Signaling by TGFB family members | 1 | 38.5× | 0.049 | RNF111 |
| DNA Repair | 1 | 32.8× | 0.052 | RNF111 |
| Class I MHC mediated antigen processing & presentation | 1 | 23.4× | 0.067 | RNF111 |
| Antigen processing: Ubiquitination & Proteasome degradation | 1 | 12.4× | 0.115 | RNF111 |
| Adaptive Immune System | 1 | 9.9× | 0.132 | RNF111 |
| RNA Polymerase II Transcription | 1 | 7.5× | 0.161 | RNF111 |
| Gene expression (Transcription) | 1 | 6.0× | 0.189 | RNF111 |
| Generic Transcription Pathway | 1 | 5.0× | 0.208 | RNF111 |
| Immune System | 1 | 4.3× | 0.226 | RNF111 |
| Signal Transduction | 1 | 3.4× | 0.267 | RNF111 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|
| diadenosine triphosphate catabolic process | 1 | 3370.4× | 0.006 | FHIT |
| global genome nucleotide-excision repair | 1 | 1685.2× | 0.006 | RNF111 |
| purine nucleotide metabolic process | 1 | 1123.5× | 0.006 | FHIT |
| neuron recognition | 1 | 674.1× | 0.007 | NTM |
| regulation of mRNA processing | 1 | 177.4× | 0.021 | SLTM |
| cell adhesion | 2 | 15.0× | 0.021 | NTM, RGMB |
| intrinsic apoptotic signaling pathway by p53 class mediator | 1 | 116.2× | 0.022 | FHIT |
| positive regulation of transforming growth factor beta receptor signaling pathway | 1 | 105.3× | 0.022 | RNF111 |
| pattern specification process | 1 | 93.6× | 0.022 | RNF111 |
| negative regulation of proteasomal ubiquitin-dependent protein catabolic process | 1 | 80.2× | 0.024 | FHIT |
| positive regulation of protein ubiquitination | 1 | 42.7× | 0.039 | RNF111 |
| BMP signaling pathway | 1 | 40.1× | 0.039 | RGMB |
| protein polyubiquitination | 1 | 23.1× | 0.062 | RNF111 |
| ubiquitin-dependent protein catabolic process | 1 | 14.8× | 0.089 | RNF111 |
| protein ubiquitination | 1 | 8.3× | 0.146 | RNF111 |
| apoptotic process | 1 | 5.7× | 0.186 | SLTM |
| positive regulation of DNA-templated transcription | 1 | 5.6× | 0.186 | RGMB |
| signal transduction | 1 | 3.2× | 0.290 | RGMB |
| regulation of transcription by RNA polymerase II | 1 | 2.3× | 0.361 | SLTM |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 4
Druggability breadth: 2 of 6 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|
| SLTM | CABOZANTINIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|
| SLTM | 1 | 4 |
| FHIT | 1 | 3 |
| RNF111 | 0 | 0 |
| NTM | 0 | 0 |
| CIMAP1D | 0 | 0 |
| RGMB | 0 | 0 |
Drugs targeting cohort genes (top 30)
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|
| FHIT | 21 | Binding:19, ADMET:2 |
| SLTM | 14 | Binding:14 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|
| RNF111 | 2.3.2.27 | RING-type E3 ubiquitin transferase |
| FHIT | 3.6.1.29 | bis(5’-adenosyl)-triphosphatase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
2 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|
| CABOZANTINIB | 4 | SLTM |
| SURAMIN | 3 | FHIT |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|
| A | Approved (phase 4 drug) | 1 | SLTM |
| B | Phased (≥1) drug, not yet approved | 1 | FHIT |
| C | Druggable family + PDB, no drug | 1 | NTM |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 3 | RNF111, CIMAP1D, RGMB |
Undrugged target profiles
4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|
| RNF111 | 0 | — |
| NTM | 0 | — |
| CIMAP1D | 0 | — |
| RGMB | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 29.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|
| Not specified | 20 |
| PHASE2 | 5 |
| PHASE4 | 1 |
| PHASE3 | 1 |
| PHASE1/PHASE2 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|
| NCT01337700 | PHASE4 | COMPLETED | Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism |
| NCT00261508 | PHASE3 | COMPLETED | A Study of the Effectiveness and Safety of Risperidone Versus Placebo in the Treatment of Children With Autistic Disorder and Other Pervasive Developmental Disorders (PDD) |
| NCT00280670 | PHASE2 | COMPLETED | CBT for Comorbid Anxiety Disorders in Children With Autism, Asperger Syndrome, or PDD-NOS |
| NCT00453180 | PHASE2 | COMPLETED | A Study of Oral N-Acetylcysteine in Children With Autism Spectrum Disorders |
| NCT00619190 | PHASE2 | COMPLETED | Study of Aripiprazole to Treat Children and Adolescents With Autism |
| NCT00725556 | PHASE1/PHASE2 | COMPLETED | The Development of Autistic Children Based on Mothers´Response in Autism Behavior Checklist |
| NCT01592747 | PHASE2 | COMPLETED | Withdrawal Study of Memantine in Pediatric Patients With Autism, Asperger’s Disorder, or Pervasive Developmental Disorder Not Otherwise Specified Previously Treated With Memantine |
| NCT01731119 | PHASE2 | COMPLETED | Study of Lurasidone in Treating Antipsychotic Naive or Quasi-Naive Children and Adolescents |
| NCT01187784 | PHASE1 | COMPLETED | Cognitive-Behavioral Therapy for Children With High-Functioning Autism Spectrum Disorder and Anxiety |
| NCT04532424 | Not specified | RECRUITING | Transcranial Magnetic Stimulation for Restricted and Repetitive Behavior in ASD |
| NCT04654260 | Not specified | ACTIVE_NOT_RECRUITING | Behavior Therapy for Irritability in Autism |
| NCT05176808 | Not specified | RECRUITING | Telehealth Parent-Implemented Intervention for Young Children With Autism Spectrum Disorder (ASD) |
| NCT06187090 | Not specified | RECRUITING | The Supplementation Therapy in Autism and Response to Treatment Study |
| NCT06227780 | Not specified | RECRUITING | Alpha Auditory Entrainment for Cognitive Enhancement and Sensory Hypersensitivity in Youth With Developmental Disorders |
| NCT06859918 | Not specified | RECRUITING | Randomized Clinical Trial of TUNE In 3.0: A Social/Emotional Program for Adults With Autism Spectrum Disorder |
| NCT00464477 | Not specified | COMPLETED | Advanced Grandparental Age as a Risk Factor for Autism |
| NCT00505830 | Not specified | UNKNOWN | Evaluation of the French Version of Screening Questionnaires for Autism and Asperger Syndrome: AQ, EQ and SQ |
| NCT00693953 | Not specified | WITHDRAWN | Using the Digital EEG Spectral Analysis in Assessing Neuroelectrical Processing Abnormalities in Autism |
| NCT00848874 | Not specified | COMPLETED | Portable Visual Guidance System Phase II |
| NCT01655173 | Not specified | COMPLETED | Cognitive Behavioural Therapy (CBT) and Recreational Activity for Autism Spectrum Disorders (ASD) |
| NCT01921244 | Not specified | COMPLETED | Shared Decision Making to Improve Care and Outcomes for Children With Autism |
| NCT02250339 | Not specified | COMPLETED | A Prospective Observational Study of Family-based Interventions for Children With Neuropsychiatric and/or Psychiatric Disorders |
| NCT02800681 | Not specified | COMPLETED | Psychopathological Differences Between Asperger Syndrome and Schizotypal Disorder in an Adult Sample |
| NCT03170453 | Not specified | COMPLETED | Confirmatory Efficacy Trial of Cognitive Enhancement Therapy for Adult Autism Spectrum Disorder |
| NCT03560453 | Not specified | COMPLETED | Facilitating Employment for Youth With Autism |
| NCT03672266 | Not specified | COMPLETED | Studies of Brain and Body Interaction |
| NCT04788537 | Not specified | COMPLETED | Services to Enhance Social Functioning in Adults With Autism Spectrum Disorders |
| NCT05509231 | Not specified | UNKNOWN | Effects of a Multimodal Exercise Program for Children With ASD |
| NCT05958680 | Not specified | UNKNOWN | ASDactive: An Integrated Theory-based Intervention to Promote Habitual Physical Activity |
Drugs tested across these trials (top 30)