ORPHA:777
X-linked non-syndromic intellectual disability
Publications
12,953
Trials
0
Interventional, condition-specific
Researchers
1,000
Distinct authors in sample
Gene link
ACSL4, AFF2, ARHGEF6
Definitive
Readiness
4/6
Stages with a signal
How rare: How common this is has not been clearly measured.
Cross-references
Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.
- MONDO:0019181
- MeSH:C564490
- UMLS:C3501611
Additional Mondo synonyms (9)
X-linked non-specific intellectual disability · intellectual disability, X-linked, nonsyndromic · intellectual disability, nonsyndromic, X-linked · mental retardation, X-linked, nonsyndromic · mental retardation, nonsyndromic, X-linked · non-specific X-linked intellectual disability · non-syndromic X-linked intellectual disability · non-syndromic intellectual disability, X-linked · nonsyndromic X-linked intellectual disability
Research stages
Trial readiness signals
Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”
4/6 stages with a signal
No matched interventional trial, but a gene association and an animal model are on record — often described as translation-ready / stalled at the clinical step.
- Gene identifiedPresent
Definitive — ACSL4, AFF2, ARHGEF6, CLCN4, DLG3…
- LiteraturePresent
12,953 matched papers (11,751 in last 10 years) Source
- Phenotype characterisedPresent
660 HPO annotations (e.g. Abnormal heart morphology; Downslanted palpebral fissures; Widely spaced teeth) Source
- Animal modelPresent
9 genotype models (Mus musculus) Source
- Orphan designationNot found
No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source
- Interventional trialNot found
No matched interventional trial under our ClinicalTrials.gov rules
Biology
Genes and phenotypes
Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.
Do we know what causes it?
Yes — we know a specific gene responsible (ACSL4, AFF2, ARHGEF6…).
GenCC classification: Definitive.
Phenotypes (Monarch / HPO)
660
Associated phenotypes · MONDO:0019181
- Abnormal heart morphology
- Downslanted palpebral fissures
- Widely spaced teeth
- Velopharyngeal insufficiency
- Small nail
Showing 5 of 660 — open Monarch for the full list.
Animal models (Monarch / Alliance)
9
Model associations linked to this Mondo ID
- Dlg3tm1Grnt/Y [background:] involves: 129P2/OlaHsd * C57BL/6J·MGI:5824730·Mus musculus
- Ftsj1tm1Tomik/Y [background:] Not Specified·MGI:7341464·Mus musculus
- Slitrk2tm1.1Jwum/Y Tg(Nes-cre)1Atp/0 [background:] involves: C57BL/6J * FVB/N·MGI:7547513·Mus musculus
- Pak3tm1.1Rpo/Y [background:] B6.129S2(Cg)-Pak3tm1.1Rpo·MGI:6466594·Mus musculus
- Iqsec2em1Frk/Y [background:] involves: C3HeB/FeJ * C57BL/6NJ·MGI:6392615·Mus musculus
- Hcfc1em1Poche/Y [background:] C57BL/6J-Hcfc1em1Poche·MGI:6860681·Mus musculus
- Gdi1tm1Toni/Y [background:] B6N.129S7-Gdi1tm1Toni·MGI:3833428·Mus musculus
- Rab39btm1Pdad/Y [background:] B6N.Cg-Rab39btm1Pdad·MGI:7547388·Mus musculus
- Iqsec2em1Csbg/Y [background:] C57BL/6NHsd-Iqsec2em1Csbg·MGI:6392161·Mus musculus
Monarch fetch 2026-07-29
Therapies
Designations, candidates, and chemicals
FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.
Orphan designation (FDA · EMA)
No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.
Open Targets candidates
No drugs or clinical candidates returned for this Mondo ID on Open Targets.
CTD chemicals (MyDisease.info)
No CTD chemical associations returned for this Mondo ID.
Literature
Is anyone studying this?
12,953
12,953 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.
12,953 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).
11,751 in the last 10 years · low confidence
Phrase hits: 135 · MeSH hits: 0
Who's working on it?
1,000
Distinct author names in 135 sampled papers — named people below.
Who's working on it?
No interventional trial matched this name; these authors publish on it in the sampled literature — a practical starting point for contact.
- 01Guy MP7 papers · 2024
a Department of Biochemistry and Biophysics; Center for RNA Biology ; University of Rochester School of Medicine ; Rochester , NY USA.
Papers in Europe PMC - 02Phizicky EM7 papers · 2023
Department of Biochemistry and Biophysics and Center for RNA Biology, University of Rochester School of Medicine, Rochester, New York 14642, USA eric_phizicky@urmc.rochester.edu hopper.64@osu.edu.
Papers in Europe PMC - 03Gecz J6 papers · 2024
Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia; Department of Paediatrics, The University of Adelaide, Adelaide, South Australia, Australia.
Papers in Europe PMC - 04D'Adamo P4 papers · 2017
Division of Neuroscience, IRCSS San Raffaele Scientific Institute, 20132 Milan, Italy.
Papers in Europe PMC - 05Bianchi V3 papers · 2017
Division of Neuroscience, IRCSS San Raffaele Scientific Institute, 20132 Milan, Italy.
Papers in Europe PMC - 06Carré C3 papers · 2021
Transgenerational Epigenetics & small RNA Biology, Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, 9 Quai Saint Bernard, 75005 Paris, France.
Papers in Europe PMC - 07Casanova JE3 papers · 2019
Department of Cell Biology, University of Virginia, Charlottesville, VA 22908.
Papers in Europe PMC - 08Castro VL3 papers · 2026
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Papers in Europe PMC - 09Dimitrova DG3 papers · 2021
Transgenerational Epigenetics & small RNA Biology, Sorbonne Université, Centre National de la Recherche Scientifique, Laboratoire de Biologie du Développement - Institut de Biologie Paris Seine, 9 Quai Saint Bernard, 75005 Paris, France.
Papers in Europe PMC - 10Funk HM3 papers · 2024
Department of Chemistry & Biochemistry, Northern Kentucky University, Highland Heights, Kentucky 41076, United States.
Papers in Europe PMC
Clinical research
Is a treatment being tested?
0
interventional trials for this specific condition
No interventional trial testing a treatment matched this specific condition name on ClinicalTrials.gov (observational studies and pan-disease registries are listed separately when present).
Data as of 11 September 2026 · last trial check 11 September 2026
No matched interventional trials. This is true for 77.2% of diseases in the trials denominator (5501 of 7126). Here are the researchers publishing on it.
low confidence · 38.6th percentile (trials denominator)
Recruiting interventional trials
From the matched ClinicalTrials.gov set
No interventional trial testing a treatment was found for this specific condition name on ClinicalTrials.gov.
See who's working on it — people publishing on this disease are often the practical next contact when no trial is listed.
Other registries (secondary)
Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.
raw 25 · after dedupe 25 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 25 · dropped 0 · fetched 2026-07-29
Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri
No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).
Uncertain / not reviewed (25)
- ctis·2025-524635-39-00·Authorised·An Open Label, Single Arm, Phase I/II Clinical Study of Autologous CD4+ T-Cells Edited Ex-Vivo at the CD40LG Locus by CRISPR/Cas9 and IDLV-based vector in Patients with X-linked Hyper IgM Syndrome Type 1 (HIGM1)
skipped — LLM skipped (--skip-llm)
- ctis·2025-523275-27-00·Authorised, recruiting·HELIOS: An Open-Label, Long-Term Study to Investigate the Safety, Tolerability, and Efficacy of DISC-1459 (Bitopertin) in Participants with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP).
skipped — LLM skipped (--skip-llm)
- ctis·2025-523213-29-00·Authorised·A Phase 1/2, Multicenter, Open-label, Dose Escalation and Expansion Clinical Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of ASP2957 in Male Participants with Invasive Ventilator-dependent X-linked Myotubular Myopathy
skipped — LLM skipped (--skip-llm)
- ctis·2024-519833-51-00·Authorised·The efficacy of pipamperone and aripiprazole on behaviors that challenge in people with intellectual disabilities: A series of N-of-1 cross-over trials
skipped — LLM skipped (--skip-llm)
- ctis·2024-519779-24-00·Authorised, ongoing·GFM-VEXAS-MMB: A single-arm phase II with safety run-in multicenter study of momelotinib in patients with VEXAS syndrome with or without associated myelodysplastic syndrome
skipped — LLM skipped (--skip-llm)
- ctis·2024-520407-27-00·Expired·APOLLO: A Randomized, Double-Blind, Placebo-Controlled Study of Bitopertin to Evaluate the Efficacy, Safety, and Tolerability in Participants with
Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)
skipped — LLM skipped (--skip-llm)
- ctis·2024-516347-41-00·Authorised, ongoing·PAXIS: A randomized, double-blind, placebo-controlled dose-finding phase 2 study (Part 1) followed by an open-label period (Part 2) to assess the efficacy and safety of pacritinib in patients with VEXAS syndrome
skipped — LLM skipped (--skip-llm)
- ctis·2024-512700-18-00·Expired·Long-Term Follow-up of Fabry Disease Subjects who were Treated with ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy
skipped — LLM skipped (--skip-llm)
- ctis·2024-518989-27-01·Cancelled·Treating Leg Symptoms in Women with X-linked Adrenoleukodystrophy: A Key to Improving Sleep and Gait Performance
skipped — LLM skipped (--skip-llm)
- ctis·2023-509390-23-00·Authorised, ongoing·A Multicenter, Open-label, Phase 1/2, Dose-escalation and Subsequent Safety Extension Study of Subcutaneous KK8123 in Adult Patients with X-linked Hypophosphatemia
skipped — LLM skipped (--skip-llm)
- ctis·2023-507994-16-00·Cancelled·A Long-term Follow-up Study to Evaluate the Safety and Efficacy of Retinal Gene Therapy in Subjects with Choroideremia Previously Treated with Adeno-Associated Viral Vector Encoding Rab Escort Protein-1 (AAV2-REP1) and in Subjects with X-Linked Retinitis Pigmentosa Previously Treated with Adeno-Associated Viral Vector Encoding RPGR (AAV8-RPGR) in an Antecedent Study (SOLSTICE)
skipped — LLM skipped (--skip-llm)
- ctis·2024-513436-14-00·Authorised, ongoing·Evaluation of oxytocin treatment in children with autism and intellectual disability’, Multiple-dose Oxytocine - ASD and Intellectual Disability
skipped — LLM skipped (--skip-llm)
- ctis·2024-511181-36-00·11·A Randomized, Controlled, Masked, Multi-center Study Evaluating the Efficacy, Safety, and Tolerability of Two Doses of AGTC-501 Compared to an Untreated Control Group in Male Participants with X-linked Retinitis Pigmentosa
skipped — LLM skipped (--skip-llm)
- ctis·2024-516306-28-00·Revoked·Interest of Oxytocin as an Adjuvant Treatment of Psycho-educational Measures in Challenging Behaviors in Children With Autism Spectrum Disorders and Moderate to Severe Intellectual Disability: Feasibility and Safety Study. (OT-DEFI)
skipped — LLM skipped (--skip-llm)
- ctis·2024-514466-38-00·Expired·A Phase 3, Multicenter, Open-label, Long-term, Extension Study to Evaluate Safety and Tolerability of Oral Dersimelagon (MT-7117) in Subjects with Erythropoietic Protoporphyria (EPP) or X-Linked Protoporphyria (XLP)
skipped — LLM skipped (--skip-llm)
- ctis·2024-512695-34-00·Cancelled·A Phase I/II, Multicenter, Open-Label, Single-Dose, Dose-Ranging Study to Assess the Safety and Tolerability of ST-920, an AAV2/6 Human Alpha Galactosidase A Gene Therapy in Subjects with Fabry Disease.
skipped — LLM skipped (--skip-llm)
- ctis·2024-513124-41-00·Cancelled·Influencing Progression of Airway Disease in Primary Antibody Deficiency
skipped — LLM skipped (--skip-llm)
- ctis·2024-512790-27-00·Cancelled·A phase I/II, non randomized, monocentric open-label study of autologous CD34+ cells transduced with the G1XCGD lentiviral vector in patients with X-linked chronic granulomatous disease
skipped — LLM skipped (--skip-llm)
- ctis·2024-511411-25-00·Expired·Phase 3 Follow-up Study of AAV5-hRKp.RPGR for the Treatment of X-linked Retinitis Pigmentosa Associated with Variants in the RPGR gene
skipped — LLM skipped (--skip-llm)
- ctis·2024-513774-21-00·Expired·AN OPEN-LABEL, MULTICENTER STUDY IN MALE PEDIATRIC PATIENTS WITH CEREBRAL X-LINKED ADRENOLEUKODYSTROPHY (CALD) TO ASSESS THE EFFECTS OF MIN-102 TREATMENT ON DISEASE PROGRESSION PRIOR TO HUMAN STEM CELL TRANSPLANT (HSCT)
skipped — LLM skipped (--skip-llm)
- ctis·2024-512632-30-00·Authorised, ongoing·A prospective, open-label, genotype-match controlled, multicenter clinical trial to investigate the efficacy and safety of intra-amniotic ER004 as a prenatal treatment for male subjects with X-linked hypohidrotic ectodermal dysplasia (XLHED)
skipped — LLM skipped (--skip-llm)
- ctis·2023-504419-34-00·Expired·A three-period multicenter study, with a randomized-withdrawal, double-blinded, placebo-controlled design to evaluate the clinical efficacy, safety and tolerability of MAS825 in patients with monogenic IL-18 driven autoinflammatory diseases, including NLRC4-GOF, XIAP deficiency, or CDC42 mutations.
skipped — LLM skipped (--skip-llm)
- ctis·2024-512637-32-00·Expired·ASPIRO: A Phase 1/2/3, Randomized, Open-Label, Ascending-Dose, Delayed-Treatment Concurrent Control Clinical Study to Evaluate the Safety and Efficacy of AT132, an AAV8-Delivered Gene Therapy in X-Linked Myotubular Myopathy (XLMTM) Patients
skipped — LLM skipped (--skip-llm)
- ctis·2023-506735-15-00·Cancelled·MT-7117-A-302 Study: A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy, Safety, and Tolerability of MT-7117 in Adults and Adolescents with Erythropoietic Protoporphyria or X-Linked Protoporphyria
skipped — LLM skipped (--skip-llm)
- ctis·2023-504534-21-00·Cancelled·Open-label extension study with Tadekinig alfa (r-hIL-18BP) to monitor safety and tolerability in patients with IL-18 driven monogenic autoinflammatory conditions: NLRC4 mutation and XIAP deficiency
skipped — LLM skipped (--skip-llm)
Where to find support
Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.
Orphanet entry for X-linked non-syndromic intellectual disability — check Associations / patient organisations on that page.
India — NPRD
Last verified 2026-07-26This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.
Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.
How we counted this
Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.
("X-linked non-syndromic intellectual disability" OR "X-linked non-specific intellectual disability" OR "intellectual disability, X-linked, nonsyndromic" OR "intellectual disability, nonsyndromic, X-linked" OR "mental retardation, X-linked, nonsyndromic" OR "mental retardation, nonsyndromic, X-linked" OR "non-specific X-linked intellectual disability" OR "non-syndromic X-linked intellectual disability" OR "non-syndromic intellectual disability, X-linked" OR "nonsyndromic X-linked intellectual disability") OR ("ACSL4" OR "ACSL4 syndrome" OR "ACSL4-related" OR "AFF2" OR "AFF2 syndrome" OR "AFF2-related" OR "ARHGEF6" OR "ARHGEF6 syndrome" OR "ARHGEF6-related")ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):
"X-linked non-syndromic intellectual disability" OR "X-linked non-specific intellectual disability" OR "intellectual disability, X-linked, nonsyndromic" OR "intellectual disability, nonsyndromic, X-linked" OR "mental retardation, X-linked, nonsyndromic" OR "mental retardation, nonsyndromic, X-linked" OR "non-specific X-linked intellectual disability" OR "non-syndromic X-linked intellectual disability" OR "non-syndromic intellectual disability, X-linked" OR "nonsyndromic X-linked intellectual disability"
Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.
Query health: ok — strategies attempted: phrase; with hits: phrase
Run this search on ClinicalTrials.gov
Confidence reasoning
- Preferred label is multi-word and distinctive
- No synonyms dropped by stoplist
- No label/synonym collisions with other diseases in this corpus
- Publication count (12953) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity
Ingested 2026-07-26T15:19:25.038Z