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ORPHA:254925

Combined oxidative phosphorylation defect type 4

low confidenceDisorder

Also known as: COXPD4

Query health: suspect — Only one of 2 strategies returned hits (phrase).

Publications

1,420

Trials

0

Interventional, condition-specific

Researchers

187

Distinct authors in sample

Gene link

TUFM

Strong

Readiness

3/6

Stages with a signal

Clinical definition (Orphanet)

Combined oxidative phosphorylation defect type 4 is a rare disorder due to a defect in protein synthesis characterized by a onset of severe and respiratory distress, persistent lactic with episodes of crises, developmental regression, microcephaly, abnormal gaze fixation and pursuit, axial with limb spasticity and reduced spontaneous movements. Neuroimaging studies reveal polymicrogyria, white matter abnormalities and multiple cystic brain lesions, including basal ganglia, and cerebral atrophy. Decreased activity of complex I and IV have been determined in muscle biopsy.

How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (4)

TUFM combined oxidative phosphorylation deficiency · combined oxidative phosphorylation defect type 4 · combined oxidative phosphorylation deficiency caused by mutation in TUFM · combined oxidative phosphorylation deficiency type 4

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.”

3/6 stages with a signal

No matched interventional trial; the gene is known and literature exists — preclinical or natural-history work may still be the practical next step.

  1. Gene identifiedPresent

    Strong — TUFM

  2. LiteraturePresent

    1,420 matched papers (1,040 in last 10 years) Source

  3. Phenotype characterisedPresent

    16 HPO annotations (e.g. Opisthotonus; Nystagmus; Hyperammonemia) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. 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 (TUFM).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

16

Associated phenotypes · MONDO:0012534

  • Opisthotonus
  • Nystagmus
  • Hyperammonemia
  • Neonatal hypotonia
  • Increased circulating lactate concentration

Showing 5 of 16 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

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?

1,420

1,420 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

1,420 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).

1,040 in the last 10 years · low confidence

Phrase hits: 24 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

187

Distinct author names in 24 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.

  1. 01
    Dong L2 papers · 2026

    Genome Engineering Core, National Eye Institute, National Institutes of Health, 6 Center Drive, Bethesda, MD, 20892, USA.

    Papers in Europe PMC
  2. 02
    Abdenur JE1 paper · 2017

    Division of Metabolic Disorders, CHOC Children's, Orange, CA, USA; Department of Pediatrics, University of California Irvine, Irvine, CA, USA. Electronic address: jabdenur@choc.org.

    Papers in Europe PMC
  3. 03
    Adams HHH1 paper · 2022

    Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.

    Papers in Europe PMC
  4. 04
    Advani J1 paper · 2022

    Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, MSC0610, 6 Center Drive, Bethesda, MD, 20892, USA.

    Papers in Europe PMC
  5. 05
    Alcántara-Ortigoza MA1 paper · 2023

    Laboratorio de Biología Molecular, Subdirección de Investigación Médica, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City CP 04530, Mexico.

    Papers in Europe PMC
  6. 06
    Algara-Ramírez C1 paper · 2023

    Facultad Mexicana de Medicina, Universidad la Salle, Mexico City CP 14070, Mexico.

    Papers in Europe PMC
  7. 07
    Alonso I1 paper · 2017

    UnIGENe, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal.

    Papers in Europe PMC
  8. 08
    Altun AN1 paper · 2024

    Department of Pediatric Metabolic Disorders, Gazi University Faculty of Medicine, Ankara, Türkiye.

    Papers in Europe PMC
  9. 09
    Aravind L1 paper · 2022

    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, 20894, USA.

    Papers in Europe PMC
  10. 10
    Arcaro A1 paper · 2016

    Dipartimento di Medicina e Scienze della Salute "V. Tiberio", Università del Molise, Campobasso 86100, Italy. alessia.arcaro@unimol.it.

    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 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-30

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).

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 Combined oxidative phosphorylation defect type 4 — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This 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.

("Combined oxidative phosphorylation defect type 4" OR "COXPD4" OR "TUFM combined oxidative phosphorylation deficiency" OR "combined oxidative phosphorylation deficiency caused by mutation in TUFM" OR "combined oxidative phosphorylation deficiency type 4") OR (MESH:"Combined Oxidative Phosphorylation Deficiency 4") OR ("TUFM" OR "TUFM syndrome" OR "TUFM-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Combined Oxidative Phosphorylation Deficiency 4

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Combined oxidative phosphorylation defect type 4" OR "COXPD4" OR "TUFM combined oxidative phosphorylation deficiency" OR "combined oxidative phosphorylation deficiency caused by mutation in TUFM" OR "combined oxidative phosphorylation deficiency type 4" OR "Combined Oxidative Phosphorylation Deficiency 4"

Study-type breakdown: 0 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.

Query health: suspect — strategies attempted: phrase, mesh; 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 (1420) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T11:09:44.240Z