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ORPHA:538934

X-linked lymphoproliferative disease due to XIAP deficiency

low confidenceDisorder

Also known as: XIAP deficiency syndrome · XLP2 · X-linked lymphoproliferative syndrome type 2

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

Publications

20,479

Trials

5

Interventional, condition-specific

Researchers

1,352

Distinct authors in sample

Gene link

XIAP

Strong

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked XIAP gene, resulting in B cell lymphoproliferation and manifesting with various phenotypes which include EBV-driven hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, recurrent , hepatitis, colitis, and intestinal bowel disease with features of Crohn's disease. Additional manifestations include variable auto-inflammatory symptoms such as uveitis, arthritis, skin abscesses, erythema nodosum, and nephritis. Neurological involvement is rare and lymphoma is never observed. Laboratory findings include normal or increased activated T cells, low or normal iNKT cells, and normal or reduced memory B cells.

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)

XIAP deficiency · XIAP deficiency/XLPs · lymphoproliferative syndrome, X-linked, 2, X-linked recessive · lymphoproliferative syndrome, X-linked, type 2

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

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Strong — XIAP

  2. LiteraturePresent

    20,479 matched papers (11,804 in last 10 years) Source

  3. Phenotype characterisedPresent

    43 HPO annotations (e.g. Crohn's disease; Hepatic failure; Immunodeficiency) 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 trialPresent

    5 matched on ClinicalTrials.gov (1 recruiting in sample)

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 (XIAP).

GenCC classification: Strong.

Phenotypes (Monarch / HPO)

43

Associated phenotypes · MONDO:0010385

  • Crohn's disease
  • Hepatic failure
  • Immunodeficiency
  • Pancytopenia
  • Jejunoileal ulceration

Showing 5 of 43 — 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?

20,479

20,479 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.

20,479 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).

11,804 in the last 10 years · low confidence

Phrase hits: 533 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,352

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Kanegane H18 papers · 2026

    Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. hkanegane.ped@tmd.ac.jp.

    Papers in Europe PMC
  2. 02
    Marsh RA8 papers · 2025

    Division of Bone Marrow Transplantation and Immune Deficiency, University of Cincinnati, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

    Papers in Europe PMC
  3. 03
    Arai K7 papers · 2026

    Division of Gastroenterology, Center for Pediatric Inflammatory Bowel Disease, National Center for Child Health and Development, Tokyo, Japan.

    Papers in Europe PMC
  4. 04
    Booth C7 papers · 2025

    Department of Paediatric Immunology, Great Ormond Street Hospital, London, United Kingdom.

    Papers in Europe PMC
  5. 05
    Hoshino A7 papers · 2026

    Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

    Papers in Europe PMC
  6. 06
    Latour S7 papers · 2022

    Laboratory of Lymphocyte Activation and Susceptibility to EBV infection, INSERM UMR 1163, Paris, France.

    Papers in Europe PMC
  7. 07
    Morio T7 papers · 2025

    Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

    Papers in Europe PMC
  8. 08
    Imai K6 papers · 2023

    Department of Community Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

    Papers in Europe PMC
  9. 09
    Speckmann C6 papers · 2023

    Universitatsklinikum Freiburg Medizinische Universitatsklinik, Freiburg im Breisgau, Baden-Württemberg, Germany.

    Papers in Europe PMC
  10. 10
    Takagi M6 papers · 2026

    Department of Community Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

5

interventional trials for this specific condition

5 interventional trials matched this specific condition name; 1 currently recruiting in our sample.

Data as of 11 September 2026 · last trial check 28 July 2026

5 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 89.2th percentile).

low confidence · 89.2th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

5 interventional trials matched after quoted-phrase search and title/condition post-filter.

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 X-linked lymphoproliferative disease due to XIAP deficiency — 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.

("X-linked lymphoproliferative disease due to XIAP deficiency" OR "XIAP deficiency syndrome" OR "X-linked lymphoproliferative syndrome type 2" OR "XIAP deficiency" OR "XIAP deficiency/XLPs" OR "lymphoproliferative syndrome, X-linked, 2, X-linked recessive" OR "lymphoproliferative syndrome, X-linked, type 2") OR (MESH:"Lymphoproliferative Syndrome, X-Linked, 2") OR ("XIAP" OR "XIAP syndrome" OR "XIAP-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Lymphoproliferative Syndrome, X-Linked, 2

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

"X-linked lymphoproliferative disease due to XIAP deficiency" OR "XIAP deficiency syndrome" OR "X-linked lymphoproliferative syndrome type 2" OR "XIAP deficiency" OR "XIAP deficiency/XLPs" OR "lymphoproliferative syndrome, X-linked, 2, X-linked recessive" OR "lymphoproliferative syndrome, X-linked, type 2" OR "Lymphoproliferative Syndrome, X-Linked, 2"

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 5 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

Synonyms dropped by stoplist: XLP2

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (20479) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-27T18:13:20.508Z