| Clinical entity/subtype | Gene (HGNC symbol) | Protein/function (cytotoxic granule pathway step or inflammasome) | Inheritance | Notes | Key evidence citation id |
|---|---|---|---|---|---|
| Familial HLH type 2 (FHL2) | PRF1 | Perforin; pore-forming effector required for granzyme entry and lymphocyte cytotoxic killing | Autosomal recessive | Core familial HLH gene; central to granule-mediated cytotoxicity | (pqac-00000031, pqac-00000032) |
| Familial HLH type 3 (FHL3) | UNC13D | Munc13-4; cytotoxic granule priming/exocytosis | Autosomal recessive | Common FHL cause; associated with poor prognosis in later cohort literature | (pqac-00000031, pqac-00000035) |
| Familial HLH type 4 (FHL4) | STX11 | Syntaxin-11; vesicle membrane fusion/exocytosis in cytotoxic granule release | Autosomal recessive | Canonical degranulation-pathway FHL gene | (pqac-00000031, pqac-00000033) |
| Familial HLH type 5 (FHL5) | STXBP2 | Munc18-2; vesicle docking/fusion for cytotoxic granule exocytosis | Autosomal recessive | Also referred to as UNC18B/Munc18-2 in some sources | (pqac-00000031, pqac-00000033) |
| Griscelli syndrome type 2 with HLH predisposition | RAB27A | Regulates cytotoxic granule trafficking/transport | Autosomal recessive | Syndromic HLH predisposition; defective granule transport | (pqac-00000031, pqac-00000034) |
| Chediak-Higashi syndrome with HLH predisposition | LYST | Required for cytotoxic granule formation/lysosome-related organelle biology | Autosomal recessive | Syndromic HLH predisposition; abnormal granule formation/trafficking | (pqac-00000031, pqac-00000034) |
| Hermansky-Pudlak syndrome type 2 with HLH predisposition | AP3B1 | Adaptor protein complex component; granule biogenesis/transport | Autosomal recessive | Syndromic HLH predisposition due to granule formation/transport defects | (pqac-00000031, pqac-00000034) |
| X-linked lymphoproliferative syndrome 1 (XLP1) | SH2D1A | SAP signaling adaptor; immune regulation with EBV susceptibility rather than classic granule-fusion defect | X-linked | X-linked HLH predisposition, often EBV-triggered | (pqac-00000031, pqac-00000032) |
| X-linked lymphoproliferative syndrome 2 (XLP2) | XIAP (BIRC4) | XIAP; inflammasome regulation/inhibition and immune homeostasis | X-linked | HLH predisposition with inflammasome-related mechanism distinct from classic degranulation genes | (pqac-00000031, pqac-00000032) |
| X-linked immunodeficiency with magnesium defect, EBV infection, and neoplasia | MAGT1 | Magnesium transporter/immune signaling regulator | X-linked | Reported among HLH-related immune dysregulation syndromes | (pqac-00000031) |
| HLH-predisposition / immune dysregulation | NLRC4 | Inflammasome component | Not clearly stated in retrieved evidence | Non-granule-related predisposition highlighted in diagnostic review | (pqac-00000036) |
| HLH-predisposition / immune dysregulation | CDC42 | Rho-family GTPase; immune cell trafficking/signaling, linked to inflammasome-associated HLH phenotypes | Not clearly stated in retrieved evidence | Non-granule-related predisposition highlighted in review/overview sources | (pqac-00000033, pqac-00000036) |
| HLH-predisposition / interferon dysregulation | ZNFX1 | Regulator of interferon responses / nucleic-acid sensing | Not clearly stated in retrieved evidence | Recently described HLH-related gene with variable penetrance | (pqac-00000035) |
| HLH-predisposition / EBV-associated immune dysregulation | ITK | T-cell signaling kinase | Not clearly stated in retrieved evidence | Mentioned among additional HLH-associated genes beyond classic FHL genes | (pqac-00000034, pqac-00000035) |
| HLH-predisposition / EBV-associated immune dysregulation | CD27 | TNF-receptor family costimulatory molecule in lymphocyte activation | Not clearly stated in retrieved evidence | Additional HLH-associated immune dysregulation gene | (pqac-00000034, pqac-00000035) |


*Table: This table summarizes HLH genetic causes and related syndromes mentioned in the retrieved evidence, emphasizing the affected gene, pathway role, inheritance, and clinical associations. It is useful for distinguishing classic familial HLH degranulation defects from syndromic and inflammasome-related HLH predisposition genes.*