Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: APOL1

Red List (low evidence)

Polymorphisms enriched in the African population are associated with increased protection from trypanosomiasis but also elevated risk of FSGS. Effect size is not that of a monogenic disorder

Created: 11 Jun 2018, 4:43 p.m.

Red List (low evidence)

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): APOL1 .PanelApp HGNC gene symbol check: APOL1 . IUIS Disease: Trypanosomiasis . IUIS Inheritance: AD .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: Somatic. IUIS Associated features: Trypanosomiasis. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Other Inborn Errors of Immunity Related to Non-Hematopoietic Tissues

Created: 2 Jul 2018, 10:35 a.m.

External expert review notes Red status due to no evident link to immunodeficiency, so I have kept this gene Red on this panel

Created: 12 Jun 2018, 3:30 p.m.

Comment on list classification: Changed status from Amber to Red. Only associated with susceptibility to Trypanosomiasis and not directly causative of it

Created: 11 May 2018, 11:25 a.m.

Only associated with susceptibility to Trypanosomiasis and not directly causative of it

Created: 11 May 2018, 11:25 a.m.

Comment on publications: Added publications to support APOL1 and susceptibility to Trypanosomiasis. Human African Trypanosomiasis, HAT (also known as sleeping sickness) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1.
Studies in the Democratic Republic of Congo (DRC), Cameroon, Cote D’Ivoire, Guinea and Uganda have found evidence for polymorphisms in HP, IL6 and APOL1 associated with outcome of infection PMID: 16720107;28537557;15894515;28827791;29077717. PMID 29470556 (2018) findings differed from recent studies carried out in the Tbr HAT another endemic area of Uganda showed the APOL1 (Apolipoprotein 1) G2 allele to be protective against the disease which merits further investigation.

Created: 11 May 2018, 11:22 a.m.

This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.

Created: 20 Apr 2018, 12:25 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: APOL-I, PanelApp HGNC gene symbol check: APOL1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Defects in innate immunity / Trypanosomias / Trypanosomias

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: APOL1, GRID_Gene_Symbol: APOL1, GRID_Transcript_ENS_Community submitted: ENST00000319136, GRID_Transcript_RefSeq: NM_145343.2, GRID_Transcript_ENS_used_on_Production: ENST00000319136

Created: 17 Apr 2018, 12:12 p.m.