Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: INO80

Red List (low evidence)

Comment on list classification: As the evidence for the association of INO80 gene with immunodeficiency is disputed, this gene should be considered for demotion to red rating in the next GMS update.

Created: 16 Oct 2025, 5:17 p.m. | Last Modified: 16 Oct 2025, 5:17 p.m.

Panel Version: 8.50

PMID:25312759 reported the identification of compound heterozygous missense variants in INO80 gene in two unrelated individuals with Immunoglobulin class-switch recombination defects. There are a total of three different variants identified, of which both patients shared one variant. These variants are found at high population frequencies in gnomAD v4.1.0. There is some supportive functional evidence available. There are no further reports of published human cases available in support of the association.

Biallelic variants in INO80 gene have been associated with 'immunodeficiency, common variable, 1' (MONDO:0011864) with 'Disputed' rating by Antibody Deficiencies GCEP expert panel in ClinGen (https://search.clinicalgenome.org/CCID:005145) This was based on the evidence presented above.

This gene has not been linked to any phenotypes either in OMIM (records accessed on 16 October 2025) or in Gene2Phenotype. It is rated amber on the 'Predominantly Antibody Deficiency' panel in PanelApp Australia (https://panelapp-aus.org/panels/222/gene/INO80/)

Created: 16 Oct 2025, 5:14 p.m. | Last Modified: 16 Oct 2025, 5:14 p.m.

Panel Version: 8.47

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
common variable immunodeficiency, MONDO:0015517

Publications

• 25312759

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

One paper describing 2 unrelated patients

Created: 20 Jun 2018, 7:32 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
severe bacterial infections

Publications

• 25312759

Green List (high evidence)

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): INO80 .PanelApp HGNC gene symbol check: INO80 . IUIS Disease: INO80 . IUIS Inheritance: AR .T cells: Nl to low number, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Severe bacterial infections. IUIS Major category: Predominantly Antibody Deficiencies. IUIS Subcategory: Severe Reduction in Serum IgG and IgA with Normal/Elevated IgM and Normal Numbers of B cells, Hyper IgM

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

Comment on list classification: Changed Amber to Green from external expert review

Created: 21 Jun 2018, 4:07 p.m.

Comment on publications: PMID: 25312759 Kracker et al (2015) reported an adult and a pediatric patients with recurrent bacterial infections, and normal IgM levels but decreased both IgA and IgG levels. AID, UNG, CD40 and CD40L sequences were normal. WES revealed missense compound heterozygous mutations in the INO80 complex subunit (INO80) gene, a protein involved in DNA repair. Defective switch junction repair was demonstrated in immortalized B cells from the patient, and was corrected with over expression of wild-type INO80.

Created: 21 Jun 2018, 3:25 p.m.

Comment on publications: added publications to support phenotype

Created: 21 Jun 2018, 3:16 p.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 supplied by GRID. GRID Gene Symbol HGNC PanelApp check: INO80, GRID_Gene_Symbol: INO80, GRID_Transcript_ENS_Community submitted: ENST00000361937, GRID_Transcript_RefSeq: NM_017553.2, GRID_Transcript_ENS_used_on_Production: ENST00000361937

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