Table 5 Characteristics of the genes identified in common AGS and GLGS-UGLI cohorts. The gene coordinates are reported in the GRCh37/hg19 build

APC

chr5: 112,073,556-112,181,936

APC Regulator of WNT Signalling Pathway

The APC gene encodes a tumour suppressor protein that acts as an antagonist of the Wnt signalling pathway.

It is also involved in other processes including cell migration, adhesion, transcriptional activation, and apoptosis.

BRCA2

chr13: 32,889,617-32,973,809

BRCA2 DNA repair associated

The BRCA2 gene is involved in maintaining genomic instability promoting efficient and precise repair of double-strand breaks.

COL3A1

chr2: 189,839,099-189,877,472

Collagen type III alpha 1 chain

The COL3A1 gene encodes for the chains of type III procollagen.

Collagen type III have been found in the lamina cribrosa and in the trabecular meshwork.

HLA-DRB1

chr6: 32,546,546-32,557,613

Major histocompatibility complex, class II, DR beta 1

The human leukocyte antigen (HLA) genes regulate the immune process promoting the adaptive immune response in the vertebrates.

HLAs are membrane glycoproteins that can be divided into two major types designated class I (encoded by the genes HLA-A, -B, and -C) and class II (encoded by the genes HLA-DR, -DP, and -DQ).

HLA-DRB5

chr6: 32,485,130-32,498,064

Major histocompatibility complex, class II, DR beta 5

HLA-DRB6

chr6: 32,520,490-32,527,779

Major histocompatibility complex, class II, DR beta 6

MFSD8

chr4: 128,838,960-128,887,139

Major Facilitator Superfamily Domain Containing 8

The MFSD8 gene encodes for ubiquitous integral membrane protein that contains a transporter domain and a major facilitator superfamily domain. Other members of the major facilitator superfamily transport small solutes through chemiosmotic ion gradients.

The protein likely localizes to lysosomal membranes.

NIPBL

chr5: 36,876,861-37,065,921

NIPBL cohesin loading factor

The NIPBL is involved in guaranteeing the cohesin complex in the chromatin and also between the enhancers and core promoters.

SCN1A

chr2: 166,845,670-166,930,180

Sodium voltage-gated channel alpha subunit 1

The SCN1A is a protein coding gene that encodes for sodium channel alpha subunits which are involved in the generation and propagation of action potential in nerve and muscle.

SDHB

chr1: 17,345,217-17,380,527

Succinate Dehydrogenase Complex Iron Sulfur Subunit B

The SDHB gene encodes for proteins that interact with the complex II of the respiratory chain, which is specifically involved in the oxidation of succinate and carries electrons from NADH to CoQ. The complex is composed of four nuclear-encoded subunits (named A to D) and is localized in the mitochondrial inner membrane.

ZDHHC11

chr5: 795,720-851,101

Zinc finger DHHC-type containing 11

The ZDHHC11 is a protein coding gene member of the DHHC domain responsible for protein palmitoylation by protein acyltransferases with zinc-finger and Asp-His-His-Cys sequence (zDHHC) where its activity is required for the activation to DNA damage.