Prevalence of mutations in germline DNA from ICI-DM patients and the general population
| Index | Gene | Gene name | Chromosome|mutation | Protein change | Top consequence | ICI-DM Patients with germline mutation (Percentage, n=13) | Prevalence in 1000 genomes project, American (1000GP) | Fisher’s Exact Test: 1000GP vs ICI-DM Mutation Prevalences (p value) *Significant with Bonferroni Correction |
| 1 | NLRC5 | NLR family CARD domain containing 5 | chr16:57025515|SNP:C>T | Pro191Leu | Missense | 9 (69.2%) | 12.80% | 0.00000598* |
| 2 | CEMIP2 | Cell migration inducing hyaluronidase 2 | chr9:71745318|SNP:C>T | Arg245Lys | Missense | 5 (38.5%) | 4.60% | 0.000284* |
| 3 | KIAA0100 | KIAA0100 | chr17:28628312|SNP:A>C | Val137Gly | Missense | 4 (30.8%) | 6.10% | 0.007287 |
| 4 | XRCC3 | X-ray repair cross complementing 3 | chr14:103699416|SNP:G>A | Thr241Met | Missense | 7 (53.8%) | 29.90% | 0.016368 |
| 5 | DNAJB11 | DnaJ heat shock protein family (Hsp40) member B11 | chr3:186583914|SNP:A>G | Ile264Val | Missense | 7 (53.8%) | 23.80% | 0.01737 |
| 6 | EIF4G2 | Eukaryotic translation initiation factor 4 gamma 2 | chr11:10806814|SNP:C>A | c.107+6G>T | Splice region variant | 5 (38.5%) | 66.10% | 0.071673 |
| 7 | MED16 | Mediator complex subunit 16 | chr19:868115|SNP:C>T | Glu874Lys | Missense | 5 (38.5%) | 20.70% | 0.161434 |
| 8 | PON2 | Paraoxonase 2 | chr7:95405463|SNP:G>C | Ser311Cys | Missense | 5 (38.5%) | 23.30% | 0.199808 |
| 9 | ERCC6L2 | ERCC excision repair 6 like 2 | chr9:95876006|SNP:A>G | −64+4737A>G | Start lost | 6 (46.2%) | 29.00% | 0.217661 |
| 10 | MAP1S | Microtubule associated protein 1S | chr19:17726616|SNP:C>G | Ser411Cys | Missense | 4 (30.8%) | 17.70% | 0.265528 |
| 11 | TEP1 | Telomerase associated protein 1 | chr14:20404722|SNP:G>T | Asn307Lys | Missense | 5 (38.5%) | 27.80% | 0.368396 |
| 12 | ISG20L2 | Interferon stimulated exonuclease gene 20 like 2 | chr1:156727264|SNP:T>C | Asn130Ser | Missense | 5 (38.5%) | 28.20% | 0.53443 |
| 13 | HKDC1 | Hexokinase domain containing 1 | chr10:69266754|SNP:C>A | Asn917Lys | Missense | 5 (38.5%) | 49.10% | 0.578612 |
| 14 | MIA3 | MIA SH3 domain ER export factor 3 | chr1:222629034|SNP:A>G | Lys188Arg | Missense | 4 (30.8%) | 39.80% | 0.580397 |
| 15 | TANC1 | Tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 1 | chr2:159097663|SNP:C>T | Pro30Ser | Missense | 4 (30.8%) | 24.90% | 0.746313 |
| 16 | ACCS | 1-aminocyclopropane-1-carboxylate synthase homolog (inactive) | chr11:44083431|SNP:C>T | Pro421Leu | Missense | 4 (30.8%) | 30.40% | >0.999999 |
*Indicates significant difference in prevalence after the Bonferroni correction.
ICI-DM, immune checkpoint inhibitor-induced diabetes mellitus.