Table 4 List of DNA repair genes with loss-of-function (LoF) variants in the discovery case cohort, grouped by pathway.

From: Exome sequencing of familial high-grade serous ovarian carcinoma reveals heterogeneity for rare candidate susceptibility genes

Repair pathway

Genesa

No. of LoF alleles in casesb (%)

No. of LoF alleles in GnomADc (%)

OR (95% CI)d

p valued

Base excision repair

RFC1, RFC2, RFC3, RFC4, RFC5, XRCC1, PCNA, PARP1, PARP2, APEX1, FEN1, POLE, POLD1, LIG3, OGG1, UNG, SMUG1, MBD4, TDG, MUTYH, NTHL1, MPG, NEIL1, NEIL2, NEIL3, APEX2, PNKP, APLF, PARP3, LIG1

16 (0.052)

2146 (0.061)

0.854 (0.49āˆ’1.39)

0.64

Mismatch repair

RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, MSH3, MSH4, MSH5, MLH3, PMS1, PMS2P3, EXO1, POLD1

4 (0.028)

1041 (0.063)

0.439 (0.12āˆ’1.13)

0.095

Nucleotide excision repair

RPA1, RPA2, RPA3, RPA4, RFC1, RFC2, RFC3, RFC4, RFC5, PCNA, ERCC1, ERCC4, ERCC2, ERCC5, XPC, ERCC6, GTF2H2, ERCC3, XPA, RAD23B, POLE, POLD1, RAD23A, LIG3, CETN2, DDB1, DDB2, GTF2H1, GTF2H3, GTF2H4, GTF2H5, CDK7, CCNH, MNAT1, LIG1, ERCC8, UVSSA, XAB2, MMS19

17 (0.043)

1691 (0.037)

1.15 (0.67āˆ’1.84)

0.51

Homologous recombination repair

ATM, RPA1, RPA2, RPA3, RPA4, RAD51, NBN, RAD50, CHEK2, PALB2, MUS81, EME1, MRE11A, RAD52, RAD51B, DMC1, XRCC2, XRCC3, RAD54L, RAD54B, SHFM1, RBBP8, SLX1A, SLX1B, GEN1

23 (0.090)

1614 (0.056)

1.62 (1.02āˆ’2.43)

0.032

Fanconi anaemia genes

ATR, ERCC1, FANCA, FANCB, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCL, FANCM, PALB2, CHEK1, SLX4, FAN1, FAAP20, FAAP24, MUS81, EME1

24 (0.12)

1980 (0.090)

1.39 (0.89āˆ’2.07)

0.12

Non-homologous end-joining

XRCC6, XRCC5, PRKDC, LIG4, XRCC4, DCLRE1C, NHEJ1

3 (0.042)

275 (0.033)

1.27 (0.26āˆ’3.74)

0.52

Direct DNA damage reversal

MGMT, ALKBH2, ALKBH3

1 (0.033)

378 (0.11)

0.305 (0.01āˆ’1.71)

0.39

All unique DNA repair genes

77 (0.066)

8268 (0.063)

1.06 (0.84āˆ’1.33)

0.59

Other associated genes, i.e. indirect regulators of genomic stability

PAXIP1, BLMe, MLL3, CRIP1, CDK12, BAP1, BARD1, WRN, BUB1, CENPE, ZW10, TTK, KNTC1, AURKB, POLB, POLH, POLQ, TDP1, TDP2, NUDT1, DUT, RRM2B, POLG, REV3L, MAD2L2, REV1, POLI, POLK, POLL, POLM, POLN, TREX1, TREX2, APTX, SPO11, ENDOV, UBE2A, UBE2B, RAD18, SHPRH, HLTF, RNF168, SPRTN, RNF8, RNF4, UBE2V2, UBE2N, H2AFX, CHAF1A, SETMAR, RECQL4, MPLKIP, DCLRE1A, DCLRE1B, PRPF19, RECQL, RECQL5, HELQ, RDM1, NABP2, ATRIP, MDC1, RAD1, RAD9A, HUS1, RAD17, TP53, TP53BP1, TOPBP1, CLK2, PER1

42 (0.057)

4733 (0.056)

1.02 (0.73āˆ’1.38)

0.88

Total (all DNA repair and other associated genes)

119 (0.063)

13,001 (0.061)

1.05 (0.87 to 1.25)

0.60

  1. aGenes and their associated pathways sourced from list curated by Chae et al.30. Table and calculations exclude known HBOC genes (BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, RAD51C, RAD51D, BRIP1), as samples with pathogenic LoF variants in these genes were removed from the cohort during filtering.
  2. bTotal nā€‰=ā€‰1020 multiplied by number of genes in pathway.
  3. cGnomAD non-Finnish European (NFE), non-cancer sub-population.
  4. dFisherā€™s exact test results (OR odds ratio, CI confidence interval).
  5. eFigure for BLM excludes additional stop-gain variant (c.2208ā€‰Tā€‰>ā€‰G) found in cis with frameshift variant (c.2206dupT) in the same individual.
Back to article page