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Table 2 Rare, predicted deleterious KLK1 and GGCX variants among 2572 PAH cases. Participants were heterozygous for the indicated variants

From: Novel risk genes and mechanisms implicated by exome sequencing of 2572 individuals with pulmonary arterial hypertension

Participant ID Gender Age at dx (years) PAH subclass Ancestry Gene** Nucleotide change Amino acid change Variant type MAF (ExAC) CADD score Revel score
08–022 F 60 IPAH EUR KLK1 c.46+1G>T p.(=) Splicing 24
10–096 F 68 IPAH EUR KLK1 c.60dup p.Ile21Aspfs*12 Frameshift 4.29E−05
28–049 F 36 APAH-CHD EUR KLK1 c.60dup p.Ile21Aspfs*12 Frameshift 4.29E−05
06–058 M 13 IPAH EUR KLK1 c.70C>T p.Arg24Trp D-Mis 8.47E−06 26 0.56
13–002 F 71 IPAH EUR KLK1 c.70C>T p.Arg24Trp D-Mis 8.47E−06 26 0.56
06–007 M 26 IPAH EUR KLK1 c.113G>A p.Trp38* Stop-gain 8.30E−06 35
12–061 F 51 IPAH EUR KLK1 c.469G>A p.Gly157Ser D-Mis 9.36E−05 29 0.72
14–018 M 61 IPAH EUR KLK1 c.469G>A p.Gly157Ser D-Mis 9.36E−05 29 0.72
17–075 F 82 APAH-CTD EUR KLK1 c.469G>A p.Gly157Ser D-Mis 9.36E−05 29 0.72
18–026 F 37 IPAH EUR KLK1 c.644G>A p.Gly215Glu D-Mis 30 0.85
19–013 F 51 IPAH EUR KLK1 c.650C>T p.Pro217Leu D-Mis 2.52E−05 29 0.60
19–033 F 37 IPAH EUR KLK1 c.689G>C p.Trp230Ser D-Mis 8.26E−06 25 0.50
06–014 M 35 FPAH EUR GGCX c.137C>G p.Ser46Cys D-Mis 5.77E−05 23 0.70
04–020 F 36 IPAH EUR GGCX c.G203G>C p.Arg68Pro D-Mis 35 0.96
12–207 F 43 IPAH EUR GGCX c.G203G>C p.Arg68Pro D-Mis 35 0.96
32–003 M 81 IPAH EUR GGCX c.248G>A p.Arg83Gln D-Mis 34 0.92
32–008 F 36 IPAH AFR GGCX c.322C>T p.Arg108Cys D-Mis 1.65E−05 31 0.55
08–013 F 66 APAH-CTD EUR GGCX c.646_647delinsCA p.Val216Gln In-frame 31 ***
26–036 F 52 IPAH EUR GGCX c.722 T>C p.Phe241Ser D-Mis 33 0.94
30–031 F 55 IPAH EUR GGCX c.722 T>C p.Phe241Ser D-Mis 33 0.94
04–029 F 60 IPAH EUR GGCX c.734 T>A p.Leu245* Stop-gain 40
04–087 F 54 IPAH EUR GGCX c.763G>A p.Val255Met D-Mis 1.65E−05 34 0.86
34–005 M 66 IPAH EUR GGCX c.763G>A p.Val255Met D-Mis 1.65E−05 34 0.86
11–004 F 24 IPAH HIS GGCX c.763G>A p.Val255Met D-Mis 1.65E−05 34 0.86
22–108 F 40 APAH-HIV AFR GGCX c.899C>T p.Ser300Phe D-Mis 2.53E−05 28 0.82
28–110 F 56 IPAH AFR GGCX c.899C>T p.Ser300Phe D-Mis 2.53E−05 28 0.82
28–096 F 23 IPAH EUR GGCX c.938_939del p.Pro313Argfs*33 Frameshift 1.00E−04
08–046 F 53 APAH-Porto EUR GGCX c.950G>A p.Arg317Gln D-Mis 1.67E−05 33 0.81
12–205 F 55 IPAH EUR GGCX c.1017_1018insT p.Ser340* Stop-gain
15–008 F 14 APAH-CHD EUR GGCX c.1075C>T p.Arg359Cys D-Mis 28 0.76
21–037 F 45 APAH-CTD AFR GGCX c.1128C>G p.Phe376Leu D-Mis 27 0.85
06–039 F 28 IPAH EUR GGCX c.1224C>A p.His408Gln D-Mis 8.24E−06 23 0.75
37–004 F 48 IPAH EUR GGCX c.1249G>A p.Asp417Asn D-Mis 1.65E−05 26 0.72
30–034 F 49 APAH-CTD HIS GGCX c.1304G>A p.Arg435Gln D-Mis 8.24E−06 29 0.67
14–029 M 48 IPAH EUR GGCX c.1306C>T p.Arg436* Stop-gain 3.30E−05 41
37–010 F 77 APAH-CTD EUR GGCX c.1306C>T p.Arg436* Stop-gain 3.30E−05 41
11–090 F 47 APAH AFR GGCX c.1465G>A p.Val489Met D-Mis 2.47E−05 26 0.68
05–013 M 63 APAH-Porto HIS GGCX c.1480 T>G p.Ser494Ala D-Mis 26 0.84
28–033 F 51 IPAH EUR GGCX c.1758C>G p.Tyr586* Stop-gain 45
17–033 F 74 APAH-CTD AFR GGCX c.1772C>T p.Thr591Met D-Mis 3.30E−05 29 0.83
  1. *Rare, deleterious variants defined as gnomAD AF ≤ 1.00E−04 and REVEL > 0.5
  2. **KLK1 transcript NM_002257.3 and GGCX transcript NM_000821.6
  3. ***REVEL score could not be computed for this 2-nt substitution because machine learning is based on 1-nt substitutions. Inclusion in the table was based on REVEL > 0.9 for single nt substitution and PROVEAN = deleterious for 2-nt substitution