Table 3

Details of the four CRPS-1-associated SNPs found in the discovery cohort

SNP detailsGeneANO10P2RX7PRKAG1SLC12A9
SNPrs41289586rs28360457rs1126930rs80308281
Chromosome location hg19chr3:
43 618 558
chr12:
121 613 129
chr12:
49 399 032
chr7:
100 457 478
Nucleotide changeC>TG>AG>CT>C
Wild typeArg 263Arg 307Thr 89Ile 350
Rare alleleHisGlnSerThr
EvoCon*=Arg=Arg=ThrIle>>Val
CDDPfam 04547
Anoctamin superfamily
Pfam 00864
ATP P2X receptor
Pfam00571
CBS domain
Pfam00324
Amino acid permease domain
1000G allele frequency0.00960.00370.0090.0005
EVS allele frequency0.0260.0140.0340.003
gnomAD allele frequency0.02690.01480.0330.0038
UK Biobank allele frequency0.02770.01770.03360.0049
SIFT score00.010.040.006
REVEL score0.7550.3980.4780.775
  • *EvoCon is an abbreviation of evolutionary conservation, and the data taken from the Human Genome Browser (see figure 2). = means complete conservation between species; >> means the first amino acid is generally conserved with the second been rare; > means that the left amino acid is more common than the right amino acid. CDD is the NCBI Conserved Domain Database, which is part of the NCBI BLAST analysis suite. EVS is the Exome Variant Server. gnomAD is the Genome Aggregation Database. SIFT is the ‘Sorting Intolerant From Tolerant’, a program that predicts whether an amino acid substitution affects protein function, where the score 0 is predicted pathogenic and one is predicted harmless. REVEL is an ensemble scoring programme combining pathogenicity predictions from 18 individual scores, where the score 0 is harmless to one which is pathogenic.

  • CRPS-1, complex regional pain syndrome type 1.