5alpha-pregnan-3beta,20alpha-diol disulfate to 5alpha-pregnan-3beta,20beta-diol monosulfate (1)

Numerator Metabolite

Structure of 5alpha-pregnan-3beta,20alpha-diol disulfate
Metabolite Accession: GCST90199838
Name: 5alpha-pregnan-3beta,20alpha-diol disulfate
Hmdb Id: HMDB0094650
Super Pathway: NA
Sub Pathway: NA
Inchikey: LSQGWMYMIHQKSA

Denominator Metabolite

Structure of 5alpha-pregnan-3beta,20beta-diol monosulfate (1)
Metabolite Accession: GCST90199853
Name: 5alpha-pregnan-3beta,20beta-diol monosulfate (1)
Hmdb Id: HMDB0240580
Super Pathway: NA
Sub Pathway: NA
Inchikey: NOGKXXMAHGCQBS

Associated Genomic Regions

Region: rs1832007

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Clumped rQTL variant

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SNP Summary

Chr:
10
Beta (Ratio):
0.227
Position:
5254847
SE (Ratio):
0.017
Effect Allele:
G
Z-score (Ratio):
13.098
Reference Allele:
A
-log10(P):
-88.588
MAF:
0.150
Beta (Num):
0.103
Novel Locus:
Yes ✔️
SE (Num):
0.022
Beta (Den):
-0.123
SE (Den):
0.022
No CNV overlap
rQTL cluster:
76
Reaction Distance:
NA
Closest Genes:
AKR1C4 AKR1CL1 AKR1C3 UCN3 TUBAL3

Region: rs4881413

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Clumped rQTL variant

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SNP Summary

Chr:
10
Beta (Ratio):
0.227
Position:
5258450
SE (Ratio):
0.017
Effect Allele:
T
Z-score (Ratio):
13.080
Reference Allele:
G
-log10(P):
-88.350
MAF:
0.150
Beta (Num):
0.103
Novel Locus:
Yes ✔️
SE (Num):
0.022
Beta (Den):
-0.124
SE (Den):
0.022
No CNV overlap
rQTL cluster:
217
Reaction Distance:
NA
Closest Genes:
AKR1C4 AKR1CL1 AKR1C3 UCN3 TUBAL3

Region: rs2151901

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Clumped rQTL variant

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SNP Summary

Chr:
10
Beta (Ratio):
0.226
Position:
5262965
SE (Ratio):
0.017
Effect Allele:
C
Z-score (Ratio):
13.062
Reference Allele:
A
-log10(P):
-88.106
MAF:
0.150
Beta (Num):
0.102
Novel Locus:
Yes ✔️
SE (Num):
0.022
Beta (Den):
-0.124
SE (Den):
0.022
No CNV overlap
rQTL cluster:
285
Reaction Distance:
NA
Closest Genes:
AKR1C4 AKR1CL1 AKR1C3 UCN3 TUBAL3

Region: rs112344408

Click a 'Plot' button in the tables to the right to view a locus plot here.

Clumped rQTL variant

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SNP Summary

Chr:
10
Beta (Ratio):
-0.232
Position:
101600737
SE (Ratio):
0.026
Effect Allele:
A
Z-score (Ratio):
-8.901
Reference Allele:
C
-log10(P):
-42.040
MAF:
0.060
Beta (Num):
-0.163
Novel Locus:
Yes ✔️
SE (Num):
0.032
Beta (Den):
0.069
SE (Den):
0.033
No CNV overlap
rQTL cluster:
68
Reaction Distance:
NA
Closest Genes:
ABCC2 DNMBP CUTC COX15 ENTPD7

LLM Analysis

Numerator Metabolite Explanation:

Steroid sulfation9[1], 10[2]

Denominator Metabolite Explanation:

Steroid sulfation11[1], 12[2]

Ratio Explanation:

The ratio likely reflects the relative activity of sulfotransferases and potentially AKR1C4, indicating a balance between the formation and clearance of different pregnanediol sulfate isomers.

Ratio Evidence:

metabolites not in a pathway but enzyme catalyzes one metabolite

Gene Ratio Phenotype Relationship:

Altered AKR1C4 and SULT2A1 activity likely modifies steroid and bile acid metabolism.5[1], 13[2], 14[3] This dysregulation, particularly in bile acid sulfation, is a known risk factor for cholelithiasis, providing a plausible link between the genetic factors and the observed phenotype.15[4], 16[5], 17[6]

Phenotype Driver:

Gene-centric:AKR1C4

Downloads

Download the full rQTL summary statistics file for this metabolite ratio. Data contains the loci listed here. For each SNP (chromosome, effect_allele, reference_allele, pos_name, position) these columns contain the summary statistics of the ratio (beta, pgain, pval, se, z), the numerator metabolite (beta_1, pval_1, n_iids_1, effect_allele_frequency_1, se_1, z_1) and the denominator metabolite (beta_2, pval_2, n_iids_2, effect_allele_frequency_2, se_2, z_2)

Download rQTL Data