5alpha-pregnan-3beta,20alpha-diol disulfate to pregnanediol-3-glucuronide

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 pregnanediol-3-glucuronide
Metabolite Accession: GCST90199917
Name: pregnanediol-3-glucuronide
Hmdb Id: HMDB0010318
Super Pathway: NA
Sub Pathway: NA
Inchikey: ZFFFJLDTCLJDHL

Associated Genomic Regions

Region: rs3750572

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Clumped rQTL variant

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SNP Summary

Chr:
10
Beta (Ratio):
0.152
Position:
5247376
SE (Ratio):
0.020
Effect Allele:
C
Z-score (Ratio):
7.581
Reference Allele:
T
-log10(P):
-31.007
MAF:
0.149
Beta (Num):
0.102
Novel Locus:
Yes ✔️
SE (Num):
0.022
Beta (Den):
-0.050
SE (Den):
0.022
No CNV overlap
rQTL cluster:
76
Reaction Distance:
NA
Closest Genes:
AKR1C4 AKR1CL1 AKR1C3 UCN3 AKR1C2

Region: rs62129966

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Clumped rQTL variant

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SNP Summary

Chr:
19
Beta (Ratio):
-0.389
Position:
48374950
SE (Ratio):
0.019
Effect Allele:
A
Z-score (Ratio):
-20.247
Reference Allele:
C
-log10(P):
-208.209
MAF:
0.161
Beta (Num):
-0.277
Novel Locus:
No
SE (Num):
0.021
Beta (Den):
0.112
SE (Den):
0.021
No CNV overlap
rQTL cluster:
7
Reaction Distance:
NA
Closest Genes:
SULT2A1 TPRX2P CRX TPRX1 SEPW1

LLM Analysis

Numerator Metabolite Explanation:

Progestin and pregnenolone metabolism, steroid sulfation.6[1], 7[2], 8[3]

Denominator Metabolite Explanation:

Steroid glucuronidation pathway.9[1], 10[2], 11[3], 12[4]

Ratio Explanation:

The ratio reflects the balance between two major steroid hormone inactivation pathways, sulfation (numerator) and glucuronidation (denominator), influenced by AKR1C4 and SULT2A1 enzyme activities.1[1], 4[2], 13[3]

Ratio Evidence:

metabolites not in a pathway but enzyme catalyzes one metabolite

Gene Ratio Phenotype Relationship:

Genetic variants in SULT2A1 and AKR1C4 alter steroid and bile acid metabolism.1[1], 4[2], 14[3] This dysregulation, reflected in the pregnanediol sulfate-to-glucuronide ratio, affects bile composition and is associated with an increased risk of cholelithiasis, as observed in genome-wide association studies.15[4], 16[5]

Phenotype Driver:

Gene-centric:SULT2A1

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