5alpha-pregnan-3beta,20beta-diol monosulfate (1) to 5alpha-pregnan-3beta,20alpha-diol monosulfate (2)

Numerator 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

Denominator Metabolite

Metabolite Accession: GCST90199854
Name: 5alpha-pregnan-3beta,20alpha-diol monosulfate (2)
Hmdb Id: NA
Super Pathway: NA
Sub Pathway: NA
Inchikey: NA

Associated Genomic Regions

Region: rs7475281

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Clumped rQTL variant

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SNP Summary

Chr:
10
Beta (Ratio):
-0.235
Position:
5252902
SE (Ratio):
0.016
Effect Allele:
C
Z-score (Ratio):
-14.901
Reference Allele:
A
-log10(P):
-113.945
MAF:
0.149
Beta (Num):
-0.124
Novel Locus:
Yes ✔️
SE (Num):
0.022
Beta (Den):
0.111
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):
-0.233
Position:
5258450
SE (Ratio):
0.016
Effect Allele:
T
Z-score (Ratio):
-14.802
Reference Allele:
G
-log10(P):
-112.480
MAF:
0.149
Beta (Num):
-0.124
Novel Locus:
Yes ✔️
SE (Num):
0.022
Beta (Den):
0.109
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):
-0.233
Position:
5262965
SE (Ratio):
0.016
Effect Allele:
C
Z-score (Ratio):
-14.764
Reference Allele:
A
-log10(P):
-111.906
MAF:
0.149
Beta (Num):
-0.124
Novel Locus:
Yes ✔️
SE (Num):
0.022
Beta (Den):
0.109
SE (Den):
0.022
No CNV overlap
rQTL cluster:
285
Reaction Distance:
NA
Closest Genes:
AKR1C4 AKR1CL1 AKR1C3 UCN3 TUBAL3

Region: rs62129966

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Clumped rQTL variant

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SNP Summary

Chr:
19
Beta (Ratio):
-0.222
Position:
48374950
SE (Ratio):
0.015
Effect Allele:
A
Z-score (Ratio):
-14.589
Reference Allele:
C
-log10(P):
-109.336
MAF:
0.160
Beta (Num):
-0.058
Novel Locus:
No
SE (Num):
0.021
Beta (Den):
0.163
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:

Steroid hormone biosynthesis, Progesterone metabolism.2[1], 6[2]

Denominator Metabolite Explanation:

Steroid hormone biosynthesis, Progesterone metabolism.2[1], 6[2]

Ratio Explanation:

The ratio reflects the 20-ketosteroid reductase activity of AKR1C4, which stereospecifically reduces a common pregnane precursor to either 20beta or 20alpha-diol forms.7[1], 6[2], 8[3]

Ratio Evidence:

canonical reaction catalyzed by the enzyme

Gene Ratio Phenotype Relationship:

Genetic variation in AKR1C4 and SULT2A1 alters steroid and bile acid metabolism.1[1], 9[2], 10[3], 5[4] This dysregulation, reflected by the pregnanediol monosulfate ratio, can lead to cholesterol supersaturation in bile, promoting the formation of gallstones (cholelithiasis).11[5], 12[6], 13[7]

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