kynurenate to xanthurenate

Numerator Metabolite

Metabolite Accession: GCST90200454

Name: kynurenate

Hmdb Id: HMDB0000715

Super Pathway: NA

Sub Pathway: NA

Inchikey: HCZHHEIFKROPDY

Denominator Metabolite

Metabolite Accession: GCST90199626

Name: xanthurenate

Hmdb Id: HMDB0000881

Super Pathway: NA

Sub Pathway: NA

Inchikey: FBZONXHGGPHHIY

Associated Genomic Regions

Region: rs61825638

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Clumped rQTL variant

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SNP Summary

Chr:

Beta (Ratio):

0.356

Position:

241713402

SE (Ratio):

0.016

Effect Allele:

Z-score (Ratio):

22.203

Reference Allele:

-log10(P):

-249.813

MAF:

0.246

Beta (Num):

0.336

Novel Locus:

SE (Num):

0.017

Beta (Den):

-0.020

SE (Den):

0.018

No CNV overlap

rQTL cluster:

227

Reaction Distance:

3.0

Closest Genes:

KMO FH OPN3 CHML WDR64

Region: rs12924700

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Clumped rQTL variant

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SNP Summary

Chr:

Beta (Ratio):

0.226

Position:

58777096

SE (Ratio):

0.026

Effect Allele:

Z-score (Ratio):

8.798

Reference Allele:

-log10(P):

-41.119

MAF:

0.079

Beta (Num):

0.178

Novel Locus:

SE (Num):

0.028

Beta (Den):

-0.048

SE (Den):

0.029

No CNV overlap

rQTL cluster:

Reaction Distance:

3.0

Closest Genes:

GOT2 SLC38A7 CNOT1 SETD6 NDRG4

Missense Variants in LD (with rs12924700)

Variant	Gene	LD (R²)	Location	Consequence
rs6979	ACD	0.24	16:67691668	Missense Variant
rs6979	ACD	0.24	16:67691668	Missense Variant

eQTL Colocalization

Exposure Gene	P(alpha)	P(IVW)	Coloc H4	Coloc (SuSiE)
SLC7A6	0.116	0.001	0.978	0.007
TRADD	0.376	0.003	4.72e-10	0.989
E2F4	0.572	NA	0.015	0.989
ACD	0.760	5.99e-04	2.19e-23	0.990
FAM65A	0.941	0.025	7.94e-25	0.997

pQTL Colocalization

Exposure Protein	P(alpha)	P(IVW)	Coloc H4	Coloc (SuSiE)	Plot
SMPD3	0.006	9.53e-30	0.991	NA

GTEx eQTL Colocalization

Tissue	Exposure Gene	P(alpha)	P(IVW)	Coloc H4	Coloc (SuSiE)
Heart Left Ventricle	NFATC3	1.10e-05	5.43e-21	0.985	0.969
Whole Blood	SLC7A6	1.54e-05	1.18e-13	0.290	1.000
Thyroid	PLA2G15	3.73e-05	1.89e-25	0.992	0.999
Esophagus Mucosa	PLA2G15	5.01e-05	1.89e-25	0.990	0.976
Small Intestine Terminal Ileum	NFATC3	5.20e-05	NA	0.942	NA
Esophagus Gastroesophageal Junction	PRMT7	6.32e-05	5.23e-14	6.04e-14	1.000
Artery Tibial	PRMT7	6.59e-05	1.18e-13	4.51e-14	1.000
Artery Tibial	PLA2G15	6.77e-05	1.89e-25	0.932	0.860
Esophagus Gastroesophageal Junction	NFATC3	1.14e-04	4.32e-15	0.005	1.000
Nerve Tibial	PLA2G15	1.31e-04	5.80e-30	0.997	0.994
Esophagus Muscularis	PLA2G15	1.36e-04	3.97e-23	0.989	0.978
Esophagus Muscularis	PRMT7	1.38e-04	1.37e-13	2.77e-14	1.000
Breast Mammary Tissue	PLA2G15	1.98e-04	NA	0.984	0.968
Brain Cortex	SMPD3	2.26e-04	NA	0.802	NA
Brain Nucleus Accumbens Basal Ganglia	NFATC3	2.47e-04	NA	0.944	NA
Colon Sigmoid	PRMT7	3.20e-04	1.37e-13	3.80e-14	1.000
Adrenal Gland	PLA2G15	3.28e-04	NA	0.991	0.987
Thyroid	SLC7A6	3.88e-04	1.23e-17	3.06e-10	1.000
Spleen	NFATC3	3.91e-04	6.32e-09	0.912	1.000
Heart Atrial Appendage	NFATC3	4.72e-04	NA	0.901	NA
Pituitary	NFATC3	4.76e-04	1.31e-11	0.705	0.997
Spleen	SMPD3	4.90e-04	NA	0.811	NA
Thyroid	PRMT7	5.29e-04	0.057	3.79e-14	1.000
Colon Sigmoid	NFATC3	5.70e-04	3.88e-15	2.62e-07	1.000
Nerve Tibial	NFATC3	6.00e-04	9.55e-10	2.10e-08	1.000
Colon Transverse	SLC7A6	6.15e-04	1.12e-14	0.897	1.000
Nerve Tibial	PRMT7	8.58e-04	7.58e-08	1.61e-14	1.000
Colon Transverse	NFATC3	8.75e-04	1.89e-25	0.961	1.000
Adipose Visceral Omentum	PLA2G15	9.65e-04	NA	0.992	0.986
Esophagus Mucosa	NFATC3	0.001	6.17e-10	0.840	NA
Brain Nucleus Accumbens Basal Ganglia	PRMT7	0.001	2.20e-13	2.61e-05	1.000
Adipose Subcutaneous	PLA2G15	0.001	NA	0.948	NA
Artery Coronary	PLA2G15	0.002	NA	0.890	NA
Thyroid	SLC7A6OS	0.002	NA	0.886	NA
Esophagus Muscularis	NFATC3	0.002	9.55e-10	0.007	1.000
Artery Coronary	PRMT7	0.002	7.58e-08	3.39e-09	1.000
Whole Blood	NFATC3	0.003	5.43e-21	0.297	0.999
Brain Caudate Basal Ganglia	NFATC3	0.003	NA	0.835	NA
Heart Left Ventricle	PLA2G15	0.003	NA	0.872	NA
Pancreas	PRMT7	0.003	1.12e-14	5.19e-13	1.000
Nerve Tibial	SLC7A6	0.003	6.23e-11	0.950	0.996
Adipose Visceral Omentum	NFATC3	0.003	9.55e-10	0.314	0.993
Colon Transverse	PRMT7	0.003	1.37e-13	3.79e-14	1.000
Stomach	PRMT7	0.003	1.37e-13	6.77e-14	1.000
Skin Not Sun Exposed Suprapubic	PRMT7	0.003	5.23e-14	5.52e-14	1.000
Esophagus Mucosa	PRMT7	0.003	6.79e-13	2.02e-14	1.000
Adipose Subcutaneous	PRMT7	0.003	7.58e-08	1.89e-14	1.000
Lung	SLC7A6	0.003	3.88e-15	6.55e-04	1.000
Pancreas	NFATC3	0.004	NA	0.969	0.954
Breast Mammary Tissue	NFATC3	0.004	2.20e-13	0.927	0.998
Muscle Skeletal	SLC7A6	0.005	NA	0.976	NA
Spleen	PRMT7	0.005	1.37e-13	2.19e-11	1.000
Brain Cortex	PRMT7	0.006	7.58e-08	9.27e-08	1.000
Breast Mammary Tissue	PRMT7	0.006	5.23e-14	2.26e-11	1.000
Lung	NFATC3	0.006	1.31e-11	0.002	1.000
Heart Atrial Appendage	PLA2G15	0.007	NA	0.955	NA
Skin Sun Exposed Lower Leg	PRMT7	0.007	5.23e-14	9.53e-14	1.000
Lung	PRMT7	0.008	0.749	7.88e-17	1.000
Brain Cerebellum	NFATC3	0.008	5.43e-21	0.984	0.977
Skin Not Sun Exposed Suprapubic	NFATC3	0.008	6.17e-10	0.009	1.000
Liver	PRMT7	0.009	1.37e-13	1.77e-09	1.000
Skin Sun Exposed Lower Leg	PLA2G15	0.013	7.27e-12	5.24e-05	1.000
Thyroid	NFATC3	0.015	6.32e-09	4.81e-09	1.000
Adipose Visceral Omentum	PRMT7	0.015	1.37e-13	5.01e-14	1.000
Artery Aorta	PRMT7	0.016	7.58e-08	1.15e-17	1.000
Pituitary	PRMT7	0.018	1.12e-14	8.78e-07	1.000
Adipose Subcutaneous	NFATC3	0.019	9.55e-10	2.47e-05	1.000
Skin Sun Exposed Lower Leg	NFATC3	0.019	6.32e-09	0.990	0.172
Brain Caudate Basal Ganglia	PRMT7	0.031	2.31e-14	4.24e-06	1.000
Testis	PLA2G15	0.040	1.18e-13	0.004	0.998
Artery Tibial	NFATC3	0.044	0.359	1.01e-15	1.000
Whole Blood	PRMT7	0.045	0.670	1.27e-13	1.000
Small Intestine Terminal Ileum	PRMT7	0.051	1.37e-13	2.58e-07	1.000
Vagina	PRMT7	0.052	2.20e-13	0.015	1.000
Brain Cerebellum	PRMT7	0.057	0.262	1.13e-05	0.996
Prostate	PRMT7	0.058	5.23e-14	4.47e-09	1.000
Artery Aorta	NFATC3	0.070	0.308	6.89e-08	0.999
Muscle Skeletal	PRMT7	0.078	6.81e-15	2.20e-12	1.000
Brain Cerebellar Hemisphere	PRMT7	0.165	0.255	8.71e-06	0.998
Brain Frontal Cortex Ba9	PRMT7	0.210	0.316	1.95e-04	0.999
Whole Blood	DUS2	0.327	0.316	9.89e-24	1.000

Region: rs887829

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Clumped rQTL variant

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SNP Summary

Chr:

Beta (Ratio):

-0.167

Position:

234668570

SE (Ratio):

0.015

Effect Allele:

Z-score (Ratio):

-11.285

Reference Allele:

-log10(P):

-66.331

MAF:

0.324

Beta (Num):

-0.008

Novel Locus:

SE (Num):

0.016

Beta (Den):

0.160

SE (Den):

0.016

No CNV overlap

rQTL cluster:

138

Reaction Distance:

3.0

Closest Genes:

UGT1A8 UGT1A9 UGT1A3 UGT1A5 UGT1A7

LLM Analysis

Numerator Metabolite Explanation:

Tryptophan metabolism4^[1]

Denominator Metabolite Explanation:

Tryptophan metabolism5^[1], 6^[2]

Ratio Explanation:

The ratio reflects the relative activity of enzymes diverting kynurenine towards either kynurenate or xanthurenate, influenced by KMO activity.1^[1], 5^[2], 7^[3]

Ratio Evidence:

reaction where the ratio is shared through a pathway

Gene Ratio Phenotype Relationship:

Reduced KMO activity, indicated by eQTL colocalization, likely shunts the kynurenine pathway towards kynurenate and away from downstream metabolites. This alteration in tryptophan metabolism is associated with an increased risk of cholelithiasis and type 2 diabetes.8^[1], 1^[2], 9^[3], 10^[4]

Phenotype Driver:

Gene-centric:KMO

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