GPR curation for Glycine, serine and threonine metabolism/Valine, leucine, and isoleucine metabolism

[JHL-452b]

Current behavior:

19 genes are discovered to be uncorrelated with their corresponding reactions in Glycine, serine and threonine metabolism/Valine, leucine, and isoleucine metabolism.

Gene	UniProtID	Reaction	GPR	Correlation	Manually check
ENSG00000166840	Q969I3	MAR03750: CoA + H+ + isobutyrylglycine <=> glycine + isobutyryl-CoA	ENSG00000149124 or ENSG00000156689 or ENSG00000166840	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000166840 encodes an acyltransferase that transfers an acyl group to the N-terminus of glutamine, using phenylacetyl-CoA as an acyl donor, catalyzing the reaction of an acyl-CoA and L-glutamine to form N(2)-acyl-L-glutamine, CoA, and H+. In contrast, the reaction provided involves the conversion of isobutyrylglycine to glycine and isobutyryl-CoA, which does not involve glutamine or the specific catalytic activity of the mentioned acyltransferase. Therefore, the gene's function and the specified reaction are unrelated.	No
ENSG00000138796	Q16836	MAR03757: 3-hydroxyisobutyrate + NAD+ --> 2-methyl-3-oxopropanoate + H+ + NADH	ENSG00000072506 or ENSG00000106049 or ENSG00000138796	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000138796 encodes for an enzyme involved in the mitochondrial fatty acid beta-oxidation, specifically catalyzing the conversion of various (3S)-3-hydroxyacyl-CoAs to their corresponding 3-oxoacyl-CoAs along with the production of NADH. The catalytic activities listed are specific to fatty acyl-CoAs of different chain lengths (C4 to C10, including hydroxybutanoyl-CoA and hydroxydecanoyl-CoA). The reaction provided, however, involves the conversion of 3-hydroxyisobutyrate to 2-methyl-3-oxopropanoate, which is not mentioned among the catalytic activities of the enzyme encoded by ENSG00000138796. Therefore, the gene is not pertinent to the provided reaction.	No
ENSG00000166840	Q969I3	MAR03772: 3-methylcrotonoylglycine + CoA + H+ <=> 3-methylcrotonyl-CoA + glycine	ENSG00000149124 or ENSG00000156689 or ENSG00000166840	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000166840 encodes an acyltransferase that transfers an acyl group to the N-terminus of glutamine using an acyl-CoA, such as phenylacetyl-CoA, as a donor. This specific reaction involves the transfer of an acyl group to glutamine to form N(2)-acyl-L-glutamine. However, the provided reaction involves 3-methylcrotonoylglycine and CoA reacting to form 3-methylcrotonyl-CoA and glycine, which is unrelated to the function of the acyltransferase encoded by this gene.	No
ENSG00000156689	Q8WU03	MAR03772: 3-methylcrotonoylglycine + CoA + H+ <=> 3-methylcrotonyl-CoA + glycine	ENSG00000149124 or ENSG00000156689 or ENSG00000166840	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000156689 encodes for a mitochondrial acyltransferase involved in transferring acyl groups to the N-terminus of glycine to form N-acylglycines with various substrates like arachidonoyl-CoA and medium to long-chain acyl-CoAs. However, the specified reaction involves the conversion of 3-methylcrotonoylglycine to 3-methylcrotonyl-CoA and glycine, which does not fall within the catalytic activities or substrate specificities described for this gene. Therefore, the gene's function does not align with the provided reaction.	No
ENSG00000161653	Q8N159	MAR03794: CoA + H+ + N-acetyl-L-alanine <=> acetyl-CoA + alanine	ENSG00000161653	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000161653 is annotated to play a role in the regulation of ureagenesis by producing N-acetylglutamate (NAG), which modulates carbamoylphosphate synthase I (CPS1) activity. Its catalytic activity involves the conversion of acetyl-CoA and L-glutamate to CoA, H+, and N-acetyl-L-glutamate. However, the provided reaction involves CoA, H+, and N-acetyl-L-alanine converting to acetyl-CoA and alanine, which does not match the substrate and product specificity of the gene's function or catalytic activity described.	No
ENSG00000111237	Q9UBQ0	MAR03843: 3-phosphoserine + H2O --> Pi + serine	ENSG00000111237 or ENSG00000146733	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000111237 is involved in processes such as cargo protein trafficking, endosome-to-plasma membrane transport, and retrieval and recycling of transmembrane proteins within the cell, as mediated by various retromer and retriever complexes. However, the reaction specified, which involves the conversion of 3-phosphoserine to serine and inorganic phosphate, is a biochemical reaction likely catalyzed by a phosphatase, not related to the functions described for ENSG00000111237.	No
ENSG00000137106	Q9UBQ7	MAR03856: H+ + methylglyoxal + NADH --> D-lactaldehyde + NAD+	ENSG00000137106	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000137106 encodes an enzyme with hydroxy-pyruvate reductase, glyoxylate reductase, and D-glycerate dehydrogenase activities, which are involved in reducing hydroxypyruvate to D-glycerate, glyoxylate to glycolate, and oxidizing D-glycerate to hydroxypyruvate. However, the reaction in question involves the conversion of methylglyoxal and NADH to D-lactaldehyde and NAD+, which is not listed among the catalytic activities associated with this enzyme. Therefore, the gene and the reaction are not related.	No
ENSG00000158578	P22557	MAR03939: 2-amino-3-oxoadipate + CoA <=> glycine + succinyl-CoA	ENSG00000023330 or ENSG00000158578 or ENSG00000178773	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000158578 encodes an enzyme that catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), along with CoA and CO2 as by-products. This is a different reaction from the one provided, which involves the interconversion of 2-amino-3-oxoadipate and glycine with CoA and succinyl-CoA. Therefore, the gene and the reaction are not related.	No
ENSG00000188676	Q6ZQW0	MAR06924: 4-methyl-2-oxopentanoate + O2 --> beta-hydroxy-beta-methylbutyrate + CO2	ENSG00000179148 or ENSG00000179477 or ENSG00000188676	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000188676 encodes for an enzyme that catalyzes the conversion of L-tryptophan to N-formyl-L-kynurenine, which is the first and rate-limiting step in the kynurenine pathway of tryptophan catabolism. The provided reaction involves the conversion of 4-methyl-2-oxopentanoate to beta-hydroxy-beta-methylbutyrate and CO2, which is unrelated to the tryptophan metabolism pathway. Therefore, the gene does not correspond to the reaction described.	No
ENSG00000121039	Q8IZV5	MAR06925: 4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+	ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000121039 encodes for a retinol dehydrogenase enzyme that specifically catalyzes the conversion of all-trans-retinol to all-trans-retinal utilizing NADP+. The reaction described involves the conversion of 4-methyl-2-oxopentanoate and NADH to alpha-hydroxyisocaproic acid and NAD+, which is a completely different substrate and cofactor system. Hence, the gene's annotated function is unrelated to the reaction given.	No
ENSG00000240857	Q9HBH5	MAR06925: 4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+	ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000240857 encodes for a retinol dehydrogenase, which catalyzes reactions involving the conversion of various forms of retinol to retinals with a preference for NADP as a cofactor, as evidenced by the specific reactions listed towards different retinol isomers. The reactions catalyzed involve substrates like all-trans-retinol, 9-cis-retinol, and 11-cis-retinol. In contrast, the provided reaction involves the conversion of 4-methyl-2-oxopentanoate with NADH to alpha-hydroxyisocaproic acid, a type of reaction that does not involve retinol or its derivatives and uses NADH instead of NADP. Therefore, the gene's annotated function and catalytic activities do not correlate with the provided reaction.	No
ENSG00000160439	Q8NBN7	MAR06925: 4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+	ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000160439 encodes a retinol dehydrogenase enzyme that specifically oxidizes all-trans-retinol and reduces all-trans-retinal with a clear preference for NADP, and has no activity toward steroids. However, the reaction provided involves the conversion of 4-methyl-2-oxopentanoate and NADH to alpha-hydroxyisocaproic acid and NAD+, which does not involve retinol or retinal and uses NADH instead of NADP. Therefore, the gene and the provided reaction are not related.	No
ENSG00000176387	P80365	MAR06925: 4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+	ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000176387 encodes an enzyme that catalyzes the conversion of 11beta-hydroxyglucocorticoids and 11beta-hydroxyandrogens into their respective 11-oxosteroids in the presence of NAD(+), specifically involved in the metabolism of cortisol, corticosterone, and androgens like testosterone. However, the reaction provided involves the conversion of 4-methyl-2-oxopentanoate to alpha-hydroxyisocaproic acid with NADH and NAD+ participation, which is not mentioned in the catalytic activities or functions attributed to the gene ENSG00000176387. Thus, the gene's annotated activities do not relate to the specified reaction.	No
ENSG00000139988	Q96NR8	MAR06925: 4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+	ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000139988 encodes for a retinoid dehydrogenase/reductase enzyme that specifically uses NADP as a cofactor and predominantly catalyzes the oxidation and reduction of various forms of retinal and lipid peroxidation products. The provided reaction involves the conversion of 4-methyl-2-oxopentanoate to alpha-hydroxyisocaproic acid using NADH, not NADP. Additionally, the enzyme described in the gene function does not exhibit activity towards the substrates involved in the provided reaction.	No
ENSG00000087076	Q9BPX1	MAR06925: 4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+	ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000087076 encodes an enzyme with NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity, which primarily converts oestradiol to oestrone and acts on 5-androstene-3-beta,17-beta-diol. The reactions annotated for this enzyme involve the conversion of 17beta-estradiol to estrone and androst-5-en-3beta,17beta-diol to 3beta-hydroxyandrost-5-en-17-one. However, the reaction provided (4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+) does not involve substrates or products that are related to the catalytic activities described for the gene ENSG00000087076. Therefore, the gene is not related to the specified reaction.	No
ENSG00000198610	P17516	MAR06925: 4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+	ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000198610 encodes a cytosolic aldo-keto reductase that primarily catalyzes the NADH and NADPH-dependent reduction of various ketosteroids to hydroxysteroids. Its functions include transforming 5-alpha-dihydrotestosterone into less active forms, reducing estrone to estradiol with low efficiency, and metabolizing a broad spectrum of steroids and other substances like chlordecone. The primary reactions it catalyzes are specific to steroid metabolism and involve substrates such as 5alpha-dihydrotestosterone, estrone, progesterone, androsterone, and testosterone. In contrast, the provided reaction involves 4-methyl-2-oxopentanoate and alpha-hydroxyisocaproic acid, which are not related to the substrates or products typically acted upon by the enzyme encoded by this gene. Thus, the gene is not relevant to the reaction provided.	No
ENSG00000099377	Q9H2F3	MAR06925: 4-methyl-2-oxopentanoate + H+ + NADH <=> alpha-hydroxyisocaproic acid + NAD+	ENSG00000087076 or ENSG00000099377 or ENSG00000100867 or ENSG00000109854 or ENSG00000121039 or ENSG00000138400 or ENSG00000139988 or ENSG00000145439 or ENSG00000159692 or ENSG00000160439 or ENSG00000164039 or ENSG00000167733 or ENSG00000170426 or ENSG00000170786 or ENSG00000176387 or ENSG00000183921 or ENSG00000184860 or ENSG00000186153 or ENSG00000187134 or ENSG00000197894 or ENSG00000198074 or ENSG00000198189 or ENSG00000198610 or ENSG00000204228 or ENSG00000227471 or ENSG00000240857	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000099377 encodes an enzyme that is involved in the metabolism of specific hydroxylated sterols and does not metabolize various C(19/21) steroids. It plays a crucial role in hormonal steroid biosynthesis and bile acid synthesis. The provided reaction involves the conversion of 4-methyl-2-oxopentanoate to alpha-hydroxyisocaproic acid, which is not related to the hydroxylated sterol substrates or the catalytic activities associated with this gene. Therefore, the gene is not relevant to the reaction provided.	No
ENSG00000116882	Q9NYQ3	MAR07703: glycolate + O2 --> glyoxalate + H2O2	ENSG00000101323 or ENSG00000116882	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. According to the function and catalytic activity annotations of the gene ENSG00000116882, the gene encodes an oxidase that specifically catalyzes the oxidation of medium and long-chain hydroxyacids such as 2-hydroxyhexadecanoate and 2-hydroxyoctanoate to the corresponding 2-oxoacids, producing H2O2 in the process. Importantly, the gene is noted to be inactive on glycolate and glyoxylate. The reaction provided involves the oxidation of glycolate to glyoxalate and does not correspond to the substrate specificity of the gene ENSG00000116882. Therefore, the gene is not relevant to this reaction.	No
ENSG00000166800	Q6ZMR3	MAR11476: 2-oxo-3-methylvalerate + H+ + NADH <=> NAD+ + 2-Hydroxy-3-Methyl-Valerate	ENSG00000111716 or ENSG00000134333 or ENSG00000166796 or ENSG00000166800 or ENSG00000166816 or ENSG00000171989	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000166800 encodes an enzyme that catalyzes the interconversion of L-lactate and pyruvate with NAD(+) as a coenzyme. However, the reaction provided involves the conversion of 2-oxo-3-methylvalerate to 2-Hydroxy-3-Methyl-Valerate using NADH, which is different from the lactate to pyruvate conversion that the gene's enzyme catalyzes. Therefore, the gene ENSG00000166800 is not relevant to the provided reaction.	No

[feiranl]

LGTM! Please go ahead to make changes. In summary, we removed several wrongly associated genes for the reactions