GPR curation for Carnitine shuttle (1)

[JHL-452b]

Current behavior:

27 genes are discovered to be uncorrelated with their corresponding reactions in Carnitine shuttle.

Gene	UniProtID	Reaction	GPR	Correlation	Manually check
ENSG00000169169	Q8TCG5	MAR02768: (11Z,14Z)-eicosadienoyl-CoA + L-carnitine <=> CoA + eicosadienoylcarnitine	ENSG00000110090 or ENSG00000169169 or ENSG00000205560	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000169169 encodes a palmitoyl thioesterase that modulates the trafficking of the glutamate receptor AMPAR by depalmitoylating GRIA1 and regulates SACM1L phosphatidylinositol-3-phosphatase activity. Its catalytic activity involves the hydrolysis of S-hexadecanoyl-L-cysteinyl-[protein] to produce hexadecanoate and L-cysteinyl-[protein]. The provided reaction involves (11Z,14Z)-eicosadienoyl-CoA and L-carnitine, resulting in the formation of eicosadienoylcarnitine, which is unrelated to the functions or catalytic activity of the gene product from ENSG00000169169.	No
ENSG00000197119	Q8N8R3	MAR02783: L-carnitine + malonyl-carnitine <=> L-carnitine + malonyl-carnitine	ENSG00000178537 or ENSG00000197119	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197119 encodes a mitochondrial transporter involved in the transport of arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. The provided reaction involves L-carnitine and malonyl-carnitine, which are not substrates transported by this gene's product. Thus, the gene and the reaction are unrelated.	No
ENSG00000169169	Q8TCG5	MAR02924: (9Z,12Z,15Z,18Z)-tetracosatetraenoyl-CoA + L-carnitine <=> (9Z,12Z,15Z,18Z)-tetracosatetraenoylcarnitine + CoA	ENSG00000110090 or ENSG00000169169 or ENSG00000205560	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000169169 encodes a protein involved in palmitoyl thioesterase activity, specifically depalmitoylating proteins such as GRIA1. It is associated with processes like AMPAR trafficking and systemic energy homeostasis. However, the provided reaction involves the conversion between tetracosatetraenoyl-CoA and tetracosatetraenoylcarnitine, a process related to enzymatic activity involving L-carnitine and fatty acid metabolism, which does not align with the functional description or catalytic activity of the gene's encoded protein.	No
ENSG00000197119	Q8N8R3	MAR02592: L-carnitine + O-acetylcarnitine --> L-carnitine + O-acetylcarnitine	ENSG00000178537 or ENSG00000197119	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000197119 encodes a mitochondrial transporter involved in the transport of basic amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine, but it explicitly does not transport carnitine nor acylcarnitines, as stated in the reference (PubMed:24652292). The reaction provided involves L-carnitine and O-acetylcarnitine, which are not substrates for the transporter encoded by this gene. Therefore, the gene is not related to the reaction involving carnitine and acetylcarnitine.	No
ENSG00000197119	Q8N8R3	MAR02596: L-carnitine + O-propanoylcarnitine <=> L-carnitine + O-propanoylcarnitine	ENSG00000178537 or ENSG00000197119	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000197119 functions as a mitochondrial transporter of various amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. It does not transport carnitine or acylcarnitines. The described reaction involves the exchange of L-carnitine with O-propanoylcarnitine, which is not among the substrates or functions of the gene's encoded protein. Therefore, there is no relevance between the gene and the provided reaction.	No
ENSG00000149742	Q8IVM8	MAR02600: L-carnitine + malonyl-carnitine --> L-carnitine + malonyl-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000149742 encodes for a sodium-independent organic anion transporter that has high specificity for sulfated conjugates of xenobiotics and steroid hormones such as estrone 3-sulfate and dehydroepiandrosterone sulfate. Its catalytic activities involve the exchange of these sulfated organic compounds with short-chain fatty acids like butanoate, propanoate, and pentanoate. However, the provided reaction involves L-carnitine and malonyl-carnitine, which are not substrates of the transporter specified by this gene. Therefore, the gene is not relevant to the reaction involving L-carnitine and malonyl-carnitine.	No
ENSG00000197119	Q8N8R3	MAR02600: L-carnitine + malonyl-carnitine --> L-carnitine + malonyl-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197119 encodes a mitochondrial transporter that specifically transports basic amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. It does not transport carnitine or acylcarnitines, as evidenced by the references provided. The reaction described involves the exchange of L-carnitine with malonyl-carnitine, which is not related to the transport activities of the gene product. Therefore, the gene and the reaction are not connected based on the defined function and catalytic activities of the gene product.	No
ENSG00000149742	Q8IVM8	MAR02603: dodecanoylcarnitine + L-carnitine <=> dodecanoylcarnitine + L-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000149742 functions as a sodium-independent organic anion transporter with high specificity for sulfated conjugates like estrone 3-sulfate and dehydroepiandrosterone sulfate, and can transport compounds such as pravastatin. The gene mediates exchanges involving short-chain fatty acids like butanoate, propanoate, and pentanoate, based on substantiated catalytic activities. However, the provided reaction involving dodecanoylcarnitine and L-carnitine does not align with the gene's known functions or catalytic activities, thus rendering the gene irrelevant to the reaction.	No
ENSG00000197119	Q8N8R3	MAR02603: dodecanoylcarnitine + L-carnitine <=> dodecanoylcarnitine + L-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197119 is a mitochondrial transporter of basic amino acids such as arginine, lysine, and others, facilitating their transport into mitochondria. The reactions it catalyzes involve the exchange or uniport of these basic amino acids. In contrast, the provided reaction involves dodecanoylcarnitine and L-carnitine, which are not substrates for the transporter identified in the gene's function. Therefore, the gene's annotated functions do not align with the described carnitine-related reaction.	No
ENSG00000149742	Q8IVM8	MAR02606: L-carnitine + tridecanoylcarnitine <=> L-carnitine + tridecanoylcarnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000149742 encodes for a sodium-independent organic anion transporter, which specifically transports sulfated conjugates of xenobiotics and steroid hormones, such as estrone 3-sulfate and dehydroepiandrosterone sulfate, and is activated by short-chain fatty acids. The reactions catalyzed by this gene involve the exchange of these sulfated organic components against short-chain fatty acids. However, the reaction provided involves the interconversion of L-carnitine and tridecanoylcarnitine, which does not match any of the catalytic activities or substrate specificities of the gene ENSG00000149742. Therefore, the gene is not related to the provided reaction.	No
ENSG00000197119	Q8N8R3	MAR02606: L-carnitine + tridecanoylcarnitine <=> L-carnitine + tridecanoylcarnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197119 encodes a mitochondrial transporter that facilitates the transport of various amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine, and does not transport carnitine nor acylcarnitines. The reaction provided involves L-carnitine and tridecanoylcarnitine, which are not substrates for the transporter encoded by this gene. Therefore, the gene and the reaction are not related.	No
ENSG00000149742	Q8IVM8	MAR02609: L-carnitine + tetradecanoylcarnitine <=> L-carnitine + tetradecanoylcarnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000149742 encodes a sodium-independent organic anion transporter that exhibits high specificity for sulfated conjugates of xenobiotics and steroid hormones and is involved in the transport of estrone 3-sulfate, dehydroepiandrosterone sulfate, and statin pravastatin. The catalytic activities indicated involve the exchange of sulfated organic components against short-chain fatty acids such as butanoate, propanoate, and pentanoate. However, the provided reaction (L-carnitine + tetradecanoylcarnitine <=> L-carnitine + tetradecanoylcarnitine) does not involve these substrates or similar catalytic functions, making the gene irrelevant to this reaction.	No
ENSG00000197119	Q8N8R3	MAR02609: L-carnitine + tetradecanoylcarnitine <=> L-carnitine + tetradecanoylcarnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000197119 functions as a mitochondrial transporter for basic amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. It does not transport carnitine nor acylcarnitines, as supported by multiple studies. The provided reaction involves L-carnitine and tetradecanoylcarnitine, substrates that the gene's transporter activity does not affect. Therefore, the gene's function is not related to the provided reaction.	No
ENSG00000197119	Q8N8R3	MAR02612: L-carnitine + tetradecenoylcarnitine(5) <=> L-carnitine + tetradecenoylcarnitine(5)	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197119 encodes a mitochondrial transporter involved in the transport of basic amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. The transporter does not transport carnitine nor acylcarnitines. The provided reaction involves L-carnitine and tetradecenoylcarnitine, which are not substrates for the transporter encoded by this gene. Therefore, there is no relevant connection between the gene's function and the provided reaction.	No
ENSG00000149742	Q8IVM8	MAR02616: L-carnitine + tetradecenoylcarnitine(7) <=> L-carnitine + tetradecenoylcarnitine(7)	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000149742 codes for a sodium-independent organic anion transporter involved in the exchange of sulfated conjugates and short-chain fatty acids such as propanoate, butanoate, and pentanoate, including compounds like estrone 3-sulfate and dehydroepiandrosterone sulfate. The reaction provided (L-carnitine + tetradecenoylcarnitine(7) <=> L-carnitine + tetradecenoylcarnitine(7)) does not involve any of these substrates or mechanisms. Therefore, the gene and the described reaction are not related based on substrate specificity and function.	No
ENSG00000197119	Q8N8R3	MAR02621: L-carnitine + tetradecenoylcarnitine(9) <=> L-carnitine + tetradecenoylcarnitine(9)	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000197119 encodes a mitochondrial transporter specifically involved in the transport of basic amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. However, the reaction provided involves the interconversion of L-carnitine and tetradecenoylcarnitine, which are not substrates transported by the gene product. This discrepancy in substrate specificity indicates that the gene is not relevant to the given reaction.	No
ENSG00000149742	Q8IVM8	MAR02624: L-carnitine + pentadecanoylcarnitine <=> L-carnitine + pentadecanoylcarnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000149742 encodes for a sodium-independent organic anion transporter that specifically transports sulfated conjugates such as estrone 3-sulfate and dehydroepiandrosterone sulfate, as well as statins like pravastatin, facilitated by short-chain fatty acids such as butanoate, propanoate, and pentanoate. In contrast, the reaction provided involves the exchange of L-carnitine and pentadecanoylcarnitine, which is unrelated to the gene's annotated function of transporting sulfated conjugates and certain statins with short-chain fatty acids. Therefore, the gene and the reaction are not related.	No
ENSG00000197119	Q8N8R3	MAR02624: L-carnitine + pentadecanoylcarnitine <=> L-carnitine + pentadecanoylcarnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. Based on the annotation, ENSG00000197119 functions as a mitochondrial transporter for basic amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine, but does not transport carnitine or acylcarnitines. The provided reaction involves L-carnitine and pentadecanoylcarnitine, which are not substrates or products associated with the gene's identified transport activities. Therefore, the gene is not related to the given reaction.	No
ENSG00000197208	Q9H015	MAR02629: L-carnitine + L-palmitoylcarnitine <=> L-carnitine + L-palmitoylcarnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000197208 encodes a transporter involved in the Na(+)-dependent and pH-dependent transport of ergothioneine, acetylcholine, (R)-carnitine, and glycine betaine, as evidenced by various studies. The reactions described for this gene involve the transport of these molecules across membranes and do not match the given reaction, which involves the exchange between L-carnitine and L-palmitoylcarnitine. Therefore, based on the gene's annotated functions and catalytic activities, it is not related to the reaction involving L-carnitine and L-palmitoylcarnitine.	No Yes
ENSG00000197119	Q8N8R3	MAR02629: L-carnitine + L-palmitoylcarnitine <=> L-carnitine + L-palmitoylcarnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197119 encodes a mitochondrial transporter of specific amino acids such as arginine, lysine, homoarginine, methylarginine, and to a lesser extent, ornithine and histidine. The annotated catalytic activities involve transportation and exchange of these amino acids. However, the reaction provided involves L-carnitine and L-palmitoylcarnitine, which are not substrates transported by this gene product. Hence, the gene does not participate in the provided reaction.	No
ENSG00000149742	Q8IVM8	MAR02634: hexadecenoylcarnitine(9) + L-carnitine <=> hexadecenoylcarnitine(9) + L-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000149742 encodes a protein that functions as a sodium-independent organic anion transporter specific for sulfated conjugates of xenobiotics and steroid hormones. The catalytic activities detailed involve the transport of estrone 3-sulfate and dehydroepiandrosterone sulfate in exchange for short-chain fatty acids like butanoate, propanoate, and pentanoate. The reaction provided involves hexadecenoylcarnitine and L-carnitine, which do not match the substrates or products associated with the gene's known transport activities. Therefore, the protein encoded by this gene is not relevant to the given reaction.	No
ENSG00000197119	Q8N8R3	MAR02634: hexadecenoylcarnitine(9) + L-carnitine <=> hexadecenoylcarnitine(9) + L-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. Based on the annotation, the gene ENSG00000197119 encodes for a mitochondrial transporter specific for transporting amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. It does not transport carnitine or acylcarnitines. In contrast, the reaction provided involves the exchange of hexadecenoylcarnitine and L-carnitine, which is unrelated to the function of this gene product. Hence, there is no relevance between the gene and the given reaction.	No
ENSG00000149742	Q8IVM8	MAR02638: L-carnitine + palmitoleoyl-carnitine <=> L-carnitine + palmitoleoyl-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000149742 functions as a sodium-independent organic anion transporter, specifically transporting sulfated conjugates such as estrone 3-sulfate and dehydroepiandrosterone sulfate. The gene is involved in the exchange of these conjugates against short-chain fatty acids like butanoate, propanoate, and pentanoate. The reaction provided involves L-carnitine and palmitoleoyl-carnitine, which are not substrates or products associated with the transport functions of the gene. Therefore, based on its annotated functions and catalytic activities, the gene and the reaction are not related.	No
ENSG00000197119	Q8N8R3	MAR02638: L-carnitine + palmitoleoyl-carnitine <=> L-carnitine + palmitoleoyl-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197119 encodes a mitochondrial transporter of specific amino acids including arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. It does not transport carnitine or acylcarnitines. The reaction provided involves L-carnitine and palmitoleoyl-carnitine, which are not substrates for the transporter encoded by this gene. Therefore, the gene is not related to the reaction provided.	No
ENSG00000149742	Q8IVM8	MAR02644: heptadecanoylcarnitine + L-carnitine <=> heptadecanoylcarnitine + L-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000149742 encodes a sodium-independent organic anion transporter specifically involved in the transport of sulfated conjugates of xenobiotics and steroid hormones, notably estrone 3-sulfate and dehydroepiandrosterone sulfate, as well as the exchange of these sulfated organic components against short-chain fatty acids like propionate, butyrate, and valerate. The provided reaction involves heptadecanoylcarnitine and L-carnitine, which are not mentioned in the gene's annotated function or known catalytic activities. Therefore, the gene is not relevant to the reaction described.	No
ENSG00000175003	O15245	MAR02644: heptadecanoylcarnitine + L-carnitine <=> heptadecanoylcarnitine + L-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000175003 encodes a voltage-dependent transporter that mediates the transport of various organic cations such as endogenous bioactive amines, cationic drugs, and xenobiotics. It is involved in the bidirectional transport of substances based on electrochemical potential and substrate selectivity. The specific catalytic activities listed include the transport of substances like 1-methylnicotinamide, dopamine, serotonin, adrenaline, histamine, guanidine, acetylcholine, thiamine, agmatine, putrescine, spermidine, L-histidyl-L-proline diketopiperazine, (R)-salsolinol, prostaglandin F2alpha, and prostaglandin E2. However, the reaction involving heptadecanoylcarnitine and L-carnitine is not listed among the functions or catalytic activities of this gene. Therefore, the gene is not relevant to the reaction provided.	No
ENSG00000197119	Q8N8R3	MAR02644: heptadecanoylcarnitine + L-carnitine <=> heptadecanoylcarnitine + L-carnitine	ENSG00000149742 or ENSG00000175003 or ENSG00000178537 or ENSG00000197119 or ENSG00000197208	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000197119 codes for a mitochondrial transporter responsible for the transport of basic amino acids such as arginine, lysine, homoarginine, methylarginine, ornithine, and histidine. It functions through counter-exchange and uniport mechanisms and does not transport carnitine or acylcarnitines. The provided reaction involves heptadecanoylcarnitine and L-carnitine, which are not transported by the gene product of ENSG00000197119.	No

[feiranl]

Please retain ENSG00000197208 for MAR02629, as it may function as a low-affinity, Na+-dependent transporter of L-carnitine across the mitochondrial membrane, supporting intracellular carnitine homeostasis (PubMed:10215651, PubMed:15107849, PubMed:16729965).

Good example for the manuscript:
ENSG00000197119 does not transport carnitine or acylcarnitines (PubMed:24652292) and should therefore be removed from carnitine transport reactions, such as MAR02783. AI is correct.
ENSG00000175003 was initially reported to transport carnitine across the hepatocyte membrane (PubMed:28942964), but a subsequent study was unable to confirm this (PubMed:28942964, PubMed:34040533). Unlike the mouse ortholog, the human version does not transport carnitine, noradrenaline, or choline (PubMed:34040533). Accordingly, this gene should be excluded from MAR02644. AI is correct.

[JHL-452b]

Fixed by #923