GPR curation for Linoleate metabolism, Fatty acid elongation and Beta oxidation of even-chain fatty acids

[JHL-452b]

Current behavior:

21 genes are discovered to be uncorrelated with their corresponding reactions in Linoleate metabolism, Fatty acid elongation and Beta oxidation of even-chain fatty acids.

Gene	UniProtID	Reaction	GPR	Correlation	Manually check
ENSG00000137869	P11511	MAR02455: H+ + linoleate + NADPH + O2 --> 9(10)-EpOME + H2O + NADP+	ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase involved in the oxidation of C19 androgens to C18 estrogens and other steroid hormone conversions. It catalyzes reactions involving androgens like testosterone and androstenedione, utilizing molecular oxygen and NADPH. The provided reaction involves linoleate, NADPH, and oxygen to produce 9(10)-EpOME, which does not involve steroid substrates or similar enzymatic activities. Thus, the gene's function does not match the reaction involving linoleate.	No
ENSG00000108242	P33260	MAR02456: H+ + linoleate + NADPH + O2 --> 9(10)-EpOME + H2O + NADP+	ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000108242 encodes a cytochrome P450 monooxygenase involved in retinoid metabolism, specifically hydroxylating all-trans-retinoic acid (atRA) to 4-hydroxyretinoate using molecular oxygen and NADPH. However, the provided reaction involves the conversion of linoleate to 9(10)-EpOME using NADPH and O2, which is unrelated to retinoid metabolism. Thus, the gene's function does not match the reaction described.	No
ENSG00000160870	P24462	MAR02457: H+ + linoleate + NADPH + O2 --> 12(13)-EpOME + H2O + NADP+	ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. ENSG00000160870 encodes a cytochrome P450 monooxygenase involved in the metabolism of steroid hormones, vitamins, and xenobiotics through specific hydroxylation reactions, primarily during embryogenesis. The gene's documented activities include the hydroxylation of steroid precursors such as dehydroepiandrosterone (DHEA) and estrone, as well as the oxidative metabolism of retinoic acid and xenobiotics. However, the provided reaction, which involves the conversion of linoleate to 12(13)-EpOME using NADPH and O2, does not fall within the metabolic functions or substrate specificities mentioned for the gene. The gene's typical processes and documented catalysis activities do not align with the reaction involving linoleate, indicating no relevance between the gene and the specified reaction.	No
ENSG00000186377	Q8N118	MAR02457: H+ + linoleate + NADPH + O2 --> 12(13)-EpOME + H2O + NADP+	ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000186377 encodes a cytochrome P450 monooxygenase that specifically catalyzes the epoxidation of the arachidonoyl moiety of anandamide, rather than acting as a hydroxylase for various fatty acids, steroids, and prostaglandins. However, the reaction in question involves the conversion of linoleate to 12(13)-EpOME, which is not aligned with the enzyme's activity described for the gene ENSG00000186377. Therefore, the gene does not relate to the specified reaction.	No
ENSG00000137869	P11511	MAR02458: H+ + linoleate + NADPH + O2 --> 12(13)-EpOME + H2O + NADP+	ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes for a cytochrome P450 monooxygenase involved in the oxidation of C19 androgens to C18 estrogens, specifically catalyzing reactions such as the conversion of testosterone to estradiol and androst-4-ene-3,17-dione to estrone. The reaction provided, H+ + linoleate + NADPH + O2 --> 12(13)-EpOME + H2O + NADP+, involves the oxidation of linoleate to 12(13)-EpOME, which does not match any of the described activities or substrates associated with the gene product. Therefore, the gene is not related to the specified reaction.	No
ENSG00000241119	O60656	MAR02469: 12,13-hydroxyoctadec-9(z)-enoate + UDP-glucuronate <=> 12-O-D-glucuronoside-13-hydroxyoctadec-(9Z)-enoate + H+ + UDP	ENSG00000109181 or ENSG00000135220 or ENSG00000135226 or ENSG00000145626 or ENSG00000156096 or ENSG00000167165 or ENSG00000168671 or ENSG00000171234 or ENSG00000173610 or ENSG00000196620 or ENSG00000197888 or ENSG00000213759 or ENSG00000288705 or ENSG00000241119 or ENSG00000241635 or ENSG00000242366 or ENSG00000242515 or ENSG00000288702 or ENSG00000244122 or ENSG00000244474	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000241119 encodes for a UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions involving the conjugation of various substrates with glucuronic acid, increasing their water solubility for excretion. It is involved in the metabolism of estrogen hormones, isoflavones, certain anticancer drugs (e.g., SN-38), and other specific compounds. The reaction provided involves 12,13-hydroxyoctadec-9(z)-enoate and UDP-glucuronate forming 12-O-D-glucuronoside-13-hydroxyoctadec-(9Z)-enoate, which is not mentioned among the substrates processed by UGT encoded by this gene. Therefore, this gene and the reaction are not related.	Yes
ENSG00000137869	P11511	MAR02456: H+ + linoleate + NADPH + O2 --> 9(10)-EpOME + H2O + NADP+	ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens to C18 estrogens and other specific oxidative reactions involving steroid derivatives, using molecular oxygen and NADPH. In contrast, the reaction provided involves the conversion of linoleate to 9(10)-EpOME using NADPH and oxygen, which is a type of fatty acid epoxidation reaction not associated with the known functions of the gene product. This indicates a non-relation between the gene and the specified reaction.	No
ENSG00000137869	P11511	MAR02457: H+ + linoleate + NADPH + O2 --> 12(13)-EpOME + H2O + NADP+	ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000137869 encodes a cytochrome P450 monooxygenase, which primarily catalyzes the conversion of C19 androgens to C18 estrogens through successive oxidations. It is involved in the metabolic processes of androst-4-ene-3,17-dione, testosterone, and other related steroids. The reactions catalyzed by this gene involve molecular oxygen and NADPH to produce estrogens, among other derivatives. However, the provided reaction describes the conversion of linoleate to 12(13)-EpOME, which does not involve the substrates or products mentioned in the functions and catalytic activities of the gene. Therefore, the gene and the reaction are not related.	No
ENSG00000108242	P33260	MAR02458: H+ + linoleate + NADPH + O2 --> 12(13)-EpOME + H2O + NADP+	ENSG00000021461 or ENSG00000100197 or ENSG00000106258 or ENSG00000108242 or ENSG00000130649 or ENSG00000134716 or ENSG00000137869 or ENSG00000138061 or ENSG00000138109 or ENSG00000138115 or ENSG00000140465 or ENSG00000140505 or ENSG00000142973 or ENSG00000155016 or ENSG00000160868 or ENSG00000160870 or ENSG00000165841 or ENSG00000167600 or ENSG00000171903 or ENSG00000186160 or ENSG00000186204 or ENSG00000186377 or ENSG00000186526 or ENSG00000197408 or ENSG00000197446 or ENSG00000197838 or ENSG00000198077 or ENSG00000255974	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000108242 encodes a cytochrome P450 monooxygenase involved in retinoid metabolism, specifically hydroxylating all-trans-retinoic acid to 4-hydroxyretinoate. The reaction in question involves the conversion of linoleate to 12(13)-EpOME, which is a different substrate and metabolic pathway. Therefore, the gene and the reaction are not related.	No
ENSG00000164303	Q6UWR7	MAR07606: 1-(1-alkenyl)-sn-glycero-3-phosphoethanolamine + H2O --> 1-(1-alkenyl)-sn-glycerol + ethanolamine-phosphate + H+	ENSG00000164303	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000164303 encodes a choline-specific glycerophosphodiesterase that hydrolyzes glycerophosphocholine (GPC) and lysophosphatidylcholine (LPC), contributing to choline supply in cells. It specifically acts on choline-containing lipids like sphingosylphosphorylcholine (SPC), platelet-activating factor (PAF), and lysoPAF. The provided reaction involves the hydrolysis of 1-(1-alkenyl)-sn-glycero-3-phosphoethanolamine, which is outside the gene's annotated substrate specificity, indicating non-relevance.	No
ENSG00000177465	Q8N9L9	MAR00249: ATP + CoA + stearate --> AMP + PPi + stearoyl-CoA	ENSG00000068366 or ENSG00000103740 or ENSG00000119673 or ENSG00000123983 or ENSG00000130377 or ENSG00000140284 or ENSG00000151726 or ENSG00000164398 or ENSG00000177465 or ENSG00000197142	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000177465 encodes a protein that catalyzes the hydrolysis of various acyl-CoAs into free fatty acids and CoA, regulating their intracellular levels. Specifically, it catalyzes reactions involving succinyl-CoA, glutaryl-CoA, long chain saturated acyl-CoAs, and other specific CoA derivatives. However, the provided reaction involves the synthesis of stearoyl-CoA from stearate, ATP, and CoA, which results in the production of AMP and PPi. This reaction is a synthesis process rather than a hydrolysis process, making it inconsistent with the functions of the gene product that predominantly acts as a thioesterase. Hence, the gene and the reaction are not related.	No
ENSG00000146066	Q9BW72	MAR02269: 3-hydroxytricosanoyl-CoA --> (2E)-tricosenoyl-CoA + H2O	ENSG00000074696 or ENSG00000146066 or ENSG00000165996 or ENSG00000188921 or ENSG00000206527	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000146066 is proposed to be a subunit of cytochrome c oxidase (COX), which plays a role in the mitochondrial respiratory chain, facilitating the reduction of oxygen to water and potentially aiding in cytochrome c oxidase activity and the assembly of respiratory supercomplexes. In contrast, the reaction involves the conversion of 3-hydroxytricosanoyl-CoA to (2E)-tricosenoyl-CoA and H2O, which is unrelated to the functions described for the gene.	No
ENSG00000167306	Q9ULV0	MAR03315: 3-oxo-cis,cis-5,8-tetradecadienoyl-CoA + CoA --> acetyl-CoA + cis,cis-3,6-dodecadienoyl-CoA	ENSG00000060971 and ENSG00000167306	Pending No, the gene is not relevant to the reaction provided. Analysis: The gene ENSG00000167306 is associated with vesicular trafficking and several specific biological processes such as transferrin receptor recycling and epithelial cell polarization. The gene function does not mention any involvement in catalytic activities or biochemical reactions involving the conversion of 3-oxo-cis,cis-5,8-tetradecadienoyl-CoA to acetyl-CoA and cis,cis-3,6-dodecadienoyl-CoA. Therefore, the gene is not related to the specified reaction.	No
ENSG00000167969	P42126	MAR03067: (2E)-docosenoyl-CoA + H2O --> 3-hydroxydocosanoyl-CoA	ENSG00000084754 and ENSG00000113790 and ENSG00000167969 and ENSG00000198721	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000167969 encodes for an enzyme involved in the isomerization of various enoyl-CoA species, specifically catalyzing the conversion of 3Z and 3E enoyl-CoAs to 2E enoyl-CoAs. However, the provided reaction describes the hydration of (2E)-docosenoyl-CoA to 3-hydroxydocosanoyl-CoA, which is a different chemical process not related to the isomerization reactions catalyzed by the enzyme encoded by this gene.	No
ENSG00000198721	O75521	MAR03091: (2E)-decenoyl-CoA + H2O --> (S)-hydroxydecanoyl-CoA	ENSG00000084754 and ENSG00000113790 and ENSG00000167969 and ENSG00000198721	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000198721 encodes a protein that functions as an enoyl-CoA isomerase, catalyzing the isomerization of various enoyl-CoA species. The catalytic activities detailed in the annotation involve isomerization reactions, such as converting (3Z)-enoyl-CoA to (2E)-enoyl-CoA, and similar processes. However, the provided reaction, which converts (2E)-decenoyl-CoA and H2O to (S)-hydroxydecanoyl-CoA, involves hydration rather than isomerization. Thus, the gene¡¯s function does not align with the reaction provided.	No
ENSG00000167306	Q9ULV0	MAR03093: 3-oxodecanoyl-CoA + CoA --> acetyl-CoA + octanoyl-CoA	ENSG00000060971 and ENSG00000167306	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000167306 is involved in vesicular trafficking and various associated processes such as transferrin receptor recycling, transport of NPC1L1 to the plasma membrane, CFTR trafficking, epithelial cell polarization, and bile salt export pump localization. It does not exhibit any catalytic activity and is not related to the reaction involving 3-oxodecanoyl-CoA and CoA to produce acetyl-CoA and octanoyl-CoA.	No
ENSG00000161533	Q15067	MAR03102: butyryl-CoA + FAD --> crotonyl-CoA + FADH2	ENSG00000087008 or ENSG00000161533	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000161533 is involved in the catalytic activity of converting 2,3-saturated acyl-CoA with O2 to (2E)-enoyl-CoA, producing H2O2. The mentioned reactions include various substrates like hexadecanoyl-CoA, dodecanoyl-CoA, octanoyl-CoA, and others, leading to their respective (2E)-enoyl-CoAs, always producing H2O2. However, the provided reaction is butyryl-CoA with FAD converting to crotonyl-CoA and FADH2, which does not involve the substrates or products mentioned for gene ENSG00000161533, nor does it involve the production of H2O2. Thus, they are not related.	No
ENSG00000198721	O75521	MAR03058: (2E)-hexacosenoyl-CoA + H2O --> 3-hydroxyhexacosanoyl-CoA	ENSG00000084754 and ENSG00000113790 and ENSG00000167969 and ENSG00000198721	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000198721 encodes for an enzyme that isomerizes 3-cis and 3-trans double bonds into the 2-trans form in various enoyl-CoA species. However, the reaction provided describes the conversion of (2E)-hexacosenoyl-CoA to 3-hydroxyhexacosanoyl-CoA, which involves a hydration step (addition of H2O) rather than isomerization. Therefore, the enzymatic activity of the gene product does not align with the described reaction.	No
ENSG00000198721	O75521	MAR03103: crotonyl-CoA + H2O --> (S)-3-hydroxybutyryl-CoA	ENSG00000084754 and ENSG00000113790 and ENSG00000167969 and ENSG00000198721	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000198721 encodes an enzyme that isomerizes double bonds in enoyl-CoA species but does not catalyze the conversion of crotonyl-CoA with water to (S)-3-hydroxybutyryl-CoA. Therefore, the gene and the reaction are not related.	No
ENSG00000161533	Q15067	MAR03506: 4,8,12-trimethyltridecanoyl-CoA + FAD --> (4R,8R,12R)-trimethyl-(2E)-tridecenoyl-CoA + FADH2	ENSG00000087008 or ENSG00000161533	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation. The gene ENSG00000161533 is involved in the beta-oxidation of very-long-chain fatty acids and catalyzes the desaturation of fatty acyl-CoAs to (2E)-enoyl-CoAs while producing hydrogen peroxide (H2O2). However, the reaction provided involves 4,8,12-trimethyltridecanoyl-CoA and FAD, resulting in (4R,8R,12R)-trimethyl-(2E)-tridecenoyl-CoA and FADH2, which is distinct from the reactions catalyzed by the gene's product. Therefore, the gene does not relate to the given reaction.	No
ENSG00000161533	Q15067	MAR03338: (11Z)-eicosenoyl-CoA + FAD --> FADH2 + trans,cis-2,11-eicosadienoyl-CoA	ENSG00000087008 or ENSG00000161533	Pending No, the gene is not relevant to the reaction provided. Analysis and explanation: The gene ENSG00000161533 is involved in the peroxisomal beta-oxidation of very-long-chain fatty acids and catalyzes the desaturation of fatty acyl-CoAs to produce (2E)-enoyl-CoAs and hydrogen peroxide (H2O2). However, the reaction provided describes the conversion of (11Z)-eicosenoyl-CoA to trans,cis-2,11-eicosadienoyl-CoA using FAD as a cofactor, which is not one of the reactions catalyzed by the gene product of ENSG00000161533. This discrepancy indicates that the gene and the provided reaction are not related.	No

[Devlin-Moyer]

The AI is right that ACOT4 (ENSG00000177465) shouldn't be in the GPR of MAR00249, since it doesn't catalyze that reaction, but ACOT2 (ENSG00000119673) should also be removed from the GPR for the same reason. This paper found that ACSBG2 (ENSG00000130377) showed no activity towards stearate (C18:0), so it should also be removed from the GPR of MAR00249.

It's also right about MYO5B (ENSG00000167306) not belonging in the GPRs of MAR03315 or MAR03093, but both ACAA1 (ENSG00000060971) and SCP2 (ENSG00000116171) can independently catalyze these reactions, so the GPRs for both reactions should be ENSG00000060971 or ENSG00000116171)

It's also right about ECI1 (ENSG00000167969) not belonging in the GPR of MAR03067, but there are other problems with that GPR:

• ECI2 (ENSG00000198721) catalyzes the same reaction as ECI1, which is not what's happening in MAR03067
• HADHA (ENSG00000084754) is mitochondrial, not peroxisomal
• HSD17B4 (ENSG00000133835) can also catalyze this reaction in peroxisomes, so it should be ORed with EHHADH (ENSG00000113790)

So the GPR of MAR03067 should just be EHHADH or HSD17B4 (ENSG00000113790 or ENSG00000133835). All of these problems also apply to MAR03091, so its GPR should also be ENSG00000113790 or ENSG00000133835.

MAR03102 and MAR03103 should just be removed from the model, since beta-oxidation of acyl-CoAs with fewer than ~8 carbons happens in mitochondria and not peroxisomes, and the mitochondrial versions of those reactions are already represented by MAR03163 and MAR03164, respectively (sources: 1, 2).

The AI is right about ACOX1 (ENSG00000161533) not being able to catalyze MAR03506, but it could be replaced with ACOX2 (ENSG00000168306), since both ACOX2 and ACOX3 (ENSG00000087008) are capable of oxidizing branched acyl-CoAs (source).

Nothing is wrong with the GPR of MAR03338; both ACOX1 (ENSG00000161533) and ACOX3 (ENSG00000087008) are absolutely capable of catalyzing that reaction (sources: 1, 2). I suspect that it is once again confused by the fact that we decided to make all of the peroxisomal acyl-CoA oxidation reactions reduce FAD to FADH₂ instead of O₂ to H₂O₂ in #639.

[JHL-452b]

Thanks for your investigation and the detailed feedback. @Devlin-Moyer
I totally agree with all your comments after checking it out.
In summary,

• The GPR of MAR00249 should be ENSG00000068366 or ENSG00000103740 or ENSG00000123983 or ENSG00000140284 or ENSG00000151726 or ENSG00000164398 or ENSG00000197142 after removing ENSG00000177465, ENSG00000119673 and ENSG00000130377.
• The GPR of MAR03315 should be ENSG00000060971 or ENSG00000116171 .
• The GPR of MAR03093 should be ENSG00000060971 or ENSG00000116171 .
• The GPR of MAR03067 should be ENSG00000113790 or ENSG00000133835.
• The GPR of MAR03091 should be ENSG00000113790 or ENSG00000133835.
• The GPR of MAR03506 should be ENSG00000087008 or ENSG00000168306.
• The GPR of MAR03338 should be ENSG00000087008 or ENSG00000161533 without any change.
• MAR03102 and MAR03103 should be removed from the model.

[feiranl]

LGTM!