GRHPR (glyoxylate and hydroxypyruvate reductase)

Gene

• Entrez ID: 9380
• Gene name: Glyoxylate and hydroxypyruvate reductase
• Gene symbol: GRHPR
• Synonyms (NCBI Gene): GLXR, GLYD, PH2
• Chromosome: 9
• Chromosome location: 9p13.2
• Summary: This gene encodes an enzyme with hydroxypyruvate reductase, glyoxylate reductase, and D-glycerate dehydrogenase enzymatic activities. The enzyme has widespread tissue expression and has a role in metabolism. Type II hyperoxaluria is caused by mutations in

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs309458	A>C,G,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance, benign	Coding sequence variant, non coding transcript variant, synonymous variant
rs34302950	TCTCTCTCTC>-,TC,TCTC,TCTCTC,TCTCTCTC,TCTCTCTCTCTC,TCTCTCTCTCTCTC,TCTCTCTCTCTCTCTC,TCTCTCTCTCTCTCTCTCTCTCTC,TCTCTCTCTCTCTCTCTCTCTCTCTC	Conflicting-interpretations-of-pathogenicity, benign	Intron variant
rs80356708	G>-	Likely-pathogenic, pathogenic	Frameshift variant, non coding transcript variant, 5 prime UTR variant, intron variant, coding sequence variant
rs111256477	G>C,T	Likely-pathogenic, uncertain-significance	Splice donor variant
rs119490108	C>T	Pathogenic	Non coding transcript variant, 5 prime UTR variant, stop gained, intron variant, coding sequence variant
rs142835989	G>A,T	Likely-pathogenic	Missense variant, non coding transcript variant, intron variant, coding sequence variant
rs148049120	G>A	Likely-pathogenic	Splice donor variant, non coding transcript variant
rs180177304	G>A	Likely-pathogenic	5 prime UTR variant, intron variant, stop gained, non coding transcript variant, coding sequence variant
rs180177305	T>C	Pathogenic	5 prime UTR variant, intron variant, missense variant, non coding transcript variant, coding sequence variant
rs180177307	G>A,T	Likely-pathogenic	5 prime UTR variant, intron variant, stop gained, missense variant, non coding transcript variant, coding sequence variant
rs180177308	G>-	Pathogenic	5 prime UTR variant, intron variant, frameshift variant, non coding transcript variant, coding sequence variant
rs180177309	AAGT>-	Pathogenic-likely-pathogenic	5 prime UTR variant, intron variant, splice donor variant, non coding transcript variant, coding sequence variant
rs180177311	A>-	Pathogenic	Frameshift variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant
rs180177312	G>A	Pathogenic	Missense variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant
rs180177313	T>A,G	Likely-pathogenic	Splice donor variant, non coding transcript variant, 5 prime UTR variant
rs180177314	G>A	Likely-pathogenic, pathogenic-likely-pathogenic, pathogenic	Missense variant, non coding transcript variant, coding sequence variant
rs180177315	T>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs180177316	CT>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs180177317	G>A	Likely-pathogenic	Non coding transcript variant, splice acceptor variant
rs180177319	A>G	Pathogenic	Intron variant, splice acceptor variant
rs180177320	CCCC>-	Pathogenic	Intron variant
rs180177321	TG>-	Pathogenic-likely-pathogenic, pathogenic	Inframe indel, frameshift variant, stop gained, non coding transcript variant, coding sequence variant
rs180177322	C>T	Likely-pathogenic, pathogenic	Missense variant, non coding transcript variant, intron variant, coding sequence variant
rs180177323	G>A	Pathogenic	Missense variant, non coding transcript variant, intron variant, coding sequence variant
rs180177324	A>G	Pathogenic	Missense variant, non coding transcript variant, intron variant, coding sequence variant
rs180177325	T>C,G	Pathogenic	Missense variant, non coding transcript variant, intron variant, coding sequence variant
rs672601351	TG>-	Pathogenic	5 prime UTR variant, non coding transcript variant, coding sequence variant, frameshift variant, intron variant
rs751101495	G>-,GG	Likely-pathogenic	Frameshift variant, intron variant, 5 prime UTR variant, coding sequence variant, non coding transcript variant
rs757796926	G>A	Likely-pathogenic	Intron variant
rs771019056	->A	Pathogenic, likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant, 5 prime UTR variant
rs779208888	G>A	Likely-pathogenic	Splice acceptor variant
rs796052077	GC>AT	Pathogenic	Coding sequence variant, missense variant, 5 prime UTR variant, non coding transcript variant
rs796052078	G>A,T	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant, 5 prime UTR variant, intron variant
rs796052079	T>A	Pathogenic	Coding sequence variant, missense variant, non coding transcript variant
rs796052080	CC>-	Pathogenic	Intron variant
rs796052081	AGT>-	Pathogenic	Coding sequence variant, non coding transcript variant, 5 prime UTR variant, splice acceptor variant, intron variant
rs796052082	C>-	Pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs979727637	C>A,T	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant, stop gained, non coding transcript variant, synonymous variant
rs1057516292	T>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1057516299	A>-	Likely-pathogenic	5 prime UTR variant, intron variant, frameshift variant, coding sequence variant, non coding transcript variant
rs1057516823	->A	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1057516831	A>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, intron variant, frameshift variant
rs1057516990	T>-	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1057517026	TG>-	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, 5 prime UTR variant
rs1057517238	->A	Likely-pathogenic	5 prime UTR variant, intron variant, frameshift variant, coding sequence variant, non coding transcript variant
rs1057517333	GC>-	Likely-pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant, 5 prime UTR variant
rs1057517398	T>G	Likely-pathogenic	Splice donor variant, intron variant
rs1244822375	G>C,T	Likely-pathogenic	Intron variant, splice donor variant
rs1257080057	A>-	Likely-pathogenic	Non coding transcript variant, splice acceptor variant
rs1422977131	G>A,C	Likely-pathogenic	Splice acceptor variant
rs1554746094	A>G,T	Likely-pathogenic	5 prime UTR variant, non coding transcript variant, missense variant, coding sequence variant, initiator codon variant
rs1554746097	T>G	Likely-pathogenic	5 prime UTR variant, non coding transcript variant, missense variant, coding sequence variant, initiator codon variant
rs1554746565	TG>-	Likely-pathogenic	5 prime UTR variant, non coding transcript variant, coding sequence variant, frameshift variant, intron variant
rs1554746793	AG>-	Likely-pathogenic	Splice acceptor variant, intron variant
rs1554746962	->TACTTACCACCTGC	Pathogenic	5 prime UTR variant, non coding transcript variant, coding sequence variant, frameshift variant, intron variant
rs1554747871	C>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1554747933	G>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, splice donor variant
rs1554748528	GG>TAC	Pathogenic, likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1554748534	->T	Likely-pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs1554748574	->G	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1554748598	G>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1564300888	CTGCCCAATCTGATTTCATCGTCGTGGCCTGCTCCTTAACACCTGCAACCGAGGG>-	Likely-pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1588757756	AG>-	Pathogenic	Coding sequence variant, frameshift variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT040697	hsa-miR-92b-3p	CLASH	23622248
MIRT035939	hsa-miR-1180-3p	CLASH	23622248
MIRT1034150	hsa-miR-1228	CLIP-seq
MIRT1034151	hsa-miR-204	CLIP-seq
MIRT1034152	hsa-miR-211	CLIP-seq
MIRT1034153	hsa-miR-3194-3p	CLIP-seq
MIRT1034154	hsa-miR-4755-5p	CLIP-seq
MIRT1034155	hsa-miR-4780	CLIP-seq
MIRT1034156	hsa-miR-623	CLIP-seq
MIRT1034157	hsa-miR-760	CLIP-seq
MIRT1034150	hsa-miR-1228	CLIP-seq
MIRT1034151	hsa-miR-204	CLIP-seq
MIRT1034152	hsa-miR-211	CLIP-seq
MIRT1034153	hsa-miR-3194-3p	CLIP-seq
MIRT1034154	hsa-miR-4755-5p	CLIP-seq
MIRT1034155	hsa-miR-4780	CLIP-seq
MIRT1034156	hsa-miR-623	CLIP-seq
MIRT1034157	hsa-miR-760	CLIP-seq
MIRT2239103	hsa-miR-3591-3p	CLIP-seq
MIRT2239104	hsa-miR-3657	CLIP-seq
MIRT2239105	hsa-miR-4501	CLIP-seq
MIRT2239106	hsa-miR-4504	CLIP-seq
MIRT2239107	hsa-miR-4669	CLIP-seq
MIRT2239108	hsa-miR-542-3p	CLIP-seq
MIRT1034150	hsa-miR-1228	CLIP-seq
MIRT1034151	hsa-miR-204	CLIP-seq
MIRT1034152	hsa-miR-211	CLIP-seq
MIRT2543032	hsa-miR-2115	CLIP-seq
MIRT1034153	hsa-miR-3194-3p	CLIP-seq
MIRT2543033	hsa-miR-3675-3p	CLIP-seq
MIRT2543034	hsa-miR-3691-5p	CLIP-seq
MIRT2543035	hsa-miR-3977	CLIP-seq
MIRT2543036	hsa-miR-4290	CLIP-seq
MIRT2543037	hsa-miR-452	CLIP-seq
MIRT2543038	hsa-miR-4676-3p	CLIP-seq
MIRT2543039	hsa-miR-4684-5p	CLIP-seq
MIRT2543040	hsa-miR-4685-5p	CLIP-seq
MIRT2543041	hsa-miR-4752	CLIP-seq
MIRT1034154	hsa-miR-4755-5p	CLIP-seq
MIRT1034155	hsa-miR-4780	CLIP-seq
MIRT2543042	hsa-miR-516a-3p	CLIP-seq
MIRT2543043	hsa-miR-564	CLIP-seq
MIRT1034156	hsa-miR-623	CLIP-seq
MIRT2543044	hsa-miR-661	CLIP-seq
MIRT1034157	hsa-miR-760	CLIP-seq
MIRT1034150	hsa-miR-1228	CLIP-seq
MIRT1034151	hsa-miR-204	CLIP-seq
MIRT1034152	hsa-miR-211	CLIP-seq
MIRT2543032	hsa-miR-2115	CLIP-seq
MIRT1034153	hsa-miR-3194-3p	CLIP-seq
MIRT2543033	hsa-miR-3675-3p	CLIP-seq
MIRT2543034	hsa-miR-3691-5p	CLIP-seq
MIRT2543035	hsa-miR-3977	CLIP-seq
MIRT2543036	hsa-miR-4290	CLIP-seq
MIRT2543037	hsa-miR-452	CLIP-seq
MIRT2543038	hsa-miR-4676-3p	CLIP-seq
MIRT2543039	hsa-miR-4684-5p	CLIP-seq
MIRT2543040	hsa-miR-4685-5p	CLIP-seq
MIRT2543041	hsa-miR-4752	CLIP-seq
MIRT1034154	hsa-miR-4755-5p	CLIP-seq
MIRT1034155	hsa-miR-4780	CLIP-seq
MIRT2543042	hsa-miR-516a-3p	CLIP-seq
MIRT2543043	hsa-miR-564	CLIP-seq
MIRT1034156	hsa-miR-623	CLIP-seq
MIRT1034157	hsa-miR-760	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005737	Component	Cytoplasm	IDA
GO:0005782	Component	Peroxisomal matrix	TAS
GO:0005829	Component	Cytosol	IBA	21873635
GO:0007588	Process	Excretion	IMP	10484776
GO:0008465	Function	Glycerate dehydrogenase activity	IBA	21873635
GO:0008465	Function	Glycerate dehydrogenase activity	IDA	10484776
GO:0016618	Function	Hydroxypyruvate reductase activity	IBA	21873635
GO:0016618	Function	Hydroxypyruvate reductase activity	IDA	10484776, 10524214, 17510093
GO:0030267	Function	Glyoxylate reductase (NADP+) activity	IBA	21873635
GO:0030267	Function	Glyoxylate reductase (NADP+) activity	IDA	10484776, 10524214
GO:0030267	Function	Glyoxylate reductase (NADP+) activity	TAS
GO:0034641	Process	Cellular nitrogen compound metabolic process	TAS
GO:0042803	Function	Protein homodimerization activity	IDA	16756993
GO:0046487	Process	Glyoxylate metabolic process	IDA	10524214
GO:0051287	Function	NAD binding	TAS	10484776
GO:0070062	Component	Extracellular exosome	HDA	19056867, 20458337, 23533145
GO:0070402	Function	NADPH binding	IDA	16756993
GO:1902494	Component	Catalytic complex	IDA	16756993

Other IDs

• MIM: 604296
• HGNC: 4570
• e!Ensembl: ENSG00000137106

Protein

• UniProt ID: Q9UBQ7
• Protein name: Glyoxylate reductase/hydroxypyruvate reductase (EC 1.1.1.79) (EC 1.1.1.81)
• Protein function: Enzyme with hydroxy-pyruvate reductase, glyoxylate reductase and D-glycerate dehydrogenase enzymatic activities. Reduces hydroxypyruvate to D-glycerate, glyoxylate to glycolate, oxidizes D-glycerate to hydroxypyruvate. {ECO:0000269|PubMed:104847
• PDB: 2GCG, 2H1S, 2Q50, 2WWR
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00389	2-Hacid_dh	9 → 327	D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain	Domain
  PF02826	2-Hacid_dh_C	116 → 295	D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous. Most abundantly expressed in the liver. {ECO:0000269|PubMed:10679197}.
• Sequence:

  MRPVRLMKVFVTRRIPAEGRVALARAADCEVEQWDSDEPIPAKELERGVAGAHGLLCLLS
  DHVDKRILDAAGANLKVISTMSVGIDHLALDEIKKRGIRVGYTPDVLTDTTAELAVSLLL
  TTCRRLPEAIEEVKNGGWTSWKPLWLCGYGLTQSTVGIIGLGRIGQAIARRLKPFGVQRF
  LYTGRQPRPEEAAEFQAEFVSTPELAAQSDFIVVACSLTPATEGLCNKDFFQKMKETAVF
  INISRGDVVNQDDLYQALASGKIAAAGLDVTSPEPLPTNHPLLTLKNCVILPHIGSATHR
  TRNTMSLLAANNLLAGLRGEPMPSELKL

• Sequence length: 328

Pathways

KEGG:

Glycine, serine and threonine metabolism
Pyruvate metabolism
Glyoxylate and dicarboxylate metabolism
Metabolic pathways

Reactome:

Glyoxylate metabolism and glycine degradation

Associated diseases

Causal
Disease term	Disease name	dbSNP ID	References
Hyperoxaluria	Hyperoxaluria, Primary Hyperoxaluria, Primary hyperoxaluria type 2	rs397509360, rs138207257, rs2041105506, rs267606763, rs267606764, rs80356708, rs119490108, rs121908520, rs121908521, rs121908522, rs121908523, rs121908524, rs121908525, rs121908526, rs121908527, rs121908528, rs121908530, rs121908529, rs180177201, rs180177238, rs180177321, rs672601351, rs180177322, rs180177157, rs180177168, rs180177195, rs180177197, rs180177207, rs180177227, rs180177239, rs180177253, rs180177259, rs786204545, rs180177267, rs180177301, rs180177156, rs180177307, rs138584408, rs180177194, rs180177213, rs180177191, rs34116584, rs180177262, rs180177268, rs180177278, rs180177162, rs180177166, rs180177170, rs180177171, rs180177172, rs180177173, rs180177177, rs767586362, rs180177181, rs180177182, rs796052058, rs796052069, rs180177183, rs180177184, rs180177185, rs180177186, rs796052059, rs180177187, rs180177189, rs180177193, rs180177198, rs796052060, rs180177199, rs180177200, rs180177202, rs180177203, rs796052061, rs180177208, rs138025751, rs796052067, rs113681235, rs796052070, rs180177210, rs180177211, rs180177214, rs180177215, rs180177217, rs180177219, rs180177220, rs180177221, rs180177222, rs180177223, rs180177224, rs180177225, rs180177231, rs180177232, rs180177233, rs180177234, rs180177235, rs180177236, rs180177237, rs180177240, rs180177241, rs180177243, rs180177244, rs796052062, rs180177245, rs180177246, rs536352238, rs180177247, rs180177248, rs180177250, rs180177251, rs180177252, rs180177254, rs111996685, rs111742810, rs180177256, rs1553648931, rs180177257, rs180177258, rs180177261, rs796052072, rs180177263, rs180177264, rs180177265, rs796052068, rs180177269, rs180177270, rs180177272, rs180177273, rs180177276, rs180177279, rs180177284, rs180177281, rs180177286, rs180177285, rs180177287, rs180177288, rs180177292, rs180177293, rs180177294, rs180177295, rs180177296, rs180177297, rs180177298, rs796052063, rs180177299, rs796052074, rs180177300, rs180177302, rs796052064, rs180177303, rs180177155, rs756437332, rs796052065, rs180177158, rs180177160, rs180177161, rs180177163, rs180177164, rs796052066, rs180177255, rs180177289, rs796052077, rs180177311, rs180177319, rs180177304, rs180177305, rs796052078, rs796052081, rs180177308, rs180177309, rs180177313, rs180177314, rs180177315, rs180177316, rs796052082, rs180177317, rs180177324, rs180177325, rs746419489, rs764396564, rs758304537, rs796052084, rs796052088, rs796052089, rs150702945, rs767405535, rs796052090, rs202047589, rs185803104, rs796052085, rs755562733, rs796052086, rs770050262, rs756489804, rs796052087, rs149150736, rs777046879, rs796052091, rs796052092, rs1057516896, rs751101495, rs1057517398, rs1057517238, rs1057516299, rs1057517333, rs1057517026, rs771019056, rs1057516990, rs1057516292, rs1057516823, rs1057516831, rs1419840309, rs757796926, rs1553648568, rs778567956, rs112673831, rs1553649375, rs1553648488, rs1553648493, rs1553649007, rs1554746094, rs1244822375, rs1554746097, rs1554746565, rs1422977131, rs1331106064, rs1554746793, rs1257080057, rs1554748528, rs1554748598, rs777683624, rs776817346, rs779208888, rs1554747871, rs111256477, rs1554747933, rs1554748534, rs1554748574, rs1425736036, rs1554874130, rs1554874148, rs746776892, rs990830655, rs752277936, rs749315029, rs1564297234, rs1564753668, rs924232072, rs1564300888, rs1564760008, rs774654020, rs1588757756, rs148049120, rs1553648979, rs1822898131	24116921, 25525159, 17510093, 25629080, 10484776, 14635115, 25644115, 16306119, 27604308, 18560364, 11477177, 11030416, 12185464, 15327387
Nephronophthisis	NEPHROLITHIASIS, CALCIUM OXALATE	rs62635288, rs267607116, rs201893408, rs267607117, rs202149403, rs118204032, rs121918244, rs750962965, rs1474058708, rs119456959, rs119456960, rs119456961, rs119456962, rs267606916, rs137852856, rs137852918, rs137852919, rs137852920, rs28940891, rs1278089386, rs137852922, rs137852923, rs1233478832, rs121907898, rs121907899, rs74315396, rs104893698, rs28936684, rs104893701, rs104893705, rs797044441, rs104893716, rs121964994, rs267607185, rs200844390, rs753348470, rs387906983, rs786205114, rs373909351, rs387907009, rs140511594, rs387907059, rs766132877, rs201188361, rs193922432, rs1565649749, rs387907309, rs387907310, rs387907311, rs145646425, rs397514728, rs397514257, rs587777024, rs587777025, rs397514258, rs375661404, rs398123285, rs398123538, rs398124546, rs368138001, rs587777350, rs587777351, rs587777352, rs587777486, rs879255575, rs368619022, rs879255576, rs587777487, rs369483167, rs587777488, rs587783011, rs144972972, rs727503968, rs727503969, rs730880299, rs757704417, rs760040426, rs758558609, rs755549444, rs763300393, rs794727964, rs182135982, rs758498695, rs775883520, rs777686211, rs756856188, rs777668842, rs756302731, rs751527253, rs138783896, rs869312915, rs769256610, rs878855332, rs376879175, rs878855335, rs886041154, rs886041637, rs766524637, rs769739938, rs201405662, rs376974221, rs201633414, rs1057519303, rs1057519304, rs202001274, rs1057519305, rs1057519306, rs752616462, rs1060499938, rs745340459, rs771215577, rs1064794347, rs201091657, rs771742823, rs1553484094, rs747861275, rs773521620, rs1456714047, rs1553773271, rs1555564134, rs752792782, rs398124289, rs1025515771, rs747052534, rs904520404, rs1553200990, rs1553178047, rs866982675, rs1182741031, rs1556026984, rs150001738, rs780247729, rs1555564214, rs372607453, rs61893682, rs549662742, rs774456004, rs1189889920, rs370210428, rs1557580413, rs1368105372, rs1559056633, rs765263671, rs1280238814, rs1560000875, rs1560002147, rs758238787, rs201237799, rs1560017690, rs1564123602, rs1425211517, rs369437168, rs764893412, rs747914869, rs778819060, rs1207804224, rs756090222, rs1564228101, rs1565455033, rs1322951938, rs1564236717, rs1565454034, rs375753623, rs374141736, rs1349732291, rs1017750255, rs1210874691, rs1379989124, rs1565582604, rs1485445500, rs758275952, rs1276839362, rs1576682880, rs1588420907, rs375416014, rs955421639, rs1596759273, rs755288504, rs1588153872, rs780020801, rs1576660495, rs1596088812, rs1576875819, rs779696701, rs759262253, rs775612958, rs1570504754, rs754862360, rs1679148969, rs1311042980, rs1682584195, rs753517219, rs1358793834, rs1560002113, rs1939543636, rs1205325321, rs1329661241, rs140611214, rs780500128, rs2061113374, rs1652115764, rs780148543, rs749866369, rs1459158279, rs756111113
Prostate cancer	Malignant neoplasm of prostate	rs121909139, rs121909140, rs121909141, rs121909142, rs121909143, rs606231169, rs606231170, rs137852584, rs137852578, rs137852580, rs137852581, rs137852582	17013881
Renal insufficiency	Renal Insufficiency	rs1596536873

Associations from Text Mining
Disease Name	Relationship Type	References
Glioma	Associate	37952042
Hyperoxaluria	Associate	11135054, 12110000, 18951670, 28569194
Hyperoxaluria Primary	Associate	11135054, 32221050, 35661454, 36151119, 40225159
Nephrocalcinosis	Associate	28569194
Obesity	Associate	28274171
Philadelphia Chromosome	Associate	15327387
Primary hyperoxaluria type 1	Associate	20797690
Primary hyperoxaluria type 2	Associate	25410531, 28569194
Primary hyperoxaluria type 2	Inhibit	28569194