MTHFS (methenyltetrahydrofolate synthetase)

Gene

• Entrez ID: 10588
• Gene name: Methenyltetrahydrofolate synthetase
• Gene symbol: MTHFS
• Synonyms (NCBI Gene): HsT19268, NEDMEHM
• Disease Acronyms (UniProt): NEDMEHM
• Chromosome: 15
• Chromosome location: 15q25.1
• Summary: The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can resu

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023879	hsa-miR-1-3p	Proteomics	18668040
MIRT029878	hsa-miR-26b-5p	Microarray	19088304
MIRT1163447	hsa-miR-1276	CLIP-seq
MIRT1163448	hsa-miR-1305	CLIP-seq
MIRT1163449	hsa-miR-1324	CLIP-seq
MIRT1163450	hsa-miR-141	CLIP-seq
MIRT1163451	hsa-miR-200a	CLIP-seq
MIRT1163452	hsa-miR-23a	CLIP-seq
MIRT1163453	hsa-miR-23b	CLIP-seq
MIRT1163454	hsa-miR-23c	CLIP-seq
MIRT1163455	hsa-miR-3148	CLIP-seq
MIRT1163456	hsa-miR-3163	CLIP-seq
MIRT1163457	hsa-miR-3179	CLIP-seq
MIRT1163458	hsa-miR-3662	CLIP-seq
MIRT1163459	hsa-miR-3920	CLIP-seq
MIRT1163460	hsa-miR-3942-3p	CLIP-seq
MIRT1163461	hsa-miR-4643	CLIP-seq
MIRT1163462	hsa-miR-466	CLIP-seq
MIRT1163463	hsa-miR-4668-5p	CLIP-seq
MIRT1163464	hsa-miR-4687-3p	CLIP-seq
MIRT1163465	hsa-miR-4742-3p	CLIP-seq
MIRT1163466	hsa-miR-4789-3p	CLIP-seq
MIRT1163467	hsa-miR-622	CLIP-seq
MIRT1163468	hsa-miR-630	CLIP-seq
MIRT1163469	hsa-miR-647	CLIP-seq
MIRT1163470	hsa-miR-128	CLIP-seq
MIRT1163471	hsa-miR-1283	CLIP-seq
MIRT1163472	hsa-miR-144	CLIP-seq
MIRT1163473	hsa-miR-27a	CLIP-seq
MIRT1163474	hsa-miR-27b	CLIP-seq
MIRT1163457	hsa-miR-3179	CLIP-seq
MIRT1163475	hsa-miR-3670	CLIP-seq
MIRT1163476	hsa-miR-4633-3p	CLIP-seq
MIRT1163477	hsa-miR-520d-5p	CLIP-seq
MIRT1163478	hsa-miR-520g	CLIP-seq
MIRT1163479	hsa-miR-520h	CLIP-seq
MIRT1163480	hsa-miR-524-5p	CLIP-seq
MIRT1163481	hsa-miR-9	CLIP-seq
MIRT1163452	hsa-miR-23a	CLIP-seq
MIRT1163453	hsa-miR-23b	CLIP-seq
MIRT1163454	hsa-miR-23c	CLIP-seq
MIRT2046991	hsa-miR-3065-5p	CLIP-seq
MIRT1163458	hsa-miR-3662	CLIP-seq
MIRT1163465	hsa-miR-4742-3p	CLIP-seq
MIRT1163467	hsa-miR-622	CLIP-seq
MIRT1163468	hsa-miR-630	CLIP-seq
MIRT2046992	hsa-miR-944	CLIP-seq
MIRT1163460	hsa-miR-3942-3p	CLIP-seq
MIRT2276030	hsa-miR-4257	CLIP-seq
MIRT2276031	hsa-miR-539	CLIP-seq
MIRT2391161	hsa-miR-142-5p	CLIP-seq
MIRT2391162	hsa-miR-340	CLIP-seq
MIRT2276031	hsa-miR-539	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005524	Function	ATP binding	IDA	19738041
GO:0005542	Function	Folic acid binding	IDA	7766710, 19738041
GO:0005737	Component	Cytoplasm	IDA	7766710
GO:0005739	Component	Mitochondrion	IBA	21873635
GO:0005759	Component	Mitochondrial matrix	IDA	7766710
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006536	Process	Glutamate metabolic process	IMP	12764149
GO:0009396	Process	Folic acid-containing compound biosynthetic process	IBA	21873635
GO:0015942	Process	Formate metabolic process	NAS	8522195
GO:0030272	Function	5-formyltetrahydrofolate cyclo-ligase activity	IBA	21873635
GO:0030272	Function	5-formyltetrahydrofolate cyclo-ligase activity	IDA	7766710, 19738041
GO:0030272	Function	5-formyltetrahydrofolate cyclo-ligase activity	IMP	12764149
GO:0030272	Function	5-formyltetrahydrofolate cyclo-ligase activity	NAS	8522195
GO:0030272	Function	5-formyltetrahydrofolate cyclo-ligase activity	TAS
GO:0035999	Process	Tetrahydrofolate interconversion	IBA	21873635
GO:0035999	Process	Tetrahydrofolate interconversion	IMP	12764149
GO:0046653	Process	Tetrahydrofolate metabolic process	IDA	7766710, 19738041
GO:0046655	Process	Folic acid metabolic process	TAS
GO:0046657	Process	Folic acid catabolic process	IMP	12764149
GO:0046872	Function	Metal ion binding	IEA

Other IDs

• MIM: 604197
• HGNC: 7437
• e!Ensembl: ENSG00000136371

Protein

• UniProt ID: P49914
• Protein name: 5-formyltetrahydrofolate cyclo-ligase (EC 6.3.3.2) (5,10-methenyl-tetrahydrofolate synthetase) (MTHFS) (Methenyl-THF synthetase)
• Protein function: Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversi
• PDB: 3HXT, 3HY3, 3HY4, 3HY6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01812	5-FTHF_cyc-lig	10 → 198	5-formyltetrahydrofolate cyclo-ligase family	Family

• Sequence:

  MAAAAVSSAKRSLRGELKQRLRAMSAEERLRQSRVLSQKVIAHSEYQKSKRISIFLSMQD
  EIETEEIIKDIFQRGKICFIPRYRFQSNHMDMVRIESPEEISLLPKTSWNIPQPGEGDVR
  EEALSTGGLDLIFMPGLGFDKHGNRLGRGKGYYDAYLKRCLQHQEVKPYTLALAFKEQIC
  LQVPVNENDMKVDEVLYEDSSTA

• Sequence length: 203

Pathways

KEGG:

One carbon pool by folate
Metabolic pathways
Folate transport and metabolism

Reactome:

Metabolism of folate and pterines

Associated diseases

Causal
Disease term	Disease name	dbSNP ID	References
Developmental delay	Global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Dysautonomia	Dysautonomia	rs111033171, rs137853022, rs28939712, rs754348901, rs749052963, rs1057517169, rs1057516865, rs763445509, rs767527819, rs781333644, rs1239081703, rs1554696574, rs539544212, rs1201626345, rs774890086, rs1554703061, rs1554703613, rs1319053366, rs1554703851, rs868073099, rs926177767, rs376078668, rs1554695299, rs1554696648, rs1554696934, rs1554699327, rs1554691572, rs1554695846, rs1554697001, rs770668926, rs1554698037, rs759412460, rs1554702142, rs765572951, rs1554702880, rs1554703831, rs760774999, rs1554696650, rs757972943, rs1554703874, rs1554703907, rs571348995
Epilepsy	Gelastic Epilepsy	rs113994140, rs28937874, rs1589762127, rs104894166, rs28939075, rs2134001459, rs104894167, rs119488099, rs119488100, rs387906420, rs121917752, rs121918622, rs281865564, rs387907313, rs397514670, rs768241563, rs587776973, rs587776974, rs587776975, rs879255234, rs587776976, rs587776977, rs121917993, rs398123588, rs13306758, rs587777458, rs587777459, rs541024038, rs797044545, rs730882240, rs786205703, rs794726859, rs796053126, rs796053035, rs796053216, rs796052839, rs869025201, rs797044999, rs797044998, rs797045045, rs794726762, rs869312971, rs869312972, rs879255652, rs886037938, rs886037958, rs886037959, rs886037960, rs886037961, rs886037962, rs886037965, rs886037966, rs886039245, rs886039246, rs886039251, rs886039252, rs772872014, rs886039253, rs886039256, rs757511744, rs886039261, rs886039263, rs578185749, rs886039266, rs886039268, rs886039269, rs886039273, rs368820286, rs1057518801, rs1057518688, rs1057519107, rs1057519273, rs752753379, rs767795673, rs1057519424, rs755946598, rs760609867, rs1057521066, rs1057524233, rs1060501488, rs1060501487, rs755127868, rs751533302, rs771373457, rs1475605360, rs1555401942, rs1553567864, rs200661329, rs766667249, rs1556607762, rs1555882921, rs1555882867, rs1555900914, rs1553546836, rs77216276, rs755595256, rs747661902, rs2105890565, rs1021001959, rs1555441032, rs1555439541, rs1556526609, rs1315483224, rs759952667, rs1555885023, rs1553456695, rs1555942720, rs1569083500, rs1559127505, rs1206309859, rs1567139896, rs1567134495, rs1431914212, rs1569166925, rs1569255443, rs1568955379, rs1567152003, rs374158137, rs1567129567, rs1569523728, rs1568991466, rs1569186093, rs1569254004, rs1372605067, rs1569067939, rs1568963062, rs1563959514, rs1569012755, rs1559118914, rs1602338615, rs1596522356, rs1364913665, rs1596522300, rs1596526976, rs1229740428, rs1596385588, rs1596500172, rs1596505517, rs1601925213, rs1601970168, rs1602010382, rs1602903591, rs1603014297, rs1603014708, rs1601875057, rs1601970824, rs1601755632, rs1587393982, rs1592977444, rs1575562076, rs1570998206, rs1588057922, rs1596528731, rs1602349641, rs1587401875, rs2065899210, rs1596526915, rs2093486364, rs2056165149, rs2056100951, rs781482552, rs1899868619, rs1900088045, rs1898675878, rs1898686157, rs1898837245, rs1898844513, rs2082841677, rs2085727988, rs2092933941, rs2091657024, rs1899864955, rs1898844907, rs2083056830, rs2084070588, rs1899713412, rs2082695884, rs1977106116, rs1977105425, rs1443687532
Microcephaly	Microcephaly	rs397704721, rs267607176, rs267607177, rs397704725, rs267606717, rs267606718, rs199422202, rs121434311, rs199422203, rs199422126, rs387906274, rs121434305, rs199422125, rs199422135, rs189678019, rs199422184, rs137852994, rs137852995, rs137852996, rs137852997, rs145489194, rs80338860, rs137852494, rs121918609, rs199422207, rs199422206, rs29001566, rs864321658, rs199422138, rs199422139, rs199422141, rs199422144, rs199422147, rs199422151, rs199422152, rs199422153, rs199422157, rs199422159, rs199422160, rs199422161, rs140602858, rs199422164, rs199422165, rs148294838, rs199422134, rs199422168, rs199422172, rs199422173, rs199422131, rs199422177, rs199422180, rs199422185, rs199422186, rs199422187, rs143931757, rs199422189, rs199422192, rs199422194, rs199422195, rs199422196, rs199422197, rs199422199, rs753597039, rs1488084787, rs387906961, rs755862917, rs387907082, rs587776899, rs387907083, rs587776900, rs587776901, rs387907084, rs863223322, rs764201220, rs202247811, rs763915472, rs587776986, rs587777036, rs398122971, rs374351172, rs373278668, rs398122976, rs121909123, rs587783393, rs730882076, rs587783211, rs144716013, rs606231255, rs587783215, rs587783216, rs587783220, rs587783221, rs587783225, rs587783227, rs587783228, rs587783230, rs587783238, rs587783239, rs587783240, rs587783245, rs587783247, rs587783248, rs587783258, rs587783259, rs587783263, rs587783265, rs587783268, rs587783269, rs587783272, rs587783275, rs587783277, rs587783278, rs587783280, rs587783282, rs587783283, rs587783285, rs587783287, rs587783288, rs587783289, rs587783292, rs587783295, rs587784452, rs587783741, rs587783735, rs587783392, rs587783390, rs587783387, rs587783410, rs202058504, rs587783423, rs587783421, rs587783414, rs587784553, rs587784558, rs587784546, rs587784549, rs587784554, rs587784412, rs876661307, rs869025200, rs747831095, rs748529285, rs797045316, rs797045315, rs797045314, rs759632528, rs797045313, rs797045311, rs754282058, rs797045441, rs797045454, rs797045430, rs869312853, rs797046109, rs767399782, rs863225127, rs863225464, rs863225465, rs780270096, rs864321621, rs864321620, rs775277800, rs879253817, rs869312824, rs761447719, rs753406334, rs147622433, rs199422137, rs879255522, rs879255524, rs879255523, rs886037892, rs886037893, rs886037894, rs886037895, rs199422169, rs886041709, rs886041282, rs138228629, rs759188041, rs769688376, rs1057517688, rs1057519087, rs1057518268, rs933106143, rs201362977, rs754909135, rs1057520873, rs1060499758, rs1060499757, rs199422146, rs748016594, rs1085307120, rs763715733, rs1064795945, rs763800571, rs1554728351, rs1553227021, rs555866170, rs1553895368, rs1334947797, rs769818500, rs1321892596, rs1553227645, rs1404276011, rs1553228275, rs1554471681, rs1554496609, rs1555420891, rs1555418825, rs587784548, rs1555723585, rs199736219, rs745997770, rs765275884, rs1553924800, rs1554730137, rs1229568621, rs1482100822, rs979186313, rs758157294, rs1555294652, rs1555299107, rs1553264033, rs1553259539, rs1553254322, rs1553259528, rs981349334, rs1553264036, rs1553253022, rs754267846, rs776034810, rs1342429887, rs752140135, rs1006898944, rs571640983, rs1477524771, rs763909256, rs199910503, rs1553223496, rs759663956, rs1553446603, rs1555139372, rs1555143325, rs1350194762, rs1555141158, rs1553225179, rs769481947, rs769364943, rs748011724, rs1334301723, rs746341112, rs149225624, rs765113367, rs1567024512, rs142865061, rs772050241, rs201721894, rs1557966012, rs1379578836, rs1568334868, rs1185537869, rs1602333390, rs1163303148, rs774338373, rs770540184, rs1571600045, rs1571601267, rs1571602991, rs1588472215, rs1599841026, rs1558328287, rs1571600860, rs1571596976, rs1309880692, rs1435239428, rs1588634016, rs1751797979, rs1810830776, rs1815354949, rs1949984655, rs886039658, rs1943461045, rs777711720, rs2031759596, rs1555710223, rs1221031683, rs774069989, rs2058919680, rs1170413397, rs1213710245, rs1599851667, rs1599760058, rs1971033478, rs746967357
Seizure	Tonic - clonic seizures	rs587784365, rs28939683, rs74315390, rs28939684, rs74315391, rs267607198, rs74315392, rs118192244, rs118192250, rs121917749, rs121917750, rs121917751, rs121917752, rs267606670, rs267607061, rs121912707, rs118192249, rs118192251, rs118192217, rs118192218, rs118192219, rs118192222, rs118192226, rs118192228, rs118192234, rs118192236, rs118192235, rs118192241, rs118192242, rs118192185, rs118192188, rs118192245, rs118192246, rs118192186, rs118192194, rs118192197, rs118192199, rs118192201, rs118192202, rs118192203, rs118192204, rs118192205, rs118192206, rs118192208, rs118192211, rs118192216, rs118192239, rs387906684, rs387906686, rs387906687, rs1596893185, rs387907126, rs387907281, rs397515405, rs587778771, rs730882067, rs730882073, rs397514579, rs397514582, rs587776976, rs398122394, rs121918784, rs121918751, rs121918735, rs398123588, rs587780450, rs61749751, rs587777620, rs727503974, rs730882124, rs794726710, rs794726697, rs794726799, rs794727444, rs794727740, rs796053166, rs794726825, rs796052676, rs796053219, rs796053220, rs796053228, rs796052653, rs759584387, rs796052650, rs796052641, rs796052626, rs796052623, rs796052663, rs796052615, rs796052802, rs797044999, rs797045047, rs797045942, rs797045941, rs118192212, rs797044938, rs777257591, rs864321712, rs879255652, rs886039268, rs886039517, rs886039529, rs199497486, rs886039496, rs886039903, rs886041300, rs769827124, rs886041339, rs886041591, rs587783092, rs1555850151, rs1057516123, rs1057516121, rs1057516115, rs1057516111, rs1057516106, rs1057516105, rs756921902, rs1057516089, rs1057516087, rs1057516080, rs1057516076, rs1060499544, rs1555850512, rs1057517919, rs118192231, rs1057520413, rs1060503101, rs1064796294, rs1064794981, rs1064794632, rs1064797245, rs1131691830, rs1131692231, rs1131691936, rs1554626549, rs1553579225, rs1553531385, rs121918736, rs1554898088, rs1553579282, rs763353895, rs1553463119, rs1554093891, rs77838305, rs1555408401, rs1554627439, rs1554097873, rs1555850403, rs1064794719, rs1315483224, rs1567134495, rs770187706, rs1057518555, rs1576983339, rs1574192005, rs1459374430, rs1586800133, rs1574641522, rs1572096837, rs1572630269, rs1574554892, rs1574556643, rs1574571769, rs1574641605, rs1574697769, rs1574716524, rs1574746733, rs1574746935, rs1574752700, rs1574754680, rs863225030, rs1601545088, rs1600714727, rs1371059392, rs1600767259, rs1339542565, rs1600785769, rs2065899210, rs1600732174, rs1162306056, rs879255709, rs1900111672, rs2066910297, rs1554122080, rs796052941, rs1600789325, rs2082695884, rs1737677036, rs1737495759, rs868389022, rs1737685202, rs1737672350, rs762737130

Unknown
Disease term	Disease name	Evidence	References	Source
Distal hereditary motor neuronopathy	neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination			GenCC

Associations from Text Mining
Disease Name	Relationship Type	References
Congenital central hypoventilation syndrome	Associate	24894164
Congenital Hereditary and Neonatal Diseases and Abnormalities	Associate	30031689
Genetic Diseases Inborn	Associate	28805617
Heart Defects Congenital	Associate	28264803
Kidney Diseases	Associate	18522750
Lung Neoplasms	Associate	17533396
Lymphoma Non Hodgkin	Associate	17119116
Muscle Spasticity	Associate	30031689
Neoplasms	Associate	17533396
Renal Insufficiency Chronic	Associate	18522750
Small Cell Lung Carcinoma	Associate	17533396