MTRR (5-methyltetrahydrofolate-homocysteine methyltransferase reductase)

Gene

• Entrez ID: 4552
• Gene name: 5-methyltetrahydrofolate-homocysteine methyltransferase reductase
• Gene symbol: MTRR
• Synonyms (NCBI Gene): MSR, cblE
• Chromosome: 5
• Chromosome location: 5p15.31
• Summary: This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires me

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137853061	G>A	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs137853062	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs142714881	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant, non coding transcript variant
rs147277149	C>T	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs148909799	A>G	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant, non coding transcript variant
rs754990692	C>T	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs768980918	GAGA>-	Pathogenic, uncertain-significance	Splice acceptor variant, coding sequence variant, non coding transcript variant
rs796052001	GTT>-	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, non coding transcript variant, inframe deletion, intron variant
rs893229476	T>C	Pathogenic	Non coding transcript variant, intron variant
rs1189298981	G>-,GG	Likely-pathogenic	Coding sequence variant, non coding transcript variant, frameshift variant
rs1293600145	A>T	Likely-pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs1554006017	T>G	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1579619636	G>-	Pathogenic	Intron variant, splice donor variant, non coding transcript variant, frameshift variant, coding sequence variant
rs1579758005	AG>-	Pathogenic	Non coding transcript variant, frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT001613	hsa-let-7b-5p	pSILAC	18668040
MIRT031186	hsa-miR-19b-3p	Sequencing	20371350
MIRT001613	hsa-let-7b-5p	Proteomics;Other	18668040
MIRT1165395	hsa-miR-2110	CLIP-seq
MIRT1165396	hsa-miR-3150a-3p	CLIP-seq
MIRT1165397	hsa-miR-3175	CLIP-seq
MIRT1165398	hsa-miR-3647-3p	CLIP-seq
MIRT1165399	hsa-miR-3670	CLIP-seq
MIRT1165400	hsa-miR-3922-5p	CLIP-seq
MIRT1165401	hsa-miR-4260	CLIP-seq
MIRT1165402	hsa-miR-4269	CLIP-seq
MIRT1165403	hsa-miR-4476	CLIP-seq
MIRT1165404	hsa-miR-4646-5p	CLIP-seq
MIRT1165405	hsa-miR-513a-5p	CLIP-seq
MIRT1165406	hsa-miR-939	CLIP-seq
MIRT1165407	hsa-miR-1271	CLIP-seq
MIRT1165395	hsa-miR-2110	CLIP-seq
MIRT1165408	hsa-miR-224	CLIP-seq
MIRT1165409	hsa-miR-3121-5p	CLIP-seq
MIRT1165396	hsa-miR-3150a-3p	CLIP-seq
MIRT1165397	hsa-miR-3175	CLIP-seq
MIRT1165410	hsa-miR-3199	CLIP-seq
MIRT1165411	hsa-miR-3202	CLIP-seq
MIRT1165399	hsa-miR-3670	CLIP-seq
MIRT1165400	hsa-miR-3922-5p	CLIP-seq
MIRT1165412	hsa-miR-3935	CLIP-seq
MIRT1165413	hsa-miR-409-3p	CLIP-seq
MIRT1165401	hsa-miR-4260	CLIP-seq
MIRT1165414	hsa-miR-4264	CLIP-seq
MIRT1165415	hsa-miR-4287	CLIP-seq
MIRT1165416	hsa-miR-4457	CLIP-seq
MIRT1165417	hsa-miR-4469	CLIP-seq
MIRT1165403	hsa-miR-4476	CLIP-seq
MIRT1165418	hsa-miR-4493	CLIP-seq
MIRT1165419	hsa-miR-4533	CLIP-seq
MIRT1165404	hsa-miR-4646-5p	CLIP-seq
MIRT1165420	hsa-miR-4677-3p	CLIP-seq
MIRT1165421	hsa-miR-4679	CLIP-seq
MIRT1165422	hsa-miR-4685-3p	CLIP-seq
MIRT1165423	hsa-miR-4704-3p	CLIP-seq
MIRT1165424	hsa-miR-4740-5p	CLIP-seq
MIRT1165425	hsa-miR-4781-3p	CLIP-seq
MIRT1165426	hsa-miR-4797-5p	CLIP-seq
MIRT1165427	hsa-miR-485-3p	CLIP-seq
MIRT1165428	hsa-miR-510	CLIP-seq
MIRT1165429	hsa-miR-512-5p	CLIP-seq
MIRT1165405	hsa-miR-513a-5p	CLIP-seq
MIRT1165430	hsa-miR-513b	CLIP-seq
MIRT1165431	hsa-miR-556-5p	CLIP-seq
MIRT1165432	hsa-miR-585	CLIP-seq
MIRT1165433	hsa-miR-593	CLIP-seq
MIRT1165434	hsa-miR-610	CLIP-seq
MIRT1165435	hsa-miR-622	CLIP-seq
MIRT1165436	hsa-miR-671-5p	CLIP-seq
MIRT1165437	hsa-miR-873	CLIP-seq
MIRT1165406	hsa-miR-939	CLIP-seq
MIRT1165438	hsa-miR-96	CLIP-seq
MIRT1165407	hsa-miR-1271	CLIP-seq
MIRT1165411	hsa-miR-3202	CLIP-seq
MIRT1165412	hsa-miR-3935	CLIP-seq
MIRT1165403	hsa-miR-4476	CLIP-seq
MIRT1165423	hsa-miR-4704-3p	CLIP-seq
MIRT1165432	hsa-miR-585	CLIP-seq
MIRT1165438	hsa-miR-96	CLIP-seq
MIRT1165407	hsa-miR-1271	CLIP-seq
MIRT2276628	hsa-miR-1278	CLIP-seq
MIRT1165408	hsa-miR-224	CLIP-seq
MIRT2276629	hsa-miR-320a	CLIP-seq
MIRT2276630	hsa-miR-320b	CLIP-seq
MIRT2276631	hsa-miR-320c	CLIP-seq
MIRT2276632	hsa-miR-320d	CLIP-seq
MIRT2276633	hsa-miR-3923	CLIP-seq
MIRT1165414	hsa-miR-4264	CLIP-seq
MIRT1165415	hsa-miR-4287	CLIP-seq
MIRT2276634	hsa-miR-4429	CLIP-seq
MIRT1165416	hsa-miR-4457	CLIP-seq
MIRT1165417	hsa-miR-4469	CLIP-seq
MIRT2276635	hsa-miR-4668-3p	CLIP-seq
MIRT1165422	hsa-miR-4685-3p	CLIP-seq
MIRT1165423	hsa-miR-4704-3p	CLIP-seq
MIRT1165428	hsa-miR-510	CLIP-seq
MIRT1165429	hsa-miR-512-5p	CLIP-seq
MIRT1165430	hsa-miR-513b	CLIP-seq
MIRT1165431	hsa-miR-556-5p	CLIP-seq
MIRT1165434	hsa-miR-610	CLIP-seq
MIRT1165435	hsa-miR-622	CLIP-seq
MIRT2276636	hsa-miR-628-3p	CLIP-seq
MIRT1165438	hsa-miR-96	CLIP-seq
MIRT2575481	hsa-miR-1263	CLIP-seq
MIRT2575482	hsa-miR-205	CLIP-seq
MIRT2575483	hsa-miR-2053	CLIP-seq
MIRT1165411	hsa-miR-3202	CLIP-seq
MIRT2575484	hsa-miR-3607-3p	CLIP-seq
MIRT2575485	hsa-miR-3646	CLIP-seq
MIRT1165412	hsa-miR-3935	CLIP-seq
MIRT1165413	hsa-miR-409-3p	CLIP-seq
MIRT1165403	hsa-miR-4476	CLIP-seq
MIRT2276635	hsa-miR-4668-3p	CLIP-seq
MIRT2575486	hsa-miR-4716-5p	CLIP-seq
MIRT2575487	hsa-miR-4762-5p	CLIP-seq
MIRT1165432	hsa-miR-585	CLIP-seq
MIRT2575488	hsa-miR-640	CLIP-seq
MIRT1165437	hsa-miR-873	CLIP-seq
MIRT2575481	hsa-miR-1263	CLIP-seq
MIRT2685514	hsa-miR-134	CLIP-seq
MIRT2575482	hsa-miR-205	CLIP-seq
MIRT2575483	hsa-miR-2053	CLIP-seq
MIRT2685515	hsa-miR-3118	CLIP-seq
MIRT2685516	hsa-miR-3164	CLIP-seq
MIRT1165411	hsa-miR-3202	CLIP-seq
MIRT2575484	hsa-miR-3607-3p	CLIP-seq
MIRT2575485	hsa-miR-3646	CLIP-seq
MIRT1165412	hsa-miR-3935	CLIP-seq
MIRT1165403	hsa-miR-4476	CLIP-seq
MIRT2276635	hsa-miR-4668-3p	CLIP-seq
MIRT2575486	hsa-miR-4716-5p	CLIP-seq
MIRT2575487	hsa-miR-4762-5p	CLIP-seq
MIRT2685517	hsa-miR-4766-5p	CLIP-seq
MIRT1165432	hsa-miR-585	CLIP-seq
MIRT2575488	hsa-miR-640	CLIP-seq
MIRT2685518	hsa-miR-758	CLIP-seq
MIRT1165437	hsa-miR-873	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003958	Function	NADPH-hemoprotein reductase activity	IDA	11466310
GO:0005515	Function	Protein binding	IPI	17288554, 25416956, 27771510
GO:0005654	Component	Nucleoplasm	IDA
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	IDA	18221906
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0008652	Process	Amino acid biosynthetic process	IEA
GO:0009086	Process	Methionine biosynthetic process	IBA
GO:0009086	Process	Methionine biosynthetic process	IDA	11466310
GO:0009086	Process	Methionine biosynthetic process	IEA
GO:0009235	Process	Cobalamin metabolic process	IEA
GO:0009235	Process	Cobalamin metabolic process	TAS
GO:0010181	Function	FMN binding	IBA
GO:0010181	Function	FMN binding	IDA	11466310
GO:0010181	Function	FMN binding	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0016723	Function	Oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor	IDA	17892308
GO:0030586	Function	[methionine synthase] reductase (NADPH) activity	IBA
GO:0030586	Function	[methionine synthase] reductase (NADPH) activity	IDA	9501215, 11466310
GO:0030586	Function	[methionine synthase] reductase (NADPH) activity	IEA
GO:0030586	Function	[methionine synthase] reductase (NADPH) activity	TAS	17892308
GO:0033353	Process	S-adenosylmethionine cycle	ISS	17369066
GO:0043418	Process	Homocysteine catabolic process	IDA	11466310
GO:0045111	Component	Intermediate filament cytoskeleton	IDA
GO:0046655	Process	Folic acid metabolic process	IDA	11466310
GO:0046655	Process	Folic acid metabolic process	IEA
GO:0046655	Process	Folic acid metabolic process	ISS
GO:0050660	Function	Flavin adenine dinucleotide binding	IBA
GO:0050660	Function	Flavin adenine dinucleotide binding	IDA	17892308
GO:0050667	Process	Homocysteine metabolic process	IBA
GO:0050667	Process	Homocysteine metabolic process	IEA
GO:0070402	Function	NADPH binding	IDA	11466310
GO:0071949	Function	FAD binding	IDA	11466310
GO:0140104	Function	Molecular carrier activity	EXP	21071249

Other IDs

• MIM: 602568
• HGNC: 7473
• e!Ensembl: ENSG00000124275

Protein

• UniProt ID: Q9UBK8
• Protein name: Methionine synthase reductase (MSR) (EC 1.16.1.8) (Aquacobalamin reductase) (AqCbl reductase)
• Protein function: Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin (PubMed:17892308). Cobalamin (vitamin B12) forms a compl
• PDB: 2QTL, 2QTZ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00258	Flavodoxin_1	6 → 142	Flavodoxin	Domain
  PF00667	FAD_binding_1	267 → 492	FAD binding domain	Domain
  PF00175	NAD_binding_1	542 → 662	Oxidoreductase NAD-binding domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Found in all tissues tested, particularly abundant in skeletal muscle.
• Sequence:

  MRRFLLLYATQQGQAKAIAEEICEQAVVHGFSADLHCISESDKYDLKTETAPLVVVVSTT
  GTGDPPDTARKFVKEIQNQTLPVDFFAHLRYGLLGLGDSEYTYFCNGGKIIDKRLQELGA
  RHFYDTGHADDCVGLELVVEPWIAGLWPALRKHFRSSRGQEEISGALPVASPASSRTDLV
  KSELLHIESQVELLRFDDSGRKDSEVLKQNAVNSNQSNVVIEDFESSLTRSVPPLSQASL
  NIPGLPPEYLQVHLQESLGQEESQVSVTSADPVFQVPISKAVQLTTNDAIKTTLLVELDI
  SNTDFSYQPGDAFSVICPNSDSEVQSLLQRLQLEDKREHCVLLKIKADTKKKGATLPQHI
  PAGCSLQFIFTWCLEIRAIPKKAFLRALVDYTSDSAEKRRLQELCSKQGAADYSRFVRDA
  CACLLDLLLAFPSCQPPLSLLLEHLPKLQPRPYSCASSSLFHPGKLHFVFNIVEFLSTAT
  TEVLRKGVCTGWLALLVASVLQPNIHASHEDSGKALAPKISISPRTTNSFHLPDDPSIPI
  IMVGPGTGIAPFIGFLQHREKLQEQHPDGNFGAMWLFFGCRHKDRDYLFRKELRHFLKHG
  ILTHLKVSFSRDAPVGEEEAPAKYVQDNIQLHGQQVARILLQENGHIYVCGDAKNMAKDV
  HDALVQIISKEVGVEKLEAMKTLATLKEEKRYLQDIWS

• Sequence length: 698

Pathways

KEGG:

Cobalamin transport and metabolism

Reactome:

Methylation
Sulfur amino acid metabolism
Cobalamin (Cbl, vitamin B12) transport and metabolism
Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE
Defective MTR causes methylmalonic aciduria and homocystinuria type cblG

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Colon adenocarcinoma	Likely pathogenic	rs2126808287	RCV005927088
Disorders of Intracellular Cobalamin Metabolism	Likely pathogenic; Pathogenic	rs137853062, rs893229476	RCV002512874 RCV002537460
Homocystinuria without methylmalonic aciduria	Pathogenic	rs754990692	RCV000825568
Methylcobalamin deficiency type cblE	Pathogenic; Likely pathogenic	rs1207820860, rs2126745614, rs1421007019, rs2126772123, rs1440404360, rs2126808162, rs761061866, rs1212701617, rs2126663415, rs2126745648, rs2126675629, rs2126793645, rs1737852706, rs772608494, rs2126727585, rs772547714, rs2126675707, rs754619743, rs1400065323, rs2126812977, rs2126676051, rs1353165398, rs757800887, rs2126692827, rs2479100979, rs2479102741, rs1254913477, rs771216289, rs147960130, rs2478802312, rs1748372023, rs2478892105, rs2478943007, rs2479100396, rs2478942663, rs201348649, rs2478740609, rs1737818730, rs2479101644, rs2479148171, rs2478805727, rs2479147977, rs2479073064, rs2126812944, rs137853061, rs2126808021, rs137853062, rs2126808287, rs147277149, rs747303076, rs2478648157, rs748533060, rs747041200, rs767610650, rs2478892282, rs1737148739, rs2479023142, rs867974337, rs1734858651, rs2478890930, rs2478700578, rs2478942096, rs2478705208, rs2478743643, rs2478703868, rs146940932, rs751833826, rs2478942250, rs919772858, rs2479102700, rs1748694912, rs1554006017, rs1293600145, rs768980918, rs1579619636, rs1579758005, rs893229476, rs754990692, rs1189298981, rs1747827267, rs375908206, rs778738842, rs1747853230, rs1408257020, rs1734931275, rs1737110583, rs1748371268, rs1734927527, rs752858024, rs1561245416, rs777997657, rs1219605974	RCV001380274 RCV001383252 RCV001380276 RCV001385070 RCV001383913 RCV001382154 RCV001836441 RCV001782470 RCV001994586 RCV001941840 RCV001960278 RCV001942388 RCV001952302 RCV002020460 RCV002000164 RCV002035229 RCV001994688 RCV001979539 RCV002033125 RCV001953506 RCV002046730 RCV002503659 RCV001914825 RCV002012576 RCV003091956 RCV003097546 RCV002595427 RCV002600189 RCV002725733 RCV002770836 RCV002820743 RCV002815149 RCV002842594 RCV002863739 RCV002881842 RCV002886271 RCV002988551 RCV003013433 RCV003003293 RCV003034051 RCV003046283 RCV003034770 RCV003047515 RCV000007443 RCV000007446 RCV000007447 RCV000007449 RCV003143428 RCV001068078 RCV004783066 RCV005036814 RCV005036815 RCV003507512 RCV005100186 RCV003486328 RCV003507681 RCV003507696 RCV003508399 RCV003507119 RCV003507172 RCV003507115 RCV003507921 RCV003507987 RCV003618182 RCV003617420 RCV003617567 RCV003825216 RCV003822840 RCV003830114 RCV003842431 RCV003873944 RCV005038715 RCV000625774 RCV001834982 RCV000824011 RCV000805731 RCV000805181 RCV000820217 RCV001869267 RCV001066391 RCV001059702 RCV001043620 RCV001042201 RCV001036277 RCV001206309 RCV001201719 RCV001206236 RCV001212318 RCV001204859 RCV001226344 RCV001226293 RCV001236196 RCV001243293 RCV001233224
MTRR-related disorder	Likely pathogenic; Pathogenic	rs2126675707, rs768980918	RCV003395318 RCV004753037
Neural tube defects, folate-sensitive	Pathogenic; Likely pathogenic	rs1421007019, rs761061866, rs772547714, rs754619743, rs1400065323, rs1353165398, rs2479100979, rs2479102741, rs147960130, rs1737818730, rs137853061, rs137853062, rs767124472, rs2126808287, rs147277149, rs2479159008, rs2476220505, rs780448175, rs2478797022, rs747303076, rs2478742432, rs1181934270, rs1748331186, rs1212701617, rs2126645870, rs2478648157, rs772608494, rs748533060, rs1189298981, rs1738695332, rs2478742839, rs2478800173, rs1532268, rs747041200, rs1737854315, rs2479147425, rs2478705556, rs767610650, rs2478947085, rs2479103276, rs2478890236, rs2479023948, rs2478965467, rs2479148728, rs143058455, rs1748694912, rs1293600145, rs768980918, rs1579619636, rs893229476, rs754990692, rs375908206, rs1734858651, rs778738842, rs1408257020, rs1734931275, rs752858024, rs777997657	RCV005038175 RCV002501867 RCV004571699 RCV003464333 RCV003470947 RCV002503659 RCV003465958 RCV003459750 RCV003465817 RCV003465890 RCV003460433 RCV003460434 RCV004572835 RCV004572859 RCV003469197 RCV003461980 RCV003461981 RCV003461982 RCV003461983 RCV003461984 RCV003470268 RCV003461985 RCV003470269 RCV003461986 RCV003470270 RCV003461987 RCV003470271 RCV003461988 RCV003461989 RCV003461990 RCV003461991 RCV003461992 RCV003461993 RCV003470272 RCV003461994 RCV003463063 RCV003470273 RCV003470274 RCV003463065 RCV003463066 RCV003463067 RCV003463068 RCV003463069 RCV003470275 RCV004576279 RCV004576280 RCV004576283 RCV003465365 RCV003465707 RCV003467413 RCV003467497 RCV002487868 RCV003461302 RCV002481908 RCV003461459 RCV003461431 RCV003462674 RCV003462692 RCV003462774 RCV004570619

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Acute myeloid leukemia	Likely benign	rs6879300	RCV005917709
Cervical cancer	Likely benign	rs6879300	RCV005917711
Down syndrome, susceptibility to	Benign; Likely benign	rs1801394	RCV000007445
Familial cancer of breast	Uncertain significance	rs757997490, rs138098668	RCV005926372 RCV005901961
Gastric cancer	Uncertain significance	rs138098668	RCV005901962
Gastrointestinal stromal tumor	Benign; Likely benign	rs162036, rs10380, rs1532268, rs1801394	RCV000144925 RCV000144924 RCV000144927 RCV000144926
Malignant lymphoma, large B-cell, diffuse	Benign	rs2303079	RCV005911391
Malignant tumor of esophagus	Likely benign; Benign	rs6879300, rs145654110	RCV005917710 RCV005899015
Malignant tumor of urinary bladder	Benign	rs145654110	RCV005899014
Melanoma	Uncertain significance	rs757997490	RCV005926373
Methotrexate response	Benign; Likely benign	rs1801394	RCV003482129
Methylcobalamin deficiency type cblG	Conflicting classifications of pathogenicity	rs1254913477	RCV004577039
Neural tube defects, folate-sensitive, susceptibility to	Benign; Likely benign	rs1801394	RCV000007444
Nonpapillary renal cell carcinoma	Uncertain significance	rs148267849	RCV005913965
Ovarian serous cystadenocarcinoma	Benign	rs75888760	RCV005924607
Sarcoma	Likely benign; Benign	rs6879300, rs75888760	RCV005917712 RCV005924606
Uterine corpus endometrial carcinoma	Benign	rs75888760	RCV005924608

Associations from Text Mining
Disease Name	Relationship Type	References
Abruptio Placentae	Associate	17376725
Adenoma	Associate	16985020, 31740010
Adrenoleukodystrophy	Associate	19353223
Anemia Macrocytic	Associate	25526710
Anemia Megaloblastic	Associate	9501215
Aortic Aneurysm Abdominal	Associate	20871623
Aortic Dissection	Associate	20871623
Autistic Disorder	Associate	22057956
Azoospermia Nonobstructive	Associate	31377750
Beckwith Wiedemann Syndrome	Associate	30165906
Birth Weight	Associate	35631247
Breast Neoplasms	Associate	18842997, 22373582, 24130171, 25598430, 25801246, 27347936
Carcinoma Hepatocellular	Associate	19035314, 25318605, 27936032
Carcinoma Non Small Cell Lung	Associate	20737570
Carcinoma Renal Cell	Associate	24278388
Cardiovascular Diseases	Associate	28253292
Cartilage Diseases	Associate	27469625
Celiac Disease	Associate	21688148
Cerebral Infarction	Associate	21935458, 30884202
Choline Deficiency	Associate	27342765
Cleft Lip	Associate	26963196, 27604992
Cleft Palate	Associate	27167580
Cognition Disorders	Associate	25526710
Colonic Neoplasms	Associate	21603981
Colorectal Neoplasms	Associate	19776626, 20549016, 21603981, 22719222, 22961839, 26108676, 29925788, 31554631, 31740010, 36364857, 38514198
Colorectal Neoplasms	Stimulate	22719222
Communication Disorders	Associate	25526710
Conotruncal cardiac defects	Associate	19493349, 24585533, 30165839, 31851787
Coronary Artery Disease	Associate	20962453
Death	Associate	25840420, 27456431
Death	Inhibit	27456431
Dental Caries	Associate	37531512
Developmental Disabilities	Associate	9501215
Diabetes Gestational	Associate	35631247
Diabetes Mellitus Type 2	Associate	27983710
Dissection Thoracic Aorta	Associate	20871623
Double Outlet Right Ventricle	Associate	22057956, 29293099
Down Syndrome	Associate	10930360, 11443546, 15585767, 18257130, 18273817, 19096127, 20868477, 21045269, 22377700
Drug Related Side Effects and Adverse Reactions	Associate	17009228, 30927276
Ductus Arteriosus Patent	Associate	22057956
Dyslipidemias	Associate	26337056, 30786773
Esophagitis	Associate	25337902
Failure to Thrive	Associate	25526710
Folate Malabsorption Hereditary	Associate	26266420, 26561410, 35631247
Hashimoto Disease	Associate	23039890
Heart Defects Congenital	Associate	22057956, 28758112, 37183022
Heart Septal Defects Ventricular	Associate	28758112, 29293099, 33757570
Hepatitis B Chronic	Associate	38634541
Homocystinuria	Associate	25878036, 9501215
Homocystinuria Megaloblastic Anemia due to Defect in Cobalamin Metabolism CblE Complementation Type	Associate	25978498, 3384945
Hyperhomocysteinemia	Associate	15612980, 30786773, 9501215
Hypertension	Associate	23188888, 26266420, 26337056, 30786773, 32410296, 37154151
Hypertriglyceridemia	Associate	26337056, 30786773
Insulin Resistance	Associate	31200713
Insulin Resistance	Stimulate	31246991
Leukemia Myelogenous Chronic BCR ABL Positive	Associate	36292614
Leukoencephalopathies	Associate	25526710
Lung Diseases	Associate	24307700
Lung Neoplasms	Associate	23372658, 24307700
Lymphatic Metastasis	Associate	25840420
Lymphoma Large B Cell Diffuse	Stimulate	18042267
Lymphoma Non Hodgkin	Associate	17119116, 18042267, 23913011, 25384508
Meningioma	Associate	18483342, 34169999
Mesothelioma Malignant	Associate	32429658
Metabolic Diseases	Associate	25318605, 28253292
Metabolic Syndrome	Associate	25429430
Metabolism Inborn Errors	Associate	31203192
Methylcobalamin Deficiency CblG Type	Associate	25526710, 25978498, 31951343
Methylmalonic Aciduria and Homocystinuria CblF Type	Associate	25978498
Microphthalmia Syndromic 10	Associate	25526710
Migraine Disorders	Associate	23430981
Migraine with Aura	Inhibit	23430981
Multiple Sclerosis	Associate	31038186
Muscle Hypotonia	Associate	25526710
Neoplasms	Inhibit	10673282
Neoplasms	Associate	14716779, 16985020, 17533396, 20549016, 31127906
Neural Tube Defects	Associate	10930360, 15060097, 26334892, 32410296
Neurocognitive Disorders	Associate	25526710
Neutropenia	Associate	30927276
Obesity	Associate	27793164, 27983710
Open Bite	Associate	35830630
Orofacial Cleft 1	Associate	26963196, 27167580
Osteoarthritis	Associate	27469625
Overweight	Associate	27793164, 27983710
Paroxysmal ventricular fibrillation	Associate	27759448
Polycystic Ovary Syndrome	Inhibit	31482954
Polycystic Ovary Syndrome	Associate	31482954, 33407572
Premature Birth	Associate	35631247
Prostatic Neoplasms	Associate	10673282, 31127906
Rectal Neoplasms	Associate	21603981
Severe Acute Respiratory Syndrome	Associate	25526710
Skin Diseases	Associate	29421402
Squamous Cell Carcinoma of Head and Neck	Associate	17596206
Stomach Neoplasms	Associate	20099281, 25337902, 25840420, 27456431, 30884202
Stomatitis	Associate	27452984
Temporomandibular Joint Disorders	Associate	21615938
Thyroiditis Autoimmune	Associate	23039890
Tourette Syndrome	Associate	21618417
Urinary Bladder Neoplasms	Associate	28348449
Urinary Tract Infections	Associate	39303450
Uterine Cervical Neoplasms	Associate	29740106
Uterine Cervicitis	Associate	32295543
Vascular Diseases	Associate	9501215
Vitiligo	Associate	30720153
Xanthomatosis Cerebrotendinous	Associate	15612980