| SNP ID |
Visualize variation |
Clinical significance |
Consequence |
| rs1805087 |
A>G |
Benign, risk-factor, uncertain-significance |
Coding sequence variant, missense variant |
| rs116836001 |
C>G,T |
Conflicting-interpretations-of-pathogenicity, uncertain-significance |
Missense variant, coding sequence variant |
| rs121913578 |
C>T |
Likely-pathogenic, pathogenic, pathogenic-likely-pathogenic |
Missense variant, coding sequence variant |
| rs121913580 |
C>T |
Pathogenic |
Stop gained, coding sequence variant |
| rs121913581 |
G>T |
Pathogenic |
Stop gained, coding sequence variant |
| rs121913582 |
G>C |
Pathogenic |
Missense variant, coding sequence variant |
| rs145006491 |
G>A,T |
Conflicting-interpretations-of-pathogenicity, uncertain-significance, benign |
Coding sequence variant, 5 prime UTR variant, missense variant |
| rs201718371 |
C>T |
Pathogenic |
Coding sequence variant, stop gained |
| rs794727395 |
TG>- |
Pathogenic |
Coding sequence variant, frameshift variant |
| rs797044443 |
AAT>- |
Pathogenic |
Coding sequence variant, inframe deletion |
| rs797044444 |
TC>- |
Pathogenic |
Coding sequence variant, intron variant, frameshift variant |
| rs797044445 |
->A |
Pathogenic |
Coding sequence variant, frameshift variant |
| rs1064796330 |
A>- |
Likely-pathogenic |
Coding sequence variant, frameshift variant |
| rs1190777785 |
G>C |
Likely-pathogenic |
5 prime UTR variant, upstream transcript variant, coding sequence variant, missense variant, genic upstream transcript variant |
| rs1242741686 |
A>G |
Likely-pathogenic |
Missense variant, coding sequence variant |
| rs1346847201 |
C>- |
Pathogenic |
Coding sequence variant, frameshift variant |
| rs1367402633 |
AT>- |
Likely-pathogenic |
Genic upstream transcript variant, 5 prime UTR variant, frameshift variant, initiator codon variant, coding sequence variant |
| rs1413989228 |
G>A |
Likely-pathogenic |
Missense variant, intron variant, coding sequence variant |
| rs1572218599 |
G>C |
Likely-pathogenic |
Splice donor variant, intron variant |
| rs1572278166 |
->ATCA |
Pathogenic |
Coding sequence variant, frameshift variant |
| rs1572309822 |
A>- |
Pathogenic |
Coding sequence variant, intron variant, stop gained |
|
|
UniProt ID
Unique identifier for the protein in the UniProt database. Click to view detailed protein information.
|
Q99707 |
| Protein name |
Methionine synthase (MS) (EC 2.1.1.13) (5-methyltetrahydrofolate--homocysteine methyltransferase) (Cobalamin-dependent methionine synthase) (Vitamin-B12 dependent methionine synthase) |
| Protein function |
Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:16769880, PubMed:17288554, PubMed:27771510). MeCbl is an active form of cobalami |
| PDB |
2O2K
, 4CCZ
|
| Family and domains |
Pfam
| Accession |
ID |
Position in sequence |
Description |
Type |
| PF02574 |
S-methyl_trans |
31 → 338 |
Homocysteine S-methyltransferase |
Family |
| PF00809 |
Pterin_bind |
375 → 613 |
Pterin binding enzyme |
Domain |
| PF02607 |
B12-binding_2 |
671 → 748 |
B12 binding domain |
Domain |
| PF02310 |
B12-binding |
773 → 874 |
B12 binding domain |
Domain |
| PF02965 |
Met_synt_B12 |
965 → 1246 |
Vitamin B12 dependent methionine synthase, activation domain |
Domain |
|
| Tissue specificity |
TISSUE SPECIFICITY: Widely expressed. Expressed at the highest levels in pancreas, heart, brain, skeletal muscle and placenta (PubMed:8968735, PubMed:8968737). Expressed at lower levels in lung, liver and kidney (PubMed:8968735, PubMed:8968737). {ECO:0000 |
| Sequence |
|
| Sequence length |
1265 |
| Interactions |
View interactions |
| Phenotype Name |
Clinical Significance |
dbSNP ID |
RCV Accession |
| Decreased methionine synthase activity |
Pathogenic; Likely pathogenic |
rs121913578, rs1190777785 |
RCV001003947 RCV001003946 |
| Disorders of Intracellular Cobalamin Metabolism |
Pathogenic |
rs121913578 |
RCV000778974 |
| Epilepsy |
Pathogenic |
rs121913578 |
RCV000162189 |
| Homocystinuria |
Pathogenic; Likely pathogenic |
rs121913578, rs1190777785 |
RCV001003947 RCV001003946 |
| Intellectual disability |
Likely pathogenic; Pathogenic |
rs1324468065 |
RCV005626831 |
| Melanoma |
Likely pathogenic |
rs1664661222 |
RCV005913543 |
| Methylcobalamin deficiency type cblG |
Pathogenic; Likely pathogenic |
rs752526782, rs1666006480, rs1400658126, rs1558334603, rs138695265, rs778242201, rs2103130072, rs774231870, rs2147922731, rs762727293, rs1664521219, rs794727395, rs1343645070, rs2528337010, rs2528074679, rs772951826, rs776216297, rs2527985401, rs1176062955, rs2528537380, rs2527909396, rs2527833447, rs2528160239, rs1666192928, rs2528435985, rs2528436693, rs2527985163, rs2527854627, rs1324468065, rs1664661129, rs2528240978, rs1663042244, rs2528522105, rs781320871, rs2527974254, rs778563154, rs121913578, rs121913579, rs1661117141, rs797044444, rs797044445, rs121913580, rs121913581, rs752220849, rs192346180, rs765288116, rs2528250134, rs763288919, rs764980259, rs2528240695, rs1572218599, rs2528537363, rs2528177941, rs915986128, rs1269957639, rs2528436006, rs768968736, rs776165231, rs2527889197, rs1666295144, rs767201867, rs2528336317, rs2528241635, rs1180704409, rs1665948819, rs2528336328, rs1346847201, rs536238004, rs145939391, rs1572278166, rs1572309822, rs201718371, rs1662641467, rs1664661222, rs1661544157, rs757963570, rs1224783275, rs1664669480, rs1665277406 View all (64 more) |
RCV001353054 RCV001353055 RCV001782469 RCV003514527 RCV001823618 RCV001837425 RCV001993759 RCV001900088 RCV002033483 RCV001996785 RCV002250130 RCV003514322 RCV002580621 RCV002880567 RCV002996912 RCV005019557 RCV005102850 RCV003629269 RCV003514640 RCV003514684 RCV003514711 RCV003514762 RCV003515287 RCV003515355 RCV003515608 RCV003515610 RCV003513807 RCV003516287 RCV003516288 RCV003516289 RCV003515047 RCV003515794 RCV003514844 RCV003515901 RCV003516102 RCV003515865 RCV000015348 RCV000015350 RCV000015351 RCV000015352 RCV000015354 RCV000015356 RCV000015357 RCV003516004 RCV003629302 RCV003629528 RCV003629572 RCV003630480 RCV003630449 RCV003630644 RCV003630657 RCV003630872 RCV003631009 RCV003631046 RCV003631073 RCV003628747 RCV003629656 RCV003629687 RCV003830230 RCV003835380 RCV003845356 RCV003840798 RCV003865344 RCV003875962 RCV003869900 RCV003990400 RCV003768229 RCV003514413 RCV003514412 RCV000803188 RCV000805410 RCV000805089 RCV000795006 RCV001071198 RCV001059608 RCV001198173 RCV001195906 RCV001244091 RCV001250117 RCV001250118 |
| MTR-related disorder |
Likely pathogenic; Pathogenic |
rs1359827243, rs1176062955, rs2528524023, rs121913578 |
RCV003393052 RCV003421021 RCV003408410 RCV005229796 |
| Neural tube defects, folate-sensitive |
Likely pathogenic; Pathogenic |
rs1400658126, rs138695265, rs772951826, rs121913580 |
RCV005006049 RCV005006080 RCV005019557 RCV005016268 |
| Profound intellectual disability |
Pathogenic |
rs121913578 |
RCV000162189 |
| Thymoma |
Likely pathogenic |
rs1666295144 |
RCV005935002 |
|
| Phenotype Name |
Clinical Significance |
dbSNP ID |
RCV Accession |
| Acute myeloid leukemia |
Benign; Uncertain significance; Likely benign |
rs11809449, rs768230559, rs114324996, rs41530146, rs10925256 |
RCV005914015 RCV005928346 RCV005891685 RCV005891671 RCV005900870 |
| Cervical cancer |
Benign |
rs11809449, rs41530146 |
RCV005914016 RCV005891672 |
| Cholangiocarcinoma |
Benign; Likely benign |
rs45468296, rs377347275, rs531027742 |
RCV005921955 RCV005925985 RCV005898814 |
| Chronic lymphocytic leukemia/small lymphocytic lymphoma |
Benign |
rs41530146 |
RCV005891680 |
| Clear cell carcinoma of kidney |
Benign |
rs61739582 |
RCV005891681 |
| Colorectal cancer |
Benign |
rs546254033 |
RCV005867111 |
| Familial cancer of breast |
Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity |
rs1491459998, rs546254033, rs753703111, rs571901048, rs144374509, rs372886393, rs144767461, rs10925256 |
RCV005867130 RCV005867110 RCV005917848 RCV005922499 RCV005924251 RCV005896725 RCV005896600 RCV005900869 |
| Familial pancreatic carcinoma |
Likely benign; Benign |
rs753703111, rs41530146, rs10925256 |
RCV005917851 RCV005891674 RCV005900873 |
| Gastric cancer |
Benign; Conflicting classifications of pathogenicity |
rs11809449, rs45468296, rs41530146, rs144767461 |
RCV005914017 RCV005921953 RCV005891676 RCV005896602 |
| Gastrointestinal stromal tumor |
Benign |
rs1805087 |
RCV000144923 |
| Hepatocellular carcinoma |
Benign; Likely benign |
rs571901048, rs151081130 |
RCV005922500 RCV005891683 |
| Lung cancer |
Benign; Likely benign |
rs571901048, rs41530146 |
RCV005922501 RCV005891678 |
| Malignant tumor of esophagus |
Benign; Likely benign; Conflicting classifications of pathogenicity |
rs1491459998, rs377347275, rs144767461 |
RCV005867131 RCV005925984 RCV005896601 |
| Neural tube defects, folate-sensitive, susceptibility to |
Benign |
rs1805087 |
RCV000015355 |
| Nonpapillary renal cell carcinoma |
Likely benign; Benign |
rs753703111, rs10925256 |
RCV005917849 RCV005900871 |
| Ovarian cancer |
Likely benign; Benign |
rs753703111, rs41530146 |
RCV005917850 RCV005891673 |
| Ovarian serous cystadenocarcinoma |
Benign |
rs41530146 |
RCV005891677 |
| Sarcoma |
Benign; Likely benign |
rs41530146, rs151081130 |
RCV005891675 RCV005891684 |
| See cases |
Conflicting classifications of pathogenicity; Uncertain significance |
rs150058137, rs201901663, rs757429726 |
RCV002253108 RCV002252091 RCV002252317 |
| Thyroid cancer, nonmedullary, 1 |
Likely benign |
rs753703111 |
RCV005917852 |
| Uterine carcinosarcoma |
Benign |
rs45468296 |
RCV005921954 |
| Uterine corpus endometrial carcinoma |
Benign |
rs41530146, rs61739582 |
RCV005891679 RCV005891682 |
| Uveal melanoma |
Benign |
rs10925256 |
RCV005900872 |
|
| Disease Name |
Relationship Type |
References |
| Adenocarcinoma |
Associate |
32894539 |
| Adenoma |
Associate |
31740010 |
| Age Related Hearing Impairment 1 |
Associate |
21385350 |
| Alzheimer Disease |
Associate |
15201366 |
| Anemia Macrocytic |
Associate |
25526710 |
| Anemia Megaloblastic |
Associate |
9501215 |
| Anemia Neonatal |
Associate |
3828532 |
| Aortic Aneurysm Abdominal |
Associate |
20871623 |
| Aortic Dissection |
Associate |
20871623 |
| Attention Deficit Disorder with Hyperactivity |
Associate |
23650422 |
| Autistic Disorder |
Inhibit |
23437274 |
| Autistic Disorder |
Associate |
28094822 |
| Birth Weight |
Associate |
35631247 |
| Brachydactyly Type E |
Inhibit |
31951343 |
| Breast Neoplasms |
Associate |
17595805, 19240236, 19389261, 19706843, 25217320, 27347936, 27404801 |
| Carcinoma Hepatocellular |
Associate |
25337902 |
| Carcinoma Non Small Cell Lung |
Inhibit |
15735045 |
| Carcinoma Non Small Cell Lung |
Associate |
20737570 |
| Cardiomyopathies |
Associate |
38168585 |
| Cardiovascular Diseases |
Associate |
27316508, 32068834 |
| Celiac Disease |
Associate |
21688148 |
| Cerebral Infarction |
Associate |
17461517 |
| Choline Deficiency |
Associate |
27342765 |
| Cleft Palate |
Associate |
25716564, 27167580 |
| Cognition Disorders |
Associate |
25526710, 25625218 |
| Cognitive Dysfunction |
Associate |
25625218 |
| Colitis Ulcerative |
Associate |
18700049 |
| Colonic Neoplasms |
Associate |
21603981 |
| Colorectal Neoplasms |
Associate |
19776626, 20615890, 21603981, 22719222, 29925788, 31740010, 38514198 |
| Communication Disorders |
Associate |
25526710 |
| Congenital contractural arachnodactyly |
Associate |
27822905 |
| Conotruncal cardiac defects |
Associate |
30165839 |
| Convulsions benign familial neonatal dominant form |
Associate |
9683607 |
| Death |
Associate |
25840420 |
| Dementia |
Associate |
15201366 |
| Dental Caries |
Associate |
37531512 |
| Depressive Disorder |
Associate |
37628752 |
| Developmental Disabilities |
Associate |
9501215, 9683607 |
| Diabetes Gestational |
Associate |
35631247, 36313769 |
| Dissection Thoracic Aorta |
Associate |
20871623 |
| Down Syndrome |
Associate |
15585767, 18060320 |
| Down Syndrome |
Inhibit |
31951343 |
| Drug Related Side Effects and Adverse Reactions |
Associate |
17009228, 31181069 |
| Esophageal Squamous Cell Carcinoma |
Associate |
16333305 |
| Failure to Thrive |
Associate |
25526710 |
| Folate Malabsorption Hereditary |
Associate |
15585767, 26266420, 35631247, 9501215 |
| Gastrointestinal Neoplasms |
Associate |
17726616 |
| Head and Neck Neoplasms |
Associate |
20490431 |
| Hearing Loss |
Associate |
21385350 |
| Heart Defects Congenital |
Associate |
26035828, 30911047, 37296303 |
| Heart Septal Defects Ventricular |
Associate |
29293099 |
| Hereditary Breast and Ovarian Cancer Syndrome |
Associate |
17595805 |
| Homocystinuria |
Associate |
3828532 |
| Homocystinuria Megaloblastic Anemia due to Defect in Cobalamin Metabolism CblE Complementation Type |
Associate |
3384945 |
| Hyperhomocysteinemia |
Associate |
12068375, 9501215 |
| Hypertension Pulmonary |
Associate |
38168585 |
| Leukemia |
Associate |
20101025 |
| Leukemia Myeloid Acute |
Associate |
20101025 |
| Leukoencephalopathies |
Associate |
25526710 |
| Lymphoma |
Associate |
11342450, 15138479, 15551285 |
| Lymphoma Follicular |
Associate |
15198953 |
| Lymphoma Large B Cell Diffuse |
Associate |
15198953 |
| Lymphoma Non Hodgkin |
Associate |
12648076, 15198953 |
| Malaria |
Associate |
27198213 |
| Methylcobalamin Deficiency CblG Type |
Associate |
12068375, 25526710, 31951343, 38168585, 9683607 |
| Methylmalonic Aciduria and Homocystinuria CblF Type |
Associate |
32068834 |
| Microphthalmia Syndromic 10 |
Associate |
25526710 |
| Multiple Myeloma |
Inhibit |
17546637 |
| Multiple Myeloma |
Associate |
17546637 |
| Multiple Sclerosis |
Associate |
25625218 |
| Muscle Hypotonia |
Associate |
25526710 |
| Neoplasms |
Associate |
15735045, 16333305, 21603981, 25531253, 30587867, 34799699, 34799701 |
| Neural Tube Defects |
Associate |
25293959, 26334892, 30848279 |
| Neurocognitive Disorders |
Associate |
21618410, 25526710 |
| Neurologic Manifestations |
Associate |
23437274, 32068834 |
| Open Bite |
Associate |
35830630 |
| Pancreatic Neoplasms |
Associate |
29474406 |
| Persistent Infection |
Associate |
31181069 |
| Precursor Cell Lymphoblastic Leukemia Lymphoma |
Associate |
19020309, 28582843 |
| Premature Birth |
Associate |
35631247 |
| Proctitis |
Associate |
18700049 |
| Prostatic Neoplasms |
Associate |
27808252, 28724269, 32770085 |
| Severe Acute Respiratory Syndrome |
Associate |
25526710 |
| Squamous Cell Carcinoma of Head and Neck |
Associate |
17596206, 20490431 |
| Stomach Neoplasms |
Associate |
25840420 |
| Taste Disorders |
Associate |
26989453 |
| Uterine Cervical Dysplasia |
Associate |
24089416 |
| Uterine Cervicitis |
Associate |
32295543 |
| Vascular Diseases |
Associate |
21688148, 9501215 |
| Xanthomatosis Cerebrotendinous |
Associate |
15612980 |
|