MAGED2 (Melanoma-associated antigen D2) variants and mutations
MAGED2 (also known as Melanoma-associated antigen D2) is a human protein-coding gene encoding a melanoma-associated antigen D2 protein. It regulates membrane-protein trafficking in renal tubule cells and helps maintain expression of salt-transport proteins during fetal kidney development. Hemizygous loss-of-function variants cause transient antenatal Bartter syndrome, which often improves substantially after birth. This analysis covers 861 MAGED2 variants and mutations. Of these, 70% have computational variant effect predictions. Disease context includes Bartter syndrome, Bartter syndrome with hypocalcemia, and neurodegenerative disease. Example MAGED2 variants include S2C, S2F, and D3D.
Variant analysis overview
- Gene: MAGED2
- Protein: Melanoma-associated antigen D2
- UniProt accession: Q9UNF1
- Organism: Homo sapiens
- Variants analyzed: 861
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 529 unspecified-consequence records; 108 synonymous variants; 199 missense variants; 11 stop-gained variants; 7 frameshift variants; 1 splice acceptor variant; 3 in-frame deletions; 1 in-frame insertions; 1 splice-region variants; 1 substitution
- Prediction scores: 607 variants have prediction scores (70% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Bartter syndrome, Bartter syndrome with hypocalcemia, neurodegenerative disease, Hypotonia, Dandy-Walker syndrome, attention deficit-hyperactivity disorder, Cerebellar atrophy, Global developmental delay, Hypoplasia of the corpus callosum, Atrophy/Degeneration affecting the central nervous system, hereditary disease, neoplasm.
Protein structure and variant hotspots
- Protein features: 1 domains; 12 post-translational modification sites.
- Structural context: 163 variants have structural context.
- PTM context: 23 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable MAGED2 variants
Examples include S2C, S2F, D3D, T4R, S5N, S5S, S5R, S7G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2C (p.Ser2Cys), rs1388401939, NCI-TCGA Cosmic COSV5449, cosmic curated COSV54497, REVEL 0.10, CADD 25.70, Variant assessed as somatic; moderate impact.
- S2F (p.Ser2Phe), cosmic curated COSV54499
- D3D (p.Asp3Asp), rs1326541051, gnomAD X-54809340-C-T, CADD 11.70
- T4R (p.Thr4Arg), ExAC rs750624649, gnomAD rs750624649
- S5N (p.Ser5Asn), cosmic curated COSV54499
- S5S (p.Ser5Ser), gnomAD X-54809346-C-T, CADD 8.31
- S5R (p.Ser5Arg), gnomAD X-54809346-C-G, REVEL 0.14, CADD 11.80
- S7G (p.Ser7Gly), Ensembl rs1929725008
- S7I (p.Ser7Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S7N (p.Ser7Asn), gnomAD X-54809351-G-A, REVEL 0.03, CADD 16.40
- S7R (p.Ser7Arg), gnomAD X-54809352-T-A, REVEL 0.02, CADD 20.60
- G8A (p.Gly8Ala), gnomAD rs1432705662, REVEL 0.07, CADD 24.20
- G8S (p.Gly8Ser), gnomAD X-54809353-G-A, REVEL 0.09, CADD 26.70
- G8V (p.Gly8Val), gnomAD X-54809354-G-T, REVEL 0.14, CADD 24.60
- A9V (p.Ala9Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L11P (p.Leu11Pro), cosmic curated COSV54498
- L11V (p.Leu11Val), gnomAD X-54809362-C-G, REVEL 0.01, CADD 7.15
- L11L (p.Leu11Leu), gnomAD X-54809364-A-G, CADD 12.90
- R13H (p.Arg13His), NCI-TCGA Cosmic COSV5449, cosmic curated COSV54496, Variant assessed as somatic; moderate impact.
- R13C (p.Arg13Cys), gnomAD X-54809368-C-T, REVEL 0.02, CADD 15.50
- F14I (p.Phe14Ile), gnomAD X-54809371-T-A, REVEL 0.01, CADD 21.80
- Q15K (p.Gln15Lys), cosmic curated COSV99514
- A16S (p.Ala16Ser), gnomAD X-54809722-G-T, REVEL 0.01, CADD 21.90
- A18V (p.Ala18Val), Ensembl rs1929737611, REVEL 0.04, CADD 23.20
- K21E (p.Lys21Glu), rs1322233424, ClinGen CA413264251, ClinVar RCV002780593, TOPMed rs1322233424, REVEL 0.02, CADD 16.50, Uncertain significance, not provided
- K21N (p.Lys21Asn), gnomAD X-54809739-G-T, REVEL 0.04, CADD 23.00
- D22G (p.Asp22Gly), TOPMed rs1487623104
- D22D (p.Asp22Asp), rs770665474, gnomAD X-54809742-C-T, CADD 9.12
- S23G (p.Ser23Gly), Ensembl rs1929738232
- S23N (p.Ser23Asn), Ensembl rs1929738405, REVEL 0.07, CADD 10.10
- S24N (p.Ser24Asn), TOPMed rs1265121302, REVEL 0.02, CADD 9.61
- S25* (p.Ser25Ter), ExAC rs774057511, gnomAD rs774057511
- S25L (p.Ser25Leu), rs774057511, NCI-TCGA Cosmic COSV5449, cosmic curated COSV54498, ExAC rs774057511, REVEL 0.01, CADD 5.59, Variant assessed as somatic; moderate impact.
- S25W (p.Ser25Trp), gnomAD X-54809750-C-G, REVEL 0.09, CADD 20.50
- S25S (p.Ser25Ser), gnomAD X-54809751-G-A, CADD 7.65
- M26I (p.Met26Ile), gnomAD X-54809754-G-A, REVEL 0.02, CADD 15.70
- M27T (p.Met27Thr), ExAC rs769357290, gnomAD rs769357290, REVEL 0.03, CADD 17.50
- M27V (p.Met27Val), 1000Genomes rs200706314, ExAC rs200706314, gnomAD rs200706314, REVEL 0.06, CADD 19.70
- T29A (p.Thr29Ala), gnomAD X-54809761-A-G, REVEL 0.02, CADD 21.70
- L30P (p.Leu30Pro), gnomAD X-54809765-T-C, REVEL 0.14, CADD 14.10
- L30L (p.Leu30Leu), gnomAD X-54809766-G-C, CADD 2.56
- L31S (p.Leu31Ser), rs147495006, ClinVar RCV004585732, AlphaMissense 0.16, MetaLR 0.17, Uncertain significance, not provided
- L31W (p.Leu31Trp), ESP rs147495006, ExAC rs147495006, TOPMed rs147495006, REVEL 0.18, AlphaMissense 0.16
- L31L (p.Leu31Leu), rs1233431594, gnomAD X-54809767-T-C, CADD 7.09
- L31* (p.Leu31Ter), gnomAD X-54809768-T-A, CADD 34.00
- T32P (p.Thr32Pro), gnomAD X-54809770-A-C, REVEL 0.04, CADD 10.50
- T34T (p.Thr34Thr), rs1294443752, gnomAD X-54809778-C-T, CADD 8.30
- Q35K (p.Gln35Lys), cosmic curated COSV99514
- Q35R (p.Gln35Arg), gnomAD X-54809776-AC-A, CADD 22.90
- N36I (p.Asn36Ile), cosmic curated COSV99029
- V39V (p.Val39Val), rs762323814, gnomAD X-54809793-C-G, CADD 7.20
- P40A (p.Pro40Ala), gnomAD X-54809794-C-G, REVEL 0.02, CADD 9.95
- T42I (p.Thr42Ile), gnomAD X-54809801-C-T, REVEL 0.03, CADD 14.10
- P43L (p.Pro43Leu), rs201160051, ClinGen CA10426642, NCI-TCGA Cosmic COSV9951, cosmic curated COSV99514, REVEL 0.03, CADD 8.70, Conflicting interpretations, Inborn genetic diseases; not provided
- P43Q (p.Pro43Gln), ESP rs201160051, ExAC rs201160051, TOPMed rs201160051, gnomAD rs201160051, REVEL 0.06, CADD 14.50, Uncertain significance
- P43P (p.Pro43Pro), rs140063708, gnomAD X-54809805-G-T, CADD 1.42
- K44E (p.Lys44Glu), rs11555928, ClinGen CA10426644, cosmic curated COSV10726, ClinVar RCV000513922, REVEL 0.22, CADD 19.70, Benign/Likely benign, not provided
- K44N (p.Lys44Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A45D (p.Ala45Asp), gnomAD rs1254401711
- A45A (p.Ala45Ala), gnomAD X-54809811-C-A, CADD 4.17
- S46P (p.Ser46Pro), gnomAD X-54809812-T-C, REVEL 0.04, CADD 10.30
- K47E (p.Lys47Glu), gnomAD X-54809815-A-G, REVEL 0.09, CADD 21.30
- A48T (p.Ala48Thr), Ensembl rs2071536521
- p.Ala48 Lys53del, gnomAD X-54809861-GGGTCT, CADD 15.30
- L49P (p.Leu49Pro), gnomAD X-54809822-T-C, REVEL 0.06, CADD 6.48
- E50G (p.Glu50Gly), gnomAD X-54809825-A-G, REVEL 0.04, CADD 17.40
- V51F (p.Val51Phe), gnomAD X-54809827-G-T, REVEL 0.05, CADD 18.90
- D54Y (p.Asp54Tyr), gnomAD X-54809836-G-T, REVEL 0.06, CADD 16.90
- D54G (p.Asp54Gly), gnomAD X-54809837-A-G, REVEL 0.03, CADD 13.10
- D54V (p.Asp54Val), gnomAD X-54809837-A-T, REVEL 0.04, CADD 11.90
- D54D (p.Asp54Asp), rs1476224619, gnomAD X-54809838-T-C, CADD 7.58
- V55L (p.Val55Leu), cosmic curated COSV10957
- V55M (p.Val55Met), NCI-TCGA Cosmic COSV9951, cosmic curated COSV99514, Variant assessed as somatic; moderate impact.
- V55E (p.Val55Glu), gnomAD X-54809837-ATG-A, CADD 19.00
- V55V (p.Val55Val), rs766564460, gnomAD X-54809841-G-C, CADD 8.09
- K56N (p.Lys56Asn), NCI-TCGA Cosmic COSV5449, cosmic curated COSV54497, REVEL 0.13, CADD 20.10, Variant assessed as somatic; moderate impact.
- K56E (p.Lys56Glu), gnomAD X-54809842-A-G, REVEL 0.09, CADD 23.40
- V57F (p.Val57Phe), cosmic curated COSV54499
- S58T (p.Ser58Thr), gnomAD X-54809848-T-A, REVEL 0.02, CADD 17.90
- S58P (p.Ser58Pro), gnomAD X-54809848-T-C, REVEL 0.03, CADD 17.40
- S58S (p.Ser58Ser), gnomAD X-54809850-A-C, CADD 9.10
- A60V (p.Ala60Val), gnomAD X-54809855-C-T, REVEL 0.06, CADD 20.30
- A60D (p.Ala60Asp), gnomAD X-54809855-C-A, REVEL 0.07, CADD 21.00
- A60A (p.Ala60Ala), rs1471540890, gnomAD X-54809856-C-T, CADD 5.37
- S61F (p.Ser61Phe), Ensembl rs1602075139, REVEL 0.03, CADD 16.90
- S61S (p.Ser61Ser), gnomAD X-54809859-T-C, CADD 8.58
- G62W (p.Gly62Trp), gnomAD X-54809860-G-T, REVEL 0.09, CADD 23.40
- G62V (p.Gly62Val), gnomAD X-54809861-G-T, REVEL 0.06, CADD 18.90
- V63A (p.Val63Ala), Ensembl rs1569544533
- V63F (p.Val63Phe), ExAC rs751676539, TOPMed rs751676539, gnomAD rs751676539
- V63I (p.Val63Ile), ExAC rs751676539, TOPMed rs751676539, gnomAD rs751676539
- S64* (p.Ser64Ter), cosmic curated COSV54499
- S64P (p.Ser64Pro), gnomAD X-54809866-T-C, REVEL 0.02, CADD 9.84
- S64S (p.Ser64Ser), gnomAD X-54809868-A-T, CADD 10.00
- K65E (p.Lys65Glu), TOPMed rs994618387
- K65R (p.Lys65Arg), cosmic curated COSV54496
- K65* (p.Lys65Ter), gnomAD X-54809869-A-T, CADD 34.00
- A66P (p.Ala66Pro), Ensembl rs11555930
- A66V (p.Ala66Val), NCI-TCGA Cosmic COSV5449, cosmic curated COSV54498, Variant assessed as somatic; moderate impact.
- A66T (p.Ala66Thr), gnomAD X-54809872-G-A, REVEL 0.05, CADD 20.70
- E68D (p.Glu68Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E68* (p.Glu68Ter), gnomAD X-54809878-G-T, CADD 32.00
- E68E (p.Glu68Glu), rs755046012, gnomAD X-54809880-G-A, CADD 9.21
- V69I (p.Val69Ile), TOPMed rs1415027568, gnomAD rs1415027568, REVEL 0.09, CADD 22.00
- p.Val69 Glu74del, rs781293899, gnomAD X-54809875-ACAGAG, CADD 17.80
- V69F (p.Val69Phe), gnomAD X-54809881-G-T, REVEL 0.09, CADD 22.40
- V69A (p.Val69Ala), gnomAD X-54809882-T-C, REVEL 0.06, CADD 22.50
- V69V (p.Val69Val), rs1287102249, gnomAD X-54809883-C-T, CADD 11.30
- S70L (p.Ser70Leu), gnomAD X-54809885-C-T, REVEL 0.17, CADD 25.20
- K71K (p.Lys71Lys), gnomAD X-54809889-G-A, CADD 10.80
- T72A (p.Thr72Ala), Ensembl rs1929743836
- T72I (p.Thr72Ile), cosmic curated COSV10581
- T72P (p.Thr72Pro), cosmic curated COSV10510, REVEL 0.07, CADD 17.10
- T72N (p.Thr72Asn), gnomAD X-54809891-C-A, REVEL 0.03, CADD 19.60
- T72T (p.Thr72Thr), rs1348116880, gnomAD X-54809892-C-G, CADD 9.86
- P73L (p.Pro73Leu), Ensembl rs1929744359
- P73T (p.Pro73Thr), Ensembl rs868270989, REVEL 0.03, CADD 15.20
- P73Q (p.Pro73Gln), gnomAD X-54809894-C-A, REVEL 0.03, CADD 16.40
- E74G (p.Glu74Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E74D (p.Glu74Asp), gnomAD X-54809898-G-T, REVEL 0.02, CADD 19.90
- A75G (p.Ala75Gly), ExAC rs781247578, TOPMed rs781247578, gnomAD rs781247578, REVEL 0.02, CADD 18.80
- A75V (p.Ala75Val), gnomAD X-54809900-C-T, REVEL 0.04, CADD 19.60
- A75A (p.Ala75Ala), rs144346983, gnomAD X-54809901-T-C, CADD 12.40
- R76G (p.Arg76Gly), TOPMed rs767820484, REVEL 0.05, CADD 15.90
- R76Q (p.Arg76Gln), cosmic curated COSV54499, ESP rs148790335, ExAC rs148790335, TOPMed rs148790335, REVEL 0.03, CADD 9.87
- R76W (p.Arg76Trp), rs767820484, NCI-TCGA Cosmic COSV9951, cosmic curated COSV99514, TOPMed rs767820484, REVEL 0.05, CADD 21.80, Variant assessed as somatic; moderate impact.
- R76R (p.Arg76Arg), rs767820484, gnomAD X-54809902-C-A, CADD 12.60
- R76L (p.Arg76Leu), gnomAD X-54809903-G-T, REVEL 0.04, CADD 13.60
- E77G (p.Glu77Gly), gnomAD X-54809906-A-G, REVEL 0.07, CADD 25.10
- A78V (p.Ala78Val), gnomAD X-54809909-C-T, REVEL 0.04, CADD 18.50
- A78A (p.Ala78Ala), gnomAD X-54809910-A-G, CADD 14.80
- P79S (p.Pro79Ser), ExAC rs777456577, TOPMed rs777456577, gnomAD rs777456577, REVEL 0.08, CADD 3.16
- A80V (p.Ala80Val), NCI-TCGA TCGA novel, REVEL 0.03, CADD 6.48, Variant assessed as somatic; moderate impact.
- A80S (p.Ala80Ser), gnomAD X-54809914-G-T, REVEL 0.02, CADD 11.80
- A80T (p.Ala80Thr), gnomAD X-54809914-G-A, REVEL 0.03, CADD 12.40
- A80D (p.Ala80Asp), gnomAD X-54809915-C-A, REVEL 0.03, CADD 13.40
- A80A (p.Ala80Ala), gnomAD X-54809916-C-T, CADD 9.84
- T81A (p.Thr81Ala), gnomAD rs1486743215, REVEL 0.02, CADD 18.00
- T81I (p.Thr81Ile), ExAC rs749072773, gnomAD rs749072773, REVEL 0.03, CADD 18.50
- T81N (p.Thr81Asn), ExAC rs749072773, gnomAD rs749072773
- T81S (p.Thr81Ser), gnomAD X-54809918-C-G, REVEL 0.04, CADD 16.30
- T81T (p.Thr81Thr), rs1929745976, gnomAD X-54809919-C-T, CADD 9.56
- Q82H (p.Gln82His), ExAC rs778707488
- Q82* (p.Gln82Ter), gnomAD X-54809920-C-T, CADD 33.00
- A83V (p.Ala83Val), TOPMed rs1266898191, gnomAD rs1266898191, REVEL 0.02, CADD 13.60
- A83P (p.Ala83Pro), gnomAD X-54809923-G-C, REVEL 0.02, CADD 12.50
- S84L (p.Ser84Leu), rs745432175, ClinGen CA10426658, cosmic curated COSV54496, ClinVar RCV003381207, REVEL 0.04, CADD 20.30, Uncertain significance, not provided
- S84* (p.Ser84Ter), gnomAD X-54809927-C-A, CADD 33.00
- S84S (p.Ser84Ser), rs1043031, gnomAD X-54809928-A-G, CADD 10.90
- S85Y (p.Ser85Tyr), gnomAD X-54809930-C-A, REVEL 0.04, CADD 19.90
- S85F (p.Ser85Phe), gnomAD X-54809930-C-T, REVEL 0.05, CADD 21.20
- S85S (p.Ser85Ser), gnomAD X-54809931-T-C, CADD 10.50
- T86A (p.Thr86Ala), Ensembl rs1929747225, REVEL 0.03, CADD 10.60
- T86I (p.Thr86Ile), gnomAD X-54809933-C-T, REVEL 0.04, CADD 15.60
- T86S (p.Thr86Ser), gnomAD X-54809933-C-G, REVEL 0.05, CADD 14.60
- T86T (p.Thr86Thr), gnomAD X-54809934-T-C, CADD 10.90
- T87A (p.Thr87Ala), gnomAD rs1408706654, REVEL 0.03, CADD 14.10, Uncertain significance, Inborn genetic diseases
- T87T (p.Thr87Thr), gnomAD X-54809937-T-A, CADD 12.10
- Q88* (p.Gln88Ter), rs1432384861, ClinGen CA413265487, ClinVar RCV003320417, AlphaMissense 0.07, MetaLR 0.05, Pathogenic
- Q88E (p.Gln88Glu), TOPMed rs1432384861, gnomAD rs1432384861, REVEL 0.01, AlphaMissense 0.07, Uncertain significance, not provided
- Q88H (p.Gln88His), cosmic curated COSV10458, Ensembl rs6614290
- p.Gln88 Thr90del, gnomAD X-54809934-TACTCA, CADD 18.30
- Q88Q (p.Gln88Gln), gnomAD X-54809940-G-A, CADD 10.50
- L89L (p.Leu89Leu), gnomAD X-54809941-C-T, CADD 11.40
- L89M (p.Leu89Met), gnomAD X-54809941-C-A, REVEL 0.07, CADD 22.20
- T90I (p.Thr90Ile), Ensembl rs1929747951
- T90T (p.Thr90Thr), rs1929748095, gnomAD X-54809946-T-C, CADD 11.80
- D91E (p.Asp91Glu), gnomAD X-54809949-T-A, REVEL 0.07, CADD 9.53
- T92I (p.Thr92Ile), TOPMed rs1216071688
- T92N (p.Thr92Asn), TOPMed rs1216071688, REVEL 0.05, CADD 22.80
- T92T (p.Thr92Thr), gnomAD X-54809952-C-A, CADD 7.99
- Q93R (p.Gln93Arg), Ensembl rs1929748473, REVEL 0.07, CADD 15.70
- Q93K (p.Gln93Lys), gnomAD X-54809953-C-A, REVEL 0.04, CADD 17.10
- Q93* (p.Gln93Ter), gnomAD X-54809953-C-T, CADD 34.00
- Q93H (p.Gln93His), gnomAD X-54809955-G-T, REVEL 0.02, CADD 16.00
- V94F (p.Val94Phe), TOPMed rs1348468833, gnomAD rs1348468833, REVEL 0.03, CADD 13.00
- V94L (p.Val94Leu), TOPMed rs1348468833, gnomAD rs1348468833
- A96V (p.Ala96Val), TOPMed rs1929749004
- A96E (p.Ala96Glu), gnomAD X-54809963-C-A, REVEL 0.01, CADD 18.90
- A96G (p.Ala96Gly), gnomAD X-54809963-C-G, REVEL 0.01, CADD 18.90
Public MAGED2 analysis runs
- MAGED2 analysis run — MAGED2 (861 variants) — completed 2026-08-21