SLC2A4 (P14672) variants and mutations
SLC2A4 (also known as P14672) is a human protein-coding gene encoding a solute carrier family 2, facilitated glucose transporter member 4 protein. It moves to the surface of skeletal muscle and adipose cells in response to insulin and mediates much of postprandial glucose uptake. Impaired trafficking or expression is a central feature of insulin resistance, although severe monogenic GLUT4 deficiency is rare. This analysis covers 618 SLC2A4 variants and mutations. Of these, 74% have computational variant effect predictions. Disease context includes hypertensive disorder, essential hypertension, and Increased blood pressure. Example SLC2A4 variants include P2L, P2Q, and P2R.
Variant analysis overview
- Gene: SLC2A4
- Protein: P14672
- UniProt accession: P14672
- Organism: Homo sapiens
- Variants analyzed: 618
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 554 unspecified-consequence records; 27 missense variants; 29 synonymous variants; 3 stop-gained variants; 1 frameshift variants; 2 splice-region variants; 1 in-frame deletions; 1 substitution
- Prediction scores: 458 variants have prediction scores (74% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypertensive disorder, essential hypertension, Increased blood pressure, cardiovascular disorder, type 2 diabetes mellitus, Alzheimer disease, Parkinson disease, neurodegenerative disease, lysosomal storage disease, multiple sclerosis, Insulin resistance, polycystic ovary syndrome.
Protein structure and variant hotspots
- Protein features: 12 transmembrane segments; 6 binding sites; 5 post-translational modification sites.
- Structural context: 255 variants have structural context.
- PTM context: 11 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, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable SLC2A4 variants
Examples include P2L, P2Q, P2R, P2T, P2S, P2P, S3L, S3*. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2L (p.Pro2Leu), 1000Genomes rs534248171, ExAC rs534248171, TOPMed rs534248171, gnomAD rs534248171, REVEL 0.45, MetaLR 0.24
- P2Q (p.Pro2Gln), 1000Genomes rs534248171, ExAC rs534248171, TOPMed rs534248171, gnomAD rs534248171
- P2R (p.Pro2Arg), 1000Genomes rs534248171, ExAC rs534248171, TOPMed rs534248171, gnomAD rs534248171, REVEL 0.46, MetaLR 0.44
- P2T (p.Pro2Thr), gnomAD 17-7281938-C-A, REVEL 0.33, CADD 25.20
- P2S (p.Pro2Ser), gnomAD 17-7281938-C-T, REVEL 0.34, CADD 25.50
- P2P (p.Pro2Pro), gnomAD 17-7281940-G-T, CADD 14.30
- S3L (p.Ser3Leu), gnomAD rs1227450234, REVEL 0.25, MetaLR 0.28
- S3* (p.Ser3Ter), gnomAD 17-7281942-C-A, CADD 37.00
- S3S (p.Ser3Ser), rs775620746, gnomAD 17-7281943-G-C, CADD 13.40
- G4D (p.Gly4Asp), ExAC rs770994699, TOPMed rs770994699, gnomAD rs770994699, REVEL 0.31, MetaLR 0.28
- G4S (p.Gly4Ser), Ensembl rs2072405544
- G4V (p.Gly4Val), ExAC rs770994699, TOPMed rs770994699, gnomAD rs770994699, REVEL 0.41, MetaLR 0.25
- G4R (p.Gly4Arg), gnomAD 17-7281944-G-C, REVEL 0.36, CADD 23.40
- G4G (p.Gly4Gly), gnomAD 17-7281946-C-A, CADD 11.60
- F5L (p.Phe5Leu), ExAC rs768920197, TOPMed rs768920197, gnomAD rs768920197, REVEL 0.29, MetaLR 0.27
- Q6* (p.Gln6Ter), gnomAD 17-7281950-C-T, CADD 39.00
- Q6Q (p.Gln6Gln), gnomAD 17-7281952-A-G, CADD 13.60
- Q7R (p.Gln7Arg), gnomAD 17-7281954-A-G, REVEL 0.39, MetaLR 0.30
- Q7Q (p.Gln7Gln), rs1567601174, gnomAD 17-7281955-G-A, CADD 13.10
- I8L (p.Ile8Leu), gnomAD rs1293103801, REVEL 0.34, MetaLR 0.26
- I8M (p.Ile8Met), rs1597598561, Ensembl rs1597598561, ClinGen CA397769577, cosmic curated COSV10516, REVEL 0.37, MetaLR 0.25, Uncertain significance, not specified
- I8T (p.Ile8Thr), NCI-TCGA TCGA novel, REVEL 0.38, MetaLR 0.29, Variant assessed as somatic; moderate impact.
- I8A (p.Ile8Ala), rs1597598553, gnomAD 17-7281953-CAGAT-, CADD 32.00
- I8K (p.Ile8Lys), gnomAD 17-7281957-T-A, REVEL 0.38, MetaLR 0.27
- G9A (p.Gly9Ala), ExAC rs777053264, gnomAD rs777053264, REVEL 0.22, MetaLR 0.34
- G9V (p.Gly9Val), ExAC rs777053264, gnomAD rs777053264, REVEL 0.26, MetaLR 0.36
- G9S (p.Gly9Ser), gnomAD 17-7281959-G-A, REVEL 0.19, MetaLR 0.27
- G9C (p.Gly9Cys), gnomAD 17-7281959-G-T, REVEL 0.35, MetaLR 0.31
- G9R (p.Gly9Arg), gnomAD 17-7281959-G-C, REVEL 0.29, MetaLR 0.29
- G9D (p.Gly9Asp), gnomAD 17-7281960-G-A, REVEL 0.29, MetaLR 0.34
- G9G (p.Gly9Gly), rs762128658, gnomAD 17-7281961-C-G, CADD 18.40
- S10C (p.Ser10Cys), Ensembl rs2072405792
- S10P (p.Ser10Pro), cosmic curated COSV10516, ExAC rs765754656, gnomAD rs765754656, REVEL 0.40, MetaLR 0.26
- S10F (p.Ser10Phe), gnomAD 17-7281963-C-T, REVEL 0.41, MetaLR 0.29
- S10S (p.Ser10Ser), rs773617393, gnomAD 17-7281964-C-A, CADD 4.08
- E11K (p.Glu11Lys), gnomAD 17-7281965-G-A, REVEL 0.09, MetaLR 0.09
- E11* (p.Glu11Ter), gnomAD 17-7281965-G-T, CADD 42.00
- E11D (p.Glu11Asp), gnomAD 17-7281967-A-T, REVEL 0.09, MetaLR 0.06
- E11E (p.Glu11Glu), gnomAD 17-7281967-A-G, CADD 18.20
- D12H (p.Asp12His), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10043, Variant assessed as somatic; moderate impact.
- D12N (p.Asp12Asn), rs562894482, NCI-TCGA Cosmic COSV1004, cosmic curated COSV10043, REVEL 0.13, MetaLR 0.27, Variant assessed as somatic; moderate impact.
- G13A (p.Gly13Ala), ExAC rs755868694, TOPMed rs755868694, gnomAD rs755868694, REVEL 0.11, MetaLR 0.26
- G13E (p.Gly13Glu), ExAC rs755868694, TOPMed rs755868694, gnomAD rs755868694, REVEL 0.21, MetaLR 0.21
- G13R (p.Gly13Arg), gnomAD 17-7283248-G-A, REVEL 0.16, MetaLR 0.27
- E14K (p.Glu14Lys), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10043, TOPMed rs2072417348, Variant assessed as somatic; moderate impact.
- E14E (p.Glu14Glu), rs1490379310, gnomAD 17-7283253-A-G, CADD 5.16
- P15H (p.Pro15His), ExAC rs757179263, REVEL 0.11, MetaLR 0.38
- P15S (p.Pro15Ser), ExAC rs763807880, TOPMed rs763807880, gnomAD rs763807880
- P15T (p.Pro15Thr), ExAC rs763807880, TOPMed rs763807880, gnomAD rs763807880, REVEL 0.05, MetaLR 0.26
- P15P (p.Pro15Pro), rs1476221037, gnomAD 17-7283256-C-T, CADD 3.91
- P16L (p.Pro16Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P16S (p.Pro16Ser), TOPMed rs1170001111, gnomAD rs1170001111, REVEL 0.26, MetaLR 0.24
- P16T (p.Pro16Thr), TOPMed rs1170001111, gnomAD rs1170001111
- Q17* (p.Gln17Ter), rs1420669714, gnomAD rs1420669714, CADD 35.00, Variant assessed as somatic; high impact.
- Q17H (p.Gln17His), gnomAD rs947358493, REVEL 0.13, MetaLR 0.33
- Q17R (p.Gln17Arg), ExAC rs778865343, TOPMed rs778865343, gnomAD rs778865343, REVEL 0.10, MetaLR 0.21
- Q17L (p.Gln17Leu), gnomAD 17-7283261-A-T, REVEL 0.16, MetaLR 0.25
- Q18H (p.Gln18His), gnomAD rs2072417661, NCI-TCGA Cosmic COSV9914, cosmic curated COSV99142, REVEL 0.29, CADD 21.30, Variant assessed as somatic; moderate impact.
- R19* (p.Arg19Ter), cosmic curated COSV10874, 1000Genomes rs139011011, ESP rs139011011, ExAC rs139011011, CADD 35.00
- R19G (p.Arg19Gly), 1000Genomes rs139011011, ESP rs139011011, ExAC rs139011011, TOPMed rs139011011, REVEL 0.08, CADD 17.40
- R19P (p.Arg19Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R19Q (p.Arg19Gln), TOPMed rs1368055195, gnomAD rs1368055195, REVEL 0.04, CADD 16.10
- V20L (p.Val20Leu), gnomAD rs1230951912, REVEL 0.14, CADD 14.90
- V20A (p.Val20Ala), gnomAD 17-7283270-T-C, REVEL 0.25, CADD 23.60
- V20V (p.Val20Val), rs755074748, gnomAD 17-7283271-G-C, CADD 13.60
- T21I (p.Thr21Ile), TOPMed rs921046882
- T21T (p.Thr21Thr), gnomAD 17-7283274-T-G, CADD 8.79
- G22E (p.Gly22Glu), NCI-TCGA Cosmic COSV5030, cosmic curated COSV50301, Variant assessed as somatic; moderate impact.
- G22R (p.Gly22Arg), gnomAD rs903206032, REVEL 0.29, CADD 22.00
- G22W (p.Gly22Trp), gnomAD 17-7283275-G-T, REVEL 0.25, CADD 24.10
- G22G (p.Gly22Gly), rs142195514, gnomAD 17-7283277-G-A, CADD 16.00
- T23S (p.Thr23Ser), Ensembl rs2072417946
- T23T (p.Thr23Thr), rs770138000, gnomAD 17-7283280-C-G, CADD 13.40
- L24L (p.Leu24Leu), rs192326501, gnomAD 17-7283283-G-A, CADD 16.20
- V25F (p.Val25Phe), 1000Genomes rs143506382, ESP rs143506382, ExAC rs143506382, TOPMed rs143506382, REVEL 0.28, CADD 22.00
- V25L (p.Val25Leu), 1000Genomes rs143506382, ESP rs143506382, ExAC rs143506382, TOPMed rs143506382, REVEL 0.21, CADD 19.40
- V25D (p.Val25Asp), gnomAD 17-7283285-T-A, REVEL 0.52, CADD 23.80
- V25V (p.Val25Val), rs1355407504, gnomAD 17-7283286-C-A, CADD 18.20
- L26I (p.Leu26Ile), TOPMed rs2072418111, gnomAD rs2072418111, REVEL 0.27, CADD 21.00
- L26V (p.Leu26Val), gnomAD 17-7283287-C-G, REVEL 0.25, CADD 19.90
- A27T (p.Ala27Thr), gnomAD 17-7283290-G-A, REVEL 0.29, CADD 21.00
- A27A (p.Ala27Ala), rs2072418135, gnomAD 17-7283292-T-C, CADD 6.83
- V28G (p.Val28Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V28V (p.Val28Val), gnomAD 17-7283295-G-A, CADD 2.70
- F29L (p.Phe29Leu), TOPMed rs1157269708, gnomAD rs1157269708, REVEL 0.36, CADD 22.50
- S30F (p.Ser30Phe), gnomAD 17-7283300-C-T, REVEL 0.36, CADD 25.50
- S30S (p.Ser30Ser), gnomAD 17-7283301-T-G, CADD 12.30
- A31V (p.Ala31Val), rs1243626579, TOPMed rs1243626579, gnomAD rs1243626579, NCI-TCGA Cosmic COSV9914, REVEL 0.73, CADD 26.50, Variant assessed as somatic; moderate impact.
- A31E (p.Ala31Glu), gnomAD 17-7283303-C-A, REVEL 0.87, CADD 26.10
- A31A (p.Ala31Ala), rs775018856, gnomAD 17-7283304-G-A, CADD 13.20
- V32M (p.Val32Met), gnomAD 17-7283305-G-A, REVEL 0.47, CADD 26.90
- L33P (p.Leu33Pro), gnomAD 17-7283309-T-C, REVEL 0.89, CADD 28.30
- G34V (p.Gly34Val), Ensembl rs2072418259
- G34G (p.Gly34Gly), gnomAD 17-7283313-C-T, CADD 16.80
- S35F (p.Ser35Phe), rs376636615, ESP rs376636615, ExAC rs376636615, TOPMed rs376636615, REVEL 0.79, CADD 25.30, Variant assessed as somatic; moderate impact.
- S35S (p.Ser35Ser), gnomAD 17-7283316-C-T, CADD 15.40
- L36L (p.Leu36Leu), rs771486330, gnomAD 17-7283317-C-T, CADD 19.20
- Q37H (p.Gln37His), Ensembl rs2072418323
- Q37K (p.Gln37Lys), gnomAD 17-7283320-C-A, REVEL 0.71, CADD 24.80
- G39A (p.Gly39Ala), gnomAD rs1259133139, REVEL 0.91, CADD 27.20
- G39E (p.Gly39Glu), gnomAD rs1259133139, REVEL 0.94, CADD 28.40
- G39V (p.Gly39Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G39G (p.Gly39Gly), rs1448302639, gnomAD 17-7283328-G-T, CADD 9.73
- N41N (p.Asn41Asn), rs775146734, gnomAD 17-7283334-C-T, CADD 12.60
- I42M (p.Ile42Met), gnomAD rs1277048692, REVEL 0.34, CADD 22.60
- I42N (p.Ile42Asn), ExAC rs533993099, TOPMed rs533993099, gnomAD rs533993099, REVEL 0.57, CADD 26.90
- I42S (p.Ile42Ser), ExAC rs533993099, TOPMed rs533993099, gnomAD rs533993099
- I42T (p.Ile42Thr), ExAC rs533993099, TOPMed rs533993099, gnomAD rs533993099, REVEL 0.37, CADD 19.10
- I42V (p.Ile42Val), 1000Genomes rs541196033, ExAC rs541196033, gnomAD rs541196033, REVEL 0.23, CADD 22.80
- I42I (p.Ile42Ile), gnomAD 17-7283337-T-C, CADD 11.30
- G43G (p.Gly43Gly), rs753595456, gnomAD 17-7283340-G-A, CADD 8.63
- V44V (p.Val44Val), rs147146068, gnomAD 17-7283343-C-T, CADD 11.00
- I45I (p.Ile45Ile), rs765115135, gnomAD 17-7283346-C-T, CADD 13.40
- N46D (p.Asn46Asp), TOPMed rs1041707570, REVEL 0.84, CADD 28.30
- N46S (p.Asn46Ser), ExAC rs750395028, gnomAD rs750395028
- A47D (p.Ala47Asp), TOPMed rs1007734551, gnomAD rs1007734551, REVEL 0.86, CADD 26.90
- A47T (p.Ala47Thr), gnomAD 17-7283350-G-A, REVEL 0.69, CADD 28.80
- A47A (p.Ala47Ala), gnomAD 17-7283352-C-T, CADD 12.00
- P48S (p.Pro48Ser), Ensembl rs2072418724, NCI-TCGA Cosmic COSV9914, cosmic curated COSV99142, REVEL 0.75, CADD 25.40, Variant assessed as somatic; moderate impact.
- P48L (p.Pro48Leu), gnomAD 17-7283354-C-T, REVEL 0.71, CADD 26.50
- Q49E (p.Gln49Glu), Ensembl rs1016481590, REVEL 0.28, CADD 18.60
- Q49R (p.Gln49Arg), TOPMed rs1245781953
- Q49H (p.Gln49His), gnomAD 17-7283358-G-C, REVEL 0.60, CADD 24.10
- K50N (p.Lys50Asn), 1000Genomes rs2143004783, REVEL 0.29, CADD 33.00
- K50del (p.Lys50del), gnomAD 17-7283356-CAGA-C, CADD 21.10
- K50K (p.Lys50Lys), gnomAD 17-7283361-G-A, CADD 25.30
- I52T (p.Ile52Thr), ExAC rs764370457, TOPMed rs764370457, gnomAD rs764370457, REVEL 0.85, CADD 27.00
- Q54K (p.Gln54Lys), NCI-TCGA Cosmic COSV9914, cosmic curated COSV99142, Variant assessed as somatic; moderate impact.
- Q54L (p.Gln54Leu), TOPMed rs2072420094
- S55R (p.Ser55Arg), rs35198331, UniProt VAR 052503, Ensembl rs35198331
- Y56C (p.Tyr56Cys), TOPMed rs2072420155, REVEL 0.71, CADD 28.00
- N57S (p.Asn57Ser), TOPMed rs1265332623, gnomAD rs1265332623, REVEL 0.26, CADD 22.60
- E58D (p.Glu58Asp), gnomAD rs1462070095, REVEL 0.13, CADD 8.19
- T59K (p.Thr59Lys), ExAC rs754117775, gnomAD rs754117775, REVEL 0.52, CADD 24.70
- T59M (p.Thr59Met), ExAC rs754117775, gnomAD rs754117775, REVEL 0.52, CADD 23.40
- W60* (p.Trp60Ter), gnomAD rs1421455239, CADD 36.00
- G62E (p.Gly62Glu), gnomAD rs1479543819, REVEL 0.17, CADD 11.70
- G62R (p.Gly62Arg), gnomAD rs1428684071, REVEL 0.12, CADD 20.50
- G65E (p.Gly65Glu), TOPMed rs1295869344, gnomAD rs1295869344, REVEL 0.51, CADD 22.30
- P66L (p.Pro66Leu), NCI-TCGA TCGA novel, Ensembl rs2072420496, Variant assessed as somatic; moderate impact.
- E67* (p.Glu67Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G68E (p.Gly68Glu), NCI-TCGA Cosmic COSV9914, cosmic curated COSV99142, REVEL 0.25, CADD 17.30, Variant assessed as somatic; moderate impact.
- G68R (p.Gly68Arg), rs1429679424, NCI-TCGA Cosmic COSV9914, cosmic curated COSV99142, TOPMed rs1429679424, REVEL 0.15, CADD 22.00, Variant assessed as somatic; moderate impact.
- G68V (p.Gly68Val), ESP rs144936940, ExAC rs144936940, TOPMed rs144936940, gnomAD rs144936940, REVEL 0.23, CADD 21.20
- P69H (p.Pro69His), TOPMed rs2072420582, gnomAD rs2072420582, REVEL 0.24, CADD 24.90
- P69L (p.Pro69Leu), NCI-TCGA Cosmic COSV5030, cosmic curated COSV50302, REVEL 0.31, CADD 23.90, Variant assessed as somatic; moderate impact.
- S70N (p.Ser70Asn), TOPMed rs2072420609
- S71C (p.Ser71Cys), Ensembl rs887663108, REVEL 0.38, CADD 23.30
- P73S (p.Pro73Ser), NCI-TCGA Cosmic COSV5030, cosmic curated COSV50302, Variant assessed as somatic; moderate impact.
- P74R (p.Pro74Arg), Ensembl rs2072420685
- G75D (p.Gly75Asp), rs1326889234, ClinGen CA397770744, ClinVar RCV004277740, gnomAD rs1326889234, REVEL 0.37, CADD 12.30, Uncertain significance, not specified
- T76P (p.Thr76Pro), Ensembl rs1597599306
- L77F (p.Leu77Phe), ExAC rs746297235, gnomAD rs746297235, REVEL 0.43, CADD 23.70
- T78S (p.Thr78Ser), rs5434, Ensembl rs5434, UniProt VAR 012060
- T79N (p.Thr79Asn), 1000Genomes rs8192703, ESP rs8192703, ExAC rs8192703, TOPMed rs8192703, REVEL 0.15, CADD 15.20, Likely benign
- T79S (p.Thr79Ser), rs8192703, ClinGen CA8340645, ClinVar RCV003413109, 1000Genomes rs8192703, REVEL 0.13, CADD 15.40, Likely benign, not provided
- W81* (p.Trp81Ter), ExAC rs746457651, gnomAD rs746457651, CADD 37.00
- A82V (p.Ala82Val), NCI-TCGA Cosmic COSV9914, cosmic curated COSV99142, Variant assessed as somatic; moderate impact.
- L83I (p.Leu83Ile), gnomAD rs1343122146, REVEL 0.30, CADD 17.10
- V85L (p.Val85Leu), ExAC rs776202606, TOPMed rs776202606, gnomAD rs776202606
- V85M (p.Val85Met), ExAC rs776202606, TOPMed rs776202606, gnomAD rs776202606, REVEL 0.85, CADD 24.90
- I87M (p.Ile87Met), cosmic curated COSV50302, ExAC rs548540381, gnomAD rs548540381, REVEL 0.60, CADD 19.90
- S89P (p.Ser89Pro), rs1167739117, TOPMed rs1167739117, Variant assessed as somatic; moderate impact.
- V90M (p.Val90Met), ExAC rs762847554, TOPMed rs762847554, gnomAD rs762847554, REVEL 0.61, CADD 25.10
- G92S (p.Gly92Ser), cosmic curated COSV50300, TOPMed rs1268203327, gnomAD rs1268203327, REVEL 0.78, CADD 28.50
- M93L (p.Met93Leu), gnomAD rs1201730133, REVEL 0.53, CADD 23.10
- I94T (p.Ile94Thr), TOPMed rs1430231976, gnomAD rs1430231976, REVEL 0.63, CADD 24.20
- F97I (p.Phe97Ile), gnomAD rs1292711972, REVEL 0.51, CADD 24.60
- F97S (p.Phe97Ser), TOPMed rs1428213073, gnomAD rs1428213073, REVEL 0.64, CADD 24.90
- I99L (p.Ile99Leu), ExAC rs754025923, gnomAD rs754025923, REVEL 0.12, CADD 16.80
- I99S (p.Ile99Ser), TOPMed rs1195616310
- I99V (p.Ile99Val), ExAC rs754025923, gnomAD rs754025923, cosmic curated COSV50301, REVEL 0.12, CADD 12.10
- I102S (p.Ile102Ser), ExAC rs750728131
- I102M (p.Ile102Met), ExAC rs758815336
- S103F (p.Ser103Phe), NCI-TCGA Cosmic COSV5030, cosmic curated COSV50300, Variant assessed as somatic; moderate impact.
- S103Y (p.Ser103Tyr), NCI-TCGA Cosmic COSV5030, Variant assessed as somatic; moderate impact.
- Q104H (p.Gln104His), ExAC rs747560627
- Q104P (p.Gln104Pro), ExAC rs780387932, gnomAD rs780387932, REVEL 0.53, CADD 24.10
- Q104R (p.Gln104Arg), ExAC rs780387932, gnomAD rs780387932, REVEL 0.35, CADD 23.80
- W105G (p.Trp105Gly), ExAC rs754431197
Public SLC2A4 analysis runs
- SLC2A4 analysis run — SLC2A4 (618 variants) — completed 2026-08-19