AGTR1 (Type-1 angiotensin II receptor) variants and mutations
AGTR1 (also known as Type-1 angiotensin II receptor) is a human protein-coding gene encoding a type-1 angiotensin II receptor protein. Its activation by angiotensin II promotes vasoconstriction, aldosterone release, sodium retention, and vascular remodeling. Excessive signaling contributes to hypertension and cardiovascular disease, and the pathway is therapeutically blocked by angiotensin-receptor blockers. This analysis covers 887 AGTR1 variants and mutations. Of these, 71% have computational variant effect predictions. Disease context includes renal tubular dysgenesis, hypertensive disorder, and renal tubular dysgenesis of genetic origin. Example AGTR1 variants include M1?, I2F, and I2S.
Variant analysis overview
- Gene: AGTR1
- Protein: Type-1 angiotensin II receptor
- UniProt accession: P30556
- Organism: Homo sapiens
- Variants analyzed: 887
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 568 unspecified-consequence records; 142 synonymous variants; 135 missense variants; 33 frameshift variants; 4 stop-gained variants; 3 in-frame deletions; 1 stop retained variant; 1 substitution
- Prediction scores: 630 variants have prediction scores (71% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: renal tubular dysgenesis, hypertensive disorder, renal tubular dysgenesis of genetic origin, essential hypertension, Hypertension, heart failure, myocardial infarction, essential hypertension, genetic, congestive heart failure, kidney disorder, stroke disorder, diabetes mellitus.
Protein structure and variant hotspots
- Protein features: 7 transmembrane segments; 7 binding sites; 3 post-translational modification sites.
- Structural context: 455 variants have structural context.
- PTM context: 9 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 AGTR1 variants
Examples include M1?, I2F, I2S, I2V, I2I, L3I, L3L, N4H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10744
- I2F (p.Ile2Phe), ESP rs372561921, ExAC rs372561921, TOPMed rs372561921, gnomAD rs372561921, REVEL 0.10, CADD 15.90
- I2S (p.Ile2Ser), ExAC rs779475784, TOPMed rs779475784, gnomAD rs779475784, REVEL 0.11, CADD 14.70
- I2V (p.Ile2Val), ESP rs372561921, ExAC rs372561921, TOPMed rs372561921, gnomAD rs372561921, REVEL 0.06, CADD 9.13
- I2I (p.Ile2Ile), rs746929368, gnomAD 3-148741041-T-C, CADD 6.32
- L3I (p.Leu3Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L3L (p.Leu3Leu), gnomAD 3-148741044-C-T, CADD 7.60
- N4H (p.Asn4His), ExAC rs754942115, gnomAD rs754942115, REVEL 0.12, CADD 24.20
- N4K (p.Asn4Lys), TOPMed rs368854069, REVEL 0.09, CADD 13.70
- N4S (p.Asn4Ser), Ensembl rs1261778963, REVEL 0.05, CADD 19.00
- S5Y (p.Ser5Tyr), cosmic curated COSV10968, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S5P (p.Ser5Pro), gnomAD 3-148741048-T-C, REVEL 0.14, CADD 16.20
- S6Y (p.Ser6Tyr), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10083, Variant assessed as somatic; moderate impact.
- S6P (p.Ser6Pro), gnomAD 3-148741051-T-C, REVEL 0.27, CADD 20.50
- S6S (p.Ser6Ser), rs1267802727, gnomAD 3-148741053-T-C, CADD 5.05
- T7I (p.Thr7Ile), gnomAD rs1477901393, REVEL 0.06, CADD 9.62
- E8A (p.Glu8Ala), gnomAD rs1714843147, REVEL 0.06, CADD 21.40
- E8G (p.Glu8Gly), cosmic curated COSV62559
- D9N (p.Asp9Asn), gnomAD 3-148741060-G-A, REVEL 0.07, CADD 18.60
- G10D (p.Gly10Asp), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10083, Variant assessed as somatic; moderate impact.
- G10R (p.Gly10Arg), 1000Genomes rs201574073, REVEL 0.12, CADD 18.00, Uncertain significance, Inborn genetic diseases
- G10S (p.Gly10Ser), 1000Genomes rs201574073, REVEL 0.07, CADD 16.10
- G10V (p.Gly10Val), ExAC rs781030550, gnomAD rs781030550, REVEL 0.14, CADD 19.40
- G10G (p.Gly10Gly), rs747843312, gnomAD 3-148741065-T-C, CADD 8.29
- I11T (p.Ile11Thr), TOPMed rs1165750203, gnomAD rs1165750203, REVEL 0.11, CADD 18.00
- I11V (p.Ile11Val), ExAC rs769583495, gnomAD rs769583495
- I11S (p.Ile11Ser), gnomAD 3-148741067-T-G, REVEL 0.16, CADD 19.10
- I11M (p.Ile11Met), gnomAD 3-148741068-T-G, REVEL 0.09, CADD 15.20
- K12E (p.Lys12Glu), TOPMed rs1714844470
- K12T (p.Lys12Thr), gnomAD rs896587204, REVEL 0.29, CADD 17.90
- R13G (p.Arg13Gly), TOPMed rs1358705034, gnomAD rs1358705034, REVEL 0.10, CADD 21.20, Uncertain significance, Renal tubular dysgenesis of genetic origin; Essential hypertension, genetic
- R13I (p.Arg13Ile), NCI-TCGA Cosmic COSV6255, cosmic curated COSV62557, Variant assessed as somatic; moderate impact.
- I14M (p.Ile14Met), gnomAD rs1013672470
- I14L (p.Ile14Leu), gnomAD 3-148741075-A-C, REVEL 0.06, CADD 19.60
- I14V (p.Ile14Val), gnomAD 3-148741075-A-G, REVEL 0.04, CADD 18.20
- I14S (p.Ile14Ser), gnomAD 3-148741076-T-G, REVEL 0.15, CADD 22.10
- I14I (p.Ile14Ile), rs1013672470, gnomAD 3-148741077-C-A, CADD 8.19
- Q15K (p.Gln15Lys), gnomAD 3-148741078-C-A, REVEL 0.11, CADD 15.40
- Q15P (p.Gln15Pro), gnomAD 3-148741079-A-C, REVEL 0.06, CADD 21.50
- Q15Q (p.Gln15Gln), rs1714845275, gnomAD 3-148741080-A-G, CADD 7.35
- D16G (p.Asp16Gly), TOPMed rs1693495472, gnomAD rs1693495472, REVEL 0.04, CADD 21.80
- D16H (p.Asp16His), cosmic curated COSV62560
- D16Y (p.Asp16Tyr), NCI-TCGA Cosmic COSV6256, Variant assessed as somatic; moderate impact.
- D16M (p.Asp16Met), rs1299028660, gnomAD 3-148741080-AG-A, CADD 26.40
- D17E (p.Asp17Glu), TOPMed rs1330784410, gnomAD rs1330784410, REVEL 0.03, CADD 8.57
- D17N (p.Asp17Asn), cosmic curated COSV10083, NCI-TCGA Cosmic COSV1008, Variant assessed as somatic; moderate impact.
- D17D (p.Asp17Asp), gnomAD 3-148741086-T-C, CADD 8.56
- C18* (p.Cys18Ter), Ensembl rs2107973900, CADD 34.00
- P19L (p.Pro19Leu), TOPMed rs1714845838
- P19S (p.Pro19Ser), gnomAD 3-148741090-C-T, REVEL 0.06, CADD 15.80
- K20N (p.Lys20Asn), cosmic curated COSV62558
- K20R (p.Lys20Arg), TOPMed rs1434001031, gnomAD rs1434001031, REVEL 0.08, CADD 20.20
- K20T (p.Lys20Thr), TOPMed rs1434001031, gnomAD rs1434001031, REVEL 0.14, CADD 20.10
- A21V (p.Ala21Val), cosmic curated COSV62557
- G22E (p.Gly22Glu), NCI-TCGA TCGA novel, REVEL 0.58, CADD 26.90, Variant assessed as somatic; moderate impact.
- R23K (p.Arg23Lys), rs1047885033, NCI-TCGA Cosmic COSV1008, cosmic curated COSV10083, TOPMed rs1047885033, REVEL 0.10, CADD 20.20, Uncertain significance, Renal tubular dysgenesis of genetic origin; Essential hypertension, genetic
- R23R (p.Arg23Arg), gnomAD 3-148741104-G-A, CADD 8.85
- N25H (p.Asn25His), gnomAD rs1362276045, REVEL 0.01, CADD 21.80
- N25T (p.Asn25Thr), NCI-TCGA Cosmic COSV6255, cosmic curated COSV62557, Variant assessed as somatic; moderate impact.
- Y26Y (p.Tyr26Tyr), gnomAD 3-148741113-C-T, CADD 8.05
- I27V (p.Ile27Val), ExAC rs773385210, gnomAD rs773385210, REVEL 0.11, CADD 17.90
- I27M (p.Ile27Met), cosmic curated COSV10083
- F28L (p.Phe28Leu), cosmic curated COSV10083
- V29L (p.Val29Leu), cosmic curated COSV62559
- V29I (p.Val29Ile), TOPMed rs1239347270, gnomAD rs1239347270, REVEL 0.05, CADD 10.50
- M30I (p.Met30Ile), cosmic curated COSV10744
- M30V (p.Met30Val), Ensembl rs1714847275, REVEL 0.09, CADD 20.10
- I31T (p.Ile31Thr), gnomAD rs1453251109, REVEL 0.25, CADD 25.70
- I31S (p.Ile31Ser), gnomAD 3-148741127-T-G, REVEL 0.36, CADD 27.50
- I31I (p.Ile31Ile), gnomAD 3-148741128-T-C, CADD 7.09
- P32A (p.Pro32Ala), TOPMed rs1283192114, gnomAD rs1283192114, REVEL 0.49, CADD 24.60
- P32L (p.Pro32Leu), cosmic curated COSV10527
- P32S (p.Pro32Ser), TOPMed rs1283192114, gnomAD rs1283192114
- P32R (p.Pro32Arg), gnomAD 3-148741130-C-G, REVEL 0.59, CADD 25.40
- T33A (p.Thr33Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T33I (p.Thr33Ile), gnomAD rs1355208421, REVEL 0.03, CADD 17.60
- T33N (p.Thr33Asn), gnomAD 3-148741133-C-A, REVEL 0.16, CADD 24.00
- L34* (p.Leu34Ter), cosmic curated COSV10886, Ensembl rs2107973962
- L34V (p.Leu34Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L34S (p.Leu34Ser), gnomAD 3-148741136-T-C, REVEL 0.25, CADD 24.20
- Y35C (p.Tyr35Cys), gnomAD 3-148741139-A-G, REVEL 0.68, CADD 27.90
- Y35Y (p.Tyr35Tyr), gnomAD 3-148741140-C-T, CADD 6.69
- S30=, rs138997091, ClinGen CA2657264, ClinVar RCV000907538, ClinVar RCV001149670, Likely benign
- S36C (p.Ser36Cys), ExAC rs770976926, gnomAD rs770976926, REVEL 0.14, CADD 22.50
- S36I (p.Ser36Ile), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10083, Variant assessed as somatic; moderate impact.
- S36N (p.Ser36Asn), ExAC rs774334785, TOPMed rs774334785, gnomAD rs774334785, REVEL 0.11, CADD 24.60
- S36H (p.Ser36His), rs1159223903, gnomAD 3-148741140-CAGTA, CADD 27.20
- S36G (p.Ser36Gly), gnomAD 3-148741141-A-G, REVEL 0.05, CADD 21.50
- S36S (p.Ser36Ser), gnomAD 3-148741143-T-C, CADD 7.31
- I37T (p.Ile37Thr), TOPMed rs1451621681, gnomAD rs1451621681, REVEL 0.11, CADD 21.60
- I37V (p.Ile37Val), cosmic curated COSV62558, Ensembl rs1559933743, REVEL 0.10, CADD 17.00, Uncertain significance, Inborn genetic diseases
- I38T (p.Ile38Thr), rs751575775, ClinGen CA2657277, ClinVar RCV001149671, ClinVar RCV002483880, REVEL 0.30, CADD 25.00, Uncertain significance, Essential hypertension, genetic; Renal tubular dysgenesis of genetic origin; Ren
- I38H (p.Ile38His), rs387906577, gnomAD 3-148741144-A-AT, CADD 25.90
- F39S (p.Phe39Ser), TOPMed rs1219761165, gnomAD rs1219761165, REVEL 0.62, CADD 28.30
- V40A (p.Val40Ala), cosmic curated COSV62558
- V40L (p.Val40Leu), TOPMed rs1714849676, REVEL 0.14, CADD 21.60
- V40M (p.Val40Met), gnomAD 3-148741153-G-A, REVEL 0.23, CADD 25.30
- V40V (p.Val40Val), rs767852386, gnomAD 3-148741155-G-A, CADD 8.61
- V41G (p.Val41Gly), Ensembl rs13095608
- V41M (p.Val41Met), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10083, REVEL 0.06, CADD 22.90, Variant assessed as somatic; moderate impact.
- V41V (p.Val41Val), gnomAD 3-148741158-G-A, CADD 6.39
- G42E (p.Gly42Glu), cosmic curated COSV62560, Ensembl rs2107974033
- G42R (p.Gly42Arg), ESP rs374930715, TOPMed rs374930715, REVEL 0.70, CADD 28.20, Uncertain significance, Inborn genetic diseases
- I43Y (p.Ile43Tyr), gnomAD 3-148741161-A-AT, CADD 25.40
- F44L (p.Phe44Leu), TOPMed rs1714850502, gnomAD rs1714850502, REVEL 0.12, CADD 22.40
- F44Y (p.Phe44Tyr), gnomAD 3-148741162-A-ATT, CADD 28.30
- G45A (p.Gly45Ala), cosmic curated COSV62560
- G45E (p.Gly45Glu), cosmic curated COSV62559
- G45R (p.Gly45Arg), NCI-TCGA Cosmic COSV6255, cosmic curated COSV62558, Variant assessed as somatic; moderate impact.
- N46K (p.Asn46Lys), rs1714850901, ClinGen CA354885835, ClinVar RCV002028112, ClinVar RCV006302564, REVEL 0.88, CADD 24.00, Uncertain significance, Inborn genetic diseases; not provided
- S47N (p.Ser47Asn), NCI-TCGA Cosmic COSV6256, cosmic curated COSV62560, Variant assessed as somatic; moderate impact.
- S47R (p.Ser47Arg), gnomAD rs1478603789, REVEL 0.40, CADD 23.10
- L48L (p.Leu48Leu), rs140046712, gnomAD 3-148741177-T-C, CADD 10.40
- V49A (p.Val49Ala), ExAC rs764573066, gnomAD rs764573066, REVEL 0.92, CADD 25.60
- V49L (p.Val49Leu), ESP rs145575818, ExAC rs145575818, TOPMed rs145575818, gnomAD rs145575818, REVEL 0.84, CADD 25.80
- V49M (p.Val49Met), ESP rs145575818, ExAC rs145575818, TOPMed rs145575818, gnomAD rs145575818, REVEL 0.87, CADD 26.40
- V50G (p.Val50Gly), Ensembl rs1576541676
- V50M (p.Val50Met), TOPMed rs1450888240, gnomAD rs1450888240, REVEL 0.59, CADD 26.40, Uncertain significance, Renal tubular dysgenesis of genetic origin; Essential hypertension, genetic
- I51M (p.Ile51Met), TOPMed rs1714852761, REVEL 0.16, CADD 13.10
- I51T (p.Ile51Thr), rs886058069, ClinGen CA10617445, ClinVar RCV000374387, TOPMed rs886058069, REVEL 0.10, CADD 21.90, Uncertain significance, Renal tubular dysgenesis
- I51K (p.Ile51Lys), gnomAD 3-148741187-T-A, REVEL 0.24, CADD 23.60
- V52A (p.Val52Ala), cosmic curated COSV10083, ESP rs150629733, ExAC rs150629733, TOPMed rs150629733, REVEL 0.57, CADD 24.40, Uncertain significance
- V52G (p.Val52Gly), rs150629733, ClinGen CA2657282, ClinVar RCV002941955, ClinVar RCV003367909, REVEL 0.76, CADD 26.50, Uncertain significance, Inborn genetic diseases; not provided
- V52Y (p.Val52Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V52I (p.Val52Ile), gnomAD 3-148741189-G-A, REVEL 0.12, CADD 23.60
- V52D (p.Val52Asp), gnomAD 3-148741190-T-A, REVEL 0.75, CADD 27.40
- I53L (p.Ile53Leu), cosmic curated COSV10527
- I53V (p.Ile53Val), gnomAD 3-148741192-A-G, REVEL 0.19, CADD 24.40
- Y54* (p.Tyr54Ter), gnomAD 3-148741197-C-A, CADD 35.00
- Y54Y (p.Tyr54Tyr), gnomAD 3-148741197-C-T, CADD 6.39
- F55I (p.Phe55Ile), cosmic curated COSV62560
- F55V (p.Phe55Val), gnomAD rs1714853406, REVEL 0.12, CADD 21.10
- F55L (p.Phe55Leu), gnomAD 3-148741198-T-C, REVEL 0.10, CADD 20.60
- Y56I (p.Tyr56Ile), rs773441421, gnomAD 3-148741197-CT-C, CADD 25.90
- Y56H (p.Tyr56His), gnomAD 3-148741201-T-C, REVEL 0.45, CADD 22.70
- M57I (p.Met57Ile), cosmic curated COSV62559
- M57T (p.Met57Thr), rs758161051, ClinGen CA2657284, ClinVar RCV000293905, ExAC rs758161051, REVEL 0.29, CADD 19.20, Uncertain significance, Renal tubular dysgenesis
- M57R (p.Met57Arg), gnomAD 3-148741205-T-G, REVEL 0.32, CADD 19.60
- K58E (p.Lys58Glu), gnomAD rs1350271075, REVEL 0.73, CADD 24.20
- K58T (p.Lys58Thr), ExAC rs765903933, gnomAD rs765903933, REVEL 0.75, CADD 24.20
- L59P (p.Leu59Pro), ExAC rs751092458, gnomAD rs751092458, REVEL 0.35, CADD 22.80
- L59L (p.Leu59Leu), gnomAD 3-148741210-C-T, CADD 7.45
- K60E (p.Lys60Glu), gnomAD 3-148741213-A-G, REVEL 0.70, CADD 26.30
- K60N (p.Lys60Asn), gnomAD 3-148741215-G-C, REVEL 0.44, CADD 24.40
- p.Thr61 Val62delinsMet, gnomAD 3-148741216-ACTG-, CADD 19.20
- T61S (p.Thr61Ser), gnomAD 3-148741217-C-G, REVEL 0.19, CADD 22.70
- T61T (p.Thr61Thr), rs1379071518, gnomAD 3-148741218-T-G, CADD 4.49
- V62A (p.Val62Ala), rs1241893519, TOPMed rs1241893519, gnomAD rs1241893519, REVEL 0.41, CADD 25.90, Variant assessed as somatic; moderate impact.
- V62M (p.Val62Met), cosmic curated COSV10649, REVEL 0.24, CADD 26.00
- V62V (p.Val62Val), gnomAD 3-148741221-G-T, CADD 7.90
- A63S (p.Ala63Ser), gnomAD rs1559933838
- A63T (p.Ala63Thr), gnomAD rs1559933838, REVEL 0.30, CADD 26.50
- S64N (p.Ser64Asn), gnomAD rs1240210108, REVEL 0.14, CADD 17.00
- S64G (p.Ser64Gly), gnomAD 3-148741225-A-G, REVEL 0.22, CADD 25.20
- S64S (p.Ser64Ser), rs959805889, gnomAD 3-148741227-T-C, CADD 8.71
- V65I (p.Val65Ile), rs111980524, ClinGen CA2657287, ClinVar RCV000901265, ClinVar RCV001149672, REVEL 0.14, CADD 9.10, Likely benign, Renal tubular dysgenesis; not provided
- V65L (p.Val65Leu), 1000Genomes rs111980524, ESP rs111980524, ExAC rs111980524, TOPMed rs111980524, REVEL 0.14, CADD 19.20, Likely benign
- F66L (p.Phe66Leu), TOPMed rs1229680209, gnomAD rs1229680209, REVEL 0.66, CADD 23.60
- L67F (p.Leu67Phe), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10083, REVEL 0.28, CADD 24.40, Variant assessed as somatic; moderate impact.
- L67H (p.Leu67His), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10083, Variant assessed as somatic; moderate impact.
- L67L (p.Leu67Leu), rs1292396405, gnomAD 3-148741236-T-C, CADD 7.40
- L68L (p.Leu68Leu), rs988598349, gnomAD 3-148741237-T-C, CADD 5.59
- N69T (p.Asn69Thr), TOPMed rs1334821430, gnomAD rs1334821430, REVEL 0.61, CADD 25.70
- L70I (p.Leu70Ile), rs753149496, ClinGen CA2657288, ClinVar RCV001997301, ClinVar RCV002563538, REVEL 0.75, CADD 23.40, Uncertain significance, not provided; Inborn genetic diseases
- L70* (p.Leu70Ter), gnomAD 3-148741244-T-G, CADD 37.00
- A71E (p.Ala71Glu), NCI-TCGA Cosmic COSV6255, cosmic curated COSV62557, Variant assessed as somatic; moderate impact.
- A71P (p.Ala71Pro), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10083, NCI-TCGA Cosmic COSV6256, Variant assessed as somatic; moderate impact.
- A71T (p.Ala71Thr), cosmic curated COSV62560
- A73P (p.Ala73Pro), gnomAD 3-148741252-G-C, REVEL 0.82, CADD 25.90
- A73A (p.Ala73Ala), gnomAD 3-148741254-T-C, CADD 9.13
- D74A (p.Asp74Ala), rs748117430, ClinGen CA2657289, ClinVar RCV001801268, ExAC rs748117430, REVEL 0.90, CADD 27.50, Uncertain significance, Renal tubular dysgenesis of genetic origin
- D74G (p.Asp74Gly), gnomAD 3-148741256-A-G, REVEL 0.92, CADD 27.60
- L75V (p.Leu75Val), TOPMed rs1714858911, REVEL 0.29, CADD 12.90, Uncertain significance, Inborn genetic diseases
- L75M (p.Leu75Met), rs762648315, gnomAD 3-148741257-CTT-C, CADD 26.60
- L75L (p.Leu75Leu), rs752098427, gnomAD 3-148741260-A-G, CADD 4.70
- C76G (p.Cys76Gly), Ensembl rs545751404, REVEL 0.22, CADD 25.60
- C76R (p.Cys76Arg), Ensembl rs545751404, REVEL 0.27, CADD 26.00
- C76A (p.Cys76Ala), gnomAD 3-148741260-AT-A, CADD 27.50
- F77C (p.Phe77Cys), ExAC rs747975618, TOPMed rs747975618, gnomAD rs747975618, REVEL 0.82, CADD 24.90, Uncertain significance, Renal tubular dysgenesis of genetic origin; Essential hypertension, genetic
- F77I (p.Phe77Ile), gnomAD 3-148741264-T-A, REVEL 0.78, CADD 26.60
Public AGTR1 analysis runs
- AGTR1 analysis run — AGTR1 (887 variants) — completed 2026-08-19