INSR (Insulin receptor) variants and mutations
INSR (also known as Insulin receptor) is a human protein-coding gene encoding an insulin receptor protein. Its activation by insulin coordinates glucose uptake, metabolism, growth, and gene expression through PI3K-AKT and MAPK pathways. Biallelic severe loss-of-function variants cause Donohue or Rabson-Mendenhall syndromes, while heterozygous variants can cause severe insulin resistance. This analysis covers 1,557 INSR variants and mutations. Of these, 73% have computational variant effect predictions. Disease context includes insulin-resistance syndrome type A, Leprechaunism, and Rabson-Mendenhall syndrome. Example INSR variants include A2G, A2S, and T3I.
Variant analysis overview
- Gene: INSR
- Protein: Insulin receptor
- UniProt accession: P06213
- Organism: Homo sapiens
- Variants analyzed: 1557
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,325 unspecified-consequence records; 1 stop retained variant; 112 synonymous variants; 95 missense variants; 10 frameshift variants; 2 in-frame deletions; 4 stop-gained variants; 3 splice-region variants; 5 substitution
- Prediction scores: 1,131 variants have prediction scores (73% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: insulin-resistance syndrome type A, Leprechaunism, Rabson-Mendenhall syndrome, type 2 diabetes mellitus, Donohue syndrome, hyperinsulinism due to INSR deficiency, diabetes mellitus, type 1 diabetes mellitus, neurodegenerative disease, hypertensive disorder, Insulin resistance, essential hypertension.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 domains; 5 binding sites; 30 post-translational modification sites.
- Structural context: 702 variants have structural context.
- PTM context: 32 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, ClinGen, MaveDB, LitVar.
Notable INSR variants
Examples include A2G, A2S, T3I, G4R, G4W, G5D, G5R, G5S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2G (p.Ala2Gly), rs7508518, ClinGen CA200288, cosmic curated COSV10513, ClinVar RCV000173085, REVEL 0.16, MetaLR 0.00, Benign, not specified; not provided; Insulin-resistant diabetes mellitus AND acanthosis
- A2S (p.Ala2Ser), gnomAD rs1231519485, REVEL 0.12, MetaLR 0.18
- T3I (p.Thr3Ile), Ensembl rs1968567916, REVEL 0.08, MetaLR 0.17
- G4R (p.Gly4Arg), rs1370875449, gnomAD rs1370875449, REVEL 0.11, MetaLR 0.23, Variant assessed as somatic; moderate impact.
- G4W (p.Gly4Trp), gnomAD rs1370875449, REVEL 0.29, MetaLR 0.21
- G5D (p.Gly5Asp), rs886054690, ClinGen CA10649260, ClinVar RCV000276320, ClinVar RCV000333796, REVEL 0.11, MetaLR 0.13, Uncertain significance, Hyperinsulinism due to INSR deficiency; Rabson-Mendenhall syndrome; Insulin-resi
- G5R (p.Gly5Arg), 1000Genomes rs1410352680, gnomAD rs1410352680, REVEL 0.06, MetaLR 0.14
- G5S (p.Gly5Ser), 1000Genomes rs1410352680, gnomAD rs1410352680, REVEL 0.09, MetaLR 0.12
- G5V (p.Gly5Val), TOPMed rs886054690, gnomAD rs886054690, REVEL 0.12, MetaLR 0.11, Uncertain significance
- R6Q (p.Arg6Gln), gnomAD rs1968567099, REVEL 0.14, MetaLR 0.20
- R6W (p.Arg6Trp), gnomAD rs1171697715, REVEL 0.15, MetaLR 0.24
- R7L (p.Arg7Leu), TOPMed rs979150286, gnomAD rs979150286, REVEL 0.11, MetaLR 0.25
- R7Q (p.Arg7Gln), TOPMed rs979150286, gnomAD rs979150286, REVEL 0.07, MetaLR 0.22
- R7W (p.Arg7Trp), rs1378312415, ClinGen CA403162630, ClinVar RCV002807803, TOPMed rs1378312415, REVEL 0.15, MetaLR 0.19, Uncertain significance, Inborn genetic diseases
- G8A (p.Gly8Ala), TOPMed rs970356148, gnomAD rs970356148, REVEL 0.08, MetaLR 0.21, Uncertain significance, Inborn genetic diseases
- A9P (p.Ala9Pro), TOPMed rs1417610197, gnomAD rs1417610197, REVEL 0.25, MetaLR 0.21
- A9R (p.Ala9Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A9T (p.Ala9Thr), TOPMed rs1417610197, gnomAD rs1417610197, REVEL 0.11, MetaLR 0.14, Likely benign, Inborn genetic diseases
- A10V (p.Ala10Val), rs1183440326, gnomAD rs1183440326, REVEL 0.13, MetaLR 0.24, Variant assessed as somatic; moderate impact.
- A11V (p.Ala11Val), Ensembl rs1968566177, REVEL 0.09, MetaLR 0.19
- A12E (p.Ala12Glu), Ensembl rs1600141287, REVEL 0.40, MetaLR 0.24
- P13L (p.Pro13Leu), rs1023611589, ClinGen CA403162594, cosmic curated COSV57163, ClinVar RCV002639916, REVEL 0.06, MetaLR 0.20, Uncertain significance, not provided
- P13Q (p.Pro13Gln), TOPMed rs1023611589, REVEL 0.22, MetaLR 0.21, Uncertain significance
- P13T (p.Pro13Thr), gnomAD rs1968565878, REVEL 0.11, MetaLR 0.17, Uncertain significance, not specified
- L14M (p.Leu14Met), Ensembl rs1968565441, REVEL 0.23, MetaLR 0.46
- L14P (p.Leu14Pro), rs745857330, ClinGen CA9136191, ClinVar RCV000308234, ClinVar RCV000365243, REVEL 0.52, MetaLR 0.48, Conflicting interpretations, Inborn genetic diseases; not provided; Leprechaunism syndrome
- L15P (p.Leu15Pro), Ensembl rs1968565240, REVEL 0.59, MetaLR 0.26
- V16L (p.Val16Leu), Ensembl rs1968565162, REVEL 0.13, MetaLR 0.21
- A17G (p.Ala17Gly), 1000Genomes rs777801415, ExAC rs777801415, gnomAD rs777801415
- A17V (p.Ala17Val), 1000Genomes rs777801415, ExAC rs777801415, gnomAD rs777801415, REVEL 0.05, MetaLR 0.20
- V18A (p.Val18Ala), Ensembl rs1968564563, REVEL 0.09, MetaLR 0.17
- V18G (p.Val18Gly), Ensembl rs1968564563, REVEL 0.31, MetaLR 0.23
- A19G (p.Ala19Gly), Ensembl rs1968564394, REVEL 0.12, MetaLR 0.23
- A19T (p.Ala19Thr), cosmic curated COSV57173, TOPMed rs1015767960, gnomAD rs1015767960, REVEL 0.04, MetaLR 0.16
- A20T (p.Ala20Thr), gnomAD rs1320365670, REVEL 0.09, MetaLR 0.14
- A20V (p.Ala20Val), TOPMed rs1449164583, gnomAD rs1449164583, REVEL 0.08, MetaLR 0.19
- L21P (p.Leu21Pro), rs1968564144, ClinGen CA403162553, ClinVar RCV003672259, TOPMed rs1968564144, REVEL 0.24, MetaLR 0.29, Uncertain significance, not provided
- L23Q (p.Leu23Gln), gnomAD rs1234918359, REVEL 0.12, MetaLR 0.24
- G24S (p.Gly24Ser), TOPMed rs1968563644, REVEL 0.13, MetaLR 0.18
- A26E (p.Ala26Glu), TOPMed rs1201722489, gnomAD rs1201722489, REVEL 0.36, MetaLR 0.23, Uncertain significance, not provided
- A26T (p.Ala26Thr), 1000Genomes rs530278666, ExAC rs530278666, TOPMed rs530278666, gnomAD rs530278666, REVEL 0.04, MetaLR 0.21, Uncertain significance, Inborn genetic diseases
- G27S (p.Gly27Ser), TOPMed rs1968563279, REVEL 0.08, MetaLR 0.19
- H28Q (p.His28Gln), rs755298967, ClinGen CA403162512, ClinVar RCV003580793, ClinGen CA209132, REVEL 0.10, MetaLR 0.11, Uncertain significance, not provided
- Y30D (p.Tyr30Asp), TOPMed rs1600141148
- Y30H (p.Tyr30His), TOPMed rs1600141148, REVEL 0.07, MetaLR 0.22
- P31L (p.Pro31Leu), NCI-TCGA TCGA novel, Ensembl rs1968562794, REVEL 0.13, MetaLR 0.22, Variant assessed as somatic; moderate impact.
- G32R (p.Gly32Arg), TOPMed rs1310944135, gnomAD rs1310944135, REVEL 0.12, MetaLR 0.26
- E33* (p.Glu33Ter), NCI-TCGA TCGA novel, CADD 39.00, Variant assessed as somatic; high impact.
- E33K (p.Glu33Lys), TOPMed rs1968562506, REVEL 0.28, MetaLR 0.33
- V34A (p.Val34Ala), TOPMed rs1967789558, REVEL 0.57, MetaLR 0.55
- V34M (p.Val34Met), Ensembl rs1568243471, REVEL 0.24, MetaLR 0.45
- C35F (p.Cys35Phe), TOPMed rs1004265500
- P36A (p.Pro36Ala), cosmic curated COSV10025, TOPMed rs796678604, gnomAD rs796678604, REVEL 0.37, MetaLR 0.49, Uncertain significance, Inborn genetic diseases
- G37S (p.Gly37Ser), cosmic curated COSV57159, ExAC rs748177213, TOPMed rs748177213, gnomAD rs748177213, REVEL 0.16, MetaLR 0.22
- M38V (p.Met38Val), TOPMed rs1967788976, REVEL 0.28, MetaLR 0.34
- D39Y (p.Asp39Tyr), gnomAD rs1408976613, REVEL 0.92, MetaLR 0.69
- R41W (p.Arg41Trp), gnomAD rs1246915228, REVEL 0.95, MetaLR 0.66, Likely pathogenic, Leprechaunism syndrome
- N42K (p.Asn42Lys), rs121913143, ClinGen CA124231, ClinVar RCV000015806, UniProt VAR 004079, Pathogenic, Rabson-Mendenhall syndrome
- N43S (p.Asn43Ser), ESP rs144718517, ExAC rs144718517, TOPMed rs144718517, gnomAD rs144718517, REVEL 0.19, MetaLR 0.28
- R46G (p.Arg46Gly), ExAC rs780532714, gnomAD rs780532714, REVEL 0.27, MetaLR 0.39
- R46K (p.Arg46Lys), ExAC rs758865457, TOPMed rs758865457, REVEL 0.28, MetaLR 0.35, Uncertain significance, Inborn genetic diseases
- R46S (p.Arg46Ser), gnomAD rs1267080515, REVEL 0.18, MetaLR 0.38
- H48Q (p.His48Gln), TOPMed rs1967787579, REVEL 0.20, MetaLR 0.26
- H48R (p.His48Arg), rs1364492874, ClinGen CA403160632, ClinVar RCV001960855, gnomAD rs1364492874, REVEL 0.16, MetaLR 0.21, Uncertain significance, not provided
- L50M (p.Leu50Met), ExAC rs757849386, TOPMed rs757849386, gnomAD rs757849386, REVEL 0.73, MetaLR 0.68
- E51D (p.Glu51Asp), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10025, NCI-TCGA Cosmic COSV5716, REVEL 0.19, MetaLR 0.38, Variant assessed as somatic; moderate impact.
- E51K (p.Glu51Lys), rs140852238, ClinGen CA9136158, ClinVar RCV000322056, ClinVar RCV000725827, REVEL 0.30, MetaLR 0.51, Conflicting interpretations, not specified; not provided; Insulin-resistant diabetes mellitus AND acanthosis
- V55A (p.Val55Ala), rs121913152, ClinGen CA124253, ClinVar RCV000015817, UniProt VAR 004080, REVEL 0.81, MetaLR 0.74, Pathogenic, Leprechaunism syndrome
- I56T (p.Ile56Thr), rs1555689937, ClinGen CA403160537, ClinVar RCV000599040, UniProt VAR 079535, not provided, Leprechaunism syndrome
- E57K (p.Glu57Lys), rs886044001, ClinGen CA10606213, ClinVar RCV000326627, TOPMed rs886044001, Uncertain significance, not provided
- G58R (p.Gly58Arg), rs52836744, ClinGen CA124247, ClinVar RCV000015814, UniProt VAR 004081, REVEL 0.91, MetaLR 0.89, Pathogenic, Leprechaunism syndrome
- I62T (p.Ile62Thr), gnomAD rs1388989393, REVEL 0.94, MetaLR 0.88
- I62V (p.Ile62Val), ExAC rs767255267, gnomAD rs767255267, REVEL 0.74, MetaLR 0.78
- M65K (p.Met65Lys), Ensembl rs78827745
- R69K (p.Arg69Lys), Ensembl rs368318921, REVEL 0.12, MetaLR 0.09
- P70S (p.Pro70Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E71K (p.Glu71Lys), NCI-TCGA Cosmic COSV5717, cosmic curated COSV57170, gnomAD rs1967785282, REVEL 0.66, MetaLR 0.54, Variant assessed as somatic; moderate impact.
- R74Q (p.Arg74Gln), rs766295952, ClinGen CA9136153, ClinVar RCV001130980, ClinVar RCV001130981, REVEL 0.49, MetaLR 0.37, Uncertain significance, Rabson-Mendenhall syndrome; Leprechaunism syndrome; Insulin-resistant diabetes m
- D75G (p.Asp75Gly), rs142910337, ClinGen CA9136152, ClinVar RCV001174372, ClinVar RCV004538395, REVEL 0.18, MetaLR 0.12, Conflicting interpretations, not specified; Monogenic diabetes
- L76H (p.Leu76His), TOPMed rs1967784237
- L76P (p.Leu76Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L76V (p.Leu76Val), rs560460825, ClinGen CA9136150, ClinVar RCV003259881, 1000Genomes rs560460825, REVEL 0.46, MetaLR 0.40, Uncertain significance, Inborn genetic diseases
- S77G (p.Ser77Gly), ExAC rs747157246, gnomAD rs747157246, REVEL 0.73, MetaLR 0.67
- S77R (p.Ser77Arg), ExAC rs747157246, gnomAD rs747157246, REVEL 0.42, MetaLR 0.44
- P79L (p.Pro79Leu), TOPMed rs1331668429, gnomAD rs1331668429, REVEL 0.78, MetaLR 0.61
- P79S (p.Pro79Ser), NCI-TCGA Cosmic COSV5715, cosmic curated COSV57158, REVEL 0.72, MetaLR 0.59, Variant assessed as somatic; moderate impact.
- K80R (p.Lys80Arg), rs775877781, ExAC rs775877781, TOPMed rs775877781, gnomAD rs775877781, REVEL 0.19, MetaLR 0.36, Variant assessed as somatic; moderate impact.
- L81V (p.Leu81Val), rs2512520687, ClinGen CA403160285, ClinVar RCV002825606, Uncertain significance, not provided
- I82T (p.Ile82Thr), ESP rs148554947, TOPMed rs148554947, gnomAD rs148554947, REVEL 0.19, MetaLR 0.11
- M83I (p.Met83Ile), gnomAD rs1345838456, REVEL 0.20, MetaLR 0.27
- M83T (p.Met83Thr), TOPMed rs1967783364, gnomAD rs1967783364, REVEL 0.39, MetaLR 0.41
- I84L (p.Ile84Leu), ExAC rs772506019, gnomAD rs772506019, Uncertain significance
- I84V (p.Ile84Val), rs772506019, ClinGen CA403160253, ClinVar RCV001787616, ExAC rs772506019, Uncertain significance, not provided
- D86G (p.Asp86Gly), UniProt VAR 015907, Pathogenic, in IRAN type A
- L88F (p.Leu88Phe), Ensembl rs1967782992, REVEL 0.78, MetaLR 0.76
- L89P (p.Leu89Pro), UniProt VAR 015908, Pathogenic, in IRAN type A
- L90F (p.Leu90Phe), ExAC rs757683491, gnomAD rs757683491, REVEL 0.72, MetaLR 0.53
- R92Q (p.Arg92Gln), ExAC rs777109581, gnomAD rs777109581, REVEL 0.87, MetaLR 0.69
- R92W (p.Arg92Trp), TOPMed rs1967782626
- V93A (p.Val93Ala), Ensembl rs1967782265
- V93I (p.Val93Ile), TOPMed rs1967782347, gnomAD rs1967782347, REVEL 0.64, MetaLR 0.74
- L96F (p.Leu96Phe), ExAC rs752292214, gnomAD rs752292214, REVEL 0.74, MetaLR 0.78
- D101N (p.Asp101Asn), ESP rs373196983, ExAC rs373196983, TOPMed rs373196983, gnomAD rs373196983, REVEL 0.29, MetaLR 0.40
- F103L (p.Phe103Leu), rs1568229181, ClinGen CA403160045, ClinVar RCV000722890, Ensembl rs1568229181, Uncertain significance, not provided
- P104H (p.Pro104His), TOPMed rs1967781333
- N105S (p.Asn105Ser), TOPMed rs1967781164, REVEL 0.85, MetaLR 0.75
- L106F (p.Leu106Phe), TOPMed rs1478172030, gnomAD rs1478172030, REVEL 0.90, MetaLR 0.96
- T107A (p.Thr107Ala), gnomAD rs1248231684, REVEL 0.26, MetaLR 0.33
- T107M (p.Thr107Met), rs140762552, ClinGen CA9136136, cosmic curated COSV57157, ClinVar RCV001817742, REVEL 0.78, MetaLR 0.70, Uncertain significance, not specified
- V108D (p.Val108Asp), TOPMed rs1967780691
- R110Q (p.Arg110Gln), rs2512520437, ClinGen CA403159970, ClinVar RCV003685116, NCI-TCGA TCGA novel, Uncertain significance, not provided
- R110W (p.Arg110Trp), cosmic curated COSV57167, ExAC rs762765697, gnomAD rs762765697, REVEL 0.93, MetaLR 0.78
- G111V (p.Gly111Val), Ensembl rs1967780536
- S112* (p.Ser112Ter), TOPMed rs1967780431, gnomAD rs1967780431, CADD 36.00
- R113* (p.Arg113Ter), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10025, CADD 35.00, Variant assessed as somatic; high impact., in LEPRCH
- R113L (p.Arg113Leu), TOPMed rs121913153, gnomAD rs121913153, REVEL 0.45, MetaLR 0.41, Pathogenic, in LEPRCH
- R113P (p.Arg113Pro), rs121913153, ClinGen CA124255, ClinVar RCV000015818, UniProt VAR 004082, Pathogenic, Leprechaunism syndrome
- R113Q (p.Arg113Gln), rs121913153, NCI-TCGA Cosmic COSV1002, cosmic curated COSV10025, TOPMed rs121913153, REVEL 0.24, MetaLR 0.17, Pathogenic, in LEPRCH
- F115L (p.Phe115Leu), ESP rs374952799, ExAC rs374952799, TOPMed rs374952799, gnomAD rs374952799, Uncertain significance
- N117K (p.Asn117Lys), TOPMed rs1967779724, gnomAD rs1967779724, REVEL 0.63, MetaLR 0.60
- Y118N (p.Tyr118Asn), ExAC rs764030120, gnomAD rs764030120, REVEL 0.91, MetaLR 0.82
- A119P (p.Ala119Pro), gnomAD rs929761465, REVEL 0.92, MetaLR 0.85
- A119T (p.Ala119Thr), gnomAD rs929761465, REVEL 0.86, MetaLR 0.80
- A119V (p.Ala119Val), rs1347473020, ClinGen CA403159910, cosmic curated COSV10610, ClinVar RCV002638095, REVEL 0.93, MetaLR 0.83, Conflicting interpretations, INSR-related disorder; not provided
- L120Q (p.Leu120Gln), UniProt VAR 031518, Pathogenic, in LEPRCH
- E124K (p.Glu124Lys), rs896894246, NCI-TCGA Cosmic COSV5717, cosmic curated COSV57172, TOPMed rs896894246, REVEL 0.88, MetaLR 0.62, Uncertain significance, Inborn genetic diseases; not provided
- M125I (p.Met125Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M125V (p.Met125Val), ExAC rs775779827, gnomAD rs775779827, REVEL 0.91, MetaLR 0.68
- K129* (p.Lys129Ter), Ensembl rs1967778211
- K129R (p.Lys129Arg), rs1310336610, ClinGen CA403159597, ClinVar RCV001820501, TOPMed rs1310336610, REVEL 0.25, MetaLR 0.24, Uncertain significance, not specified
- E130V (p.Glu130Val), gnomAD rs1413502338, REVEL 0.81, MetaLR 0.75
- G132S (p.Gly132Ser), rs886037750, ClinGen CA10575769, NCI-TCGA Cosmic COSV1002, cosmic curated COSV10025, Pathogenic, Rabson-Mendenhall syndrome
- L133F (p.Leu133Phe), gnomAD rs1414682481
- L136R (p.Leu136Arg), ExAC rs749713053, gnomAD rs749713053, REVEL 0.88, MetaLR 0.85
- M137I (p.Met137Ile), NCI-TCGA Cosmic COSV5715, cosmic curated COSV57157, REVEL 0.41, MetaLR 0.35, Variant assessed as somatic; moderate impact.
- M137L (p.Met137Leu), ExAC rs778361303, gnomAD rs778361303, REVEL 0.44, MetaLR 0.36
- M137V (p.Met137Val), ExAC rs778361303, gnomAD rs778361303, REVEL 0.51, MetaLR 0.36
- I139V (p.Ile139Val), TOPMed rs1967776372, REVEL 0.59, MetaLR 0.68
- R141Q (p.Arg141Gln), rs747649085, ClinGen CA9136123, ClinVar RCV003054497, ExAC rs747649085, REVEL 0.73, MetaLR 0.68, Uncertain significance, not provided
- R141W (p.Arg141Trp), rs1555689823, ClinGen CA403159519, ClinVar RCV000507254, Ensembl rs1555689823, REVEL 0.81, MetaLR 0.74, Uncertain significance, not specified
- R145C (p.Arg145Cys), rs1967775472, ClinVar RCV004821005, Ensembl rs1967775472, REVEL 0.85, MetaLR 0.74, Pathogenic/Likely pathogenic, Insulin resistance; Rabson-Mendenhall syndrome
- R145H (p.Arg145His), gnomAD rs1210993396, REVEL 0.86, MetaLR 0.71
- R145S (p.Arg145Ser), Ensembl rs1967775472, Likely pathogenic
- I146F (p.Ile146Phe), TOPMed rs1967775054, gnomAD rs1967775054, REVEL 0.77, MetaLR 0.65
- I146M (p.Ile146Met), rs121913159, ClinGen CA124271, ClinVar RCV000015826, UniProt VAR 015539, REVEL 0.67, MetaLR 0.75, Pathogenic, Leprechaunism syndrome
- E147K (p.Glu147Lys), NCI-TCGA Cosmic COSV5716, cosmic curated COSV57160, TOPMed rs1967774741, REVEL 0.84, MetaLR 0.67, Variant assessed as somatic; moderate impact.
- K148* (p.Lys148Ter), rs121913155, ClinGen CA124259, ClinVar RCV000015820, Ensembl rs121913155, Pathogenic
- N150D (p.Asn150Asp), rs2512520109, ClinGen CA403159462, ClinVar RCV003263449, REVEL 0.22, MetaLR 0.28, Uncertain significance, Inborn genetic diseases
- C153Y (p.Cys153Tyr), Ensembl rs1967774215
- Y154H (p.Tyr154His), TOPMed rs1967774121
- A156T (p.Ala156Thr), ExAC rs750269551, gnomAD rs750269551, REVEL 0.26, MetaLR 0.27
- A156V (p.Ala156Val), cosmic curated COSV57157, TOPMed rs1967773839
- I158V (p.Ile158Val), ExAC rs765224661, TOPMed rs765224661, gnomAD rs765224661, REVEL 0.32, MetaLR 0.38
- D159N (p.Asp159Asn), cosmic curated COSV10965, NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- W160* (p.Trp160Ter), rs121913146, ClinGen CA124238, ClinVar RCV000015809, Ensembl rs121913146, CADD 38.00, Pathogenic
- S161F (p.Ser161Phe), cosmic curated COSV57175, Ensembl rs140955974
- R162H (p.Arg162His), ExAC rs767746469, TOPMed rs767746469, gnomAD rs767746469, REVEL 0.26, MetaLR 0.36, Uncertain significance, not provided
- R162L (p.Arg162Leu), ExAC rs767746469, TOPMed rs767746469, gnomAD rs767746469, REVEL 0.18, MetaLR 0.19
- I163V (p.Ile163Val), NCI-TCGA Cosmic COSV5716, cosmic curated COSV57165, REVEL 0.57, MetaLR 0.61, Variant assessed as somatic; moderate impact.
- D165Y (p.Asp165Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S166C (p.Ser166Cys), TOPMed rs267605760, gnomAD rs267605760, REVEL 0.62, MetaLR 0.68
- S166F (p.Ser166Phe), cosmic curated COSV57170, TOPMed rs267605760, gnomAD rs267605760
- V167L (p.Val167Leu), rs938519025, cosmic curated COSV10459, UniProt VAR 015910, TOPMed rs938519025, REVEL 0.53, MetaLR 0.52, Pathogenic, in IRAN type A
- V167M (p.Val167Met), cosmic curated COSV57161, TOPMed rs938519025, REVEL 0.55, MetaLR 0.69
- D169V (p.Asp169Val), gnomAD rs1161177676, REVEL 0.70, MetaLR 0.54
- Y171F (p.Tyr171Phe), gnomAD rs1967772190, REVEL 0.43, MetaLR 0.43
- Y171H (p.Tyr171His), rs1051692, UniProt VAR 058396, Ensembl rs1051692, REVEL 0.50, MetaLR 0.46
- I172F (p.Ile172Phe), ExAC rs771145256, TOPMed rs771145256, gnomAD rs771145256, REVEL 0.70, MetaLR 0.61
- I172N (p.Ile172Asn), ESP rs147233169, TOPMed rs147233169, REVEL 0.89, MetaLR 0.72
- V173L (p.Val173Leu), TOPMed rs1967771809, REVEL 0.15, MetaLR 0.42
- V173M (p.Val173Met), NCI-TCGA Cosmic COSV5715, cosmic curated COSV57158, Variant assessed as somatic; moderate impact.
- N175K (p.Asn175Lys), NCI-TCGA Cosmic COSV5716, cosmic curated COSV57164, Variant assessed as somatic; moderate impact.
- D178N (p.Asp178Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N179D (p.Asn179Asp), Ensembl rs1967771548
- E180K (p.Glu180Lys), TOPMed rs1240458376, gnomAD rs1240458376, REVEL 0.50, MetaLR 0.70, Uncertain significance, Inborn genetic diseases
- E181K (p.Glu181Lys), gnomAD rs1188129008, REVEL 0.74, MetaLR 0.79
- I185N (p.Ile185Asn), gnomAD rs1967770854, REVEL 0.46, MetaLR 0.51
- I185V (p.Ile185Val), cosmic curated COSV10459, ExAC rs770317587, TOPMed rs770317587, gnomAD rs770317587, REVEL 0.18, MetaLR 0.15, Uncertain significance, Inborn genetic diseases
- P187L (p.Pro187Leu), cosmic curated COSV57166, TOPMed rs1412618950, REVEL 0.83, MetaLR 0.95
- P187S (p.Pro187Ser), rs868743082, NCI-TCGA Cosmic COSV5716, cosmic curated COSV57166, Ensembl rs868743082, Variant assessed as somatic; moderate impact.
Public INSR analysis runs
- INSR analysis run — INSR (1,557 variants) — completed 2026-08-19