ARNT (P27540) variants and mutations
ARNT (also known as P27540) is a human protein-coding gene encoding an aryl hydrocarbon receptor nuclear translocator protein. It heterodimerizes with HIF-alpha proteins and the aryl-hydrocarbon receptor to regulate transcriptional responses to hypoxia and environmental ligands. Disruption can therefore affect oxygen sensing, xenobiotic responses, and developmental programs, although monogenic disease associations are uncommon. This analysis covers 1,019 ARNT variants and mutations. Of these, 71% have computational variant effect predictions. Disease context includes neurodegenerative disease, cutaneous melanoma, and breast ductal adenocarcinoma. Example ARNT variants include A3T, A3V, and T4A.
Variant analysis overview
- Gene: ARNT
- Protein: P27540
- UniProt accession: P27540
- Organism: Homo sapiens
- Variants analyzed: 1019
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 772 unspecified-consequence records; 1 stop lost; 92 synonymous variants; 124 missense variants; 6 stop-gained variants; 13 frameshift variants; 3 in-frame deletions; 2 splice-region variants; 6 substitution
- Prediction scores: 728 variants have prediction scores (71% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, cutaneous melanoma, breast ductal adenocarcinoma, bile duct carcinoma, endometrial endometrioid adenocarcinoma, hepatobiliary neoplasm, hemangioblastoma, carcinoma of liver and intrahepatic biliary tract, ovarian endometrioid adenocarcinoma with squamous differentiation, Alzheimer disease, Parkinson disease, multiple sclerosis.
Protein structure and variant hotspots
- Protein features: 4 domains; 2 post-translational modification sites.
- Structural context: 226 variants have structural context.
- PTM context: 2 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable ARNT variants
Examples include A3T, A3V, T4A, T5I, T5S, A6S, N7K, N7Y. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A3T (p.Ala3Thr), TOPMed rs1268420256, gnomAD rs1268420256, REVEL 0.15, CADD 24.00
- A3V (p.Ala3Val), gnomAD rs1193355203, REVEL 0.15, CADD 27.60
- T4A (p.Thr4Ala), gnomAD rs1265421807, REVEL 0.05, CADD 21.80
- T5I (p.Thr5Ile), TOPMed rs1343634119, gnomAD rs1343634119, REVEL 0.06, CADD 25.10
- T5S (p.Thr5Ser), TOPMed rs1343634119, gnomAD rs1343634119
- A6S (p.Ala6Ser), TOPMed rs1668301257, REVEL 0.16, CADD 23.50
- N7K (p.Asn7Lys), ExAC rs747271228, TOPMed rs747271228, gnomAD rs747271228, REVEL 0.07, CADD 25.30
- N7Y (p.Asn7Tyr), gnomAD rs1227142569, REVEL 0.13, CADD 26.80
- P8=, NCI-TCGA TCGA novel, Variant assessed as somatic; low impact.
- P8A (p.Pro8Ala), gnomAD rs1303125672, REVEL 0.14, CADD 23.60
- E9V (p.Glu9Val), TOPMed rs1432128766, gnomAD rs1432128766, REVEL 0.12, CADD 26.40
- M10T (p.Met10Thr), ESP rs146030272, ExAC rs146030272, TOPMed rs146030272, gnomAD rs146030272
- M10V (p.Met10Val), TOPMed rs1665016413
- T11A (p.Thr11Ala), TOPMed rs1665015478
- S12P (p.Ser12Pro), ExAC rs754657234, gnomAD rs754657234, REVEL 0.11, CADD 24.40
- D13G (p.Asp13Gly), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10059, REVEL 0.14, CADD 27.10, Variant assessed as somatic; moderate impact.
- P15L (p.Pro15Leu), gnomAD rs1242778324, REVEL 0.14, CADD 24.80
- G18A (p.Gly18Ala), ExAC rs754424632, gnomAD rs754424632, REVEL 0.15, CADD 19.30
- G18R (p.Gly18Arg), TOPMed rs1665011550, REVEL 0.18, CADD 23.30
- P19A (p.Pro19Ala), ExAC rs764027746, gnomAD rs764027746
- P19L (p.Pro19Leu), ExAC rs760782153, gnomAD rs760782153, REVEL 0.11, CADD 23.10
- A20T (p.Ala20Thr), gnomAD rs1393596166
- A22V (p.Ala22Val), Ensembl rs965633110
- N25S (p.Asn25Ser), ExAC rs759809720, TOPMed rs759809720, gnomAD rs759809720, REVEL 0.12, CADD 17.90
- S26C (p.Ser26Cys), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10059, Variant assessed as somatic; moderate impact.
- S26P (p.Ser26Pro), Ensembl rs2102293075
- G27E (p.Gly27Glu), TOPMed rs1190052109, gnomAD rs1190052109, REVEL 0.12, CADD 21.70
- G29E (p.Gly29Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G29R (p.Gly29Arg), ExAC rs770745835, gnomAD rs770745835, REVEL 0.12, CADD 25.80
- I30S (p.Ile30Ser), gnomAD rs1199394942
- Q31* (p.Gln31Ter), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62232, Variant assessed as somatic; high impact.
- G32D (p.Gly32Asp), ExAC rs773179687, TOPMed rs773179687, gnomAD rs773179687, REVEL 0.09, CADD 23.00
- G32S (p.Gly32Ser), gnomAD rs1453244649
- G34A (p.Gly34Ala), ExAC rs769659709, TOPMed rs769659709, gnomAD rs769659709, REVEL 0.10, CADD 22.50
- G34R (p.Gly34Arg), gnomAD rs1447316068, REVEL 0.20, CADD 24.90
- A35D (p.Ala35Asp), ExAC rs780629150, TOPMed rs780629150, gnomAD rs780629150, REVEL 0.13, CADD 22.70
- A35G (p.Ala35Gly), ExAC rs780629150, TOPMed rs780629150, gnomAD rs780629150, REVEL 0.07, CADD 20.30
- A35T (p.Ala35Thr), rs201499435, NCI-TCGA Cosmic COSV1005, cosmic curated COSV10059, ExAC rs201499435, REVEL 0.02, CADD 15.80, Variant assessed as somatic; moderate impact.
- A35V (p.Ala35Val), ExAC rs780629150, TOPMed rs780629150, gnomAD rs780629150, REVEL 0.04, CADD 19.30
- I36T (p.Ile36Thr), ExAC rs754603094, TOPMed rs754603094, gnomAD rs754603094, REVEL 0.11, CADD 23.10
- I36V (p.Ile36Val), cosmic curated COSV10591, TOPMed rs1230813269, gnomAD rs1230813269, REVEL 0.04, CADD 10.80
- V37I (p.Val37Ile), TOPMed rs1229201640
- Q38* (p.Gln38Ter), rs746667101, ExAC rs746667101, TOPMed rs746667101, gnomAD rs746667101, Variant assessed as somatic; high impact.
- Q38R (p.Gln38Arg), Ensembl rs995636924, REVEL 0.08, CADD 21.70
- A40T (p.Ala40Thr), TOPMed rs1664999152, REVEL 0.02, CADD 19.30
- I41V (p.Ile41Val), cosmic curated COSV62230, gnomAD rs1322104083, REVEL 0.05, CADD 14.00
- R43Q (p.Arg43Gln), ExAC rs757715657, gnomAD rs757715657, REVEL 0.19, CADD 26.50
- R43W (p.Arg43Trp), TOPMed rs1386729618, gnomAD rs1386729618, REVEL 0.26, CADD 31.00, Uncertain significance, not specified
- R44* (p.Arg44Ter), cosmic curated COSV10968, ExAC rs754299833, gnomAD rs754299833, CADD 35.00
- R44Q (p.Arg44Gln), ExAC rs764626976, TOPMed rs764626976, gnomAD rs764626976, REVEL 0.11, CADD 23.80
- P45R (p.Pro45Arg), Ensembl rs1664992987, REVEL 0.12, CADD 19.10
- P45S (p.Pro45Ser), NCI-TCGA TCGA novel, TOPMed rs1664993700, REVEL 0.06, CADD 8.98, Uncertain significance, not specified
- L47P (p.Leu47Pro), TOPMed rs1663871564
- D48H (p.Asp48His), NCI-TCGA Cosmic COSV6223, Variant assessed as somatic; moderate impact.
- D48N (p.Asp48Asn), cosmic curated COSV62232, ExAC rs771835083, gnomAD rs771835083, REVEL 0.13, CADD 26.10
- F49C (p.Phe49Cys), ESP rs147957446, ExAC rs147957446, TOPMed rs147957446, gnomAD rs147957446, REVEL 0.20, CADD 28.00
- D50N (p.Asp50Asn), gnomAD rs1663869986, REVEL 0.15, CADD 32.00
- D52V (p.Asp52Val), cosmic curated COSV10059, TOPMed rs1663869446, REVEL 0.12, CADD 24.80
- G53R (p.Gly53Arg), rs778132479, []
- G55E (p.Gly55Glu), ExAC rs778132479, gnomAD rs778132479, REVEL 0.07, CADD 23.30
- S57C (p.Ser57Cys), cosmic curated COSV62230, Ensembl rs1663866797, REVEL 0.10, CADD 22.80
- K58N (p.Lys58Asn), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10059, Variant assessed as somatic; moderate impact.
- K58T (p.Lys58Thr), NCI-TCGA Cosmic COSV1044, cosmic curated COSV10441, Variant assessed as somatic; moderate impact.
- L60V (p.Leu60Val), ExAC rs748595298, TOPMed rs748595298, gnomAD rs748595298, REVEL 0.08, CADD 22.10
- R61W (p.Arg61Trp), TOPMed rs1223087092, gnomAD rs1223087092, REVEL 0.16, CADD 34.00
- D64G (p.Asp64Gly), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62231, Variant assessed as somatic; moderate impact.
- D65H (p.Asp65His), TOPMed rs1478084024
- Q66H (p.Gln66His), ExAC rs773854292, gnomAD rs773854292, REVEL 0.04, CADD 22.30
- Q66R (p.Gln66Arg), gnomAD rs1205325539, REVEL 0.08, CADD 20.70
- M67I (p.Met67Ile), ESP rs141051493, ExAC rs141051493, TOPMed rs141051493, gnomAD rs141051493, REVEL 0.07, CADD 17.90
- N69D (p.Asn69Asp), Ensembl rs940467216, REVEL 0.10, CADD 22.10
- N69I (p.Asn69Ile), gnomAD rs1272091771, REVEL 0.10, CADD 23.50
- D70N (p.Asp70Asn), rs1312509595, NCI-TCGA Cosmic COSV1005, cosmic curated COSV10059, TOPMed rs1312509595, REVEL 0.17, CADD 25.10, Variant assessed as somatic; moderate impact.
- D70V (p.Asp70Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K71Q (p.Lys71Gln), TOPMed rs1422231816, gnomAD rs1422231816, REVEL 0.08, CADD 24.20
- R73L (p.Arg73Leu), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62230, Variant assessed as somatic; moderate impact.
- R73Q (p.Arg73Gln), rs146813760, NCI-TCGA Cosmic COSV6223, cosmic curated COSV62231, 1000Genomes rs146813760, REVEL 0.20, CADD 26.70, Variant assessed as somatic; moderate impact.
- R73W (p.Arg73Trp), cosmic curated COSV62230, ExAC rs769096175, TOPMed rs769096175, gnomAD rs769096175, REVEL 0.23, CADD 27.50
- R76M (p.Arg76Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S77* (p.Ser77Ter), ExAC rs779105288, TOPMed rs779105288, gnomAD rs779105288, CADD 42.00, Uncertain significance
- S77L (p.Ser77Leu), rs779105288, ClinGen CA1081241, cosmic curated COSV10525, ClinVar RCV004074389, REVEL 0.13, CADD 23.40, Uncertain significance, not specified
- D78E (p.Asp78Glu), gnomAD rs1428483610, REVEL 0.12, CADD 23.30
- D79Y (p.Asp79Tyr), gnomAD rs1460673481, REVEL 0.35, CADD 31.00
- Q81L (p.Gln81Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S82N (p.Ser82Asn), gnomAD rs943817666, REVEL 0.18, CADD 23.40
- S82T (p.Ser82Thr), gnomAD rs943817666
- S83F (p.Ser83Phe), ExAC rs749523683, gnomAD rs749523683, REVEL 0.11, CADD 22.60
- A84G (p.Ala84Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A84T (p.Ala84Thr), rs1238485591, TOPMed rs1238485591, gnomAD rs1238485591, REVEL 0.20, CADD 20.90, Uncertain significance, not specified
- A84V (p.Ala84Val), ESP rs143641553, ExAC rs143641553, TOPMed rs143641553, gnomAD rs143641553, REVEL 0.27, CADD 23.80
- K86R (p.Lys86Arg), ExAC rs767352759, TOPMed rs767352759, gnomAD rs767352759, REVEL 0.24, CADD 25.20, Uncertain significance, not specified
- A90S (p.Ala90Ser), Ensembl rs867973621, REVEL 0.22, CADD 23.60
- A90T (p.Ala90Thr), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62230, Ensembl rs867973621, Variant assessed as somatic; moderate impact.
- R91K (p.Arg91Lys), cosmic curated COSV62230, Ensembl rs1661450891
- N93S (p.Asn93Ser), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62231, Variant assessed as somatic; moderate impact.
- H94Y (p.His94Tyr), NCI-TCGA Cosmic COSV6222, cosmic curated COSV62229, Variant assessed as somatic; moderate impact.
- E98V (p.Glu98Val), Ensembl rs2101952763
- R99Q (p.Arg99Gln), Ensembl rs2101952652, REVEL 0.74, CADD 29.30
- R99W (p.Arg99Trp), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62230, TOPMed rs1271141043, gnomAD rs1271141043, Variant assessed as somatic; moderate impact.
- R100G (p.Arg100Gly), Ensembl rs2101952540
- R100Q (p.Arg100Gln), cosmic curated COSV10818, Ensembl rs2101952506, REVEL 0.72, CADD 29.50
- R100W (p.Arg100Trp), Ensembl rs2101952540, REVEL 0.74, CADD 32.00
- R101* (p.Arg101Ter), cosmic curated COSV62230, ExAC rs751549820, gnomAD rs751549820, CADD 37.00
- R101G (p.Arg101Gly), ExAC rs751549820, gnomAD rs751549820
- R101Q (p.Arg101Gln), gnomAD rs1660915592, REVEL 0.89, CADD 29.40
- R102G (p.Arg102Gly), gnomAD rs1660915119
- R102Q (p.Arg102Gln), rs1490240303, NCI-TCGA Cosmic COSV1005, NCI-TCGA Cosmic COSV6222, cosmic curated COSV62229, REVEL 0.90, CADD 32.00, Variant assessed as somatic; moderate impact.
- R102W (p.Arg102Trp), NCI-TCGA Cosmic COSV6222, cosmic curated COSV62229, gnomAD rs1660915119, REVEL 0.94, CADD 29.40, Variant assessed as somatic; moderate impact.
- N103D (p.Asn103Asp), Ensembl rs2101952198
- N103S (p.Asn103Ser), rs948601239, Ensembl rs948601239, REVEL 0.62, CADD 26.10, Variant assessed as somatic; moderate impact.
- M105I (p.Met105Ile), Ensembl rs2101952118
- T106I (p.Thr106Ile), TOPMed rs1235347029, gnomAD rs1235347029, REVEL 0.76, CADD 33.00
- A107G (p.Ala107Gly), TOPMed rs1660912435, Uncertain significance, not specified
- A107S (p.Ala107Ser), Ensembl rs2101951969
- A107T (p.Ala107Thr), Ensembl rs2101951969
- A107V (p.Ala107Val), cosmic curated COSV10525, TOPMed rs1660912435
- I109V (p.Ile109Val), TOPMed rs1177252825, gnomAD rs1177252825, REVEL 0.83, CADD 25.40
- T110S (p.Thr110Ser), Ensembl rs2101951696
- E111* (p.Glu111Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E111K (p.Glu111Lys), Ensembl rs1660909776
- E111Q (p.Glu111Gln), Ensembl rs1660909776
- L112P (p.Leu112Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S113* (p.Ser113Ter), Ensembl rs2101951371
- S113T (p.Ser113Thr), Ensembl rs2101951422
- M115I (p.Met115Ile), Ensembl rs2101951242
- M115V (p.Met115Val), ExAC rs749979422, gnomAD rs749979422, REVEL 0.89, CADD 25.60
- V116I (p.Val116Ile), Ensembl rs2101951208, REVEL 0.56, CADD 25.20
- P117A (p.Pro117Ala), Ensembl rs2101951149
- P117S (p.Pro117Ser), Ensembl rs2101951149
- T118P (p.Thr118Pro), Ensembl rs2101951093
- T118S (p.Thr118Ser), Ensembl rs2101951039
- S120N (p.Ser120Asn), Ensembl rs2101950965
- A121V (p.Ala121Val), gnomAD rs1252013102, REVEL 0.52, CADD 28.80
- L122M (p.Leu122Met), Ensembl rs2101950882
- L122P (p.Leu122Pro), gnomAD rs1347997303, REVEL 0.79, CADD 29.70
- A123V (p.Ala123Val), gnomAD rs1660906854, REVEL 0.50, CADD 29.10
- R124* (p.Arg124Ter), Ensembl rs2101950711, CADD 37.00
- R124Q (p.Arg124Gln), cosmic curated COSV10610, TOPMed rs1660906433, REVEL 0.72, CADD 28.80
- D127N (p.Asp127Asn), Ensembl rs2101950566
- D127Y (p.Asp127Tyr), Ensembl rs2101950566
- T130A (p.Thr130Ala), Ensembl rs1056979657, REVEL 0.89, CADD 26.40
- I131V (p.Ile131Val), ExAC rs761507962, gnomAD rs761507962, REVEL 0.69, CADD 23.70
- R133C (p.Arg133Cys), TOPMed rs770206803, gnomAD rs770206803, REVEL 0.92, CADD 31.00
- R133H (p.Arg133His), rs752945065, NCI-TCGA Cosmic COSV6223, cosmic curated COSV62230, ExAC rs752945065, REVEL 0.88, CADD 27.70, Variant assessed as somatic; moderate impact.
- R133L (p.Arg133Leu), ExAC rs752945065, TOPMed rs752945065, gnomAD rs752945065, REVEL 0.87, CADD 27.30
- M134I (p.Met134Ile), Ensembl rs2101950050
- M134L (p.Met134Leu), gnomAD rs1660901060, REVEL 0.80, CADD 25.90
- A135P (p.Ala135Pro), 1000Genomes rs181961097, ExAC rs181961097, TOPMed rs181961097, gnomAD rs181961097
- A135S (p.Ala135Ser), 1000Genomes rs181961097, ExAC rs181961097, TOPMed rs181961097, gnomAD rs181961097
- A135T (p.Ala135Thr), 1000Genomes rs181961097, ExAC rs181961097, TOPMed rs181961097, gnomAD rs181961097, REVEL 0.70, CADD 26.60
- A135V (p.Ala135Val), Ensembl rs2101949898
- V136I (p.Val136Ile), ExAC rs759919140, gnomAD rs759919140
- S137A (p.Ser137Ala), Ensembl rs1571321206
- H138R (p.His138Arg), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10059, Variant assessed as somatic; moderate impact.
- K140E (p.Lys140Glu), TOPMed rs965443011
- K140R (p.Lys140Arg), ExAC rs771390470, TOPMed rs771390470, gnomAD rs771390470, REVEL 0.82, CADD 27.80
- S141F (p.Ser141Phe), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62230, Variant assessed as somatic; moderate impact.
- L142F (p.Leu142Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R143Q (p.Arg143Gln), ExAC rs763121654, TOPMed rs763121654, gnomAD rs763121654, REVEL 0.40, CADD 27.30
- R143W (p.Arg143Trp), NCI-TCGA TCGA novel, TOPMed rs1660896814, gnomAD rs1660896814, REVEL 0.47, CADD 25.20, Variant assessed as somatic; moderate impact.
- G144R (p.Gly144Arg), Ensembl rs2101949520
- G146D (p.Gly146Asp), cosmic curated COSV10441, ExAC rs773484109, gnomAD rs773484109, REVEL 0.38, CADD 25.50
- N147S (p.Asn147Ser), ExAC rs751934130, TOPMed rs751934130, gnomAD rs751934130, REVEL 0.21, CADD 22.50
- T148A (p.Thr148Ala), ESP rs373016604, ExAC rs373016604, gnomAD rs373016604, REVEL 0.38, CADD 23.80
- S149P (p.Ser149Pro), 1000Genomes rs116774603, ExAC rs116774603, TOPMed rs116774603, gnomAD rs116774603, REVEL 0.11, CADD 22.70
- T150I (p.Thr150Ile), ESP rs369482161, ExAC rs369482161, TOPMed rs369482161, gnomAD rs369482161, REVEL 0.33, CADD 24.00
- T150N (p.Thr150Asn), ESP rs369482161, ExAC rs369482161, TOPMed rs369482161, gnomAD rs369482161
- D151H (p.Asp151His), ExAC rs780013660, TOPMed rs780013660, gnomAD rs780013660, REVEL 0.33, CADD 26.80
- G152S (p.Gly152Ser), ESP rs139158737, ExAC rs139158737, TOPMed rs139158737, gnomAD rs139158737
- S153F (p.Ser153Phe), TOPMed rs1660891444, gnomAD rs1660891444, REVEL 0.30, CADD 24.90
- Y154H (p.Tyr154His), Ensembl rs1660890462
- K155E (p.Lys155Glu), gnomAD rs1311021347, REVEL 0.35, CADD 26.10
- K155Q (p.Lys155Gln), gnomAD rs1311021347, REVEL 0.39, CADD 26.00
- K155T (p.Lys155Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P156L (p.Pro156Leu), ExAC rs778405288, gnomAD rs778405288, REVEL 0.49, CADD 29.30
- P156Q (p.Pro156Gln), rs778405288, ExAC rs778405288, gnomAD rs778405288, REVEL 0.45, CADD 28.20, Variant assessed as somatic; moderate impact.
- L159F (p.Leu159Phe), gnomAD rs1280793940, REVEL 0.47, CADD 27.60
- Q162E (p.Gln162Glu), Ensembl rs1660885714
- Q162P (p.Gln162Pro), NCI-TCGA Cosmic COSV6223, cosmic curated COSV62230, Variant assessed as somatic; moderate impact.
- H166R (p.His166Arg), TOPMed rs1660347709
Public ARNT analysis runs
- ARNT analysis run — ARNT (1,019 variants) — completed 2026-08-19