ANGPTL4 (Angiopoietin-related protein 4) variants and mutations
ANGPTL4 (also known as Angiopoietin-related protein 4) is a human protein-coding gene encoding an angiopoietin-related protein 4 protein. It regulates lipid partitioning by inhibiting lipoprotein lipase in a tissue- and nutritional-state-dependent manner. Loss-of-function variants can lower triglyceride levels and have been associated with reduced coronary-disease risk, although the protein also has broader roles in metabolism and tissue responses. This analysis covers 935 ANGPTL4 variants and mutations. Of these, 88% have computational variant effect predictions. Disease context includes coronary artery disorder, coronary atherosclerosis, and type 2 diabetes mellitus. Example ANGPTL4 variants include M1I, S2C, and S2G.
Variant analysis overview
- Gene: ANGPTL4
- Protein: Angiopoietin-related protein 4
- UniProt accession: Q9BY76
- Organism: Homo sapiens
- Variants analyzed: 935
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 499 unspecified-consequence records; 275 missense variants; 21 frameshift variants; 108 synonymous variants; 21 stop-gained variants; 3 in-frame deletions; 1 splice-region variants; 9 substitution
- Prediction scores: 827 variants have prediction scores (88% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: coronary artery disorder, coronary atherosclerosis, type 2 diabetes mellitus, diabetes mellitus, metabolic disease, hyperlipidemia, familial lipoprotein lipase deficiency, familial hyperlipidemia, response to statin, Hypercholesterolemia, heart disorder, alcohol drinking.
Protein structure and variant hotspots
- Protein features: 1 domains; 1 post-translational modification sites.
- Structural context: 279 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 ANGPTL4 variants
Examples include M1I, S2C, S2G, S2N, S2R, S2I, S2S, G3A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs780416714, []
- S2C (p.Ser2Cys), gnomAD 19-8364325-A-T, REVEL 0.04, CADD 14.10
- S2G (p.Ser2Gly), gnomAD 19-8364325-A-G, REVEL 0.07, CADD 16.90
- S2N (p.Ser2Asn), gnomAD 19-8364326-G-A, REVEL 0.12, CADD 22.00
- S2R (p.Ser2Arg), rs1224422944, gnomAD 19-8364326-GC-G, CADD 23.10
- S2I (p.Ser2Ile), gnomAD 19-8364326-G-T, REVEL 0.13, CADD 22.60
- S2S (p.Ser2Ser), rs537310571, gnomAD 19-8364327-C-T, CADD 10.20
- G3A (p.Gly3Ala), ExAC rs768253869, gnomAD rs768253869
- G3D (p.Gly3Asp), ExAC rs768253869, gnomAD rs768253869, REVEL 0.15, CADD 14.40
- G3S (p.Gly3Ser), ExAC rs746583639, gnomAD rs746583639, REVEL 0.14, CADD 1.62
- G3R (p.Gly3Arg), gnomAD 19-8364328-G-C, REVEL 0.18, CADD 3.16
- G3C (p.Gly3Cys), gnomAD 19-8364328-G-T, REVEL 0.17, CADD 0.38
- G3V (p.Gly3Val), gnomAD 19-8364329-G-T, REVEL 0.11, CADD 14.20
- G3G (p.Gly3Gly), rs1208335927, gnomAD 19-8364330-T-C, CADD 6.95
- A4T (p.Ala4Thr), 1000Genomes rs1264197315, gnomAD rs1264197315, REVEL 0.09, CADD 6.76
- A4S (p.Ala4Ser), gnomAD 19-8364331-G-T, REVEL 0.09, CADD 5.34
- A4D (p.Ala4Asp), gnomAD 19-8364332-C-A, REVEL 0.14, CADD 17.70
- A4V (p.Ala4Val), gnomAD 19-8364332-C-T, REVEL 0.11, CADD 14.30
- A4A (p.Ala4Ala), gnomAD 19-8364333-T-A, CADD 8.42
- P5L (p.Pro5Leu), rs761583091, UniProt VAR 032642, ExAC rs761583091, TOPMed rs761583091, REVEL 0.15, CADD 19.00
- P5S (p.Pro5Ser), ExAC rs776244357, TOPMed rs776244357, gnomAD rs776244357, REVEL 0.03, CADD 9.37
- P5T (p.Pro5Thr), gnomAD 19-8364334-C-A, REVEL 0.05, CADD 13.90
- P5Q (p.Pro5Gln), gnomAD 19-8364335-C-A, REVEL 0.16, CADD 18.30
- P5P (p.Pro5Pro), gnomAD 19-8364336-G-T, CADD 4.30
- T6K (p.Thr6Lys), TOPMed rs1568213565, gnomAD rs1568213565, REVEL 0.07, CADD 17.20, Uncertain significance, not specified
- T6A (p.Thr6Ala), gnomAD 19-8364337-A-G, REVEL 0.03, CADD 17.10
- T6M (p.Thr6Met), gnomAD 19-8364338-C-T, REVEL 0.10, CADD 21.80
- T6R (p.Thr6Arg), gnomAD 19-8364338-C-G, REVEL 0.09, CADD 17.60
- T6T (p.Thr6Thr), rs1470759460, gnomAD 19-8364339-G-A, CADD 0.81
- A7V (p.Ala7Val), Ensembl rs866272907, REVEL 0.11, CADD 20.90
- A7G (p.Ala7Gly), rs1568213571, gnomAD 19-8364338-C-CGG, CADD 21.20
- A7T (p.Ala7Thr), gnomAD 19-8364340-G-A, REVEL 0.08, CADD 19.90
- A7S (p.Ala7Ser), gnomAD 19-8364340-G-T, REVEL 0.10, CADD 22.30
- A7D (p.Ala7Asp), gnomAD 19-8364341-C-A, REVEL 0.14, CADD 23.00
- A7A (p.Ala7Ala), gnomAD 19-8364342-C-G, CADD 7.82
- G8E (p.Gly8Glu), TOPMed rs993269648, gnomAD rs993269648, REVEL 0.06, CADD 19.10
- G8W (p.Gly8Trp), Ensembl rs1970950184, REVEL 0.16, CADD 18.80
- G8R (p.Gly8Arg), gnomAD 19-8364343-G-A, REVEL 0.03, CADD 7.56
- G8V (p.Gly8Val), gnomAD 19-8364344-G-T, REVEL 0.06, CADD 15.80
- G8G (p.Gly8Gly), gnomAD 19-8364345-G-T, CADD 1.46
- A9S (p.Ala9Ser), TOPMed rs1025526193, gnomAD rs1025526193, REVEL 0.17, CADD 23.70, Uncertain significance, not specified
- A9T (p.Ala9Thr), rs1025526193, ClinGen CA403712145, ClinVar RCV004211204, TOPMed rs1025526193, REVEL 0.14, CADD 24.10, Uncertain significance, not specified
- A9Q (p.Ala9Gln), gnomAD 19-8364342-CG-C, CADD 14.80
- A9V (p.Ala9Val), gnomAD 19-8364347-C-T, REVEL 0.14, CADD 17.30
- A9E (p.Ala9Glu), gnomAD 19-8364347-C-A, REVEL 0.21, CADD 23.10
- A9A (p.Ala9Ala), gnomAD 19-8364348-A-G, CADD 9.69
- A10T (p.Ala10Thr), ExAC rs773147922, TOPMed rs773147922, gnomAD rs773147922, REVEL 0.14, CADD 23.80
- A10V (p.Ala10Val), gnomAD rs1406301475, REVEL 0.11, CADD 19.80
- A10S (p.Ala10Ser), gnomAD 19-8364349-G-T, REVEL 0.14, CADD 24.60
- A10D (p.Ala10Asp), gnomAD 19-8364350-C-A, REVEL 0.21, CADD 24.10
- A10A (p.Ala10Ala), gnomAD 19-8364351-C-T, CADD 10.80
- L11P (p.Leu11Pro), ExAC rs766397887, TOPMed rs766397887, gnomAD rs766397887, REVEL 0.27, CADD 23.80
- L11* (p.Leu11Ter), gnomAD 19-8364349-GC-G, CADD 24.00
- L11L (p.Leu11Leu), rs762653036, gnomAD 19-8364352-C-T, CADD 8.90
- L11V (p.Leu11Val), gnomAD 19-8364352-C-G, REVEL 0.04, CADD 18.10
- L11M (p.Leu11Met), gnomAD 19-8364352-C-A, REVEL 0.18, CADD 20.90
- L11Q (p.Leu11Gln), gnomAD 19-8364353-T-A, REVEL 0.35, CADD 25.80
- M12I (p.Met12Ile), Ensembl rs1970950914, REVEL 0.16, CADD 21.00
- M12L (p.Met12Leu), gnomAD 19-8364355-A-T, REVEL 0.08, CADD 8.45
- M12T (p.Met12Thr), gnomAD 19-8364356-T-C, REVEL 0.14, CADD 18.70
- L13F (p.Leu13Phe), gnomAD rs1442836943, REVEL 0.22, CADD 24.00
- L13I (p.Leu13Ile), gnomAD 19-8364358-C-A, REVEL 0.16, CADD 18.50
- L13V (p.Leu13Val), gnomAD 19-8364358-C-G, REVEL 0.11, CADD 18.10
- L13P (p.Leu13Pro), gnomAD 19-8364359-T-C, REVEL 0.32, CADD 23.60
- L13L (p.Leu13Leu), gnomAD 19-8364360-C-A, CADD 6.51
- C14S (p.Cys14Ser), ExAC rs751429634, TOPMed rs751429634, gnomAD rs751429634, REVEL 0.23, CADD 22.70
- C14Y (p.Cys14Tyr), ExAC rs751429634, TOPMed rs751429634, gnomAD rs751429634, REVEL 0.13, CADD 22.70
- C14R (p.Cys14Arg), gnomAD 19-8364361-T-C, REVEL 0.38, CADD 23.20
- C14F (p.Cys14Phe), gnomAD 19-8364362-G-T, REVEL 0.16, CADD 22.80
- C14* (p.Cys14Ter), gnomAD 19-8364363-C-A, CADD 34.00
- C14C (p.Cys14Cys), gnomAD 19-8364363-C-T, CADD 10.00
- C14W (p.Cys14Trp), gnomAD 19-8364363-C-G, REVEL 0.24, CADD 23.30
- A15V (p.Ala15Val), gnomAD rs1348684847, REVEL 0.08, CADD 13.80
- A15T (p.Ala15Thr), gnomAD 19-8364364-G-A, REVEL 0.09, CADD 23.20
- A15S (p.Ala15Ser), gnomAD 19-8364364-G-T, REVEL 0.12, CADD 22.90
- A15D (p.Ala15Asp), gnomAD 19-8364365-C-A, REVEL 0.33, CADD 23.00
- A15A (p.Ala15Ala), gnomAD 19-8364366-C-T, CADD 1.07
- A16G (p.Ala16Gly), TOPMed rs926847231, REVEL 0.15, CADD 21.80
- A16T (p.Ala16Thr), TOPMed rs980968097, gnomAD rs980968097, REVEL 0.07, CADD 15.30
- A16P (p.Ala16Pro), gnomAD 19-8364367-G-C, REVEL 0.10, CADD 19.20
- A16S (p.Ala16Ser), gnomAD 19-8364367-G-T, REVEL 0.04, CADD 17.40
- A16V (p.Ala16Val), gnomAD 19-8364368-C-T, REVEL 0.14, CADD 18.00
- A16D (p.Ala16Asp), gnomAD 19-8364368-C-A, REVEL 0.25, CADD 22.40
- A16A (p.Ala16Ala), rs1264025944, gnomAD 19-8364369-C-A, CADD 8.22
- T17A (p.Thr17Ala), gnomAD 19-8364370-A-G, REVEL 0.04, CADD 16.60
- T17I (p.Thr17Ile), gnomAD 19-8364371-C-T, REVEL 0.11, CADD 19.50
- T17N (p.Thr17Asn), gnomAD 19-8364371-C-A, REVEL 0.11, CADD 15.40
- T17T (p.Thr17Thr), gnomAD 19-8364372-C-A, CADD 5.03
- A18T (p.Ala18Thr), gnomAD rs1347337468, REVEL 0.14, CADD 25.50
- A18V (p.Ala18Val), gnomAD rs1199096784, REVEL 0.11, CADD 22.90
- A18S (p.Ala18Ser), gnomAD 19-8364373-G-T, REVEL 0.12, CADD 24.50
- A18P (p.Ala18Pro), gnomAD 19-8364373-G-C, REVEL 0.24, CADD 26.10
- A18D (p.Ala18Asp), gnomAD 19-8364374-C-A, REVEL 0.25, CADD 24.50
- A18A (p.Ala18Ala), rs760847575, gnomAD 19-8364375-C-G, CADD 6.99
- V19M (p.Val19Met), TOPMed rs1970951786, REVEL 0.11, CADD 21.30
- V19C (p.Val19Cys), gnomAD 19-8364373-GC-G, CADD 24.50
- V19L (p.Val19Leu), gnomAD 19-8364376-G-T, REVEL 0.10, CADD 16.40
- V19V (p.Val19Val), gnomAD 19-8364378-G-A, CADD 8.35
- L20P (p.Leu20Pro), gnomAD rs1438957737, REVEL 0.19, CADD 22.50
- L20I (p.Leu20Ile), gnomAD 19-8364379-C-A, REVEL 0.05, CADD 15.20
- L20L (p.Leu20Leu), gnomAD 19-8364379-C-T, CADD 9.44
- L20Q (p.Leu20Gln), gnomAD 19-8364380-T-A, REVEL 0.27, CADD 25.00
- L21* (p.Leu21Ter), gnomAD 19-8364380-TA-T, CADD 22.60
- L21M (p.Leu21Met), gnomAD 19-8364382-C-A, REVEL 0.06, CADD 21.30
- L21V (p.Leu21Val), gnomAD 19-8364382-C-G, REVEL 0.04, CADD 20.10
- L21P (p.Leu21Pro), gnomAD 19-8364383-T-C, REVEL 0.21, CADD 22.70
- L21L (p.Leu21Leu), gnomAD 19-8364384-G-T, CADD 10.30
- S22G (p.Ser22Gly), gnomAD rs1396061104, REVEL 0.14, CADD 21.80
- S22N (p.Ser22Asn), ExAC rs764188393, gnomAD rs764188393, REVEL 0.14, CADD 22.70
- S22R (p.Ser22Arg), 1000Genomes rs541624403, gnomAD rs541624403, REVEL 0.16, CADD 18.30
- S22T (p.Ser22Thr), ExAC rs764188393, gnomAD rs764188393, REVEL 0.13, CADD 22.60
- S22C (p.Ser22Cys), gnomAD 19-8364385-A-T, REVEL 0.17, CADD 23.30
- S22I (p.Ser22Ile), gnomAD 19-8364386-G-T, REVEL 0.16, CADD 24.10
- S22S (p.Ser22Ser), rs541624403, gnomAD 19-8364387-C-T, CADD 9.57
- A23T (p.Ala23Thr), cosmic curated COSV10003, ExAC rs753864074, TOPMed rs753864074, gnomAD rs753864074, REVEL 0.14, CADD 24.30
- A23S (p.Ala23Ser), gnomAD 19-8364388-G-T, REVEL 0.11, CADD 22.90
- A23D (p.Ala23Asp), gnomAD 19-8364389-C-A, REVEL 0.21, CADD 23.60
- A23V (p.Ala23Val), gnomAD 19-8364389-C-T, REVEL 0.16, CADD 21.80
- A23A (p.Ala23Ala), gnomAD 19-8364390-T-A, CADD 3.58
- Q24E (p.Gln24Glu), TOPMed rs1364494864, gnomAD rs1364494864, REVEL 0.06, CADD 11.30
- Q24K (p.Gln24Lys), gnomAD 19-8364391-C-A, REVEL 0.05, CADD 12.80
- Q24* (p.Gln24Ter), gnomAD 19-8364391-C-T, CADD 34.00
- Q24R (p.Gln24Arg), gnomAD 19-8364392-A-G, REVEL 0.03, CADD 15.60
- Q24H (p.Gln24His), gnomAD 19-8364393-G-C, REVEL 0.10, CADD 20.80
- Q24Q (p.Gln24Gln), rs1180762892, gnomAD 19-8364393-G-A, CADD 9.74
- G25D (p.Gly25Asp), TOPMed rs1299216887, REVEL 0.15, CADD 21.70
- G25S (p.Gly25Ser), gnomAD rs1429567126, REVEL 0.17, CADD 23.70
- G25C (p.Gly25Cys), gnomAD 19-8364394-G-T, REVEL 0.20, CADD 26.20
- G25G (p.Gly25Gly), gnomAD 19-8364396-C-T, CADD 8.89
- G26R (p.Gly26Arg), TOPMed rs1419581329, REVEL 0.05, CADD 7.28
- G26V (p.Gly26Val), ExAC rs757481474, TOPMed rs757481474, gnomAD rs757481474, REVEL 0.15, CADD 14.60
- G26D (p.Gly26Asp), gnomAD 19-8364395-GC-G, CADD 21.20
- G26* (p.Gly26Ter), gnomAD 19-8364397-G-T, CADD 32.00
- G26A (p.Gly26Ala), gnomAD 19-8364398-G-C, REVEL 0.09, CADD 11.50
- G26E (p.Gly26Glu), gnomAD 19-8364398-G-A, REVEL 0.11, CADD 14.90
- G26G (p.Gly26Gly), rs1970953001, gnomAD 19-8364399-A-G, CADD 10.00
- P27R (p.Pro27Arg), 1000Genomes rs964963416, TOPMed rs964963416, gnomAD rs964963416, REVEL 0.23, CADD 21.80
- P27S (p.Pro27Ser), gnomAD rs1170667853, REVEL 0.17, CADD 13.10
- P27A (p.Pro27Ala), gnomAD 19-8364400-C-G, REVEL 0.12, CADD 8.42
- P27T (p.Pro27Thr), gnomAD 19-8364400-C-A, REVEL 0.20, CADD 19.70
- P27H (p.Pro27His), gnomAD 19-8364401-C-A, REVEL 0.23, CADD 23.20
- P27L (p.Pro27Leu), gnomAD 19-8364401-C-T, REVEL 0.21, CADD 23.10
- P27P (p.Pro27Pro), gnomAD 19-8364402-C-T, CADD 1.33
- V28L (p.Val28Leu), gnomAD rs1309741165, REVEL 0.03, CADD 8.84
- V28M (p.Val28Met), gnomAD 19-8364403-G-A, REVEL 0.12, CADD 13.90
- V28A (p.Val28Ala), gnomAD 19-8364404-T-C, REVEL 0.12, CADD 5.64
- V28E (p.Val28Glu), gnomAD 19-8364404-T-A, REVEL 0.12, CADD 11.20
- V28V (p.Val28Val), rs1368589015, gnomAD 19-8364405-G-A, CADD 5.96
- Q29R (p.Gln29Arg), Ensembl rs1970953492, REVEL 0.05, CADD 1.46
- Q29K (p.Gln29Lys), gnomAD 19-8364406-C-A, REVEL 0.04, CADD 2.71
- Q29* (p.Gln29Ter), gnomAD 19-8364406-C-T, CADD 33.00
- Q29E (p.Gln29Glu), gnomAD 19-8364406-C-G, REVEL 0.02, CADD 1.57
- Q29Q (p.Gln29Gln), gnomAD 19-8364408-G-A, CADD 0.35
- Q29H (p.Gln29His), gnomAD 19-8364408-G-C, REVEL 0.18, CADD 0.07
- S30P (p.Ser30Pro), gnomAD rs1409312087, REVEL 0.05, CADD 7.24
- S30Y (p.Ser30Tyr), rs2512701362, ClinGen CA403712783, ClinVar RCV004183014, REVEL 0.13, CADD 18.70, Uncertain significance, not specified
- S30F (p.Ser30Phe), gnomAD 19-8364410-C-T, REVEL 0.14, CADD 22.60
- S30C (p.Ser30Cys), gnomAD 19-8364410-C-G, REVEL 0.15, CADD 22.40
- S30S (p.Ser30Ser), gnomAD 19-8364411-C-A, CADD 1.50
- K31R (p.Lys31Arg), TOPMed rs1458461260, gnomAD rs1458461260, REVEL 0.12, CADD 17.80
- K31E (p.Lys31Glu), gnomAD 19-8364412-A-G, REVEL 0.05, CADD 15.10
- K31* (p.Lys31Ter), gnomAD 19-8364412-A-T, CADD 35.00
- K31N (p.Lys31Asn), gnomAD 19-8364414-G-T, REVEL 0.11, CADD 16.40
- K31K (p.Lys31Lys), gnomAD 19-8364414-G-A, CADD 6.19
- S32T (p.Ser32Thr), gnomAD 19-8364415-T-A, REVEL 0.06, CADD 6.79
- S32L (p.Ser32Leu), gnomAD 19-8364416-C-T, REVEL 0.04, CADD 14.80
- S32W (p.Ser32Trp), gnomAD 19-8364416-C-G, REVEL 0.15, CADD 22.80
- S32* (p.Ser32Ter), gnomAD 19-8364416-C-A, CADD 34.00
- S32S (p.Ser32Ser), gnomAD 19-8364417-G-T, CADD 5.35
- P33L (p.Pro33Leu), rs1283942970, gnomAD 19-8364415-TCGCCG, CADD 23.20
- P33S (p.Pro33Ser), gnomAD 19-8364418-C-T, REVEL 0.09, CADD 13.30
- P33Q (p.Pro33Gln), gnomAD 19-8364419-C-A, REVEL 0.03, CADD 1.48
- P33P (p.Pro33Pro), gnomAD 19-8364420-G-T, CADD 6.63
- R34S (p.Arg34Ser), 1000Genomes rs199968545, ExAC rs199968545, gnomAD rs199968545, REVEL 0.36, CADD 24.10
- R34C (p.Arg34Cys), gnomAD 19-8364421-C-T, REVEL 0.52, CADD 25.90
- R34P (p.Arg34Pro), gnomAD 19-8364422-G-C, REVEL 0.48, CADD 26.50
- R34L (p.Arg34Leu), gnomAD 19-8364422-G-T, REVEL 0.32, CADD 25.60
- R34R (p.Arg34Arg), gnomAD 19-8364423-C-G, CADD 11.80
- F35I (p.Phe35Ile), Ensembl rs1970953946, REVEL 0.19, CADD 23.50
- F35L (p.Phe35Leu), gnomAD 19-8364424-T-C, REVEL 0.14, CADD 23.50
Public ANGPTL4 analysis runs
- ANGPTL4 analysis run — ANGPTL4 (935 variants) — completed 2026-08-22