KRT18 (Keratin, type I cytoskeletal 18) variants and mutations
KRT18 (also known as Keratin, type I cytoskeletal 18) is a human protein-coding gene encoding a keratin, type I cytoskeletal 18 protein. It pairs with keratin 8 to form intermediate filaments in simple epithelia, helping cells withstand mechanical and metabolic stress. Rare variants can increase susceptibility to liver injury, while altered expression is widely used as an epithelial and tumor marker. This analysis covers 863 KRT18 variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes Cirrhosis, cirrhosis, familial, and metabolic dysfunction-associated steatotic liver disease. Example KRT18 variants include S2N, S2T, and S2S.
Variant analysis overview
- Gene: KRT18
- Protein: Keratin, type I cytoskeletal 18
- UniProt accession: P05783
- Organism: Homo sapiens
- Variants analyzed: 863
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 580 unspecified-consequence records; 131 synonymous variants; 118 missense variants; 6 stop-gained variants; 6 in-frame deletions; 15 frameshift variants; 2 splice-region variants; 1 in-frame insertions; 1 protein altering variant; 3 substitution
- Prediction scores: 680 variants have prediction scores (79% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Cirrhosis, cirrhosis, familial, metabolic dysfunction-associated steatotic liver disease, neoplasm, prostate carcinoma, metabolic dysfunction-associated steatohepatitis, breast carcinoma, breast cancer, infection, hepatocellular carcinoma, colorectal carcinoma, cancer.
Protein structure and variant hotspots
- Protein features: 1 domains; 34 post-translational modification sites.
- Structural context: 550 variants have structural context.
- PTM context: 86 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, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable KRT18 variants
Examples include S2N, S2T, S2S, F3C, T4A, T4I, T4S, T4T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2N (p.Ser2Asn), ESP rs369198778, ExAC rs369198778, gnomAD rs369198778
- S2T (p.Ser2Thr), ESP rs369198778, ExAC rs369198778, gnomAD rs369198778, REVEL 0.36, CADD 22.10
- S2S (p.Ser2Ser), rs141170056, gnomAD 12-52949179-C-T, CADD 11.90
- F3C (p.Phe3Cys), ExAC rs756991398, gnomAD rs756991398, REVEL 0.48, CADD 23.70
- T4A (p.Thr4Ala), gnomAD rs1241148678, REVEL 0.32, CADD 22.90
- T4I (p.Thr4Ile), rs76301931, ClinGen CA6590708, NCI-TCGA Cosmic COSV6631, cosmic curated COSV66315, REVEL 0.28, CADD 15.30, Uncertain significance, not specified
- T4S (p.Thr4Ser), ExAC rs76301931, gnomAD rs76301931, REVEL 0.11, CADD 12.80, Uncertain significance
- T4T (p.Thr4Thr), rs769641289, gnomAD 12-52949185-C-A, CADD 9.99
- T5A (p.Thr5Ala), cosmic curated COSV66315
- R6C (p.Arg6Cys), cosmic curated COSV66316, gnomAD rs1270182586
- R6H (p.Arg6His), Ensembl rs1942414092, REVEL 0.29, CADD 15.30
- R6S (p.Arg6Ser), cosmic curated COSV10118
- R6G (p.Arg6Gly), gnomAD 12-52949189-C-G, REVEL 0.25, CADD 21.60
- R6L (p.Arg6Leu), gnomAD 12-52949190-G-T, REVEL 0.41, CADD 16.30
- R6R (p.Arg6Arg), rs1453803582, gnomAD 12-52949191-C-T, CADD 12.10
- S7F (p.Ser7Phe), ExAC rs775547844, gnomAD rs775547844, REVEL 0.62, CADD 23.20
- S7Y (p.Ser7Tyr), ExAC rs775547844, gnomAD rs775547844, REVEL 0.57, CADD 21.10
- T8T (p.Thr8Thr), rs1246474436, gnomAD 12-52949197-C-T, CADD 12.10
- F9C (p.Phe9Cys), gnomAD rs945689746, REVEL 0.41, CADD 23.30
- F9L (p.Phe9Leu), gnomAD 12-52949200-C-G, REVEL 0.30, CADD 16.00
- T11A (p.Thr11Ala), ExAC rs748718547, gnomAD rs748718547, REVEL 0.29, CADD 15.10
- T11I (p.Thr11Ile), gnomAD rs1381635123, REVEL 0.51, CADD 23.10
- T11T (p.Thr11Thr), rs768280963, gnomAD 12-52949206-C-T, CADD 16.20
- Y13C (p.Tyr13Cys), Ensembl rs1166470792, REVEL 0.60, CADD 25.60
- Y13* (p.Tyr13Ter), gnomAD 12-52949212-C-A, CADD 36.00
- Y13Y (p.Tyr13Tyr), rs761560727, gnomAD 12-52949212-C-T, CADD 13.30
- R14L (p.Arg14Leu), ExAC rs777157164, gnomAD rs777157164
- R14Q (p.Arg14Gln), ExAC rs777157164, gnomAD rs777157164, REVEL 0.26, CADD 23.30
- R14W (p.Arg14Trp), cosmic curated COSV10532, ExAC rs766809169, gnomAD rs766809169, REVEL 0.50, CADD 23.10
- R14R (p.Arg14Arg), gnomAD 12-52949213-C-A, CADD 17.40
- S15F (p.Ser15Phe), gnomAD rs1447813465, REVEL 0.64, CADD 23.00
- S15P (p.Ser15Pro), ExAC rs753311520, gnomAD rs753311520, REVEL 0.46, CADD 24.40
- S15S (p.Ser15Ser), gnomAD 12-52949218-C-T, CADD 14.70
- L16L (p.Leu16Leu), rs80354424, gnomAD 12-52949221-G-A, CADD 15.20
- G17D (p.Gly17Asp), cosmic curated COSV66315, ExAC rs79476176, gnomAD rs79476176, REVEL 0.60, CADD 27.20
- G17R (p.Gly17Arg), gnomAD rs1239570081, REVEL 0.56, CADD 27.90
- G17V (p.Gly17Val), ExAC rs79476176, gnomAD rs79476176
- G17S (p.Gly17Ser), gnomAD 12-52949222-G-A, REVEL 0.21, CADD 22.80
- G17G (p.Gly17Gly), gnomAD 12-52949224-C-T, CADD 14.20
- S18C (p.Ser18Cys), ESP rs147350452, ExAC rs147350452, gnomAD rs147350452, REVEL 0.60, CADD 22.90
- S18T (p.Ser18Thr), TOPMed rs1479948631, gnomAD rs1479948631, REVEL 0.56, CADD 22.00
- S18Y (p.Ser18Tyr), ESP rs147350452, ExAC rs147350452, gnomAD rs147350452, REVEL 0.63, CADD 24.40
- S18P (p.Ser18Pro), gnomAD 12-52949225-T-C, REVEL 0.59, CADD 22.50
- S18F (p.Ser18Phe), gnomAD 12-52949226-C-T, REVEL 0.68, CADD 24.90
- V19A (p.Val19Ala), Ensembl rs1942416434, REVEL 0.08, CADD 13.90
- V19I (p.Val19Ile), cosmic curated COSV10971
- V19F (p.Val19Phe), gnomAD 12-52949228-G-T, REVEL 0.33, CADD 17.10
- V19V (p.Val19Val), rs780920567, gnomAD 12-52949230-C-T, CADD 8.54
- Q20R (p.Gln20Arg), gnomAD 12-52949232-A-G, REVEL 0.11, CADD 5.53
- A21E (p.Ala21Glu), Ensembl rs1565737187
- A21A (p.Ala21Ala), rs1427397993, gnomAD 12-52949236-G-A, CADD 8.35
- P22P (p.Pro22Pro), rs1438689472, gnomAD 12-52949239-C-T, CADD 12.60
- S23G (p.Ser23Gly), cosmic curated COSV66316
- S23I (p.Ser23Ile), Ensembl rs1942416913, REVEL 0.46, CADD 21.00
- S23S (p.Ser23Ser), rs141066547, gnomAD 12-52949242-C-T, CADD 12.40
- Y24* (p.Tyr24Ter), gnomAD rs1239572921, CADD 26.30
- Y24C (p.Tyr24Cys), 1000Genomes rs1307456366, REVEL 0.12, CADD 17.70
- Y24Y (p.Tyr24Tyr), rs1239572921, gnomAD 12-52949245-C-T, CADD 4.46
- G25C (p.Gly25Cys), cosmic curated COSV66316, ExAC rs750200705, gnomAD rs750200705, REVEL 0.22, CADD 11.60
- G25D (p.Gly25Asp), Ensembl rs1942417465, REVEL 0.30, CADD 15.30
- G25R (p.Gly25Arg), ExAC rs750200705, gnomAD rs750200705, REVEL 0.06, CADD 6.21
- G25S (p.Gly25Ser), ExAC rs750200705, gnomAD rs750200705, REVEL 0.04, CADD 4.63
- G25G (p.Gly25Gly), rs1942417544, gnomAD 12-52949248-C-T, CADD 7.09
- A26T (p.Ala26Thr), cosmic curated COSV66315, gnomAD rs78514003, REVEL 0.06, CADD 10.20
- A26V (p.Ala26Val), Ensembl rs11551634, REVEL 0.10, CADD 6.14
- A26S (p.Ala26Ser), gnomAD 12-52949249-G-T, REVEL 0.04, CADD 8.08
- A26D (p.Ala26Asp), gnomAD 12-52949250-C-A, REVEL 0.18, CADD 9.87
- A26A (p.Ala26Ala), rs755980643, gnomAD 12-52949251-C-T, CADD 12.40
- R27P (p.Arg27Pro), gnomAD rs1368538220, REVEL 0.23, CADD 23.10
- R27W (p.Arg27Trp), cosmic curated COSV66315, gnomAD rs77825282, REVEL 0.35, CADD 20.50
- R27L (p.Arg27Leu), gnomAD 12-52949253-G-T, REVEL 0.17, CADD 22.60
- R27R (p.Arg27Arg), rs1473739765, gnomAD 12-52949254-G-A, CADD 14.30
- P28A (p.Pro28Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P28L (p.Pro28Leu), rs74379840, NCI-TCGA Cosmic COSV6631, cosmic curated COSV66316, REVEL 0.21, CADD 21.50, Uncertain significance, not specified
- P28Q (p.Pro28Gln), cosmic curated COSV66315, ExAC rs74379840, TOPMed rs74379840, gnomAD rs74379840, REVEL 0.33, CADD 24.40
- P28R (p.Pro28Arg), ExAC rs74379840, TOPMed rs74379840, gnomAD rs74379840, REVEL 0.19, CADD 21.30
- P28S (p.Pro28Ser), gnomAD 12-52949255-C-T, REVEL 0.25, CADD 23.00
- P28T (p.Pro28Thr), gnomAD 12-52949255-C-A, REVEL 0.17, CADD 22.50
- P28P (p.Pro28Pro), rs528903225, gnomAD 12-52949257-G-A, CADD 9.10
- V29A (p.Val29Ala), Ensembl rs1942418545, REVEL 0.13, CADD 11.90
- V29I (p.Val29Ile), gnomAD rs1465913307, REVEL 0.10, CADD 16.30
- V29V (p.Val29Val), rs1942418645, gnomAD 12-52949260-C-G, CADD 15.30
- S30G (p.Ser30Gly), Ensembl rs1942418738, REVEL 0.46, CADD 25.10
- S30R (p.Ser30Arg), gnomAD 12-52949261-A-C, REVEL 0.69, CADD 23.50
- S30S (p.Ser30Ser), rs1333085811, gnomAD 12-52949263-C-T, CADD 17.00
- S31C (p.Ser31Cys), gnomAD rs1398440164, REVEL 0.56, CADD 29.20
- S31I (p.Ser31Ile), ESP rs374064321, ExAC rs374064321, gnomAD rs374064321, REVEL 0.54, CADD 25.40
- S31R (p.Ser31Arg), gnomAD 12-52949266-C-G, REVEL 0.33, CADD 22.50
- A32S (p.Ala32Ser), cosmic curated COSV66315, gnomAD rs74953757, REVEL 0.33, CADD 22.70
- A32V (p.Ala32Val), gnomAD rs1297779360, REVEL 0.31, CADD 23.20
- A32E (p.Ala32Glu), gnomAD 12-52949268-C-A, REVEL 0.53, CADD 24.50
- A32A (p.Ala32Ala), rs778594717, gnomAD 12-52949269-G-A, CADD 7.36
- A33A (p.Ala33Ala), gnomAD 12-52949272-C-A, CADD 15.90
- S34R (p.Ser34Arg), cosmic curated COSV66315, ESP rs78343594, ExAC rs78343594, TOPMed rs78343594, REVEL 0.58, CADD 23.00
- S34T (p.Ser34Thr), Ensembl rs1427838806, REVEL 0.56, CADD 23.80
- S34G (p.Ser34Gly), gnomAD 12-52949273-A-G, REVEL 0.57, CADD 24.60
- S34S (p.Ser34Ser), rs78343594, gnomAD 12-52949275-C-T, CADD 15.70
- V35I (p.Val35Ile), gnomAD rs1243265591
- V35A (p.Val35Ala), gnomAD 12-52949277-T-C, REVEL 0.58, CADD 30.00
- V35G (p.Val35Gly), gnomAD 12-52949277-T-G, REVEL 0.70, CADD 32.00
- Y36C (p.Tyr36Cys), TOPMed rs891346528, gnomAD rs891346528, REVEL 0.62, CADD 24.20, Uncertain significance
- Y36H (p.Tyr36His), gnomAD rs1227971336
- Y36S (p.Tyr36Ser), rs891346528, ClinGen CA237289602, ClinVar RCV004087252, TOPMed rs891346528, REVEL 0.70, CADD 26.00, Uncertain significance, not specified
- Y36F (p.Tyr36Phe), gnomAD 12-52949280-A-T, REVEL 0.58, CADD 25.10
- Y36Y (p.Tyr36Tyr), gnomAD 12-52949281-T-C, CADD 14.00
- A37G (p.Ala37Gly), gnomAD rs1319072747, REVEL 0.30, CADD 23.60
- A37T (p.Ala37Thr), cosmic curated COSV66316, gnomAD rs1281260117, REVEL 0.48, CADD 26.50
- G38C (p.Gly38Cys), cosmic curated COSV10748, 1000Genomes rs77999286, gnomAD rs77999286, REVEL 0.73, CADD 33.00
- G38D (p.Gly38Asp), rs1486318507, NCI-TCGA Cosmic COSV1011, cosmic curated COSV10118, gnomAD rs1486318507, REVEL 0.84, CADD 32.00, Variant assessed as somatic; moderate impact.
- G38S (p.Gly38Ser), 1000Genomes rs77999286, gnomAD rs77999286, REVEL 0.61, CADD 27.00
- G38G (p.Gly38Gly), rs75380684, gnomAD 12-52949287-C-T, CADD 16.50
- A39V (p.Ala39Val), ExAC rs771828609, gnomAD rs771828609, REVEL 0.55, CADD 23.30
- A39del (p.Ala39del), gnomAD 12-52949286-GCGC-, CADD 23.00
- A39T (p.Ala39Thr), gnomAD 12-52949288-G-A, REVEL 0.53, CADD 23.30
- A39A (p.Ala39Ala), gnomAD 12-52949290-T-A, CADD 9.11
- G40R (p.Gly40Arg), ExAC rs773038025, gnomAD rs773038025, REVEL 0.58, CADD 23.20
- G40A (p.Gly40Ala), gnomAD 12-52949291-G-GCC, CADD 33.00
- G40W (p.Gly40Trp), gnomAD 12-52949291-G-T, REVEL 0.63, CADD 25.00
- G40G (p.Gly40Gly), gnomAD 12-52949293-G-A, CADD 12.30
- G41A (p.Gly41Ala), gnomAD rs1256261258, REVEL 0.59, CADD 24.70
- G41D (p.Gly41Asp), NCI-TCGA Cosmic COSV1011, cosmic curated COSV10118, Variant assessed as somatic; moderate impact.
- G41S (p.Gly41Ser), ExAC rs759814479, gnomAD rs759814479, REVEL 0.57, CADD 25.40
- G41C (p.Gly41Cys), gnomAD 12-52949294-G-T, REVEL 0.71, CADD 32.00
- G41R (p.Gly41Arg), gnomAD 12-52949294-G-C, REVEL 0.65, CADD 25.50
- G41V (p.Gly41Val), gnomAD 12-52949295-G-T, REVEL 0.74, CADD 29.00
- S42P (p.Ser42Pro), ExAC rs770250195, gnomAD rs770250195, REVEL 0.55, CADD 22.30
- S42F (p.Ser42Phe), gnomAD 12-52949298-C-T, REVEL 0.52, CADD 23.50
- G43C (p.Gly43Cys), 1000Genomes rs75441140, ExAC rs75441140, TOPMed rs75441140, gnomAD rs75441140, REVEL 0.69, CADD 32.00
- G43D (p.Gly43Asp), gnomAD rs1263244013
- G43R (p.Gly43Arg), cosmic curated COSV10748, 1000Genomes rs75441140, ExAC rs75441140, TOPMed rs75441140, REVEL 0.52, CADD 25.30
- G43S (p.Gly43Ser), 1000Genomes rs75441140, ExAC rs75441140, TOPMed rs75441140, gnomAD rs75441140, REVEL 0.45, CADD 29.50
- G43V (p.Gly43Val), gnomAD 12-52949301-G-T, REVEL 0.66, CADD 24.70
- G43G (p.Gly43Gly), rs2120763166, gnomAD 12-52949302-T-G, CADD 11.70
- S44A (p.Ser44Ala), ExAC rs763522746, gnomAD rs763522746, REVEL 0.31, CADD 21.00
- S44C (p.Ser44Cys), gnomAD rs1447084165, REVEL 0.45, CADD 22.50
- S44T (p.Ser44Thr), gnomAD 12-52949303-T-A, REVEL 0.27, CADD 22.70
- S44F (p.Ser44Phe), gnomAD 12-52949304-C-T, REVEL 0.49, CADD 23.10
- R45L (p.Arg45Leu), ExAC rs200221269, gnomAD rs200221269, REVEL 0.48, CADD 24.90
- R45P (p.Arg45Pro), rs200221269, ClinGen CA144197, cosmic curated COSV66315, ClinVar RCV000049578, REVEL 0.52, CADD 25.20, not provided, Hepatitis C virus, susceptibility to
- R45W (p.Arg45Trp), gnomAD rs1478096062, REVEL 0.27, CADD 22.60
- R45Q (p.Arg45Gln), gnomAD 12-52949307-G-A, REVEL 0.36, CADD 23.40
- R45R (p.Arg45Arg), rs1437036447, gnomAD 12-52949308-G-T, CADD 10.80
- I46F (p.Ile46Phe), ExAC rs760412718, gnomAD rs760412718, REVEL 0.45, CADD 23.30
- I46L (p.Ile46Leu), ExAC rs760412718, gnomAD rs760412718, REVEL 0.41, CADD 21.10
- I46T (p.Ile46Thr), cosmic curated COSV66315
- I46V (p.Ile46Val), ExAC rs760412718, gnomAD rs760412718
- I46I (p.Ile46Ile), gnomAD 12-52949311-C-A, CADD 12.70
- S47F (p.Ser47Phe), Ensembl rs1452035555, REVEL 0.73, CADD 25.70
- S47C (p.Ser47Cys), gnomAD 12-52949312-TCC-T, CADD 26.80
- S47P (p.Ser47Pro), gnomAD 12-52949312-T-C, REVEL 0.69, CADD 24.60
- S47S (p.Ser47Ser), rs80004568, gnomAD 12-52949314-C-T, CADD 10.30
- V48A (p.Val48Ala), ExAC rs761933454, gnomAD rs761933454, REVEL 0.44, CADD 18.60
- V48L (p.Val48Leu), 1000Genomes rs1359140246, gnomAD rs1359140246, REVEL 0.45, CADD 10.30
- V48M (p.Val48Met), cosmic curated COSV66315, 1000Genomes rs1359140246, gnomAD rs1359140246, REVEL 0.29, CADD 9.03
- V48V (p.Val48Val), rs1454746282, gnomAD 12-52949317-G-T, CADD 9.12
- S49P (p.Ser49Pro), gnomAD 12-52949313-CCG-C, CADD 22.60
- S49C (p.Ser49Cys), gnomAD 12-52949315-G-GTC, CADD 23.70
- S49T (p.Ser49Thr), gnomAD 12-52949318-T-A, REVEL 0.27, CADD 15.60
- S49F (p.Ser49Phe), gnomAD 12-52949319-C-T, REVEL 0.55, CADD 21.50
- S49S (p.Ser49Ser), rs1393274749, gnomAD 12-52949320-C-T, CADD 9.90
- R50C (p.Arg50Cys), cosmic curated COSV66315, 1000Genomes rs78479490, gnomAD rs78479490, REVEL 0.30, CADD 18.70
- R50G (p.Arg50Gly), 1000Genomes rs78479490, gnomAD rs78479490, REVEL 0.34, CADD 16.70
- R50L (p.Arg50Leu), ExAC rs11551633, gnomAD rs11551633
- R50A (p.Arg50Ala), gnomAD 12-52949318-TC-T, CADD 25.10
- R50R (p.Arg50Arg), gnomAD 12-52949323-C-T, CADD 13.10
- S51F (p.Ser51Phe), gnomAD rs1394324153, REVEL 0.52, CADD 19.20
- S51P (p.Ser51Pro), Ensembl rs1555191110, REVEL 0.55, CADD 21.60
- T52I (p.Thr52Ile), gnomAD rs1333552689, REVEL 0.38, CADD 21.00
- T52P (p.Thr52Pro), gnomAD 12-52949327-A-C, REVEL 0.44, CADD 19.00
- T52A (p.Thr52Ala), gnomAD 12-52949327-A-G, REVEL 0.17, CADD 8.07
- T52T (p.Thr52Thr), rs1942423083, gnomAD 12-52949329-C-A, CADD 9.05
- S53G (p.Ser53Gly), gnomAD rs1341730231, REVEL 0.22, CADD 17.60
- S53T (p.Ser53Thr), gnomAD 12-52949331-G-C, REVEL 0.35, CADD 13.90
- F54C (p.Phe54Cys), TOPMed rs1429253751, gnomAD rs1429253751, REVEL 0.30, CADD 11.90
- F54L (p.Phe54Leu), ExAC rs750714548, REVEL 0.27, CADD 6.08
- F54S (p.Phe54Ser), TOPMed rs1429253751, gnomAD rs1429253751, REVEL 0.27, CADD 12.60
- F54F (p.Phe54Phe), gnomAD 12-52949335-C-T, CADD 10.10
- R55T (p.Arg55Thr), ExAC rs755849994, REVEL 0.42, CADD 22.50
- R55W (p.Arg55Trp), 1000Genomes rs78718957, gnomAD rs78718957
- R55R (p.Arg55Arg), rs78718957, gnomAD 12-52949336-A-C, CADD 12.30
Public KRT18 analysis runs
- KRT18 analysis run — KRT18 (863 variants) — completed 2026-08-22