DNAJC6 (Auxilin) variants and mutations
DNAJC6 (also known as Auxilin) is a human protein-coding gene encoding an auxilin protein. It recruits HSC70 to clathrin-coated vesicles and promotes uncoating during synaptic-vesicle recycling. Biallelic pathogenic variants can cause severe juvenile parkinsonism with developmental and other neurologic abnormalities. This analysis covers 1,293 DNAJC6 variants and mutations. Of these, 53% have computational variant effect predictions. Disease context includes Young adult-onset Parkinsonism, atypical juvenile parkinsonism, and Parkinson disease 19B, early-onset. Example DNAJC6 variants include K2E, K2R, and D3G.
Variant analysis overview
- Gene: DNAJC6
- Protein: Auxilin
- UniProt accession: O75061
- Organism: Homo sapiens
- Variants analyzed: 1293
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,138 unspecified-consequence records; 101 missense variants; 28 synonymous variants; 8 stop-gained variants; 15 frameshift variants; 1 in-frame deletions; 1 protein altering variant; 1 splice-region variants
- Prediction scores: 690 variants have prediction scores (53% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Young adult-onset Parkinsonism, atypical juvenile parkinsonism, Parkinson disease 19B, early-onset, young-onset Parkinson disease, neurodegenerative disease, juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndro, hereditary disease, Familial prostate cancer, prostate cancer, Parkinson disease, hepatocellular carcinoma, atypical teratoid rhabdoid tumor.
Protein structure and variant hotspots
- Protein features: 3 domains; 7 post-translational modification sites.
- Structural context: 443 variants have structural context.
- PTM context: 5 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 DNAJC6 variants
Examples include K2E, K2R, D3G, D3Y, D3D, D3E, S4Y, S4F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- K2E (p.Lys2Glu), TOPMed rs1653265024, CADD 23.20, SIFT 0.06
- K2R (p.Lys2Arg), TOPMed rs1344102872, gnomAD rs1344102872, CADD 18.30, SIFT 1.00
- D3G (p.Asp3Gly), ExAC rs749679056, TOPMed rs749679056, gnomAD rs749679056, CADD 23.20, SIFT 0.10
- D3Y (p.Asp3Tyr), cosmic curated COSV99675, ESP rs369238276, ExAC rs369238276, TOPMed rs369238276, CADD 25.40, SIFT 0.01
- D3D (p.Asp3Asp), rs950568157, gnomAD 1-65264919-T-C, CADD 14.10
- D3E (p.Asp3Glu), gnomAD 1-65264919-T-G, CADD 20.40, SIFT 1.00
- S4Y (p.Ser4Tyr), Ensembl rs1553131592, SIFT 0.00
- S4F (p.Ser4Phe), gnomAD 1-65264921-C-T, CADD 28.80, SIFT 0.03
- S4S (p.Ser4Ser), rs148507710, gnomAD 1-65264922-T-G, CADD 13.80
- S4C (p.Ser4Cys), gnomAD 1-65309749-A-T, REVEL 0.74, CADD 29.00
- S4I (p.Ser4Ile), gnomAD 1-65309750-G-T, REVEL 0.77, CADD 28.70
- S4N (p.Ser4Asn), gnomAD 1-65309762-G-A, REVEL 0.18, CADD 21.50
- E5* (p.Glu5Ter), gnomAD 1-65254547-G-T, CADD 16.30
- E5G (p.Glu5Gly), gnomAD 1-65254548-A-G, CADD 17.40, SIFT 0.00
- E5E (p.Glu5Glu), gnomAD 1-65254549-G-A, CADD 15.30
- E5K (p.Glu5Lys), gnomAD 1-65264923-G-A, CADD 26.90, SIFT 0.02
- N6S (p.Asn6Ser), cosmic curated COSV54782
- N6K (p.Asn6Lys), gnomAD 1-65264923-G-GA, CADD 32.00
- N6N (p.Asn6Asn), rs566079959, gnomAD 1-65264928-T-C, CADD 14.40
- N6I (p.Asn6Ile), gnomAD 1-65309783-A-T, REVEL 0.22, MetaLR 0.04
- K7N (p.Lys7Asn), Ensembl rs2101141555
- K7R (p.Lys7Arg), gnomAD 1-65254549-GA-G, CADD 9.59
- K7E (p.Lys7Glu), gnomAD 1-65254550-A-G, CADD 13.10, SIFT 0.00
- K7K (p.Lys7Lys), gnomAD 1-65254552-G-A, CADD 14.30
- K7* (p.Lys7Ter), gnomAD 1-65254562-A-T, CADD 15.50
- K7S (p.Lys7Ser), gnomAD 1-65254570-GA-G, CADD 14.40
- K7Q (p.Lys7Gln), rs1184190071, gnomAD 1-65254571-A-C, CADD 16.50, SIFT 0.03
- K7M (p.Lys7Met), gnomAD 1-65309774-A-T, REVEL 0.55, CADD 31.00
- G8D (p.Gly8Asp), ExAC rs765766449, gnomAD rs765766449, CADD 15.60, SIFT 0.00
- G8V (p.Gly8Val), ExAC rs765766449, gnomAD rs765766449, CADD 15.30, SIFT 0.00
- G8S (p.Gly8Ser), gnomAD 1-65254538-G-A, CADD 15.70, SIFT 0.00
- G8C (p.Gly8Cys), gnomAD 1-65254538-G-T, CADD 15.30, SIFT 0.00
- G8G (p.Gly8Gly), gnomAD 1-65254540-C-A, CADD 15.20
- G8* (p.Gly8Ter), gnomAD 1-65254553-G-T, CADD 14.00
- G8R (p.Gly8Arg), gnomAD 1-65254553-G-A, CADD 14.40, SIFT 0.00
- G8E (p.Gly8Glu), gnomAD 1-65254554-G-A, CADD 15.10, SIFT 0.00
- G8A (p.Gly8Ala), gnomAD 1-65254554-G-C, CADD 14.80, SIFT 0.00
- A9D (p.Ala9Asp), gnomAD rs1292796531
- A9G (p.Ala9Gly), gnomAD rs1292796531
- A9P (p.Ala9Pro), ExAC rs758919489, TOPMed rs758919489, gnomAD rs758919489
- A9S (p.Ala9Ser), ExAC rs758919489, TOPMed rs758919489, gnomAD rs758919489
- A9T (p.Ala9Thr), ExAC rs758919489, TOPMed rs758919489, gnomAD rs758919489
- A9V (p.Ala9Val), gnomAD 1-65254542-C-T, CADD 15.60, SIFT 0.00
- A9A (p.Ala9Ala), gnomAD 1-65254543-C-A, CADD 12.20
- S10L (p.Ser10Leu), Ensembl rs1645628976
- S10P (p.Ser10Pro), gnomAD rs1221846482
- S10T (p.Ser10Thr), gnomAD rs1221846482, SIFT 0.00
- S11F (p.Ser11Phe), gnomAD rs1266852488
- S11Y (p.Ser11Tyr), gnomAD rs1266852488, SIFT 0.36
- S11G (p.Ser11Gly), gnomAD 1-65254565-A-G, CADD 17.00, SIFT 0.68
- S11I (p.Ser11Ile), gnomAD 1-65254566-G-T, CADD 15.50, SIFT 0.03
- S11N (p.Ser11Asn), rs1170289347, gnomAD 1-65254566-G-A, CADD 15.80, SIFT 0.05
- S11S (p.Ser11Ser), gnomAD 1-65254567-C-T, CADD 16.30
- S11R (p.Ser11Arg), gnomAD 1-65254567-C-A, CADD 15.90, SIFT 0.04
- P12S (p.Pro12Ser), gnomAD rs1645629030
- D13Y (p.Asp13Tyr), NCI-TCGA Cosmic COSV9967, cosmic curated COSV99674, SIFT 1.00, Variant assessed as somatic; moderate impact.
- M14I (p.Met14Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M14L (p.Met14Leu), ESP rs369051822, ExAC rs369051822, gnomAD rs369051822, SIFT 0.00
- E15G (p.Glu15Gly), Ensembl rs1570329825
- E15K (p.Glu15Lys), NCI-TCGA TCGA novel, SIFT 0.00, Variant assessed as somatic; moderate impact.
- E15E (p.Glu15Glu), gnomAD 1-65309796-A-G, CADD 13.20
- P16R (p.Pro16Arg), gnomAD rs1263677964, SIFT 0.00
- P16T (p.Pro16Thr), gnomAD 1-65254592-C-A, CADD 16.70, SIFT 0.08
- P16S (p.Pro16Ser), rs867192361, gnomAD 1-65254592-C-T, CADD 17.10, SIFT 0.20
- P16L (p.Pro16Leu), rs1376257471, gnomAD 1-65254593-C-T, CADD 15.50, SIFT 0.02
- P16Q (p.Pro16Gln), rs1376257471, gnomAD 1-65254593-C-A, CADD 15.10, SIFT 0.06
- P16P (p.Pro16Pro), gnomAD 1-65254594-G-A, CADD 13.80
- S17G (p.Ser17Gly), cosmic curated COSV54773
- S17R (p.Ser17Arg), cosmic curated COSV10504, SIFT 0.00
- S17P (p.Ser17Pro), gnomAD 1-65254576-GT-G, CADD 12.00
- S17F (p.Ser17Phe), rs1450797012, gnomAD 1-65254581-C-T, CADD 13.30, SIFT 0.02
- S17Y (p.Ser17Tyr), gnomAD 1-65254581-C-A, CADD 12.80, SIFT 0.16
- S17S (p.Ser17Ser), rs990097806, gnomAD 1-65254582-C-T, CADD 4.85
- S17L (p.Ser17Leu), gnomAD 1-65309814-C-CTT, CADD 28.20
- p.Ser24delinsLysCys, gnomAD 1-65309815-A-AAGT, CADD 29.90
- Y18C (p.Tyr18Cys), rs1394529150, ClinGen CA340672733, ClinVar RCV001907639, gnomAD rs1394529150, AlphaMissense 0.17, MetaLR 0.75, Uncertain significance, Juvenile onset Parkinson disease 19A
- G19G (p.Gly19Gly), rs761277268, gnomAD 1-65309790-T-G, CADD 15.50
- G20V (p.Gly20Val), Ensembl rs1645629218, SIFT 0.00
- L22F (p.Leu22Phe), ExAC rs781240666, gnomAD rs781240666, SIFT 0.10
- L22L (p.Leu22Leu), gnomAD 1-65254574-C-T, CADD 15.80
- L22M (p.Leu22Met), gnomAD 1-65254574-C-A, CADD 15.50, SIFT 0.18
- L22P (p.Leu22Pro), gnomAD 1-65254575-T-C, CADD 17.30, SIFT 0.03
- L22V (p.Leu22Val), gnomAD 1-65254583-T-G, CADD 9.76, SIFT 0.29
- L22S (p.Leu22Ser), rs921544252, gnomAD 1-65254584-T-C, CADD 8.35, SIFT 0.13
- F23V (p.Phe23Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F23I (p.Phe23Ile), gnomAD 1-65254577-T-A, CADD 14.50, SIFT 0.32
- F23L (p.Phe23Leu), rs1652994069, gnomAD 1-65254577-T-C, CADD 14.80, SIFT 1.00
- F23S (p.Phe23Ser), gnomAD 1-65254578-T-C, CADD 15.70, SIFT 0.08
- F23F (p.Phe23Phe), gnomAD 1-65254579-T-C, CADD 14.80
- D24Y (p.Asp24Tyr), rs1359963867, gnomAD 1-65309812-G-T, REVEL 0.61, CADD 29.70
- D24N (p.Asp24Asn), gnomAD 1-65309812-G-A, REVEL 0.44, CADD 29.30
- D24D (p.Asp24Asp), rs1313432390, gnomAD 1-65309814-C-T, CADD 14.40
- M25I (p.Met25Ile), ExAC rs774073389, gnomAD rs774073389, cosmic curated COSV99675
- M25L (p.Met25Leu), ExAC rs768425147, gnomAD rs768425147
- M25V (p.Met25Val), ExAC rs768425147, gnomAD rs768425147, SIFT 0.07
- V26L (p.Val26Leu), gnomAD rs1435472720, SIFT 0.04
- V26A (p.Val26Ala), gnomAD 1-65309810-T-C, REVEL 0.47, CADD 29.00
- V26V (p.Val26Val), rs1297286892, gnomAD 1-65309811-G-A, CADD 14.30
- V26F (p.Val26Phe), gnomAD 1-65309848-G-T, REVEL 0.21, CADD 15.80
- V26G (p.Val26Gly), rs779764117, gnomAD 1-65309849-T-G, REVEL 0.20, CADD 15.50
- p.Lys22 Trp28del, rs1180480142, gnomAD 1-65254593-CGTGGA, CADD 18.10
- K27R (p.Lys27Arg), gnomAD 1-65254597-GA-G, CADD 15.70
- K27E (p.Lys27Glu), gnomAD 1-65254598-A-G, CADD 17.90, SIFT 0.01
- K27* (p.Lys27Ter), gnomAD 1-65254598-A-T, CADD 17.60
- K27T (p.Lys27Thr), gnomAD 1-65254599-A-C, CADD 16.60, SIFT 0.01
- K27M (p.Lys27Met), gnomAD 1-65254599-A-T, CADD 16.60, SIFT 0.00
- K27K (p.Lys27Lys), gnomAD 1-65254600-G-A, CADD 15.30
- K27N (p.Lys27Asn), gnomAD 1-65254600-G-T, CADD 15.00, SIFT 0.01
- G28R (p.Gly28Arg), gnomAD 1-65309821-G-A, REVEL 0.19, CADD 24.00
- G28G (p.Gly28Gly), gnomAD 1-65309823-G-A, CADD 14.30
- A30S (p.Ala30Ser), cosmic curated COSV54779
- A30T (p.Ala30Thr), gnomAD rs1348382365, REVEL 0.17, CADD 17.30
- A30V (p.Ala30Val), Ensembl rs914092483, SIFT 0.20
- A30E (p.Ala30Glu), gnomAD 1-65254602-C-A, CADD 16.20, SIFT 0.66
- A30A (p.Ala30Ala), gnomAD 1-65254603-G-A, CADD 9.08
- A30P (p.Ala30Pro), gnomAD 1-65254631-G-C, CADD 14.70, SIFT 0.10
- A30D (p.Ala30Asp), rs1309466558, gnomAD 1-65254632-C-A, CADD 15.90, SIFT 0.04
- A30G (p.Ala30Gly), gnomAD 1-65254640-GC-G, CADD 16.30
- A30R (p.Ala30Arg), rs1645080977, gnomAD 1-65309870-A-AC, CADD 18.40
- A30Q (p.Ala30Gln), rs1443589400, gnomAD 1-65309872-GC-G, CADD 23.80
- G31W (p.Gly31Trp), NCI-TCGA Cosmic COSV5478, cosmic curated COSV54781, Variant assessed as somatic; moderate impact.
- G31S (p.Gly31Ser), gnomAD 1-65254649-G-A, CADD 18.40, SIFT 0.04
- G31R (p.Gly31Arg), gnomAD 1-65309836-G-A, REVEL 0.21, CADD 21.00
- G31G (p.Gly31Gly), gnomAD 1-65309844-C-T, CADD 11.40
- G31E (p.Gly31Glu), gnomAD 1-65309846-G-A, REVEL 0.28, CADD 16.30
- G31A (p.Gly31Ala), rs956622990, gnomAD 1-65309846-G-C, REVEL 0.33, CADD 10.30
- G31D (p.Gly31Asp), gnomAD 1-65309855-G-A, REVEL 0.23, CADD 17.80
- R32G (p.Arg32Gly), NCI-TCGA Cosmic COSV5478, cosmic curated COSV54782, Variant assessed as somatic; moderate impact.
- R32K (p.Arg32Lys), Ensembl rs1645629564
- R32S (p.Arg32Ser), TOPMed rs1299153826, gnomAD rs1299153826
- R32R (p.Arg32Arg), gnomAD 1-65254568-C-A, CADD 16.00
- R32W (p.Arg32Trp), rs1480529913, gnomAD 1-65254568-C-T, CADD 16.40, SIFT 0.02
- R32Q (p.Arg32Gln), gnomAD 1-65254568-CGG-C, CADD 14.70
- R32L (p.Arg32Leu), gnomAD 1-65254569-G-T, CADD 13.10, SIFT 0.11
- R32P (p.Arg32Pro), gnomAD 1-65254569-G-C, CADD 13.20, SIFT 0.25
- R32M (p.Arg32Met), gnomAD 1-65254620-G-T, CADD 17.00, SIFT 0.10
- R32C (p.Arg32Cys), rs1000690631, gnomAD 1-65254625-C-T, CADD 16.40, SIFT 0.01
- R32H (p.Arg32His), gnomAD 1-65254626-G-A, CADD 16.20, SIFT 0.02
- R32I (p.Arg32Ile), rs754115488, gnomAD 1-65309864-G-T, REVEL 0.22, CADD 21.90
- R32T (p.Arg32Thr), gnomAD 1-65309864-G-C, REVEL 0.24, CADD 18.70
- L33F (p.Leu33Phe), ExAC rs771959839, TOPMed rs771959839, gnomAD rs771959839, SIFT 0.02
- L33V (p.Leu33Val), gnomAD 1-65309827-T-G, REVEL 0.26, CADD 15.10
- L33* (p.Leu33Ter), gnomAD 1-65309828-T-A, CADD 35.00
- L33S (p.Leu33Ser), rs1233618088, gnomAD 1-65309828-T-C, REVEL 0.27, CADD 21.10
- F34I (p.Phe34Ile), cosmic curated COSV10504
- F34L (p.Phe34Leu), TOPMed rs896749653, SIFT 0.09
- S35N (p.Ser35Asn), gnomAD rs1288867331
- S35T (p.Ser35Thr), cosmic curated COSV54778, SIFT 0.49
- S35P (p.Ser35Pro), gnomAD 1-65254628-T-C, CADD 16.10, SIFT 0.21
- S35* (p.Ser35Ter), gnomAD 1-65254629-C-A, CADD 14.50
- S35L (p.Ser35Leu), rs1652994887, gnomAD 1-65254629-C-T, CADD 14.90, SIFT 0.22
- S35S (p.Ser35Ser), rs897375595, gnomAD 1-65254630-A-G, CADD 16.40
- S35G (p.Ser35Gly), rs981764572, gnomAD 1-65309830-A-G, REVEL 0.20, CADD 16.30
- S35C (p.Ser35Cys), rs1190625878, gnomAD 1-65309839-A-T, REVEL 0.26, CADD 22.70
- S35R (p.Ser35Arg), rs755667643, gnomAD 1-65309841-C-A, REVEL 0.25, CADD 22.20
- N36I (p.Asn36Ile), gnomAD 1-65309819-A-T, REVEL 0.26, CADD 23.10
- N36K (p.Asn36Lys), gnomAD 1-65309820-C-A, REVEL 0.17, MetaLR 0.41
- K38* (p.Lys38Ter), cosmic curated COSV10504
- K38N (p.Lys38Asn), cosmic curated COSV54774, SIFT 0.85
- D39N (p.Asp39Asn), Ensembl rs2101554757, SIFT 0.16
- N40T (p.Asn40Thr), rs1258883206, gnomAD 1-65309868-GA-G, CADD 19.20
- N40K (p.Asn40Lys), rs1645080945, gnomAD 1-65309871-C-A, REVEL 0.16, CADD 2.56
- L41M (p.Leu41Met), 1000Genomes rs74486665, ExAC rs74486665, TOPMed rs74486665, gnomAD rs74486665
- L41S (p.Leu41Ser), NCI-TCGA TCGA novel, SIFT 0.11, Variant assessed as somatic; moderate impact.
- T44A (p.Thr44Ala), gnomAD 1-65254544-A-G, CADD 13.90, SIFT 0.00
- T44I (p.Thr44Ile), gnomAD 1-65254545-C-T, CADD 15.10, SIFT 0.00
- T44N (p.Thr44Asn), gnomAD 1-65254545-C-A, CADD 14.70, SIFT 0.00
- T44T (p.Thr44Thr), rs1287465963, gnomAD 1-65254546-T-C, CADD 14.00
- T44S (p.Thr44Ser), rs1317452323, gnomAD 1-65254605-C-G, CADD 13.80, SIFT 0.04
- L45F (p.Leu45Phe), cosmic curated COSV99674, Ensembl rs1645629868, SIFT 0.54
- D47G (p.Asp47Gly), TOPMed rs1645629898, gnomAD rs1645629898
- D47Y (p.Asp47Tyr), NCI-TCGA Cosmic COSV5477, cosmic curated COSV54778, SIFT 0.77, Variant assessed as somatic; moderate impact.
- T48A (p.Thr48Ala), ExAC rs776147302, TOPMed rs776147302, gnomAD rs776147302
- T48P (p.Thr48Pro), ExAC rs776147302, TOPMed rs776147302, gnomAD rs776147302
- S49P (p.Ser49Pro), TOPMed rs1645629975, SIFT 0.32
- S49R (p.Ser49Arg), gnomAD 1-65309890-A-AG, CADD 29.70
- S49G (p.Ser49Gly), rs1331529842, gnomAD 1-65309890-A-G, REVEL 0.27, CADD 22.60
- S49N (p.Ser49Asn), gnomAD 1-65309891-G-A, REVEL 0.29, CADD 22.20
- R51W (p.Arg51Trp), rs12753869, gnomAD 1-65309887-C-T, REVEL 0.24, CADD 22.90
- R51P (p.Arg51Pro), rs911273317, gnomAD 1-65309888-G-C, REVEL 0.20, CADD 23.20
Public DNAJC6 analysis runs
- DNAJC6 analysis run — DNAJC6 (1,293 variants) — completed 2026-08-18