DDI2
geneOn this page
Also known as MGC14844
Summary
DDI2 (DDI proteasomal shuttling factor 2, HGNC:24578) is a protein-coding gene on chromosome 1p36.21, encoding Protein DDI1 homolog 2 (Q5TDH0). Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at ‘Leu-104’, thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane.
Enables aspartic-type endopeptidase activity; identical protein binding activity; and ubiquitin binding activity. Involved in several processes, including cellular response to hydroxyurea; proteolysis; and regulation of DNA stability. Located in cytosol and nucleoplasm.
Source: NCBI Gene 84301 — RefSeq curated summary.
At a glance
- GWAS associations: 7
- Clinical variants (ClinVar): 133 total — 1 pathogenic
- MANE Select transcript:
NM_032341
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:24578 |
| Approved symbol | DDI2 |
| Name | DDI proteasomal shuttling factor 2 |
| Location | 1p36.21 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | MGC14844 |
| Ensembl gene | ENSG00000197312 |
| Ensembl biotype | protein_coding |
| OMIM | 620871 |
| Entrez | 84301 |
Gene structure
Transcript identifiers
Ensembl transcripts: 8 — 3 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay
ENST00000320153, ENST00000480945, ENST00000483899, ENST00000486680, ENST00000546927, ENST00000548451, ENST00000711098, ENST00000711099
RefSeq mRNA: 1 — MANE Select: NM_032341
NM_032341
CCDS: CCDS30607
Canonical transcript exons
ENST00000480945 — 10 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001351972 | 15638307 | 15638434 |
| ENSE00001368705 | 15633439 | 15633565 |
| ENSE00001925600 | 15617458 | 15617808 |
| ENSE00003566844 | 15643522 | 15643650 |
| ENSE00003584951 | 15630325 | 15630561 |
| ENSE00003648620 | 15649720 | 15649823 |
| ENSE00003690124 | 15626669 | 15626798 |
| ENSE00003690768 | 15651706 | 15651895 |
| ENSE00004014538 | 15659837 | 15669044 |
| ENSE00004014540 | 15656617 | 15656679 |
Expression profiles
Bgee: expression breadth ubiquitous, 254 present calls, max score 97.33.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.0789 / max 161.3156, expressed in 1804 samples.
FANTOM5 promoters (5 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 886 | 16.2476 | 1795 |
| 888 | 2.8579 | 1398 |
| 885 | 1.1892 | 731 |
| 887 | 0.4182 | 212 |
| 889 | 0.3659 | 155 |
Top tissues by expression
256 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| tibialis anterior | UBERON:0001385 | 97.33 | gold quality |
| deltoid | UBERON:0001476 | 96.57 | gold quality |
| upper arm skin | UBERON:0004263 | 95.76 | gold quality |
| palpebral conjunctiva | UBERON:0001812 | 95.05 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 94.66 | gold quality |
| quadriceps femoris | UBERON:0001377 | 94.55 | gold quality |
| vastus lateralis | UBERON:0001379 | 94.44 | gold quality |
| sural nerve | UBERON:0015488 | 94.22 | gold quality |
| trabecular bone tissue | UBERON:0002483 | 94.18 | gold quality |
| oviduct epithelium | UBERON:0004804 | 93.70 | gold quality |
| skeletal muscle tissue of rectus abdominis | UBERON:0004511 | 93.62 | gold quality |
| skeletal muscle tissue of biceps brachii | UBERON:0004502 | 93.48 | gold quality |
| ileal mucosa | UBERON:0000331 | 93.47 | gold quality |
| oral cavity | UBERON:0000167 | 93.09 | gold quality |
| biceps brachii | UBERON:0001507 | 93.02 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 92.83 | gold quality |
| kidney epithelium | UBERON:0004819 | 91.74 | gold quality |
| jejunal mucosa | UBERON:0000399 | 91.53 | gold quality |
| nasal cavity epithelium | UBERON:0005384 | 91.44 | gold quality |
| bronchial epithelial cell | CL:0002328 | 91.18 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 91.09 | gold quality |
| muscle tissue | UBERON:0002385 | 90.79 | gold quality |
| bronchus | UBERON:0002185 | 90.75 | gold quality |
| skin of hip | UBERON:0001554 | 89.55 | gold quality |
| liver | UBERON:0002107 | 89.54 | gold quality |
| upper leg skin | UBERON:0004262 | 89.54 | gold quality |
| corpus epididymis | UBERON:0004359 | 89.43 | gold quality |
| pigmented layer of retina | UBERON:0001782 | 89.32 | gold quality |
| jejunum | UBERON:0002115 | 89.17 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 88.65 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 7.91 |
| E-MTAB-9689 | no | 148.66 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
114 targeting DDI2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-6833-3P | 100.00 | 70.63 | 3197 |
| HSA-MIR-4768-5P | 100.00 | 69.49 | 2861 |
| HSA-MIR-4500 | 99.99 | 72.72 | 2367 |
| HSA-LET-7A-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7B-5P | 99.98 | 72.31 | 1790 |
| HSA-LET-7C-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7E-5P | 99.98 | 72.29 | 1790 |
| HSA-LET-7F-5P | 99.98 | 72.56 | 1784 |
| HSA-LET-7G-5P | 99.98 | 72.37 | 1784 |
| HSA-LET-7I-5P | 99.98 | 72.37 | 1788 |
| HSA-MIR-98-5P | 99.98 | 72.33 | 1787 |
| HSA-MIR-520D-5P | 99.98 | 73.34 | 4883 |
| HSA-MIR-524-5P | 99.98 | 73.43 | 4882 |
| HSA-LET-7D-5P | 99.96 | 71.76 | 1632 |
| HSA-MIR-4458 | 99.96 | 71.64 | 1650 |
| HSA-MIR-4267 | 99.96 | 66.53 | 2368 |
| HSA-MIR-4778-3P | 99.93 | 70.40 | 1818 |
| HSA-MIR-3682-5P | 99.93 | 67.97 | 1163 |
| HSA-MIR-6753-3P | 99.93 | 66.57 | 637 |
| HSA-MIR-7107-3P | 99.93 | 66.73 | 627 |
| HSA-MIR-205-3P | 99.92 | 69.92 | 3165 |
| HSA-MIR-1305 | 99.91 | 71.43 | 3443 |
| HSA-MIR-6809-3P | 99.91 | 71.45 | 3814 |
| HSA-MIR-627-3P | 99.90 | 71.42 | 3316 |
| HSA-MIR-5003-3P | 99.85 | 69.29 | 2517 |
| HSA-MIR-202-3P | 99.84 | 71.41 | 1290 |
| HSA-MIR-5010-3P | 99.83 | 70.60 | 2357 |
| HSA-MIR-6875-3P | 99.82 | 70.26 | 2983 |
| HSA-MIR-4659A-3P | 99.80 | 72.62 | 4248 |
| HSA-MIR-4659B-3P | 99.80 | 72.62 | 4248 |
Literature-anchored findings (GeneRIF, showing 6)
- the 3D structures of the human Ddi2 UBL and RVP domains were solved and identified a new helical domain that extends on either side of the Rretroviral protease-like dimer. (PMID:27461074)
- Here the authors show that the aspartyl protease DNA-damage inducible 1 homolog 2 (DDI2) is required to cleave and activate Nrf1. (PMID:27528193)
- DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1. (PMID:32521225)
- Multiple myeloma cells depend on the DDI2/NRF1-mediated proteasome stress response for survival. (PMID:34649278)
- The aspartyl protease DDI2 drives adaptation to proteasome inhibition in multiple myeloma. (PMID:35589686)
- UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage. (PMID:37084817)
Cross-species orthologs
3 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | ddi2 | ENSDARG00000006477 |
| drosophila_melanogaster | rngo | FBGN0030753 |
| caenorhabditis_elegans | WBGENE00015308 |
Paralogs (4): NRIP2 (ENSG00000053702), UBAC2 (ENSG00000134882), DDI1 (ENSG00000170967), NRIP3 (ENSG00000175352)
Protein
Protein identifiers
Protein DDI1 homolog 2 — Q5TDH0 (reviewed: Q5TDH0)
All UniProt accessions (5): A0AA34QVL7, A0AA34QVV2, H0YI90, H0YII4, Q5TDH0
UniProt curated annotations — full annotation on UniProt →
Function. Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at ‘Leu-104’, thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane. Ubiquitination of NFE2L1/NRF1 is a prerequisite for cleavage, suggesting that DDI2 specifically recognizes and binds ubiquitinated NFE2L1/NRF1. Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2. Required, with DDI1, for cellular survival following replication stress. Together or redudantly with DDI1, removes RTF2 from stalled forks to allow cell cycle progression after replication stress and maintains genome integrity.
Subunit / interactions. Homodimer. Interacts with MCM6; PCNA; PSMD4; PSMD8; RPA2 and RPN2. Interacts with RTF2.
Subcellular location. Cytoplasm. Cytosol. Chromosome.
Similarity. Belongs to the DDI1 family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q5TDH0-1 | 1 | yes |
| Q5TDH0-2 | 2 | |
| Q5TDH0-3 | 3 |
RefSeq proteins (1): NP_115717* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000626 | Ubiquitin-like_dom | Domain |
| IPR019103 | Peptidase_aspartic_DDI1-type | Domain |
| IPR021109 | Peptidase_aspartic_dom_sf | Homologous_superfamily |
| IPR029071 | Ubiquitin-like_domsf | Homologous_superfamily |
| IPR033882 | DDI1_N | Domain |
| IPR057273 | Ddi1/2_HDD | Domain |
Pfam: PF00240, PF09668, PF24669
UniProt features (43 total): strand 13, helix 12, modified residue 6, turn 3, splice variant 2, chain 1, domain 1, mutagenesis site 1, region of interest 1, short sequence motif 1, compositionally biased region 1, active site 1
Structure
Experimental structures (PDB)
3 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 4RGH | X-RAY DIFFRACTION | 1.9 |
| 2N7D | SOLUTION NMR | |
| 5K57 | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q5TDH0-F1 | 79.85 | 0.44 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1): 252
Post-translational modifications (6): 150, 194, 104, 106, 121, 128
Mutagenesis-validated functional residues (1):
| Position | Phenotype |
|---|---|
| 252 | abolishes aspartic protease activity. |
Function
Pathways and Gene Ontology
Reactome pathways
0 pathways
MSigDB gene sets: 242 (showing top):
GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_CARBOHYDRATE_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, MORF_RAD51L3, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, GOBP_PROTEIN_MATURATION, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT
GO Biological Process (6): proteasomal protein catabolic process (GO:0010498), protein processing (GO:0016485), regulation of protein stability (GO:0031647), cellular response to hydroxyurea (GO:0072711), regulation of DNA stability (GO:0097752), proteolysis (GO:0006508)
GO Molecular Function (6): aspartic-type endopeptidase activity (GO:0004190), identical protein binding (GO:0042802), ubiquitin binding (GO:0043130), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)
GO Cellular Component (4): nucleoplasm (GO:0005654), chromosome (GO:0005694), cytosol (GO:0005829), cytoplasm (GO:0005737)
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 3 |
| regulation of biological quality | 2 |
| protein catabolic process | 1 |
| proteolysis | 1 |
| protein maturation | 1 |
| response to hydroxyurea | 1 |
| cellular response to nitrogen compound | 1 |
| protein metabolic process | 1 |
| endopeptidase activity | 1 |
| aspartic-type peptidase activity | 1 |
| protein binding | 1 |
| ubiquitin-like protein binding | 1 |
| binding | 1 |
| hydrolase activity | 1 |
| catalytic activity, acting on a protein | 1 |
| catalytic activity | 1 |
| nuclear lumen | 1 |
| intracellular membraneless organelle | 1 |
| cytoplasm | 1 |
| intracellular anatomical structure | 1 |
Protein interactions and networks
STRING
758 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| DDI2 | NGLY1 | Q96IV0 | 722 |
| DDI2 | NFE2L1 | Q14494 | 719 |
| DDI2 | PSMD2 | Q13200 | 570 |
| DDI2 | PSMD4 | P55036 | 568 |
| DDI2 | RTF2 | Q9BY42 | 545 |
| DDI2 | RAD23A | P54725 | 524 |
| DDI2 | UBQLN1 | Q9UMX0 | 516 |
| DDI2 | ADRM1 | Q16186 | 495 |
| DDI2 | MAFF | Q9ULX9 | 494 |
| DDI2 | MAFG | O15525 | 493 |
| DDI2 | RAD23B | P54727 | 489 |
| DDI2 | NFE2L3 | Q9Y4A8 | 480 |
| DDI2 | MAFK | O60675 | 480 |
| DDI2 | UBQLN2 | Q9UHD9 | 476 |
| DDI2 | PSMC4 | P43686 | 469 |
IntAct
55 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| ZNF7 | IPO8 | psi-mi:“MI:0914”(association) | 0.530 |
| CPNE2 | HIP1 | psi-mi:“MI:0914”(association) | 0.530 |
| HP1BP3 | IPO8 | psi-mi:“MI:0914”(association) | 0.530 |
| RDH5 | NME2P1 | psi-mi:“MI:0914”(association) | 0.530 |
| ZG16B | ITIH2 | psi-mi:“MI:0914”(association) | 0.530 |
| ZDHHC1 | PIK3CA | psi-mi:“MI:0914”(association) | 0.530 |
| CPNE2 | DNM1L | psi-mi:“MI:0914”(association) | 0.530 |
| UBL4A | DDI2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| DDI2 | LRRC41 | psi-mi:“MI:0915”(physical association) | 0.400 |
| DDI2 | H2BC9 | psi-mi:“MI:0915”(physical association) | 0.400 |
| MOGAT2 | DDI2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| DDI2 | USP47 | psi-mi:“MI:0915”(physical association) | 0.400 |
| CYP2B6 | DDI2 | psi-mi:“MI:0915”(physical association) | 0.400 |
| JAZF1 | TNPO2 | psi-mi:“MI:0914”(association) | 0.350 |
| SUZ12 | TNPO2 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF578 | IPO8 | psi-mi:“MI:0914”(association) | 0.350 |
| ZIM3 | IPO8 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF138 | PPM1G | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF222 | PPM1G | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF267 | DNAJB6 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF419 | IPO8 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF441 | PPP2CB | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF480 | IPO8 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF549 | IPO8 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF695 | PDCD5 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF763 | CSNK2A2 | psi-mi:“MI:0914”(association) | 0.350 |
| ZNF846 | IPO8 | psi-mi:“MI:0914”(association) | 0.350 |
| C1QC | C1QL1 | psi-mi:“MI:0914”(association) | 0.350 |
| RAD23B | UBE4B | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (148): DDI2 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), CCDC6 (Co-fractionation), COA7 (Co-fractionation), DDI2 (Co-fractionation), HAT1 (Co-fractionation), TLN2 (Co-fractionation), TOM1 (Co-fractionation), TRMT6 (Co-fractionation), TTC4 (Co-fractionation), DDI2 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), DDI2 (Affinity Capture-MS), DDI2 (Affinity Capture-MS)
ESM2 similar proteins: A0A8I6G705, A1L3K1, B5DFF2, B5DFI8, G3MWR8, O19048, O19137, O88508, P06730, P29338, P57721, P57722, P60335, Q12800, Q13888, Q15365, Q15366, Q16763, Q1LZ53, Q1RML1, Q28D01, Q2TBV5, Q4W5Z4, Q5E9A3, Q5FVR7, Q5NVP9, Q5TDH0, Q61990, Q6AYU1, Q6DH13, Q6P1K8, Q6ZRY4, Q7RTP6, Q8C6G8, Q8CCI5, Q8CJ19, Q8IY57, Q8N488, Q8VC52, Q921J4
Diamond homologs: A0JPP7, A1CDT9, A1DCU5, A2ADY9, I7HUG0, P0CS14, P0CS15, P40087, Q0CJ13, Q0U3Y6, Q10256, Q17569, Q1DNB9, Q1EBV4, Q2H085, Q2T9Z1, Q2USD7, Q497D6, Q4WGS4, Q54JB0, Q5AY89, Q5TDH0, Q6BK42, Q6CFI3, Q6CNS3, Q6FQE9, Q6TH22, Q754R2, Q7S906, Q7ZYA7, Q8WTU0, Q95JI3, Q9DAF3, Q9BQI9, P0C273, P0C275, P0C276, P0CG82, P0CH10, P0CH11
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
133 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 0 |
| Uncertain significance | 109 |
| Likely benign | 10 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (1)
| Variant ID | HGVS | Classification |
|---|---|---|
| 584380 | NC_000001.10:g.(?15764961)(16063358_?)del | Pathogenic |
SpliceAI
1851 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 1:15617804:GCCAG:G | donor_gain | 1.0000 |
| 1:15617805:CCAGG:C | donor_loss | 1.0000 |
| 1:15617806:CAGGT:C | donor_loss | 1.0000 |
| 1:15617809:G:C | donor_loss | 1.0000 |
| 1:15617810:T:G | donor_loss | 1.0000 |
| 1:15626666:TAG:T | acceptor_loss | 1.0000 |
| 1:15626667:A:AC | acceptor_loss | 1.0000 |
| 1:15626667:A:AG | acceptor_gain | 1.0000 |
| 1:15626668:G:GT | acceptor_gain | 1.0000 |
| 1:15626668:GATC:G | acceptor_gain | 1.0000 |
| 1:15626799:G:GG | donor_gain | 1.0000 |
| 1:15630322:CAGAC:C | acceptor_loss | 1.0000 |
| 1:15630323:A:AG | acceptor_gain | 1.0000 |
| 1:15630324:G:GG | acceptor_gain | 1.0000 |
| 1:15630324:G:GT | acceptor_loss | 1.0000 |
| 1:15630324:GACTT:G | acceptor_gain | 1.0000 |
| 1:15630562:G:GC | donor_loss | 1.0000 |
| 1:15630562:G:GG | donor_gain | 1.0000 |
| 1:15630563:TAAG:T | donor_loss | 1.0000 |
| 1:15633429:A:AG | acceptor_gain | 1.0000 |
| 1:15633430:T:G | acceptor_gain | 1.0000 |
| 1:15633434:T:TA | acceptor_gain | 1.0000 |
| 1:15633435:GTAG:G | acceptor_loss | 1.0000 |
| 1:15633436:TAGA:T | acceptor_gain | 1.0000 |
| 1:15633437:A:AG | acceptor_gain | 1.0000 |
| 1:15633437:AG:A | acceptor_loss | 1.0000 |
| 1:15633438:G:GA | acceptor_gain | 1.0000 |
| 1:15633438:GA:G | acceptor_gain | 1.0000 |
| 1:15633438:GAGA:G | acceptor_gain | 1.0000 |
| 1:15633438:GAGAA:G | acceptor_gain | 1.0000 |
AlphaMissense
2603 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 1:15630511:T:C | L152P | 1.000 |
| 1:15633542:G:C | Q203H | 1.000 |
| 1:15633542:G:T | Q203H | 1.000 |
| 1:15638338:G:C | A222P | 1.000 |
| 1:15638339:C:A | A222D | 1.000 |
| 1:15638362:T:C | F230L | 1.000 |
| 1:15638363:T:G | F230C | 1.000 |
| 1:15638364:T:A | F230L | 1.000 |
| 1:15638364:T:G | F230L | 1.000 |
| 1:15638378:T:C | M235T | 1.000 |
| 1:15638379:G:A | M235I | 1.000 |
| 1:15638379:G:C | M235I | 1.000 |
| 1:15638379:G:T | M235I | 1.000 |
| 1:15638381:T:A | L236H | 1.000 |
| 1:15638381:T:C | L236P | 1.000 |
| 1:15638383:T:G | Y237D | 1.000 |
| 1:15638392:T:C | C240R | 1.000 |
| 1:15638393:G:A | C240Y | 1.000 |
| 1:15638394:C:G | C240W | 1.000 |
| 1:15638420:C:A | A249D | 1.000 |
| 1:15638422:T:C | F250L | 1.000 |
| 1:15638423:T:C | F250S | 1.000 |
| 1:15638423:T:G | F250C | 1.000 |
| 1:15638424:T:A | F250L | 1.000 |
| 1:15638424:T:G | F250L | 1.000 |
| 1:15638426:T:A | V251D | 1.000 |
| 1:15638428:G:A | D252N | 1.000 |
| 1:15638428:G:C | D252H | 1.000 |
| 1:15638429:A:C | D252A | 1.000 |
| 1:15638429:A:G | D252G | 1.000 |
dbSNP variants (sampled 300 via entrez): RS1000104427 (1:15634862 A>G), RS1000114925 (1:15653253 G>A), RS1000119115 (1:15617041 C>G), RS1000181848 (1:15633065 A>G), RS1000212771 (1:15630478 T>C), RS1000235591 (1:15632843 T>C), RS1000340036 (1:15651149 G>A), RS1000354464 (1:15627665 A>G), RS1000445948 (1:15624294 A>G), RS1000483957 (1:15621576 G>C), RS1000520418 (1:15663216 A>G), RS1000641473 (1:15648773 G>C), RS1000734015 (1:15658975 T>C), RS1000954659 (1:15662786 A>G), RS1001082077 (1:15643344 A>G)
Disease associations
OMIM: gene MIM:620871 | disease phenotypes: MIM:167800
GenCC curated gene-disease
Mondo (1): hereditary chronic pancreatitis (MONDO:0008185)
Orphanet (1): Autosomal dominant hereditary chronic pancreatitis (Orphanet:676)
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
7 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST004860_117 | Alcoholic chronic pancreatitis | 3.000000e-08 |
| GCST004860_134 | Alcoholic chronic pancreatitis | 1.000000e-06 |
| GCST007269_9 | Pulse pressure | 2.000000e-10 |
| GCST007565_187 | Morning person | 3.000000e-16 |
| GCST007576_356 | Chronotype | 3.000000e-16 |
| GCST007876_63 | Estimated glomerular filtration rate | 4.000000e-16 |
| GCST012020_63 | Serum metabolite levels | 4.000000e-77 |
EFO canonical traits (2, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0005763 | pulse pressure measurement |
| EFO:0008328 | chronotype measurement |
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| C537262 | Hereditary pancreatitis (supp.) |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: no
PharmGKB: 1 entry (VIP=true, CPIC=false)
CTD chemical–gene interactions
29 total (human), top 29 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| GSK-J4 | increases expression | 1 |
| dicrotophos | increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| bisphenol A | increases expression | 1 |
| pyrogallol 1,3-dimethyl ether | affects localization, increases expression, affects cotreatment | 1 |
| sodium arsenite | decreases expression | 1 |
| butyraldehyde | increases expression | 1 |
| benzo(e)pyrene | decreases methylation | 1 |
| aflatoxin B2 | decreases methylation | 1 |
| 4-aminophenylarsenoxide | affects binding, decreases reaction | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| bisphenol S | increases expression | 1 |
| bisphenol AF | increases expression | 1 |
| Arsenic Trioxide | affects binding, decreases reaction | 1 |
| Leflunomide | decreases expression | 1 |
| Benzo(a)pyrene | decreases expression | 1 |
| Caffeine | increases phosphorylation | 1 |
| Dimethyl Sulfoxide | increases expression | 1 |
| Estradiol | increases expression | 1 |
| Furaldehyde | affects cotreatment, affects localization, decreases expression | 1 |
| Hydrogen Peroxide | affects cotreatment, increases expression | 1 |
| Ivermectin | decreases expression | 1 |
| Methapyrilene | decreases methylation | 1 |
| Sodium Chloride | affects localization, decreases expression, increases expression, affects cotreatment | 1 |
| Theophylline | affects cotreatment, increases expression | 1 |
| Valproic Acid | increases expression | 1 |
| Sodium Selenite | decreases expression | 1 |
| Cadmium Chloride | decreases expression | 1 |
| Okadaic Acid | decreases expression | 1 |
Cellosaurus cell lines
4 cell lines: 4 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_SK53 | HAP1 DDI2 (-) 1 | Cancer cell line | Male |
| CVCL_SK54 | HAP1 DDI2 (-) 2 | Cancer cell line | Male |
| CVCL_SK55 | HAP1 DDI2 (-) 3 | Cancer cell line | Male |
| CVCL_SK56 | HAP1 DDI2 (-) 4 | Cancer cell line | Male |
Clinical trials (associated diseases)
7 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00830557 | Not specified | RECRUITING | Collecting Medical Information and Tissue Samples From Patients With Pancreatic Cancer or Other Pancreatic Disorders |
| NCT02078245 | Not specified | UNKNOWN | Quality Control Study of MR Based Screening of Individual With Increased Risk for Pancreas Cancer. |
| NCT02206360 | Not specified | ACTIVE_NOT_RECRUITING | Pancreatic Cancer Early Detection Program |
| NCT02309632 | Not specified | WITHDRAWN | Pancreatic Cancer Screening of High-Risk Individuals in Arkansas |
| NCT04095195 | Not specified | RECRUITING | Registry of Subjects at Risk of Pancreatic Cancer |
| NCT04743479 | Not specified | RECRUITING | Artificial Intelligence-based Early Screening of Pancreatic Cancer and High Risk Tracing (ESPRIT-AI) |
| NCT07413029 | Not specified | RECRUITING | French National Cohort of Patients With PRSS1 Mutations |
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): alcoholic pancreatitis, hereditary chronic pancreatitis