GRWD1
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Also known as WDR28GRWDRRB1
Summary
GRWD1 (glutamate rich WD repeat containing 1, HGNC:21270) is a protein-coding gene on chromosome 19q13.33, encoding Glutamate-rich WD repeat-containing protein 1 (Q9BQ67). Histone binding-protein that regulates chromatin dynamics and loading of minichromosome maintenance (MCM) complex at replication origins, possibly by promoting chromatin openness. It is a common-essential gene (DepMap: required in 92.5% of cancer cell lines).
This gene encodes a glutamate-rich protein that contains five WD-repeat motifs. The encoded protein may play a critical role in ribosome biogenesis and may also play a role in histone methylation through interactions with CUL4-DDB1 ubiquitin E3 ligase.
Source: NCBI Gene 83743 — RefSeq curated summary.
At a glance
- Gene–disease (curated): congenital diarrhea (Limited, GenCC)
- Clinical variants (ClinVar): 116 total — 2 likely-pathogenic
- Phenotypes (HPO): 4
- Druggable target: yes
- Cancer dependency (DepMap): dependent in 92.5% of screened cell lines (common-essential)
- MANE Select transcript:
NM_031485
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:21270 |
| Approved symbol | GRWD1 |
| Name | glutamate rich WD repeat containing 1 |
| Location | 19q13.33 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | WDR28, GRWD, RRB1 |
| Ensembl gene | ENSG00000105447 |
| Ensembl biotype | protein_coding |
| OMIM | 610597 |
| Entrez | 83743 |
Gene structure
Transcript identifiers
Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron
ENST00000253237, ENST00000598711, ENST00000599949, ENST00000928855
RefSeq mRNA: 1 — MANE Select: NM_031485
NM_031485
CCDS: CCDS12720
Canonical transcript exons
ENST00000253237 — 7 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000896536 | 48451034 | 48451231 |
| ENSE00000896537 | 48450666 | 48450808 |
| ENSE00000896542 | 48445983 | 48446192 |
| ENSE00001249491 | 48452708 | 48457022 |
| ENSE00002212624 | 48450313 | 48450526 |
| ENSE00003485287 | 48446385 | 48446502 |
| ENSE00003627273 | 48446681 | 48446843 |
Expression profiles
Bgee: expression breadth ubiquitous, 285 present calls, max score 88.53.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.1248 / max 205.5598, expressed in 1818 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 176787 | 24.9020 | 1814 |
| 176785 | 2.6609 | 1451 |
| 176786 | 1.5619 | 1042 |
Top tissues by expression
291 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| tongue squamous epithelium | UBERON:0006919 | 88.53 | silver quality |
| gastrocnemius | UBERON:0001388 | 88.20 | gold quality |
| muscle of leg | UBERON:0001383 | 87.36 | gold quality |
| type B pancreatic cell | CL:0000169 | 85.75 | silver quality |
| stromal cell of endometrium | CL:0002255 | 85.24 | gold quality |
| skeletal muscle organ | UBERON:0014892 | 84.68 | gold quality |
| muscle organ | UBERON:0001630 | 84.67 | gold quality |
| olfactory bulb | UBERON:0002264 | 84.45 | silver quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 84.17 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 84.02 | gold quality |
| esophagus mucosa | UBERON:0002469 | 83.79 | gold quality |
| left uterine tube | UBERON:0001303 | 83.68 | gold quality |
| skin of leg | UBERON:0001511 | 83.59 | gold quality |
| apex of heart | UBERON:0002098 | 83.44 | gold quality |
| granulocyte | CL:0000094 | 83.35 | gold quality |
| body of stomach | UBERON:0001161 | 83.30 | gold quality |
| right adrenal gland | UBERON:0001233 | 83.29 | gold quality |
| skin of abdomen | UBERON:0001416 | 83.26 | gold quality |
| left adrenal gland | UBERON:0001234 | 83.19 | gold quality |
| pancreatic ductal cell | CL:0002079 | 83.17 | silver quality |
| right coronary artery | UBERON:0001625 | 83.12 | gold quality |
| ectocervix | UBERON:0012249 | 83.03 | gold quality |
| lymph node | UBERON:0000029 | 82.99 | gold quality |
| heart left ventricle | UBERON:0002084 | 82.96 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 82.95 | gold quality |
| hair follicle | UBERON:0002073 | 82.94 | silver quality |
| vena cava | UBERON:0004087 | 82.91 | silver quality |
| mucosa of transverse colon | UBERON:0004991 | 82.89 | gold quality |
| esophagus | UBERON:0001043 | 82.86 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 82.82 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | no | 0.00 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): GLI3
miRNA regulators (miRDB)
39 targeting GRWD1, 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-9-5P | 100.00 | 72.28 | 2361 |
| HSA-MIR-518D-5P | 100.00 | 67.51 | 979 |
| HSA-MIR-518E-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-518F-5P | 100.00 | 67.51 | 979 |
| HSA-MIR-519A-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-519B-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-519C-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-520C-5P | 100.00 | 67.51 | 979 |
| HSA-MIR-522-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-523-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-526A-5P | 100.00 | 67.51 | 979 |
| HSA-MIR-4650-5P | 99.98 | 64.69 | 999 |
| HSA-MIR-495-3P | 99.96 | 72.81 | 4197 |
| HSA-MIR-5688 | 99.96 | 73.23 | 4504 |
| HSA-MIR-6756-5P | 99.82 | 67.97 | 2466 |
| HSA-MIR-6766-5P | 99.68 | 67.70 | 2325 |
| HSA-MIR-7112-5P | 99.59 | 65.76 | 104 |
| HSA-MIR-4441 | 99.49 | 66.56 | 3216 |
| HSA-MIR-3123 | 99.47 | 67.15 | 2693 |
| HSA-MIR-6828-5P | 99.31 | 69.21 | 1433 |
| HSA-MIR-3925-5P | 99.21 | 67.90 | 1466 |
| HSA-MIR-371A-5P | 99.08 | 66.51 | 1914 |
| HSA-MIR-4270 | 99.02 | 66.26 | 1987 |
| HSA-MIR-330-5P | 98.73 | 67.63 | 1788 |
| HSA-MIR-7851-3P | 98.72 | 64.88 | 980 |
| HSA-MIR-6754-5P | 98.60 | 65.54 | 1627 |
| HSA-MIR-6776-5P | 98.54 | 67.43 | 1304 |
| HSA-MIR-326 | 98.25 | 66.44 | 1565 |
| HSA-MIR-4717-5P | 98.19 | 67.97 | 894 |
| HSA-MIR-340-3P | 98.11 | 68.25 | 679 |
Functional genomics
DepMap (CRISPR cell-line fitness): dependent in 92.5% of screened cell lines, common-essential.
Literature-anchored findings (GeneRIF, showing 6)
- Cdt1-binding protein GRWD1 promotes chromatin fluidity by influencing nucleosome structures, e.g., by transient eviction of H2A-H2B, and thereby promotes efficient MCM loading at replication origins. (PMID:27552915)
- GRWD1 overexpression in combination with HPV16 E7 and activated KRAS confers anchorage-independent growth and tumorigenic capacity on normal human fibroblasts. Consistent with this, GRWD1 overexpression is associated with poor prognosis in cancer patients. (PMID:27856536)
- findings suggest a novel oncogenic function of GRWD1 as a transcriptional regulator of p53 and that GRWD1 might be an attractive therapeutic target and prognostic marker in cancer therapy (PMID:31545368)
- GRWD1 promotes cell proliferation and migration in non-small cell lung cancer by activating the Notch pathway. (PMID:31891681)
- Comprehensive Analysis of Glutamate-Rich WD Repeat-Containing Protein 1 and Its Potential Clinical Significance for Pancancer. (PMID:34616846)
- GRWD1-WDR5-MLL2 Epigenetic Complex Mediates H3K4me3 Mark and Is Essential for Kaposi’s Sarcoma-Associated Herpesvirus-Induced Cellular Transformation. (PMID:34933446)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | grwd1 | ENSDARG00000004806 |
| mus_musculus | Grwd1 | ENSMUSG00000053801 |
| rattus_norvegicus | Grwd1 | ENSRNOG00000021058 |
| drosophila_melanogaster | l(2)09851 | FBGN0022288 |
| caenorhabditis_elegans | WBGENE00021899 |
Paralogs (9): ERCC8 (ENSG00000049167), GEMIN5 (ENSG00000082516), RBBP7 (ENSG00000102054), WDR59 (ENSG00000103091), PEX7 (ENSG00000112357), WDR77 (ENSG00000116455), WDR24 (ENSG00000127580), RBBP4 (ENSG00000162521), WDR73 (ENSG00000177082)
Protein
Protein identifiers
Glutamate-rich WD repeat-containing protein 1 — Q9BQ67 (reviewed: Q9BQ67)
All UniProt accessions (2): Q9BQ67, M0QX71
UniProt curated annotations — full annotation on UniProt →
Function. Histone binding-protein that regulates chromatin dynamics and loading of minichromosome maintenance (MCM) complex at replication origins, possibly by promoting chromatin openness. Plays a role in ribosomal biogenesis.
Subunit / interactions. Interacts with pre-ribosomal ribonucleoprotein complexes. Interacts with METTL18. Interacts with CDT1; origin binding of GRWD1 is dependent on CDT1. Interacts with CDC6; origin binding of GRWD1 is dependent on CDC6. Interacts with RPL3. Binds to histone H2A-H2B and H3-H4 complexes.
Subcellular location. Nucleus. Nucleolus. Chromosome.
Tissue specificity. Widely expressed.
Disease relevance. Diarrhea 14, congenital (DIAR14) [MIM:621160] An autosomal recessive disorder characterized by diarrhea manifesting within the first year of life, and diffuse arterial hypoplasia. The disease is caused by variants affecting the gene represented in this entry.
Induction. Induced by E2F transcription factors.
RefSeq proteins (1): NP_113673* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001680 | WD40_rpt | Repeat |
| IPR015943 | WD40/YVTN_repeat-like_dom_sf | Homologous_superfamily |
| IPR019775 | WD40_repeat_CS | Conserved_site |
| IPR020472 | WD40_PAC1 | Repeat |
| IPR022052 | Histone-bd_RBBP4-like_N | Domain |
| IPR036322 | WD40_repeat_dom_sf | Homologous_superfamily |
| IPR051972 | Glutamate-rich_WD_repeat | Family |
Pfam: PF00400, PF12265
UniProt features (18 total): repeat 7, modified residue 4, sequence variant 3, region of interest 2, chain 1, compositionally biased region 1
Structure
Experimental structures (PDB)
0 structures.
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q9BQ67-F1 | 89.21 | 0.77 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Post-translational modifications (4): 10, 119, 122, 344
Function
Pathways and Gene Ontology
Reactome pathways
0 pathways
MSigDB gene sets: 165 (showing top):
RRAGTTGT_UNKNOWN, GOBP_RIBOSOME_BIOGENESIS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, AACWWCAANK_UNKNOWN, OCT1_03, WTGAAAT_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, FISCHER_DREAM_TARGETS, RFX1_02, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, HAN_SATB1_TARGETS_DN, GOBP_CHROMATIN_REMODELING, BURTON_ADIPOGENESIS_2, HAMAI_APOPTOSIS_VIA_TRAIL_DN
GO Biological Process (4): DNA replication (GO:0006260), nucleosome assembly (GO:0006334), nucleosome disassembly (GO:0006337), ribosome biogenesis (GO:0042254)
GO Molecular Function (5): chromatin binding (GO:0003682), DNA replication origin binding (GO:0003688), RNA binding (GO:0003723), histone binding (GO:0042393), protein binding (GO:0005515)
GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), cytosol (GO:0005829), protein-containing complex (GO:0032991)
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| nucleosome organization | 2 |
| binding | 2 |
| nuclear lumen | 2 |
| cellular anatomical structure | 2 |
| intracellular membraneless organelle | 2 |
| DNA metabolic process | 1 |
| DNA biosynthetic process | 1 |
| chromatin organization | 1 |
| protein-DNA complex assembly | 1 |
| protein-DNA complex disassembly | 1 |
| ribonucleoprotein complex biogenesis | 1 |
| sequence-specific double-stranded DNA binding | 1 |
| nucleic acid binding | 1 |
| protein binding | 1 |
| intracellular membrane-bounded organelle | 1 |
| cytoplasm | 1 |
| cellular_component | 1 |
Protein interactions and networks
STRING
2374 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| GRWD1 | RPL3 | P39023 | 952 |
| GRWD1 | BOP1 | Q14137 | 945 |
| GRWD1 | CDT1 | Q9H211 | 935 |
| GRWD1 | TSR2 | Q969E8 | 776 |
| GRWD1 | RPL11 | P25121 | 753 |
| GRWD1 | HEATR3 | Q7Z4Q2 | 736 |
| GRWD1 | DCAF5 | Q96JK2 | 599 |
| GRWD1 | SURF6 | O75683 | 574 |
| GRWD1 | RPL5 | P46777 | 545 |
| GRWD1 | ORC6 | Q9Y5N6 | 534 |
| GRWD1 | METTL18 | O95568 | 509 |
| GRWD1 | COPS7A | Q9UBW8 | 508 |
| GRWD1 | BCCIP | Q9P287 | 486 |
| GRWD1 | PPM1G | O15355 | 471 |
| GRWD1 | DDB1 | Q16531 | 471 |
IntAct
89 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| DTL | DDB1 | psi-mi:“MI:0914”(association) | 0.740 |
| CUL4B | CUL4A | psi-mi:“MI:0914”(association) | 0.730 |
| SPTLC1 | SPTLC2 | psi-mi:“MI:0914”(association) | 0.680 |
| SEC13 | SEC16A | psi-mi:“MI:0914”(association) | 0.640 |
| CUL4B | EED | psi-mi:“MI:0914”(association) | 0.560 |
| COP1 | DDB1 | psi-mi:“MI:0914”(association) | 0.530 |
| TNFAIP3 | LRRIQ3 | psi-mi:“MI:2364”(proximity) | 0.420 |
| SDC1 | ILVBL | psi-mi:“MI:0915”(physical association) | 0.400 |
| JUN | psi-mi:“MI:0914”(association) | 0.350 | |
| JUN | TPM3 | psi-mi:“MI:0914”(association) | 0.350 |
| Xpo1 | IFT56 | psi-mi:“MI:0914”(association) | 0.350 |
| CUL4B | TLE1 | psi-mi:“MI:0914”(association) | 0.350 |
| SNRNP40 | WDR5 | psi-mi:“MI:0914”(association) | 0.350 |
| WDR26 | DDB1 | psi-mi:“MI:0914”(association) | 0.350 |
| WDR5B | DDB1 | psi-mi:“MI:0914”(association) | 0.350 |
| WDR5 | DDB1 | psi-mi:“MI:0914”(association) | 0.350 |
| PPM1G | HADHA | psi-mi:“MI:0914”(association) | 0.350 |
| RRP1B | ZNF785 | psi-mi:“MI:0914”(association) | 0.350 |
| psi-mi:“MI:0914”(association) | 0.350 | ||
| NUDCD1 | TUBAL3 | psi-mi:“MI:0914”(association) | 0.350 |
| Prdm16 | ESYT2 | psi-mi:“MI:0914”(association) | 0.350 |
| Mecom | ESYT2 | psi-mi:“MI:0914”(association) | 0.350 |
| ESR1 | ESYT2 | psi-mi:“MI:0914”(association) | 0.350 |
| CAND1 | GTPBP10 | psi-mi:“MI:0914”(association) | 0.350 |
| CUL1 | LGALS8 | psi-mi:“MI:0914”(association) | 0.350 |
| COPS5 | FBLL1 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (602): GRWD1 (Affinity Capture-RNA), GRWD1 (Affinity Capture-RNA), GRWD1 (Reconstituted Complex), GRWD1 (Co-fractionation), GRWD1 (Co-fractionation), GRWD1 (Co-fractionation), GRWD1 (Co-fractionation), GRWD1 (Co-fractionation), GRWD1 (Co-fractionation), GRWD1 (Co-fractionation), GRWD1 (Co-fractionation), NOC2L (Co-fractionation), POLR1E (Co-fractionation), RBM19 (Co-fractionation), GRWD1 (Affinity Capture-MS)
ESM2 similar proteins: A1L112, A4IHS2, A8NZM5, B2ZZS9, O00423, O80775, O95834, P93107, P97452, Q05BC3, Q0DYP5, Q13216, Q13610, Q13685, Q15269, Q1JQD2, Q2HJ56, Q32KQ2, Q32P44, Q3SZK1, Q4V8C3, Q562C2, Q58DT8, Q5BIM8, Q5F3K4, Q5R9T6, Q5RCG7, Q5RFQ3, Q5VU92, Q5XI13, Q5ZK69, Q6DRF9, Q6P6T4, Q6PFM9, Q7TNG5, Q7YR70, Q810D6, Q8BH57, Q8BHB4, Q8BU03
Diamond homologs: A1CH75, A1CXL0, A2QI22, A3LQ86, A4R2Q6, A5DL92, A5DST9, A6R3K5, A6S0T8, A6ZPA9, A7ECP3, A7TMF9, A8IR43, B0Y5V6, B2B5V0, B2VZH2, B3RQN1, G0SFB5, O74184, P41318, P61480, Q0CLJ4, Q0UXP3, Q12024, Q1DJF7, Q1JQD2, Q2GXT0, Q2T9T9, Q2UGK1, Q4WP10, Q5APF0, Q5B4R1, Q5BJ90, Q5XI13, Q5XUX1, Q5ZJW8, Q6BLS5, Q6CEW7, Q6CU59, Q6FKK3
SIGNOR signaling
0 interactions.
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 123 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Signaling by ALK fusions and activated point mutants | 7 | 12.7× | 9e-04 |
| Neddylation | 10 | 5.7× | 3e-03 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| cell surface receptor protein tyrosine kinase signaling pathway | 8 | 13.5× | 1e-04 |
| ribosomal small subunit biogenesis | 5 | 11.1× | 7e-03 |
| insulin receptor signaling pathway | 5 | 10.8× | 7e-03 |
| positive regulation of protein catabolic process | 5 | 9.9× | 1e-02 |
| regulation of cell cycle | 8 | 5.8× | 7e-03 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
116 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 2 |
| Uncertain significance | 91 |
| Likely benign | 11 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (2)
| Variant ID | HGVS | Classification |
|---|---|---|
| 3252071 | NM_031485.4(GRWD1):c.920A>G (p.His307Arg) | Likely pathogenic |
| 3252072 | NM_031485.4(GRWD1):c.1102G>T (p.Val368Phe) | Likely pathogenic |
SpliceAI
1114 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 19:48446162:GCC:G | donor_gain | 1.0000 |
| 19:48446188:GACTG:G | donor_gain | 1.0000 |
| 19:48446499:ACAGG:A | donor_loss | 1.0000 |
| 19:48446501:AGG:A | donor_loss | 1.0000 |
| 19:48446504:T:G | donor_loss | 1.0000 |
| 19:48446677:CCA:C | acceptor_loss | 1.0000 |
| 19:48446678:CAGA:C | acceptor_loss | 1.0000 |
| 19:48446679:A:AG | acceptor_gain | 1.0000 |
| 19:48446679:AGAC:A | acceptor_loss | 1.0000 |
| 19:48446679:AGACT:A | acceptor_gain | 1.0000 |
| 19:48446680:G:GA | acceptor_gain | 1.0000 |
| 19:48446680:GA:G | acceptor_gain | 1.0000 |
| 19:48446680:GAC:G | acceptor_gain | 1.0000 |
| 19:48446680:GACT:G | acceptor_gain | 1.0000 |
| 19:48446680:GACTG:G | acceptor_gain | 1.0000 |
| 19:48446839:TTCGG:T | donor_gain | 1.0000 |
| 19:48446840:TCGG:T | donor_gain | 1.0000 |
| 19:48446841:CGG:C | donor_gain | 1.0000 |
| 19:48446841:CGGGT:C | donor_gain | 1.0000 |
| 19:48446842:GG:G | donor_gain | 1.0000 |
| 19:48446842:GGG:G | donor_gain | 1.0000 |
| 19:48446843:GG:G | donor_gain | 1.0000 |
| 19:48446843:GGTA:G | donor_loss | 1.0000 |
| 19:48446844:G:GG | donor_gain | 1.0000 |
| 19:48446844:GT:G | donor_loss | 1.0000 |
| 19:48450307:CTGCA:C | acceptor_loss | 1.0000 |
| 19:48450308:TGCAG:T | acceptor_loss | 1.0000 |
| 19:48450309:GCA:G | acceptor_loss | 1.0000 |
| 19:48450310:CAGGT:C | acceptor_loss | 1.0000 |
| 19:48450311:A:C | acceptor_loss | 1.0000 |
AlphaMissense
2899 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 19:48451181:A:C | S325R | 0.999 |
| 19:48451183:T:A | S325R | 0.999 |
| 19:48451183:T:G | S325R | 0.999 |
| 19:48452825:T:A | W381R | 0.999 |
| 19:48452825:T:C | W381R | 0.999 |
| 19:48452909:T:C | F409L | 0.999 |
| 19:48452911:C:A | F409L | 0.999 |
| 19:48452911:C:G | F409L | 0.999 |
| 19:48450496:T:C | F218L | 0.998 |
| 19:48450498:T:A | F218L | 0.998 |
| 19:48450498:T:G | F218L | 0.998 |
| 19:48451041:C:A | A278D | 0.998 |
| 19:48451073:T:A | W289R | 0.998 |
| 19:48451073:T:C | W289R | 0.998 |
| 19:48451076:G:C | D290H | 0.998 |
| 19:48451077:A:C | D290A | 0.998 |
| 19:48451077:A:T | D290V | 0.998 |
| 19:48452765:T:A | W361R | 0.998 |
| 19:48452765:T:C | W361R | 0.998 |
| 19:48452827:G:C | W381C | 0.998 |
| 19:48452827:G:T | W381C | 0.998 |
| 19:48446399:A:C | S68R | 0.997 |
| 19:48446401:C:A | S68R | 0.997 |
| 19:48446401:C:G | S68R | 0.997 |
| 19:48446471:G:T | G92W | 0.997 |
| 19:48450508:T:A | W222R | 0.997 |
| 19:48450508:T:C | W222R | 0.997 |
| 19:48450707:T:A | W242R | 0.997 |
| 19:48450707:T:C | W242R | 0.997 |
| 19:48450788:T:A | W269R | 0.997 |
dbSNP variants (sampled 300 via entrez): RS1000055611 (19:48456853 A>G,T), RS1000126016 (19:48454942 ATTTCT>A), RS1000178712 (19:48455144 A>G,T), RS1000278968 (19:48449874 G>A), RS1000430115 (19:48457139 G>C), RS1000511465 (19:48454071 C>A,T), RS1000851469 (19:48452298 A>G), RS1000915004 (19:48451744 G>A,T), RS1001012202 (19:48448662 G>T), RS1001674836 (19:48449012 G>T), RS1001945327 (19:48446231 G>C), RS1002184073 (19:48452911 C>A,G,T), RS1002235592 (19:48456491 G>A), RS1002285330 (19:48447460 G>A), RS1002408610 (19:48447624 G>A)
Disease associations
OMIM: gene MIM:610597 | disease phenotypes: MIM:214700, MIM:621160
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| congenital diarrhea | Limited | Autosomal recessive |
Mondo (3): prostate cancer (MONDO:0008315), congenital diarrhea (MONDO:0000824), diarrhea 14, congenital (MONDO:0976266)
Orphanet (1): Familial prostate cancer (Orphanet:1331)
HPO phenotypes
4 total (4 of 4 shown, HPO-id order):
| HPO | Term |
|---|---|
| HP:0000007 | Autosomal recessive inheritance |
| HP:0002014 | Diarrhea |
| HP:0003577 | Congenital onset |
| HP:0033994 | Dependency on parenteral nutrition |
GWAS associations
0 associations (top):
MeSH disease descriptors (1)
| Descriptor | Name | Tree numbers |
|---|---|---|
| D011471 | Prostatic Neoplasms | C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5724692 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
CTD chemical–gene interactions
49 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| sodium arsenite | increases expression, affects expression, decreases expression, affects cotreatment, increases abundance | 3 |
| bisphenol A | decreases expression | 2 |
| Smoke | decreases expression, increases abundance, increases expression | 2 |
| Valproic Acid | affects cotreatment, increases expression, increases methylation | 2 |
| Cadmium Chloride | decreases expression, increases abundance, increases expression | 2 |
| FR900359 | increases phosphorylation | 1 |
| TAK-243 | increases sumoylation | 1 |
| TL8-506 | affects cotreatment, increases expression | 1 |
| cinobufagin | decreases expression | 1 |
| 2,4,6-tribromophenol | decreases expression | 1 |
| deoxynivalenol | increases expression | 1 |
| decabromobiphenyl ether | increases expression | 1 |
| tris(1,3-dichloro-2-propyl)phosphate | decreases expression | 1 |
| tetrabromobisphenol A | increases expression | 1 |
| manganese chloride | affects cotreatment, increases abundance, increases expression | 1 |
| nivalenol | increases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| cylindrospermopsin | increases expression | 1 |
| K 7174 | decreases expression | 1 |
| erucylphospho-N,N,N-trimethylpropylammonium | decreases expression | 1 |
| ICG 001 | decreases expression | 1 |
| abrine | increases expression | 1 |
| 2,2’,4,4’-tetrabromodiphenyl ether | decreases expression | 1 |
| (+)-JQ1 compound | decreases expression | 1 |
| 4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid | decreases expression | 1 |
| Temozolomide | increases expression | 1 |
| Air Pollutants | increases abundance, increases expression | 1 |
| Arsenic | affects cotreatment, increases abundance, increases expression | 1 |
| Cadmium | increases abundance, increases expression | 1 |
| Caffeine | decreases phosphorylation | 1 |
ChEMBL screening assays
6 unique, capped per target: 6 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL5697358 | Binding | Inhibition of GRWD1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis | Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature |
Clinical trials (associated diseases)
300 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT00029224 | PHASE4 | COMPLETED | Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions |
| NCT00035997 | PHASE4 | COMPLETED | Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis |
| NCT00063609 | PHASE4 | COMPLETED | The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy |
| NCT00103623 | PHASE4 | SUSPENDED | The Plenaxis® Experience Study |
| NCT00106392 | PHASE4 | COMPLETED | A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy |
| NCT00185029 | PHASE4 | UNKNOWN | MR-Lymphography and Lymph Node Staging in Prostate Cancer |
| NCT00199485 | PHASE4 | COMPLETED | Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer |
| NCT00219219 | PHASE4 | COMPLETED | Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases |
| NCT00219271 | PHASE4 | COMPLETED | Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer |
| NCT00237146 | PHASE4 | COMPLETED | Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy |
| NCT00242554 | PHASE4 | COMPLETED | Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases |
| NCT00280098 | PHASE4 | COMPLETED | Docetaxel in the Treatment of Hormone Refractory Prostate Cancer |
| NCT00293696 | PHASE4 | COMPLETED | Casodex/Zoladex Biomarkers in Localised Prostate Cancer |
| NCT00334139 | PHASE4 | COMPLETED | Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer |
| NCT00375765 | PHASE4 | COMPLETED | Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer |
| NCT00391690 | PHASE4 | COMPLETED | Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer |
| NCT00422708 | PHASE4 | COMPLETED | Local Anesthesia for Prostate Biopsy |
| NCT00526331 | PHASE4 | COMPLETED | Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy |
| NCT00590213 | PHASE4 | COMPLETED | Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX |
| NCT00629330 | PHASE4 | TERMINATED | Dissemination of Prostate Cancer Screening to PCP’s in African American Communities |
| NCT00771966 | PHASE4 | COMPLETED | Radical Prostatectomy and Perioperative Fluid Therapy |
| NCT00805701 | PHASE4 | COMPLETED | Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation |
| NCT00859027 | PHASE4 | COMPLETED | Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer |
| NCT00906269 | PHASE4 | UNKNOWN | Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer |
| NCT00953277 | PHASE4 | COMPLETED | Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer |
| NCT00982800 | PHASE4 | COMPLETED | Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy? |
| NCT01083199 | PHASE4 | COMPLETED | Global Performance Evaluation of the AMS CONTINUUM™ Device |
| NCT01136226 | PHASE4 | COMPLETED | Evaluate Recovery of Testosterone for Patients Using Eligard |
| NCT01161563 | PHASE4 | COMPLETED | Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration |
| NCT01230905 | PHASE4 | COMPLETED | Study to Monitor the Effects of Androgen Suppression Treatment on the Heart |
| NCT01296672 | PHASE4 | COMPLETED | 3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer |
| NCT01365143 | PHASE4 | TERMINATED | Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy |
| NCT01379742 | PHASE4 | UNKNOWN | Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy |
| NCT01486563 | PHASE4 | COMPLETED | Hydroxyethyl Starch and Renal Function After Radical Prostatectomy |
| NCT01511874 | PHASE4 | COMPLETED | Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer |
| NCT01512472 | PHASE4 | TERMINATED | Firmagon (Degarelix) Intermittent Therapy |
| NCT01547416 | PHASE4 | COMPLETED | The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function |
| NCT01571544 | PHASE4 | COMPLETED | The Use of Thermal Suits as Preventing Hypothermia During Surgery |
| NCT01581749 | PHASE4 | UNKNOWN | Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer |
| NCT01649635 | PHASE4 | COMPLETED | Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer |
Related Atlas pages
- Associated diseases: congenital diarrhea
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): congenital diarrhea, diarrhea 14, congenital