WDR91
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Also known as HSPC049SORF-1
Summary
WDR91 (WD repeat domain 91, HGNC:24997) is a protein-coding gene on chromosome 7q33, encoding WD repeat-containing protein 91 (A4D1P6). Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex.
Enables phosphatidylinositol 3-kinase inhibitor activity. Involved in early endosome to late endosome transport and regulation of protein catabolic process. Located in cytosol; early endosome membrane; and late endosome membrane.
Source: NCBI Gene 29062 — RefSeq curated summary.
At a glance
- Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC)
- GWAS associations: 4
- Clinical variants (ClinVar): 80 total — 1 pathogenic, 2 likely-pathogenic
- Druggable target: yes
- MANE Select transcript:
NM_014149
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:24997 |
| Approved symbol | WDR91 |
| Name | WD repeat domain 91 |
| Location | 7q33 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | HSPC049, SORF-1 |
| Ensembl gene | ENSG00000105875 |
| Ensembl biotype | protein_coding |
| OMIM | 616303 |
| Entrez | 29062 |
Gene structure
Transcript identifiers
Ensembl transcripts: 25 — 11 retained_intron, 8 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined
ENST00000354475, ENST00000423565, ENST00000462707, ENST00000466182, ENST00000474411, ENST00000476775, ENST00000479698, ENST00000485942, ENST00000497853, ENST00000682160, ENST00000682250, ENST00000682339, ENST00000682534, ENST00000682759, ENST00000682802, ENST00000683628, ENST00000683848, ENST00000683947, ENST00000684322, ENST00000684339, ENST00000684486, ENST00000956716, ENST00000956717, ENST00000956718, ENST00000956719
RefSeq mRNA: 4 — MANE Select: NM_014149
NM_001362736, NM_001362737, NM_001362738, NM_014149
CCDS: CCDS34758
Canonical transcript exons
ENST00000354475 — 15 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001806523 | 135183839 | 135186315 |
| ENSE00003458865 | 135204268 | 135204433 |
| ENSE00003499037 | 135205928 | 135206058 |
| ENSE00003512649 | 135193578 | 135193672 |
| ENSE00003519624 | 135197993 | 135198151 |
| ENSE00003522554 | 135196144 | 135196337 |
| ENSE00003562847 | 135207120 | 135207202 |
| ENSE00003564829 | 135194934 | 135195084 |
| ENSE00003598904 | 135186972 | 135187169 |
| ENSE00003617687 | 135189344 | 135189452 |
| ENSE00003640565 | 135211380 | 135211526 |
| ENSE00003665157 | 135208791 | 135208998 |
| ENSE00003668190 | 135209576 | 135209755 |
| ENSE00003671111 | 135188433 | 135188545 |
| ENSE00003682915 | 135193231 | 135193399 |
Expression profiles
Bgee: expression breadth ubiquitous, 242 present calls, max score 97.26.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.2114 / max 316.5239, expressed in 1809 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 86355 | 17.1761 | 1809 |
| 86352 | 0.0277 | 6 |
| 86353 | 0.0076 | 4 |
Top tissues by expression
275 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| right uterine tube | UBERON:0001302 | 97.26 | gold quality |
| metanephros cortex | UBERON:0010533 | 95.85 | gold quality |
| body of pancreas | UBERON:0001150 | 94.23 | gold quality |
| left ovary | UBERON:0002119 | 92.87 | gold quality |
| right ovary | UBERON:0002118 | 92.76 | gold quality |
| right lung | UBERON:0002167 | 92.71 | gold quality |
| sural nerve | UBERON:0015488 | 91.79 | gold quality |
| esophagus mucosa | UBERON:0002469 | 91.58 | gold quality |
| mucosa of stomach | UBERON:0001199 | 91.48 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 90.44 | gold quality |
| tendon of biceps brachii | UBERON:0008188 | 90.19 | silver quality |
| esophagus | UBERON:0001043 | 90.07 | gold quality |
| descending thoracic aorta | UBERON:0002345 | 89.95 | gold quality |
| endocervix | UBERON:0000458 | 89.56 | gold quality |
| adult mammalian kidney | UBERON:0000082 | 89.52 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 89.48 | gold quality |
| tibial nerve | UBERON:0001323 | 89.45 | gold quality |
| ovary | UBERON:0000992 | 89.28 | gold quality |
| body of stomach | UBERON:0001161 | 89.20 | gold quality |
| upper lobe of lung | UBERON:0008948 | 89.20 | gold quality |
| skin of abdomen | UBERON:0001416 | 89.17 | gold quality |
| right coronary artery | UBERON:0001625 | 89.17 | gold quality |
| skin of leg | UBERON:0001511 | 88.99 | gold quality |
| ectocervix | UBERON:0012249 | 88.96 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 88.92 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 88.89 | gold quality |
| thoracic aorta | UBERON:0001515 | 88.79 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 88.79 | gold quality |
| minor salivary gland | UBERON:0001830 | 88.78 | gold quality |
| lower esophagus | UBERON:0013473 | 88.78 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 5.01 |
| E-MTAB-7303 | no | 158.69 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
69 targeting WDR91, 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-3924 | 100.00 | 72.09 | 2394 |
| HSA-MIR-5011-5P | 100.00 | 83.46 | 5820 |
| HSA-MIR-200B-3P | 100.00 | 73.31 | 2693 |
| HSA-MIR-200C-3P | 100.00 | 73.35 | 2685 |
| HSA-MIR-429 | 100.00 | 73.44 | 2698 |
| HSA-MIR-6127 | 100.00 | 66.76 | 2188 |
| HSA-MIR-3692-3P | 99.98 | 70.27 | 2139 |
| HSA-MIR-1229-3P | 99.97 | 66.49 | 906 |
| HSA-MIR-2110 | 99.96 | 66.68 | 1930 |
| HSA-MIR-4753-3P | 99.90 | 71.03 | 3786 |
| HSA-MIR-6739-5P | 99.80 | 67.87 | 2806 |
| HSA-MIR-6733-5P | 99.74 | 67.94 | 2759 |
| HSA-MIR-2116-3P | 99.74 | 64.32 | 889 |
| HSA-MIR-4306 | 99.72 | 70.50 | 3630 |
| HSA-MIR-1208 | 99.70 | 68.28 | 1533 |
| HSA-MIR-4530 | 99.69 | 66.47 | 1509 |
| HSA-MIR-670-5P | 99.67 | 69.94 | 1565 |
| HSA-MIR-6516-3P | 99.65 | 68.57 | 1238 |
| HSA-MIR-6832-5P | 99.58 | 64.82 | 1132 |
| HSA-MIR-3942-3P | 99.57 | 69.03 | 2854 |
| HSA-MIR-3153 | 99.55 | 67.59 | 2337 |
| HSA-MIR-4437 | 99.52 | 65.29 | 1266 |
| HSA-MIR-4441 | 99.49 | 66.56 | 3216 |
| HSA-MIR-143-3P | 99.49 | 69.05 | 1457 |
| HSA-MIR-4770 | 99.49 | 69.09 | 1451 |
| HSA-MIR-3182 | 99.40 | 68.15 | 2454 |
| HSA-MIR-185-5P | 99.35 | 68.60 | 2497 |
| HSA-MIR-4506 | 99.34 | 67.47 | 526 |
| HSA-MIR-130A-5P | 99.33 | 70.26 | 2623 |
| HSA-MIR-6088 | 99.29 | 68.45 | 1284 |
Literature-anchored findings (GeneRIF, showing 2)
- suggest a role for the WDR81-WDR91 complex in the fusion of endolysosomal compartments and the absence of WDR81 leads to impaired receptor trafficking and degradation (PMID:27126989)
- WDR91 serves as a Rab7 effector that is essential for neuronal development by facilitating endosome conversion in the endosome-lysosome pathway. (PMID:28860274)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | wdr91 | ENSDARG00000015153 |
| mus_musculus | Wdr91 | ENSMUSG00000058486 |
| rattus_norvegicus | Wdr91 | ENSRNOG00000010421 |
| drosophila_melanogaster | CG6005 | FBGN0038672 |
| caenorhabditis_elegans | WBGENE00022769 |
Protein
Protein identifiers
WD repeat-containing protein 91 — A4D1P6 (reviewed: A4D1P6)
All UniProt accessions (6): A4D1P6, A0A804HHS8, A0A804HI90, A0A804HJP3, A0A804HKV2, C9J1X0
UniProt curated annotations — full annotation on UniProt →
Function. Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes via BECN1, a core subunit of the PI3K complex. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport. It is for instance, required for the delivery of cargos like BST2/tetherin from early to late endosome and thereby participates indirectly to their degradation by the lysosome. May play a role in meiosis.
Subunit / interactions. Interacts with WDR81; involved in early to late endosome cargo transport. Interacts with BECN1; negatively regulates the PI3 kinase/PI3K activity associated with endosomal membranes.
Subcellular location. Early endosome membrane. Late endosome membrane.
Similarity. Belongs to the WD repeat WDR91 family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| A4D1P6-1 | 1 | yes |
| A4D1P6-2 | 2 | |
| A4D1P6-3 | 3 |
RefSeq proteins (4): NP_001349665, NP_001349666, NP_001349667, NP_054868* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001680 | WD40_rpt | Repeat |
| IPR015943 | WD40/YVTN_repeat-like_dom_sf | Homologous_superfamily |
| IPR036322 | WD40_repeat_dom_sf | Homologous_superfamily |
| IPR039724 | WDR91 | Family |
| IPR056327 | ARMC9_CTLH-like_dom | Domain |
Pfam: PF00400, PF23138
UniProt features (64 total): strand 36, repeat 7, splice variant 4, sequence conflict 4, modified residue 3, turn 3, compositionally biased region 2, chain 1, sequence variant 1, helix 1, region of interest 1, coiled-coil region 1
Structure
Experimental structures (PDB)
10 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 8KB9 | X-RAY DIFFRACTION | 1.9 |
| 6VYC | X-RAY DIFFRACTION | 2.1 |
| 9DTA | X-RAY DIFFRACTION | 2.1 |
| 8T55 | X-RAY DIFFRACTION | 2.2 |
| 8SHJ | X-RAY DIFFRACTION | 2.21 |
| 9EJP | X-RAY DIFFRACTION | 2.22 |
| 9DTB | X-RAY DIFFRACTION | 2.31 |
| 9MK7 | X-RAY DIFFRACTION | 2.31 |
| 9EJO | X-RAY DIFFRACTION | 2.4 |
| 8KB8 | X-RAY DIFFRACTION | 2.49 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-A4D1P6-F1 | 75.01 | 0.39 |
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 (3): 256, 288, 293
Function
Pathways and Gene Ontology
Reactome pathways
1 pathways
| ID | Pathway |
|---|---|
| R-HSA-9013148 | CDC42 GTPase cycle |
MSigDB gene sets: 121 (showing top):
GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT_BETWEEN_ENDOSOMAL_COMPARTMENTS, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, GOBP_PROTEIN_CATABOLIC_PROCESS, KONDO_PROSTATE_CANCER_HCP_WITH_H3K27ME3, GOCC_LATE_ENDOSOME_MEMBRANE, GOCC_EARLY_ENDOSOME_MEMBRANE, GOBP_PROTEOLYSIS, GOMF_ENZYME_REGULATOR_ACTIVITY
GO Biological Process (3): regulation of protein catabolic process (GO:0042176), early endosome to late endosome transport (GO:0045022), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898)
GO Molecular Function (3): phosphatidylinositol 3-kinase regulator activity (GO:0035014), phosphatidylinositol 3-kinase inhibitor activity (GO:0141039), protein binding (GO:0005515)
GO Cellular Component (8): cytosol (GO:0005829), endosome membrane (GO:0010008), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), endosome (GO:0005768), early endosome (GO:0005769), late endosome (GO:0005770), membrane (GO:0016020)
Reactome top-level categories
Rollup of top-1 pathways:
| Category | Pathways |
|---|---|
| RHO GTPase cycle | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| endosome | 3 |
| cytoplasm | 2 |
| cellular anatomical structure | 2 |
| endosome membrane | 2 |
| regulation of catabolic process | 1 |
| protein catabolic process | 1 |
| regulation of protein metabolic process | 1 |
| vesicle-mediated transport between endosomal compartments | 1 |
| phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1 |
| regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1 |
| negative regulation of intracellular signal transduction | 1 |
| kinase regulator activity | 1 |
| phosphatidylinositol 3-kinase catalytic subunit binding | 1 |
| phosphatidylinositol 3-kinase regulator activity | 1 |
| binding | 1 |
| cytoplasmic vesicle membrane | 1 |
| bounding membrane of organelle | 1 |
| early endosome | 1 |
| late endosome | 1 |
| endomembrane system | 1 |
| cytoplasmic vesicle | 1 |
Protein interactions and networks
STRING
610 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| WDR91 | WDR81 | Q562E7 | 916 |
| WDR91 | PIK3C3 | Q8NEB9 | 624 |
| WDR91 | CCZ1B | P86790 | 593 |
| WDR91 | VPS18 | Q9P253 | 549 |
| WDR91 | BECN1 | Q14457 | 532 |
| WDR91 | MON1A | Q86VX9 | 498 |
| WDR91 | CCDC93 | Q567U6 | 472 |
| WDR91 | RMC1 | Q96DM3 | 447 |
| WDR91 | PRRC2B | Q5JSZ5 | 444 |
| WDR91 | CCDC22 | O60826 | 439 |
| WDR91 | ASCC3 | Q8N3C0 | 422 |
| WDR91 | MFSD12 | Q6NUT3 | 421 |
| WDR91 | RAB7A | P51149 | 411 |
| WDR91 | PIKFYVE | Q9Y2I7 | 408 |
| WDR91 | MTMR10 | Q9NXD2 | 401 |
IntAct
43 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| WDR91 | HTT | psi-mi:“MI:0915”(physical association) | 0.670 |
| HTT | WDR91 | psi-mi:“MI:0915”(physical association) | 0.670 |
| RAB8A | WDR91 | psi-mi:“MI:0914”(association) | 0.600 |
| WDR81 | WDR91 | psi-mi:“MI:0915”(physical association) | 0.590 |
| WDR91 | WDR81 | psi-mi:“MI:0915”(physical association) | 0.590 |
| NAPA | NBAS | psi-mi:“MI:0914”(association) | 0.530 |
| WDR91 | bec-1 | psi-mi:“MI:0915”(physical association) | 0.400 |
| NUDC | WDR91 | psi-mi:“MI:0915”(physical association) | 0.400 |
| Xpo1 | IFT56 | psi-mi:“MI:0914”(association) | 0.350 |
| PRNP | WDR91 | psi-mi:“MI:0914”(association) | 0.350 |
| LRRK2 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (41): WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-MS), WDR91 (Affinity Capture-RNA), WDR91 (Affinity Capture-Western), WDR91 (Co-localization), WDR91 (Affinity Capture-RNA)
ESM2 similar proteins: A0A0G2KIZ8, A0A1L8GXY4, A0A571BF63, A0A8M9QN10, A2CEI4, A2RRP1, A4D1P6, A6H8T2, A9X1C6, B0FXQ5, B1WC10, B2KIQ4, B2RY71, B2RYI0, B7FF09, B7FF12, E9PYY5, F1QHZ6, Q1LXZ7, Q2HJE1, Q3UMY5, Q402B2, Q4V8G4, Q5R6T6, Q5RE88, Q5U1Z0, Q5VTH9, Q5XIZ9, Q5ZLL7, Q6DFC6, Q6DTM3, Q6GPB9, Q6P2C0, Q6TEN6, Q7TMQ7, Q7ZVR1, Q8BMG7, Q8BX17, Q8C147, Q8IWG1
Diamond homologs: A4D1P6, B2RYI0, Q05B30, Q23533, Q2HJE1, Q5R6T6, Q5ZLL7, Q6TEN6, Q7TMQ7, Q5F3D7, Q9HCU5, Q9WTV0, Q9WUQ2, Q55FJ2, Q68FJ6, B6GZD3, C4JZS6, F1DLK1, O74340, P33750, P87314, Q0D0X6, Q26458, Q4ICM0, Q4P4R3, Q5R4T8, Q5ZKU8, Q5ZLK1, Q6NVS5, Q6PAC3, Q6TNS2, Q7KWL3, Q7ZYQ6, Q803X4, Q9NV06, Q54PE0, A0CH87, A0DB19, A1CF18, A1CQI9
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
80 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 1 |
| Likely pathogenic | 2 |
| Uncertain significance | 58 |
| Likely benign | 6 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (3)
| Variant ID | HGVS | Classification |
|---|---|---|
| 2502091 | NM_014149.4(WDR91):c.1768+1G>A | Pathogenic |
| 2430172 | NM_014149.4(WDR91):c.511+1A>G | Likely pathogenic |
| 3064663 | NM_014149.4(WDR91):c.1000C>T (p.Gln334Ter) | Likely pathogenic |
SpliceAI
3226 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 7:135186311:CCCAG:C | acceptor_gain | 1.0000 |
| 7:135186312:CCAG:C | acceptor_gain | 1.0000 |
| 7:135186312:CCAGC:C | acceptor_gain | 1.0000 |
| 7:135186313:CAG:C | acceptor_gain | 1.0000 |
| 7:135186313:CAGC:C | acceptor_gain | 1.0000 |
| 7:135186314:AG:A | acceptor_gain | 1.0000 |
| 7:135186315:GC:G | acceptor_loss | 1.0000 |
| 7:135186316:C:CC | acceptor_gain | 1.0000 |
| 7:135186316:C:CG | acceptor_loss | 1.0000 |
| 7:135186967:GTTAC:G | donor_loss | 1.0000 |
| 7:135186968:TTAC:T | donor_loss | 1.0000 |
| 7:135186969:TACC:T | donor_loss | 1.0000 |
| 7:135186970:A:C | donor_loss | 1.0000 |
| 7:135189342:A:AC | donor_gain | 1.0000 |
| 7:135189343:C:CC | donor_gain | 1.0000 |
| 7:135189448:TGGAG:T | acceptor_gain | 1.0000 |
| 7:135189450:GAGC:G | acceptor_loss | 1.0000 |
| 7:135189453:C:CA | acceptor_loss | 1.0000 |
| 7:135189453:C:CC | acceptor_gain | 1.0000 |
| 7:135189456:T:TC | acceptor_gain | 1.0000 |
| 7:135193225:CCGTA:C | donor_loss | 1.0000 |
| 7:135193226:CGTAC:C | donor_loss | 1.0000 |
| 7:135193227:GTAC:G | donor_loss | 1.0000 |
| 7:135193228:TA:T | donor_loss | 1.0000 |
| 7:135193230:CCTG:C | donor_gain | 1.0000 |
| 7:135193670:GAG:G | acceptor_gain | 1.0000 |
| 7:135194928:ACT:A | donor_loss | 1.0000 |
| 7:135194929:CTC:C | donor_loss | 1.0000 |
| 7:135194930:TCA:T | donor_loss | 1.0000 |
| 7:135194931:CA:C | donor_loss | 1.0000 |
AlphaMissense
4896 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 7:135186203:G:T | A731D | 1.000 |
| 7:135186240:A:G | W719R | 1.000 |
| 7:135186240:A:T | W719R | 1.000 |
| 7:135188451:G:C | S621R | 1.000 |
| 7:135188451:G:T | S621R | 1.000 |
| 7:135188453:T:G | S621R | 1.000 |
| 7:135189385:A:G | L576P | 1.000 |
| 7:135194955:C:A | W458C | 1.000 |
| 7:135194955:C:G | W458C | 1.000 |
| 7:135194957:A:G | W458R | 1.000 |
| 7:135194957:A:T | W458R | 1.000 |
| 7:135195026:A:G | W435R | 1.000 |
| 7:135195026:A:T | W435R | 1.000 |
| 7:135195054:G:C | S425R | 1.000 |
| 7:135195054:G:T | S425R | 1.000 |
| 7:135195056:T:G | S425R | 1.000 |
| 7:135195058:G:T | A424D | 1.000 |
| 7:135208920:A:G | W128R | 1.000 |
| 7:135208920:A:T | W128R | 1.000 |
| 7:135208929:A:G | W125R | 1.000 |
| 7:135208929:A:T | W125R | 1.000 |
| 7:135186191:C:A | G735V | 0.999 |
| 7:135186191:C:T | G735D | 0.999 |
| 7:135186201:A:G | S732P | 0.999 |
| 7:135186204:C:G | A731P | 0.999 |
| 7:135187006:A:G | L682P | 0.999 |
| 7:135187160:A:G | W631R | 0.999 |
| 7:135187160:A:T | W631R | 0.999 |
| 7:135189352:C:G | R587P | 0.999 |
| 7:135189373:C:T | G580E | 0.999 |
dbSNP variants (sampled 300 via entrez): RS1000006460 (7:135191697 C>A,T), RS1000209767 (7:135188466 C>T), RS1000243621 (7:135208095 G>A), RS1000447724 (7:135186743 C>T), RS1000453269 (7:135196619 G>T), RS1000619778 (7:135200738 G>A,C), RS1000704804 (7:135195616 T>C), RS1000762574 (7:135183842 G>A,T), RS1000827453 (7:135200259 A>G), RS1000862461 (7:135186420 C>T), RS1000899664 (7:135184118 A>G), RS1001255177 (7:135186098 C>T), RS1001490227 (7:135207964 C>A,T), RS1001605880 (7:135200135 G>A), RS1001681545 (7:135192927 G>A,C,T)
Disease associations
OMIM: gene MIM:616303 | disease phenotypes:
GenCC curated gene-disease
| Disease | Classification | Inheritance |
|---|---|---|
| complex neurodevelopmental disorder | Strong | Autosomal recessive |
Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
4 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST90011898_147 | Alanine aminotransferase levels | 2.000000e-10 |
| GCST90011899_93 | Aspartate aminotransferase levels | 6.000000e-14 |
| GCST90013663_27 | Alanine aminotransferase levels | 1.000000e-13 |
| GCST90013664_78 | Aspartate aminotransferase levels | 7.000000e-15 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0004736 | aspartate aminotransferase measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5465256 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
ChEMBL bioactivities
4 potent at pChembl≥5 of 18 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 5.22 | Kd | 6000 | nM | CHEMBL5416881 |
| 5.22 | Kd | 6000 | nM | CHEMBL5423537 |
| 5.10 | Kd | 8000 | nM | CHEMBL5431441 |
| 5.10 | Kd | 8000 | nM | CHEMBL5424848 |
PubChem BioAssay actives
4 with measured affinity, of 31 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| N-[3-(4-chlorophenyl)oxetan-3-yl]-4-(4-hydroxypiperidin-1-yl)benzamide | 2023202: Binding affinity to C-terminal His6-tagged truncated WDR91 (unknown origin) (P392 to A747 residues) expressed in baculovirus-infected Sf9 cells assessed as dissociation constant incubated for 72 to 96 hrs by SPR analysis | kd | 6.0000 | uM |
| N-[3-(4-chlorophenyl)oxetan-3-yl]-4-(3-hydroxypyrrolidin-1-yl)benzamide | 2023202: Binding affinity to C-terminal His6-tagged truncated WDR91 (unknown origin) (P392 to A747 residues) expressed in baculovirus-infected Sf9 cells assessed as dissociation constant incubated for 72 to 96 hrs by SPR analysis | kd | 6.0000 | uM |
| N-[3-(4-chlorophenyl)oxetan-3-yl]-6-methyl-5,7-dihydro-4H-thieno[2,3-c]pyridine-2-carboxamide | 2023202: Binding affinity to C-terminal His6-tagged truncated WDR91 (unknown origin) (P392 to A747 residues) expressed in baculovirus-infected Sf9 cells assessed as dissociation constant incubated for 72 to 96 hrs by SPR analysis | kd | 8.0000 | uM |
| N-[3-(4-chlorophenyl)oxetan-3-yl]-5-(1H-pyrazol-5-yl)thiophene-2-carboxamide | 2023202: Binding affinity to C-terminal His6-tagged truncated WDR91 (unknown origin) (P392 to A747 residues) expressed in baculovirus-infected Sf9 cells assessed as dissociation constant incubated for 72 to 96 hrs by SPR analysis | kd | 8.0000 | uM |
CTD chemical–gene interactions
21 total (human), top 21 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| bisphenol A | decreases expression | 2 |
| 3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide | decreases expression | 1 |
| GSK-J4 | decreases expression | 1 |
| FR900359 | increases phosphorylation | 1 |
| 2,4,6-tribromophenol | increases expression | 1 |
| triphenyl phosphate | affects expression | 1 |
| decabromobiphenyl ether | increases expression | 1 |
| tetrabromobisphenol A | increases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| abrine | increases expression | 1 |
| 2,2’,4,4’-tetrabromodiphenyl ether | decreases expression | 1 |
| pentabrominated diphenyl ether 100 | increases expression | 1 |
| hexabrominated diphenyl ether 153 | increases expression | 1 |
| Benzene | increases expression | 1 |
| Cisplatin | increases expression | 1 |
| Estradiol | affects cotreatment, increases expression | 1 |
| Ivermectin | decreases expression | 1 |
| Progesterone | affects response to substance | 1 |
| Thiram | decreases expression | 1 |
| Tobacco Smoke Pollution | decreases expression | 1 |
| Cadmium Chloride | decreases expression | 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 |
|---|---|---|---|
| CHEMBL5377212 | Binding | Binding affinity to C-terminal His6-tagged truncated WDR91 (unknown origin) (P392 to A747 residues) expressed in baculovirus-infected Sf9 cells assessed as dissociation constant incubated for 72 to 96 hrs by SPR analysis | Discovery of a First-in-Class Small-Molecule Ligand for WDR91 Using DNA-Encoded Chemical Library Selection Followed by Machine Learning. — J Med Chem |
Cellosaurus cell lines
2 cell lines: 2 cancer cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_TX96 | HAP1 WDR91 (-) 1 | Cancer cell line | Male |
| CVCL_XV09 | HAP1 WDR91 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
2 trials via MONDO — disease-level, not drug-specific.
| Trial | Phase | Status | Title |
|---|---|---|---|
| NCT06310681 | Not specified | COMPLETED | Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability |
| NCT07303049 | Not specified | NOT_YET_RECRUITING | Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder |
Related Atlas pages
- Associated diseases: complex neurodevelopmental disorder
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): complex neurodevelopmental disorder