WDR26

Summary

WDR26 (WD repeat domain 26, HGNC:21208) is a protein-coding gene on chromosome 1q42.11-q42.12, encoding WD repeat-containing protein 26 (Q9H7D7). G-beta-like protein involved in cell signal transduction. It is a selective cancer dependency (DepMap: 48.9% of cell lines) and haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Two transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 80232 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Skraban-Deardorff syndrome (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 280 total — 42 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 95
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 48.9% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001379403

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21208
Approved symbol	WDR26
Name	WD repeat domain 26
Location	1q42.11-q42.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21016, GID7
Ensembl gene	ENSG00000162923
Ensembl biotype	protein_coding
OMIM	617424
Entrez	80232

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000414423, ENST00000443112, ENST00000445239, ENST00000477425, ENST00000479727, ENST00000479778, ENST00000480676, ENST00000486652, ENST00000489825, ENST00000651911, ENST00000678307, ENST00000678555, ENST00000678879, ENST00000678917, ENST00000704632, ENST00000704640

RefSeq mRNA: 3 — MANE Select: NM_001379403 NM_001115113, NM_001379403, NM_025160

CCDS: CCDS31037, CCDS91162

Canonical transcript exons

ENST00000414423 — 14 exons

Exon	Start	End
ENSE00001849884	224385146	224389860
ENSE00003462147	224400950	224401069
ENSE00003472596	224431682	224431781
ENSE00003475540	224419518	224419615
ENSE00003477391	224398515	224398593
ENSE00003505752	224418260	224418416
ENSE00003506821	224398889	224399034
ENSE00003509193	224431477	224431581
ENSE00003527274	224411427	224411565
ENSE00003559799	224398097	224398226
ENSE00003579469	224393828	224394013
ENSE00003645199	224404430	224404570
ENSE00003647579	224424518	224424654
ENSE00003687371	224433684	224434797

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.8546 / max 920.3541, expressed in 1825 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17682	53.4334	1825
17681	0.1723	50
17680	0.1217	33
17679	0.1183	23
17683	0.0088	3

Top tissues by expression

288 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.78	gold quality
secondary oocyte	CL:0000655	98.53	gold quality
tongue squamous epithelium	UBERON:0006919	98.51	gold quality
male germ cell	CL:0000015	98.20	gold quality
esophagus squamous epithelium	UBERON:0006920	98.13	gold quality
epithelium of esophagus	UBERON:0001976	97.94	gold quality
oocyte	CL:0000023	97.65	gold quality
lower esophagus mucosa	UBERON:0035834	97.31	gold quality
pharyngeal mucosa	UBERON:0000355	96.78	gold quality
colonic epithelium	UBERON:0000397	96.77	gold quality
bone marrow cell	CL:0002092	96.71	gold quality
stromal cell of endometrium	CL:0002255	96.58	gold quality
bone marrow	UBERON:0002371	96.52	gold quality
trabecular bone tissue	UBERON:0002483	96.37	gold quality
oral cavity	UBERON:0000167	96.35	gold quality
squamous epithelium	UBERON:0006914	96.24	gold quality
adrenal tissue	UBERON:0018303	96.16	gold quality
upper leg skin	UBERON:0004262	96.05	gold quality
amniotic fluid	UBERON:0000173	96.03	gold quality
skin of leg	UBERON:0001511	95.81	gold quality
monocyte	CL:0000576	95.67	gold quality
mononuclear cell	CL:0000842	95.66	gold quality
tonsil	UBERON:0002372	95.60	gold quality
esophagus mucosa	UBERON:0002469	95.59	gold quality
leukocyte	CL:0000738	95.58	gold quality
zone of skin	UBERON:0000014	95.49	gold quality
blood	UBERON:0000178	95.48	gold quality
cartilage tissue	UBERON:0002418	95.43	gold quality
skin of abdomen	UBERON:0001416	95.35	gold quality
right lung	UBERON:0002167	95.30	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

309 targeting WDR26, 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-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4775	99.98	75.00	6394

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 48.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 17)

• WDR26 may act as a negative regulator in MAPK signaling pathway and play an important role in cell signal transduction. (PMID:15378603)
• The results of this study indicated that WDR26 was up-regulated by oxidative stress and played a key role in H2O2-induced SH-SY5Y cell death, which may be mediated by the down-regulation of AP-1 transcriptional activity. (PMID:19446606)
• these data suggest that MIP2 may participate in the progression of cell proliferation in H9c2 cells. (PMID:20171191)
• WDR26 is a novel Gbetagamma-binding protein that is required for the efficacy of Gbetagamma signaling and leukocyte migration (PMID:22065575)
• WDR26 functions as a scaffolding protein to promote PLCbeta2 membrane translocation and interaction with Gbetagamma, thereby enhancing PLCbeta2 activation in leukocytes. (PMID:23625927)
• The WDR26 gene was differentially methylated in monozygotic twins discordant for depressive disorder. (PMID:25918994)
• WDR26 serves as a scaffold that fosters assembly of a specific signaling complex consisting of Gbetagamma, PI3Kbeta and AKT2 in breast cancer. (PMID:26895380)
• WDR26 affected beta-catenin levels. WDR26/Axin binding is involved in the ubiquitination of beta-catenin. (PMID:27098453)
• It has been shown that WDR26 promotes Rac1 membrane translocation following a Coro1A-like and Coro1A-dependent mechanism. (PMID:27835684)
• haploinsufficiency of WDR26 contributes to the pathology of 1q41q42 microdeletion syndrome. (PMID:28686853)
• WD40 Repeat Protein 26 Negatively Regulates Formyl Peptide Receptor-1 Mediated Wound Healing in Intestinal Epithelial Cells. (PMID:32958140)
• Skraban-Deardorff syndrome: Six new cases of WDR26-related disease and expansion of the clinical phenotype. (PMID:33506510)
• Expanding the clinical phenotype of the ultra-rare Skraban-Deardorff syndrome: Two novel individuals with WDR26 loss-of-function variants and a literature review. (PMID:33675273)
• GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme. (PMID:33905682)
• Two Novel Variants of WDR26 in Chinese Patients with Intellectual Disability. (PMID:35627197)
• Skraban-Deardorff intellectual disability syndrome-associated mutations in WDR26 impair CTLH E3 complex assembly. (PMID:38575527)
• Non-canonical substrate recognition by the human WDR26-CTLH E3 ligase regulates prodrug metabolism. (PMID:38759627)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr26b	ENSDARG00000006812
danio_rerio	wdr26a	ENSDARG00000062310
mus_musculus	Wdr26	ENSMUSG00000038733
rattus_norvegicus	Wdr26	ENSRNOG00000003723
drosophila_melanogaster	CG7611	FBGN0037094

Paralogs (1): WDR13 (ENSG00000101940)

Protein

Protein identifiers

WD repeat-containing protein 26 — Q9H7D7 (reviewed: Q9H7D7)

Alternative names: CUL4- and DDB1-associated WDR protein 2, Myocardial ischemic preconditioning up-regulated protein 2

All UniProt accessions (11): A0A499FIZ0, A0A7I2V3I7, A0A7I2YQL3, A0A7I2YQQ9, A0A7P0SXD0, A0A994J579, A0A994J7J9, C9JCS7, Q9H7D7, H0Y917, H0Y9R3

UniProt curated annotations — full annotation on UniProt →

Function. G-beta-like protein involved in cell signal transduction. Acts as a negative regulator in MAPK signaling pathway. Functions as a scaffolding protein to promote G beta:gamma-mediated PLCB2 plasma membrane translocation and subsequent activation in leukocytes. Core component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1. Acts as a negative regulator of the canonical Wnt signaling pathway through preventing ubiquitination of beta-catenin CTNNB1 by the beta-catenin destruction complex, thus negatively regulating CTNNB1 degradation. Serves as a scaffold to coordinate PI3K/AKT pathway-driven cell growth and migration. Protects cells from oxidative stress-induced apoptosis via the down-regulation of AP-1 transcriptional activity as well as by inhibiting cytochrome c release from mitochondria. Also protects cells by promoting hypoxia-mediated autophagy and mitophagy.

Subunit / interactions. Forms homooligomers. Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5. Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles. Interacts with DDB1-CUL4A/B E3 ligase complexes. Forms a complex composed of at least WDR26, a G-beta:gamma unit, and PLCB2. Interacts with AXIN1.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion.

Tissue specificity. Broadly expressed, with highest levels in heart and skeletal muscle.

Disease relevance. Skraban-Deardorff syndrome (SKDEAS) [MIM:617616] An autosomal dominant syndrome characterized by psychomotor developmental delay, intellectual disability with delayed speech, febrile and non-febrile seizures, abnormal gait, and facial dysmorphism. Facial features include a prominent maxilla and upper lip that readily reveal the upper gingiva, widely spaced teeth, and a broad nasal tip. The disease is caused by variants affecting the gene represented in this entry.

Induction. Expression is significantly up-regulated by oxidative stress.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9H7D7-1	1	yes
Q9H7D7-2	2
Q9H7D7-3	3
Q9H7D7-4	4

RefSeq proteins (3): NP_001108585, NP_001366332, NP_079436 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR006594	LisH	Conserved_site
IPR006595	CTLH_C	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR051350	WD_repeat-ST_regulator	Family
IPR054532	TPL_SMU1_LisH-like	Domain

Pfam: PF00400, PF17814

UniProt features (68 total): strand 29, sequence variant 9, repeat 6, splice variant 5, helix 4, turn 4, compositionally biased region 3, domain 2, region of interest 2, modified residue 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8QBN	ELECTRON MICROSCOPY	3.2
9RSD	ELECTRON MICROSCOPY	3.38
9RSC	ELECTRON MICROSCOPY	3.42
8QE8	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H7D7-F1	81.30	0.57

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 (2): 121, 123

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9861718	Regulation of pyruvate metabolism

MSigDB gene sets: 511 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_MATURE_CELL, CTATGCA_MIR153, CAGCAGG_MIR370, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, ATTACAT_MIR3803P, TATCTGG_MIR488, GUO_HEX_TARGETS_UP, TCCAGAT_MIR5165P, ACTTTAT_MIR1425P, BOYAULT_LIVER_CANCER_SUBCLASS_G12_UP, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, ACEVEDO_LIVER_CANCER_UP, GTGACTT_MIR224

GO Biological Process (1): proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): ubiquitin ligase complex (GO:0000151), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), GID complex (GO:0034657)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Pyruvate metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membrane-bounded organelle	2
cytoplasm	2
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
nuclear lumen	1
intracellular anatomical structure	1
ubiquitin ligase complex	1

Protein interactions and networks

STRING

1558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR26	RMND5A	Q9H871	947
WDR26	ARMC8	Q8IUR7	932
WDR26	GID8	Q9NWU2	923
WDR26	GID4	Q8IVV7	898
WDR26	MKLN1	Q9UL63	840
WDR26	RMND5B	Q96G75	836
WDR26	MAEA	Q7L5Y9	799
WDR26	RANBP10	Q6VN20	783
WDR26	YPEL5	P62699	760
WDR26	RANBP9	Q96S59	716
WDR26	UBE2H	P37286	586
WDR26	NOLC1	Q14978	531
WDR26	AXIN1	O15169	496
WDR26	SIX3	O95343	493
WDR26	YPEL1	O60688	480

IntAct

173 interactions, top by confidence:

A	B	Type	Score
BAIAP2	YWHAZ	psi-mi:“MI:0914”(association)	0.800
ARMC8	HTRA2	psi-mi:“MI:0914”(association)	0.750
CUL4B	CUL4A	psi-mi:“MI:0914”(association)	0.730
WDR26	AXIN1	psi-mi:“MI:0915”(physical association)	0.640
GID8	PGRMC2	psi-mi:“MI:0914”(association)	0.640
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
RANBP10	MAEA	psi-mi:“MI:0914”(association)	0.640
RANBP9	YPEL5	psi-mi:“MI:0914”(association)	0.640
CRIPTO	AIP	psi-mi:“MI:0914”(association)	0.640
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
NDUFS6	NDUFS8	psi-mi:“MI:0914”(association)	0.640
PRG2	YPEL5	psi-mi:“MI:0914”(association)	0.640
GID8	HTRA2	psi-mi:“MI:0914”(association)	0.610
SKI	WDR26	psi-mi:“MI:0915”(physical association)	0.560
FAF2	PJA2	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
INSL6	POTEF	psi-mi:“MI:0914”(association)	0.530
JPH4	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
TIGD5	P4HA2	psi-mi:“MI:0914”(association)	0.530
MAGEA1	MAGEB3	psi-mi:“MI:0914”(association)	0.530
EMILIN3	ZZEF1	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	SIAH2	psi-mi:“MI:0914”(association)	0.530
CBFA2T3	CBFA2T2	psi-mi:“MI:0914”(association)	0.530
BMP1	TLL1	psi-mi:“MI:0914”(association)	0.530

BioGRID (544): WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Co-fractionation), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), WDR26 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QFQ6, A0A2R8RWN9, D3Z7P3, E9PV86, G3MWR8, O54865, O60907, O89050, O94925, P13264, P16068, P20595, P58058, Q02153, Q08211, Q12800, Q13042, Q14722, Q28141, Q28D01, Q3MHJ2, Q3ULA2, Q4R8H1, Q4ZHR9, Q5R874, Q5RB35, Q5SP67, Q5SRY7, Q5ZHN3, Q6DN14, Q7RTP6, Q7T2U9, Q7Z6J6, Q8BTG7, Q8C6G8, Q8CJ19, Q8K4Q0, Q8N122, Q8N2K0, Q8R349

Diamond homologs: A1CQL6, A1D3I2, A2QPW4, A3LVM1, A5DHD2, A5DXE2, A5E2R6, A6RT32, A6ZYM0, A7RWD2, A7TLU2, A8PWQ8, B0XAF3, B0XQ15, B3RNR8, B6H7A3, B6K1G6, B7QKS1, B8MWR8, B9WHJ2, C1BK83, D4AZ50, D4DG66, F1LTR1, O17468, O42611, O80990, P0CS30, P0CS31, P54198, P79987, Q05583, Q0CCS0, Q0USG2, Q17GR9, Q1DR81, Q2UG43, Q2UPI0, Q4ICM0, Q4P5F5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
Regulation of pyruvate metabolism	9	36.2×	7e-10
Pyruvate metabolism	5	14.4×	7e-03
Deactivation of the beta-catenin transactivating complex	6	9.8×	7e-03
Aerobic respiration and respiratory electron transport	9	5.6×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
proteasome-mediated ubiquitin-dependent protein catabolic process	21	6.0×	7e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

280 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	18
Uncertain significance	155
Likely benign	32
Benign	7

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1034092	NM_001379403.1(WDR26):c.1319+1G>A	Pathogenic
1319614	NM_001379403.1(WDR26):c.1113G>A (p.Trp371Ter)	Pathogenic
1325817	NM_001379403.1(WDR26):c.390_412del (p.Leu132fs)	Pathogenic
1679406	NM_001379403.1(WDR26):c.1822C>T (p.Arg608Ter)	Pathogenic
1686300	NM_001379403.1(WDR26):c.773_776del (p.Pro258fs)	Pathogenic
1686301	NM_001379403.1(WDR26):c.492dup (p.Ser165fs)	Pathogenic
1686302	NM_001379403.1(WDR26):c.365del (p.Gly122fs)	Pathogenic
1698772	NM_001379403.1(WDR26):c.1498del (p.His500fs)	Pathogenic
1712271	NM_001379403.1(WDR26):c.834_838del (p.Asp278fs)	Pathogenic
1802591	NM_001379403.1(WDR26):c.1376G>A (p.Trp459Ter)	Pathogenic
2228077	NM_001379403.1(WDR26):c.1193del (p.Pro398fs)	Pathogenic
2297832	NM_001379403.1(WDR26):c.1776G>A (p.Trp592Ter)	Pathogenic
2635151	NM_001379403.1(WDR26):c.1204C>T (p.Gln402Ter)	Pathogenic
3027209	NM_001379403.1(WDR26):c.1354dup (p.Thr452fs)	Pathogenic
3062076	NM_001379403.1(WDR26):c.1039dup (p.Thr347fs)	Pathogenic
3068439	Single allele	Pathogenic
3189916	NM_001379403.1(WDR26):c.1849del (p.Thr618fs)	Pathogenic
3337742	NM_001379403.1(WDR26):c.1777del (p.Cys593fs)	Pathogenic
3772687	NM_001379403.1(WDR26):c.1944+5G>A	Pathogenic
433006	NM_001379403.1(WDR26):c.1576G>T (p.Glu526Ter)	Pathogenic
433007	NM_001379403.1(WDR26):c.1461_1462del (p.His489fs)	Pathogenic
433008	NM_001379403.1(WDR26):c.1757del (p.Val586fs)	Pathogenic
433009	NM_001379403.1(WDR26):c.1204_1205del (p.Gln402fs)	Pathogenic
433010	NM_001379403.1(WDR26):c.1150G>A (p.Asp384Asn)	Pathogenic
433011	NM_001379403.1(WDR26):c.1062T>G (p.Ser354Arg)	Pathogenic
452733	NM_001379403.1(WDR26):c.356del (p.Gly119fs)	Pathogenic
4531391	NM_001379403.1(WDR26):c.807_810del (p.Gly270fs)	Pathogenic
4814222	NM_001379403.1(WDR26):c.2093G>A (p.Trp698Ter)	Pathogenic
488458	NM_001379403.1(WDR26):c.373_374insA (p.Gly125fs)	Pathogenic
504158	NM_001379403.1(WDR26):c.627del (p.Glu209fs)	Pathogenic

SpliceAI

2250 predictions. Top by Δscore:

Variant	Effect	Δscore
1:224398592:CT:C	acceptor_gain	1.0000
1:224398594:C:CC	acceptor_gain	1.0000
1:224398601:C:CT	acceptor_gain	1.0000
1:224398887:A:AC	donor_gain	1.0000
1:224398888:C:CC	donor_gain	1.0000
1:224398893:T:A	donor_gain	1.0000
1:224398898:T:C	donor_gain	1.0000
1:224400944:ACTT:A	donor_loss	1.0000
1:224400945:CTTAC:C	donor_loss	1.0000
1:224400946:TT:T	donor_loss	1.0000
1:224400948:A:AC	donor_gain	1.0000
1:224400948:A:C	donor_loss	1.0000
1:224400949:C:CA	donor_gain	1.0000
1:224400949:CA:C	donor_gain	1.0000
1:224400949:CACA:C	donor_gain	1.0000
1:224401067:TGT:T	acceptor_gain	1.0000
1:224401068:GT:G	acceptor_gain	1.0000
1:224401070:C:CC	acceptor_gain	1.0000
1:224404399:AAAAG:A	donor_gain	1.0000
1:224404400:A:C	donor_gain	1.0000
1:224404428:A:AC	donor_gain	1.0000
1:224404429:C:CC	donor_gain	1.0000
1:224404438:T:A	donor_gain	1.0000
1:224411422:CATA:C	donor_loss	1.0000
1:224411424:TACC:T	donor_loss	1.0000
1:224411425:A:AC	donor_gain	1.0000
1:224411425:A:C	donor_loss	1.0000
1:224411426:C:CC	donor_gain	1.0000
1:224411426:C:CT	donor_loss	1.0000
1:224411565:CCTAA:C	acceptor_loss	1.0000

AlphaMissense

4919 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:224393865:C:A	W641C	1.000
1:224393865:C:G	W641C	1.000
1:224393866:C:G	W641S	1.000
1:224393867:A:G	W641R	1.000
1:224393867:A:T	W641R	1.000
1:224393871:T:A	R639S	1.000
1:224393871:T:G	R639S	1.000
1:224393872:C:G	R639T	1.000
1:224393875:A:T	V638D	1.000
1:224393884:T:A	D635V	1.000
1:224393884:T:G	D635A	1.000
1:224393885:C:A	D635Y	1.000
1:224393885:C:G	D635H	1.000
1:224393886:A:C	D634E	1.000
1:224393886:A:T	D634E	1.000
1:224393887:T:A	D634V	1.000
1:224393887:T:C	D634G	1.000
1:224393887:T:G	D634A	1.000
1:224393888:C:A	D634Y	1.000
1:224393888:C:G	D634H	1.000
1:224393890:G:A	S633L	1.000
1:224393891:A:G	S633P	1.000
1:224393893:G:T	A632D	1.000
1:224393895:G:C	S631R	1.000
1:224393895:G:T	S631R	1.000
1:224393897:T:G	S631R	1.000
1:224393899:G:T	A630D	1.000
1:224393925:C:A	W621C	1.000
1:224393925:C:G	W621C	1.000
1:224393927:A:G	W621R	1.000

dbSNP variants (sampled 300 via entrez): RS1000053043 (1:224406419 G>C), RS1000082127 (1:224400875 C>A,T), RS1000151898 (1:224417551 A>T), RS1000179175 (1:224414265 C>A,T), RS1000190896 (1:224421165 T>C), RS1000193589 (1:224432109 C>A), RS1000204906 (1:224431526 A>C), RS1000277387 (1:224386633 T>C), RS1000517005 (1:224423802 T>C), RS1000552856 (1:224413211 C>A,G,T), RS1000635554 (1:224427754 T>C), RS1000647415 (1:224420867 A>G), RS1000710921 (1:224386234 A>C), RS1000738719 (1:224407347 G>T), RS1000822507 (1:224427369 C>G)

Disease associations

OMIM: gene MIM:617424 | disease phenotypes: MIM:617616, MIM:162200

GenCC curated gene-disease

Disease	Classification	Inheritance
Skraban-Deardorff syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Skraban-Deardorff syndrome	Definitive	AD

Mondo (4): Skraban-Deardorff syndrome (MONDO:0054636), long QT syndrome (MONDO:0002442), neurofibromatosis type 1 (MONDO:0018975), intellectual disability (MONDO:0001071)

Orphanet (3): Intellectual disability-seizures-abnormal gait-facial dysmorphism syndrome (Orphanet:513456), Neurofibromatosis type 1 (Orphanet:636), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

95 total (30 of 95 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000168	Abnormality of the gingiva
HP:0000175	Cleft palate
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000215	Thick upper lip vermilion
HP:0000219	Thin upper lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000336	Prominent supraorbital ridges
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000403	Recurrent otitis media
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000520	Proptosis
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000582	Upslanted palpebral fissure
HP:0000646	Amblyopia
HP:0000687	Widely spaced teeth
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000856_1	Major depressive disorder	4.000000e-06
GCST004610_36	White blood cell count	4.000000e-09
GCST90002380_123	Basophil percentage of white cells	4.000000e-10
GCST90002394_99	Monocyte percentage of white cells	3.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007992	basophil percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D009456	Neurofibromatosis 1	C04.557.580.600.580.590.650; C04.700.631.650; C10.562.600.500; C10.574.500.549.400; C10.668.829.675; C16.320.400.560.400; C16.320.700.633.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725059 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.85	IC50	140	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178437: Inhibition of WDR26 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1400	uM

CTD chemical–gene interactions

48 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
bisphenol F	decreases methylation, decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects expression, affects methylation	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
14-deoxy-11,12-didehydroandrographolide	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
(+)-JQ1 compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	decreases expression	1
Copper	affects binding, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, 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
CHEMBL5697167	Binding	Inhibition of WDR26 (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

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2NX	HAP1 WDR26 (-) 1	Cancer cell line	Male
CVCL_E2NY	HAP1 WDR26 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00169611	PHASE4	COMPLETED	NF1-Attention: Study of Children With Neurofibromatosis Type 1 Treated by Methylphenidate
NCT03975829	PHASE4	RECRUITING	Pediatric Long-Term Follow-up and Rollover Study
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02471339	PHASE3	COMPLETED	Acceptance and Commitment Training for Adolescents and Young Adults With Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain
NCT03871257	PHASE3	ACTIVE_NOT_RECRUITING	A Study of the Drugs Selumetinib Versus Carboplatin/Vincristine in Patients With Neurofibromatosis and Low-Grade Glioma
NCT04461886	PHASE3	TERMINATED	A Long-term Study of NPC-12G Gel in Neurofibromatosis Type I
NCT04924608	PHASE3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Selumetinib in Adults With NF1 Who Have Symptomatic, Inoperable Plexiform Neurofibromas
NCT05913037	PHASE3	ACTIVE_NOT_RECRUITING	FCN-159 in Adult Patients With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00021541	PHASE2	COMPLETED	R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
NCT00030264	PHASE2	COMPLETED	Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas
NCT00076102	PHASE2	COMPLETED	Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas
NCT00304083	PHASE2	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III or Stage IV Malignant Peripheral Nerve Sheath Tumors
NCT00326872	PHASE2	TERMINATED	AZD2171 in Treating Patients With Neurofibromatosis Type 1 and Plexiform Neurofibroma and/or Neurofibroma Near the Spine
NCT00589784	PHASE2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00634270	PHASE2	COMPLETED	A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis Type 1 Related Plexiform Neurofibromas
NCT00754780	PHASE2	COMPLETED	Clinical Trial of Pirfenidone in Adult Patients With Neurofibromatosis 1
NCT00846430	PHASE2	COMPLETED	Medical Treatment of High-Risk Neurofibromas
NCT00853580	PHASE2	COMPLETED	A Randomized Placebo-Controlled Study of Lovastatin in Children With Neurofibromatosis Type 1
NCT01125046	PHASE2	COMPLETED	Bevacizumab in Treating Patients With Recurrent or Progressive Meningiomas
NCT01402817	PHASE2	TERMINATED	Study of Sutent®/Sunitinib (SU11248) in Subjects With NF-1 Plexiform Neurofibromas
NCT01412892	PHASE2	COMPLETED	Use of RAD001 as Monotherapy in the Treatment of Neurofibromatosis 1 Related Internal Plexiform Neurofibromas
NCT01553149	PHASE2	COMPLETED	Low-Dose or High-Dose Lenalidomide in Treating Younger Patients With Recurrent, Refractory, or Progressive Pilocytic Astrocytoma or Optic Pathway Glioma
NCT01673009	PHASE2	COMPLETED	Phase II Study of Gleevec/Imatinib Mesylate (STI-571, NCS 716051) in Neurofibromatosis (NF1) Patients With Plexiform Neurofibromas
NCT01968590	PHASE2	TERMINATED	Vitamin D Supplementation for Adults With Neurofibromatosis Type 1 (NF1)
NCT02096471	PHASE2	COMPLETED	MEK Inhibitor PD-0325901 Trial in Adolescents and Adults With NF1
NCT02101736	PHASE2	COMPLETED	Cabozantinib for Plexiform Neurofibromas (PN) in Subjects With NF1 in Children and Adults
NCT02332902	PHASE2	COMPLETED	Everolimus for Treatment of Disfiguring Cutaneous Lesions in Neurofibromatosis1 CRAD001CUS232T
NCT02407405	PHASE2	ACTIVE_NOT_RECRUITING	MEK 1/2 Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Adults With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas
NCT02728388	PHASE2	RECRUITING	Photodynamic Therapy for Benign Dermal Neurofibromas- Phase II