WDR36

Summary

WDR36 (WD repeat domain 36, HGNC:30696) is a protein-coding gene on chromosome 5q22.1, encoding WD repeat-containing protein 36 (Q8NI36). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

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. Mutations in this gene have been associated with adult-onset primary open-angle glaucoma (POAG).

Source: NCBI Gene 134430 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glaucoma 1, open angle, G (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 31
• Clinical variants (ClinVar): 317 total
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_139281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30696
Approved symbol	WDR36
Name	WD repeat domain 36
Location	5q22.1
Locus type	gene with protein product
Status	Approved
Aliases	TA-WDRP, UTP21
Ensembl gene	ENSG00000134987
Ensembl biotype	protein_coding
OMIM	609669
Entrez	134430

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 3 retained_intron

ENST00000504122, ENST00000505303, ENST00000513710, ENST00000515784, ENST00000856282, ENST00000856283, ENST00000929671, ENST00000946909, ENST00000946910

RefSeq mRNA: 1 — MANE Select: NM_139281 NM_139281

CCDS: CCDS4102

Canonical transcript exons

ENST00000513710 — 23 exons

Exon	Start	End
ENSE00000917782	111120996	111121141
ENSE00000972210	111113074	111113153
ENSE00001082457	111119013	111119120
ENSE00001121409	111123805	111123924
ENSE00001121450	111111170	111111278
ENSE00001265113	111126734	111130502
ENSE00001265155	111124108	111124189
ENSE00001265175	111120496	111120593
ENSE00002067322	111092348	111092618
ENSE00002270343	111125608	111125795
ENSE00003715361	111097079	111097179
ENSE00003716489	111102345	111102399
ENSE00003717004	111104697	111104817
ENSE00003720972	111103786	111103918
ENSE00003723323	111110189	111110303
ENSE00003724816	111105295	111105360
ENSE00003728486	111106057	111106143
ENSE00003731150	111094920	111094947
ENSE00003731708	111098722	111098839
ENSE00003735278	111110788	111110953
ENSE00003735579	111107294	111107439
ENSE00003739974	111100589	111100721
ENSE00003744504	111104177	111104352

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 92.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.3399 / max 299.2983, expressed in 1821 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57963	37.6844	1821
57964	0.6555	379

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.09	gold quality
tibialis anterior	UBERON:0001385	90.40	gold quality
deltoid	UBERON:0001476	89.73	gold quality
upper arm skin	UBERON:0004263	88.88	gold quality
adrenal tissue	UBERON:0018303	88.79	gold quality
epithelial cell of pancreas	CL:0000083	88.44	gold quality
esophagus squamous epithelium	UBERON:0006920	87.98	gold quality
tendon	UBERON:0000043	86.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.21	gold quality
parietal pleura	UBERON:0002400	86.09	gold quality
germinal epithelium of ovary	UBERON:0001304	85.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.48	gold quality
ileal mucosa	UBERON:0000331	85.47	gold quality
visceral pleura	UBERON:0002401	85.47	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	85.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	84.66	gold quality
islet of Langerhans	UBERON:0000006	84.60	gold quality
thoracic mammary gland	UBERON:0005200	83.91	gold quality
biceps brachii	UBERON:0001507	83.87	gold quality
mammary gland	UBERON:0001911	83.83	gold quality
cauda epididymis	UBERON:0004360	83.68	gold quality
quadriceps femoris	UBERON:0001377	83.51	gold quality
vermiform appendix	UBERON:0001154	83.47	gold quality
mammary duct	UBERON:0001765	83.47	gold quality
colonic epithelium	UBERON:0000397	83.45	gold quality
epithelium of mammary gland	UBERON:0003244	83.43	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.36	gold quality
endometrium	UBERON:0001295	83.34	gold quality
mammalian vulva	UBERON:0000997	83.04	gold quality
vastus lateralis	UBERON:0001379	82.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6, MYC

miRNA regulators (miRDB)

156 targeting WDR36, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
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-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 24)

• First series of WDR36 mutations in subjects with high- and low-pressure adult-onset primary open angle glaucoma. First mRNA expression profiling of this gene in various ocular and non-ocular tissues for human and mouse. (PMID:15677485)
• role in etiology of both high- and low-pressure glaucoma. (PMID:15677485)
• Our results provided mapping of a novel locus for juvenile-onset primary open angle glaucoma at 5q and excluded coding or splicing junctions mutations within the WDR36 gene. (PMID:16518310)
• The association of WDR36 sequence variants with more severe disease in affected individuals suggests that defects in the WDR36 gene can contribute to POAG and that WDR36 may be a glaucoma modifier gene. (PMID:16723468)
• The WDR36 D658G is a neutral variant in the Australian population. (PMID:16876519)
• The finding that the WDR36 gene is probably not the responsible gene in this family further documents the genetic heterogeneity of POAG (primary open-angle glaucoma). (PMID:16966629)
• WDR36 gene variants may be only rare causes of normal tension glaucoma in the German population. (PMID:17563723)
• One nonsynonymous variant, p.S664L, and association of allelic variants (p.I264V and c.1965-30A>G) in WDR36 and their prevalence in unrelated Japanese patients with high tension glaucoma (HTG) suggest they are probably involved in pathogenesis of HTG. (PMID:17960130)
• The occurrence of several rare putative disease-causing variants in patients with glaucoma suggests that WDR36 may be a minor disease-causing gene in glaucoma, at least in the German population. (PMID:18172102)
• Timolol can reduce MYOC RNA levels in HTM cultures from some individuals. Timolol does not alter OPTN or WDR36 levels or ameliorate MYOC induction by dexamethasone in vitro. (PMID:18195223)
• WDR36 sequence variants can lead to an altered cellular phenotype, supporting the theory that WDR36 participates in polygenic forms of glaucoma. (PMID:19150991)
• SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma. (PMID:19198610)
• WDR36 is associated with sporadic high tension glaucoma but not with normal tension glaucoma or juvenile-onset primary open-angle glaucoma. (PMID:19347049)
• Genetic variants of CYP1B1 and WDR36 in the patients with primary congenital glaucoma and primary open angle glaucoma from Saint-Petersburg (PMID:20198978)
• WDR36 sequence variance was only a rare cause of primary open-angel glaucoma glaucoma in Italian families with glaucoma. (PMID:20813748)
• Rare WDR36 variants and the P53 p.R72P polymorphism behaved as moderate glaucoma risk factors in Spanish patients. The authors provide evidence for a genetic interaction between WDR36 and P53 variants in glaucoma susceptibility. (PMID:21931130)
• WDR36 acts as a scaffold protein tethering a G-protein-coupled receptor, Galphaq and phospholipase C beta 2 in a signalling complex (PMID:21940795)
• Single nucleotide polymorphism in the WDR36 gene, rs10038177 (c.710+30C>T), was found to be strongly associated with the high tension glaucoma cases, but not with controls in the East Indian population. (PMID:22025897)
• According to molecular genetic studies, WDR36 causative gene involved in the development of Primary open-angle glaucoma. (PMID:25711070)
• Familial linkage studies for primary angle-closure glaucoma have been performed and identified WDR36 causative primary angle-closure glaucoma disease (PMID:26497787)
• The association between WDR36 and POAG was not supported, and the majority of POAG cases did not harbor a potentially disease-causing variant in the remaining Mendelian genes. (PMID:28282485)
• Meta-analysis does not support a significant role of WDR36 in the genetic susceptibility of primary open angle glaucoma or its subtypes. (PMID:28658128)
• Study suggests that WDR36 gene is involved in the pathogenesis of juvenile open-angle glaucoma in Taiwan population as a subordinate modifier gene. (PMID:29104481)
• WDR36-Associated Neurodegeneration: A Case Report Highlights Possible Mechanisms of Normal Tension Glaucoma. (PMID:34681019)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr36	ENSDARG00000004774
mus_musculus	Wdr36	ENSMUSG00000038299
rattus_norvegicus	Wdr36	ENSRNOG00000027355
drosophila_melanogaster	CG9799	FBGN0038146
caenorhabditis_elegans		WBGENE00012887

Paralogs (1): PRPF19 (ENSG00000110107)

Protein

Protein identifiers

WD repeat-containing protein 36 — Q8NI36 (reviewed: Q8NI36)

Alternative names: T-cell activation WD repeat-containing protein

All UniProt accessions (2): A0A0A0MTB8, Q8NI36

UniProt curated annotations — full annotation on UniProt →

Function. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in the nucleolar processing of SSU 18S rRNA. Involved in T-cell activation and highly coregulated with IL2.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Expressed in heart, placenta, liver, skeletal muscle, kidney and pancreas. In ocular tissues, strong expression in iris, sclera, ciliary muscle, ciliary body, retina and optic nerve.

Disease relevance. Glaucoma 1, open angle, G (GLC1G) [MIM:609887] A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WD repeats are grouped into two tandem seven-bladed beta-propeller regions.

Miscellaneous. Depletion of WDR36 mRNA in cultured cells causes apoptotic cell death and consistently associates with a reduced 21S rRNA and delay of 18S rRNA maturation.

RefSeq proteins (1): NP_644810* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR007319	WDR36/Utp21_C	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR059157	WDR36-Utp21_N	Domain

Pfam: PF04192, PF25168, PF25171

UniProt features (35 total): sequence variant 15, repeat 14, sequence conflict 3, modified residue 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7MQA	ELECTRON MICROSCOPY	2.7
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NI36-F1	87.47	0.66

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): 382, 399

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6790901	rRNA modification in the nucleus and cytosol
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol

MSigDB gene sets: 180 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_RIBOSOME_BIOGENESIS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_MATURATION_OF_SSU_RRNA, GOBP_RIBOSOMAL_SMALL_SUBUNIT_BIOGENESIS, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, MODULE_206, GARY_CD5_TARGETS_DN, BENPORATH_NOS_TARGETS, GOBP_SENSORY_PERCEPTION, MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, DANG_BOUND_BY_MYC, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

GO Biological Process (3): rRNA processing (GO:0006364), visual perception (GO:0007601), ribosomal small subunit biogenesis (GO:0042274)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): nucleoplasm (GO:0005654), small-subunit processome (GO:0032040), Pwp2p-containing subcomplex of 90S preribosome (GO:0034388)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribosome biogenesis	2
nucleolus	2
nuclear protein-containing complex	2
RNA processing	1
rRNA metabolic process	1
sensory perception of light stimulus	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
preribosome	1
t-UTP complex	1
90S preribosome	1

Protein interactions and networks

STRING

2925 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR36	UTP18	Q9Y5J1	972
WDR36	MYOC	Q99972	970
WDR36	UTP6	Q9NYH9	951
WDR36	TBL3	Q12788	934
WDR36	OPTN	Q96CV9	923
WDR36	ASB10	Q8WXI3	906
WDR36	PWP2	Q15269	887
WDR36	UTP4	Q969X6	813
WDR36	CYP1B1	Q16678	813
WDR36	WDR3	Q9UNX4	807
WDR36	HEATR1	Q9H583	788
WDR36	NTF4	P34130	758
WDR36	UTP3	Q9NQZ2	744
WDR36	WDR46	O15213	731
WDR36	UTP15	Q8TED0	710

IntAct

98 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
PWP2	FBL	psi-mi:“MI:0914”(association)	0.610
FGF3	GTPBP10	psi-mi:“MI:0914”(association)	0.530
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
ZNF71	NVL	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
HSD3B2	NARS1	psi-mi:“MI:0914”(association)	0.530
FBL	ZNF316	psi-mi:“MI:0914”(association)	0.530
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RBM4	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	MAGEB2	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
WDR36	NUDC	psi-mi:“MI:0915”(physical association)	0.400
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
HNRNPU		psi-mi:“MI:0914”(association)	0.350
EXOSC1	MPHOSPH6	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
OASL	LARP1	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (267): WDR36 (Affinity Capture-MS), WDR36 (Affinity Capture-MS), UTP6 (Affinity Capture-Western), WDR36 (Affinity Capture-MS), WDR36 (Affinity Capture-MS), WDR36 (Affinity Capture-MS), AATF (Co-fractionation), CTPS1 (Co-fractionation), DDX56 (Co-fractionation), DUS3L (Co-fractionation), GRWD1 (Co-fractionation), MPHOSPH10 (Co-fractionation), NIFK (Co-fractionation), NOB1 (Co-fractionation), NOC2L (Co-fractionation)

ESM2 similar proteins: A5PK39, A8WGE3, B0R0D7, O89046, O89053, P31146, P49754, Q4R4J2, Q569Z1, Q5E9L7, Q5KU39, Q5MNZ6, Q5NVK4, Q5R7W0, Q5RJG1, Q5T5C0, Q5VZK9, Q5ZL16, Q640T2, Q66H99, Q68F45, Q6DJD8, Q6EDY6, Q6H8D5, Q6H8D6, Q6NVM6, Q6NYH1, Q7T0Q5, Q7ZUW6, Q8BH44, Q8C0P5, Q8K400, Q8NI36, Q8QFR2, Q91VM3, Q91W86, Q91ZN1, Q920J3, Q920Q4, Q92176

Diamond homologs: A0JMQ0, A1CF18, A1CQI9, A1D3F5, A2QEV8, A2QPZ4, A3LXF0, A4H6F7, A4HUV2, A4IHS2, A4R0Q1, A4RDD7, A5DBG1, A5DWF4, A6QX61, A6RRD4, A6RUL1, A6ZMA9, A7EF03, A8ID74, A8NWR2, A8PWB6, A8QD31, A8XYW9, A9UZS7, B0R0D7, B0WC36, B0XQ42, B2AY28, B2VR76, B3MHX6, B3NLK7, B4GIU9, B4HN85, B4J9K1, B4KQU8, B4LKS9, B4MYI5, B4P528, B6GZD3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WDR36	“form complex”	“UTP-B complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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
rRNA modification in the nucleus and cytosol	6	13.5×	1e-03
Major pathway of rRNA processing in the nucleolus and cytosol	14	10.4×	2e-08
Peptide chain elongation	6	9.2×	4e-03
Viral mRNA Translation	6	9.2×	4e-03
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	6	9.1×	4e-03
Selenocysteine synthesis	6	8.7×	4e-03
Eukaryotic Translation Termination	6	8.7×	4e-03
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	6	8.5×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
ribosomal large subunit biogenesis	7	27.2×	2e-06
rRNA processing	12	14.9×	2e-08
ribosomal small subunit biogenesis	6	12.0×	3e-03
RNA processing	6	11.5×	3e-03
cytoplasmic translation	6	9.8×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	153
Likely benign	58
Benign	69

Top pathogenic / likely-pathogenic (0)

SpliceAI

3080 predictions. Top by Δscore:

Variant	Effect	Δscore
5:111092615:TGACG:T	donor_loss	1.0000
5:111092616:GAC:G	donor_gain	1.0000
5:111092618:CG:C	donor_loss	1.0000
5:111092619:G:GG	donor_gain	1.0000
5:111092619:GTG:G	donor_loss	1.0000
5:111092620:T:A	donor_loss	1.0000
5:111094917:CA:C	acceptor_loss	1.0000
5:111094918:A:AC	acceptor_loss	1.0000
5:111094944:GTAA:G	donor_gain	1.0000
5:111094948:G:GG	donor_gain	1.0000
5:111097175:AAGAG:A	donor_loss	1.0000
5:111097176:AGAGG:A	donor_loss	1.0000
5:111097177:GAG:G	donor_gain	1.0000
5:111097178:AGG:A	donor_loss	1.0000
5:111097179:GGTT:G	donor_loss	1.0000
5:111097180:GTTG:G	donor_loss	1.0000
5:111097181:T:G	donor_loss	1.0000
5:111100587:A:AG	acceptor_gain	1.0000
5:111100588:G:GG	acceptor_gain	1.0000
5:111102343:A:AG	acceptor_gain	1.0000
5:111102344:G:GG	acceptor_gain	1.0000
5:111103780:TTTTA:T	acceptor_loss	1.0000
5:111103784:A:AG	acceptor_gain	1.0000
5:111103784:A:AT	acceptor_loss	1.0000
5:111103785:G:GA	acceptor_loss	1.0000
5:111103785:G:GG	acceptor_gain	1.0000
5:111103915:ACAG:A	donor_loss	1.0000
5:111103916:CAGG:C	donor_loss	1.0000
5:111103917:AG:A	donor_loss	1.0000
5:111103918:GG:G	donor_loss	1.0000

AlphaMissense

5886 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:111104227:T:A	W317R	0.999
5:111104227:T:C	W317R	0.999
5:111104811:A:C	S397R	0.999
5:111104813:T:A	S397R	0.999
5:111104813:T:G	S397R	0.999
5:111113104:A:C	S639R	0.999
5:111113106:T:A	S639R	0.999
5:111113106:T:G	S639R	0.999
5:111119119:T:A	W691R	0.999
5:111119119:T:C	W691R	0.999
5:111104327:C:A	T350K	0.998
5:111107362:T:A	W473R	0.998
5:111107362:T:C	W473R	0.998
5:111111242:A:C	R616S	0.998
5:111111242:A:T	R616S	0.998
5:111113093:G:C	R635P	0.998
5:111113134:T:A	W649R	0.998
5:111113134:T:C	W649R	0.998
5:111119081:T:C	L678P	0.998
5:111094947:A:C	S120R	0.997
5:111097080:T:A	S120R	0.997
5:111097080:T:G	S120R	0.997
5:111103913:G:C	R298P	0.997
5:111104203:A:C	S309R	0.997
5:111104205:C:A	S309R	0.997
5:111104205:C:G	S309R	0.997
5:111104321:T:C	L348P	0.997
5:111104327:C:G	T350R	0.997
5:111104700:T:A	W360R	0.997
5:111104700:T:C	W360R	0.997

dbSNP variants (sampled 300 via entrez): RS1000109866 (5:111091513 C>T), RS1000127135 (5:111120218 T>C,G), RS1000135911 (5:111111519 G>A), RS1000293775 (5:111096004 G>A), RS1000351482 (5:111095401 A>C,G), RS1000359331 (5:111117707 A>C,G), RS1000428303 (5:111129817 A>C,T), RS1000463613 (5:111101155 G>C), RS1000582110 (5:111096231 G>A), RS1000620484 (5:111123269 A>G), RS1000726565 (5:111100185 G>A), RS1000740188 (5:111091900 G>A,T), RS1000752115 (5:111105957 T>C,G), RS1000794004 (5:111117417 G>C), RS1000798635 (5:111100004 T>G)

Disease associations

OMIM: gene MIM:609669 | disease phenotypes: MIM:605472, MIM:137760

GenCC curated gene-disease

Disease	Classification	Inheritance
glaucoma 1, open angle, G	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
obsolete glaucoma 1, open angle, G	Disputed	AD

Mondo (3): Usher syndrome type 2C (MONDO:0011558), OPTN-related open angle glaucoma (MONDO:0100553), (MONDO:0012357)

Orphanet (2): Usher syndrome type 2 (Orphanet:231178), Usher syndrome (Orphanet:886)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0012108	Open angle glaucoma

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000339_5	Eosinophil count	1.000000e-06
GCST000620_1	Eosinophilic esophagitis (pediatric)	3.000000e-09
GCST002083_18	Self-reported allergy	2.000000e-20
GCST002084_11	Allergic sensitization	5.000000e-14
GCST002136_1	Periodontitis (PAL4Q3)	2.000000e-06
GCST002322_3	Asthma and hay fever	3.000000e-11
GCST003990_2	Allergy	3.000000e-17
GCST004136_30	Methadone dose in opioid dependence	6.000000e-06
GCST004624_85	Sum eosinophil basophil counts	1.000000e-22
GCST005038_18	Allergic disease (asthma, hay fever or eczema)	5.000000e-46
GCST006408_18	Allergic sensitization	2.000000e-07
GCST006409_36	Allergic rhinitis	3.000000e-26
GCST006911_26	Asthma (moderate or severe)	3.000000e-13
GCST007563_10	Allergic disease (asthma, hay fever or eczema)	5.000000e-20
GCST007797_27	Asthma onset (childhood vs adult)	2.000000e-10
GCST007798_74	Asthma	6.000000e-37
GCST007800_33	Asthma (childhood onset)	4.000000e-66
GCST007943_3	Medication use (antihistamines for systemic use)	3.000000e-09
GCST008916_116	Asthma	4.000000e-20
GCST008916_14	Asthma	4.000000e-10
GCST008916_94	Asthma	1.000000e-51
GCST009719_1	Allergic rhinitis	5.000000e-26
GCST009798_4	Asthma	1.000000e-14
GCST009798_60	Asthma	1.000000e-44
GCST009798_71	Asthma	2.000000e-18
GCST010984_16	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	9.000000e-12
GCST010985_51	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	5.000000e-12
GCST011975_7	Childhood asthma with severe exacerbations	1.000000e-10
GCST012137_2	Motor coordination	8.000000e-06
GCST012381_3	Eosinophilic esophagitis	1.000000e-13

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004842	eosinophil count
EFO:0005298	allergic sensitization measurement
EFO:0007907	methadone dose measurement
EFO:0005090	basophil count
EFO:0004847	age at onset
EFO:0009943	Antihistamine use measurement
EFO:0007614	asthma exacerbation measurement
EFO:0010749	motor function measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C563692	Glaucoma 1, Open Angle, G (supp.)
C536492	Usher syndrome, type 2C (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067422 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.95	Kd	1127	nM	CHEMBL5653589
5.95	ED50	1127	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149777: Binding affinity to human WDR36 incubated for 45 mins by Kinobead based pull down assay	kd	1.1270	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Estradiol	increases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, increases expression	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652819	Binding	Binding affinity to human WDR36 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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