WDR36

Chr 5

WD repeat domain 36

Also known as: GLC1G, TA-WDRP, TAWDRP, UTP21

NCBI Gene: 134430ENSG00000134987UniProt: Q8NI36

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). [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Glaucoma 1, open angle, GMIM #609887
368
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— WDR36
🧬
Gene-Disease Validity (ClinGen)
obsolete glaucoma 1, open angle, G · ADDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 197 VUS of 368 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.47LOEUF
pLI 0.001
Z-score 4.64
OE 0.31 (0.21–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.80Z-score
OE missense 1.23 (1.15–1.31)
616 obs / 502.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.31 (0.21–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.23 (1.15–1.31)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.26
0≤1.21.6
LoF obs/exp: 16 / 52.1Missense obs/exp: 616 / 502.7Syn Z: -2.69

ClinVar Variant Classifications

368 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
VUS197
Likely Benign73
Benign71
Conflicting3
24
Pathogenic
197
VUS
73
Likely Benign
71
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
0
0
0
VUS
1
166
30
0
197
Likely Benign
0
9
53
11
73
Benign
0
4
58
9
71
Conflicting
—3
Total117916520368

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

WDR36 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Glaucoma 1, open angle, G

MIM #609887

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Mini-Review on Gene Therapy in Glaucoma and Future Directions.
Anton N et al.·Int J Mol Sci
2024Review
Genetics of primary glaucoma.
Khan AO·Curr Opin Ophthalmol
2011Review
WDR36-Associated Neurodegeneration: A Case Report Highlights Possible Mechanisms of Normal Tension Glaucoma.
Meer E et al.·Genes (Basel)
2021Case report
WDR36 variants in East Indian primary open-angle glaucoma patients.
Mookherjee S et al.·Mol Vis
2011Cohort
A Glaucoma Case-control Study of the WDR36 Gene D658G sequence variant.
Hewitt AW et al.·Am J Ophthalmol
2006
Mapping the Proteomic Landscape of Pancreatic Cancer: Prognostic Insights and Subtype Stratification.
Aref AT et al.·Cancer Res Commun
2025
Detection of mutations in MYOC, OPTN, NTF4, WDR36 and CYP1B1 in Chinese juvenile onset open-angle glaucoma using exome sequencing.
Huang C et al.·Sci Rep
2018
Association between primary open-angle glaucoma and WDR36 DNA sequence variants in Japanese.
Miyazawa A et al.·Mol Vis
2007
The role of the WDR36 gene on chromosome 5q22.1 in a large family with primary open-angle glaucoma mapped to this region.
Kramer PL et al.·Arch Ophthalmol
2006
Co-variation of STI1 and WDR36/UTP21 alters cell proliferation in a glaucoma model.
Footz T et al.·Mol Vis
2011Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools