OCRL

Chr XXLR

OCRL inositol polyphosphate-5-phosphatase

Also known as: DENT2, Dent-2, LOCR, OCRL-1, OCRL1

This gene encodes an inositol polyphosphate 5-phosphatase that hydrolyzes phosphatidylinositol 4,5-bisphosphate and other phosphoinositides to regulate membrane trafficking, endosomal transport, and primary cilium formation. Mutations cause X-linked Lowe syndrome (oculocerebrorenal syndrome) and Dent disease 2, affecting the eyes, kidneys, and nervous system. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.155) and follows X-linked recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.153 OMIM phenotypes
Clinical SummaryOCRL
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Gene-Disease Validity (ClinGen)
oculocerebrorenal syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 5.62
OE 0.05 (0.020.15)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.96Z-score
OE missense 0.55 (0.490.62)
194 obs / 350.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.15)
00.351.4
Missense OE0.55 (0.490.62)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 2 / 40.7Missense obs/exp: 194 / 350.0Syn Z: 0.49
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveOCRL-related Dent DiseaseOTHERXLR
definitiveOCRL-related Lowe oculocerebrorenal syndromeLOFXLR
DN
0.2798th %ile
GOF
0.3689th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.15

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

OCRL · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗