OCRL

Chr X

OCRL inositol polyphosphate-5-phosphatase

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

NCBI Gene: 4952ENSG00000122126UniProt: Q01968

This gene encodes an inositol polyphosphate 5-phosphatase. This protein is involved in regulating membrane trafficking and is located in numerous subcellular locations including the trans-Golgi network, clathrin-coated vesicles and, endosomes and the plasma membrane. This protein may also play a role in primary cilium formation. Mutations in this gene cause oculocerebrorenal syndrome of Lowe and also Dent disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

UniProtLowe oculocerebrorenal syndrome
UniProtDent disease 2
337
ClinVar variants
25
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— OCRL
🧬
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.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 90 VUS of 337 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.15LOEUF
pLI 1.000
Z-score 5.62
OE 0.05 (0.02–0.15)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.96Z-score
OE missense 0.55 (0.49–0.62)
194 obs / 350.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.05 (0.02–0.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.49–0.62)
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.0.94
0≤1.21.6
LoF obs/exp: 2 / 40.7Missense obs/exp: 194 / 350.0Syn Z: 0.49

ClinVar Variant Classifications

337 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic8
VUS90
Likely Benign208
Benign4
Conflicting10
17
Pathogenic
8
Likely Pathogenic
90
VUS
208
Likely Benign
4
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
11
0
17
Likely Pathogenic
5
2
1
0
8
VUS
1
80
9
0
90
Likely Benign
0
11
105
92
208
Benign
0
0
4
0
4
Conflicting
—10
Total129313092337

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

View 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.

Gene2Phenotype Curations

OCRL-related Dent Disease

definitive
Monoallelic X HemizygousUndeterminedUncertain
Dev. Disorders
G2P ↗

OCRL-related Lowe oculocerebrorenal syndrome

definitive
Monoallelic X HemizygousLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — OCRL
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inherited cerebrorenal syndromes.
Schurman SJ et al.·Nat Rev Nephrol
2009Review
Novel pathogenic OCRL mutations and genotype-phenotype analysis of Chinese children affected by oculocerebrorenal syndrome: two cases and a literature review.
Zhang Y et al.·BMC Med Genomics
2021Review
The 5-phosphatase OCRL in Lowe syndrome and Dent disease 2.
De Matteis MA et al.·Nat Rev Nephrol
2017Review
The role of the Lowe syndrome protein OCRL in the endocytic pathway.
Sharma S et al.·Biol Chem
2015Review
Genotype-Phenotype Correlation Reanalysis in 83 Chinese Cases with OCRL Mutations.
Zhang L et al.·Genet Res (Camb)
2022Cohort
Dent disease: classification, heterogeneity and diagnosis.
Jin YY et al.·World J Pediatr
2021Review
Clinical and Molecular Genetic Characteristics of Patients with Hereditary Hypophosphatemia.
Eltan M et al.·J Clin Endocrinol Metab
2025Cohort
A role for OCRL in glomerular function and disease.
Preston R et al.·Pediatr Nephrol
2020Case report
Clinical features and genetic analysis of nine Chinese children with Dent disease and identification of three novel CLCN5 and OCRL variants.
Jiang X et al.·Ren Fail
2025
The oculocerebrorenal syndrome of Lowe: an update.
Bökenkamp A et al.·Pediatr Nephrol
2016Review
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
Adenine Phosphoribosyltransferase DeficiencyAH AmyloidosisAHL Amyloidosis

National Registry of Rare Kidney Diseases

RECRUITING
NCT06065852UK Kidney AssociationStarted 2009-11-06
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools