Details of Disease

General Information of Disease (ID: DIS8TEDY)

• Disease Name: Oculocerebrorenal syndrome
• Synonyms: Ocrl1; phosphatidylinositol 4,5-bisphosphate 5-phosphatase deficiency; OCR; Lowe syndrome; phosphatidylinositol 4,5-biphosphate 5-phosphatase deficiency; Lowe oculo-cerebro-renal syndrome; Lowe syndrome, X-linked recessive; oculocerebrorenal syndrome of Lowe; Lowe oculocerebrorenal syndrome; oculo-cerebro-renal dystrophy; Lowe disease; OCRL; oculocerebrorenal dystrophy; oculocerebrorenal syndrome; oculo-cerebro-renal syndrome
• Definition: Oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, glaucoma, intellectual disabilities, postnatal growth retardation and renal tubular dysfunction with chronic renal failure.
• Disease Hierarchy:
  DISZ75RJ: Inherited renal tubular disease
  DISB52BH: Eye disorder
  DIS6SVEE: Syndromic disease
  DIS1BLHT: Inborn disorder of amino acid transport
  DIS8TEDY: Oculocerebrorenal syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0010645
  MESH ID: D009800
  UMLS CUI: C0028860
  OMIM ID: 309000
  MedGen ID: 18145
  Orphanet ID: 534
  SNOMED CT ID: 79385002

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 5 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
INPP5D	TTTP2Z1	Strong	Biomarker	[1]
MCOLN1	TT9XBVO	Strong	Altered Expression	[2]
MTM1	TTY2TCU	Strong	Biomarker	[3]
SLC22A6	TTTYH7A	Strong	Biomarker	[4]
SLC22A8	TTTQR47	Strong	Biomarker	[4]

This Disease Is Related to 22 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
APPL1	OT8VR95S	Strong	Biomarker	[5]
ARHGAP1	OT0H2ZBZ	Strong	Biomarker	[5]
ARSH	OTG0X9UQ	Strong	Genetic Variation	[5]
BFAR	OTTBG0V7	Strong	Biomarker	[6]
CLCN5	OT9YXZSO	Strong	Biomarker	[7]
INPP5A	OT9CMGMS	Strong	Genetic Variation	[8]
INPP5B	OT0SC8W5	Strong	Biomarker	[9]
INPP5E	OTJF2AZ9	Strong	Biomarker	[1]
INPP5K	OTQFLQKA	Strong	Biomarker	[1]
NBAS	OTW9IBRI	Strong	Biomarker	[10]
PALLD	OTZ2MUJZ	Strong	Biomarker	[11]
PHETA1	OT4IMC0X	Strong	Biomarker	[12]
PHETA2	OTR0Z4U5	Strong	Biomarker	[5]
PIP	OTH719AH	Strong	Biomarker	[13]
PTBP2	OTF4S7NE	Strong	Biomarker	[5]
RAB5A	OTFR2KM4	Strong	Biomarker	[5]
SCN7A	OTK05PXY	Strong	Biomarker	[10]
SCRN1	OTELM5C2	Strong	Biomarker	[5]
SCRN2	OTSG9EUS	Strong	Biomarker	[5]
SIX2	OTYOVGSC	Strong	Biomarker	[14]
SNX9	OTLNQ0ZM	Strong	Biomarker	[15]
OCRL	OTQ3L42N	Definitive	X-linked	[16]

References

• [1] Functional overlap between murine Inpp5b and Ocrl1 may explain why deficiency of the murine ortholog for OCRL1 does not cause Lowe syndrome in mice.J Clin Invest. 1998 May 15;101(10):2042-53. doi: 10.1172/JCI2414.
• [2] Autophagosome-lysosome fusion triggers a lysosomal response mediated by TLR9 and controlled by OCRL.Nat Cell Biol. 2016 Aug;18(8):839-850. doi: 10.1038/ncb3386. Epub 2016 Jul 11.
• [3] Phosphoinositide signaling disorders in human diseases.FEBS Lett. 2003 Jul 3;546(1):25-31. doi: 10.1016/s0014-5793(03)00437-x.
• [4] A pharmacogenetic candidate gene study of tenofovir-associated Fanconi syndrome. Pharmacogenet Genomics. 2015 Feb;25(2):82-92.
• [5] Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3511-6. doi: 10.1073/pnas.0914658107. Epub 2010 Feb 2.
• [6] IPIP27 Coordinates PtdIns(4,5)P(2) Homeostasis for Successful Cytokinesis.Curr Biol. 2019 Mar 4;29(5):775-789.e7. doi: 10.1016/j.cub.2019.01.043. Epub 2019 Feb 21.
• [7] Proteinuria in Dent disease: a review of the literature.Pediatr Nephrol. 2017 Oct;32(10):1851-1859. doi: 10.1007/s00467-016-3499-x. Epub 2016 Oct 18.
• [8] The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease.Biochem J. 2009 Apr 1;419(1):29-49. doi: 10.1042/BJ20081673.
• [9] Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy.J Am Soc Nephrol. 2017 May;28(5):1399-1407. doi: 10.1681/ASN.2016080913. Epub 2016 Nov 28.
• [10] Lysosomal enzymuria is a feature of hereditary Fanconi syndrome and is related to elevated CI-mannose-6-P-receptor excretion.Nephrol Dial Transplant. 2008 Sep;23(9):2795-803. doi: 10.1093/ndt/gfm898. Epub 2008 Jan 3.
• [11] PALLD Regulates Phagocytosis by Enabling Timely Actin Polymerization and Depolymerization.J Immunol. 2017 Sep 1;199(5):1817-1826. doi: 10.4049/jimmunol.1602018. Epub 2017 Jul 24.
• [12] The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway.Mol Biol Cell. 2011 Mar 1;22(5):606-23. doi: 10.1091/mbc.E10-08-0730. Epub 2011 Jan 13.
• [13] The deficiency of PIP2 5-phosphatase in Lowe syndrome affects actin polymerization.Am J Hum Genet. 2002 Dec;71(6):1420-7. doi: 10.1086/344517. Epub 2002 Nov 11.
• [14] Kidney-differentiated cells derived from Lowe Syndrome patient's iPSCs show ciliogenesis defects and Six2 retention at the Golgi complex.PLoS One. 2018 Feb 14;13(2):e0192635. doi: 10.1371/journal.pone.0192635. eCollection 2018.
• [15] Control of actin polymerization via the coincidence of phosphoinositides and high membrane curvature.J Cell Biol. 2017 Nov 6;216(11):3745-3765. doi: 10.1083/jcb.201704061. Epub 2017 Sep 18.
• [16] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.