Incidental Mutation 'D4043:Ocrl'
ID 244
Institutional Source Beutler Lab
Gene Symbol Ocrl
Ensembl Gene ENSMUSG00000001173
Gene Name OCRL, inositol polyphosphate-5-phosphatase
Synonyms 9530014D17Rik, OCRL1
Accession Numbers

Genbank: NM_177215; MGI: 109589

Is this an essential gene? Possibly non essential (E-score: 0.369) question?
Stock # D4043 (G3) of strain 483
Quality Score
Status Validated
Chromosome X
Chromosomal Location 47912387-47965868 bp(+) (GRCm38)
Type of Mutation missense
DNA Base Change (assembly) T to C at 47936323 bp (GRCm38)
Zygosity Homozygous
Amino Acid Change Valine to Alanine at position 359 (V359A)
Ref Sequence ENSEMBL: ENSMUSP00000110672 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000001202] [ENSMUST00000115020]
AlphaFold Q6NVF0
Predicted Effect probably benign
Transcript: ENSMUST00000001202
AA Change: V359A

PolyPhen 2 Score 0.440 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000001202
Gene: ENSMUSG00000001173
AA Change: V359A

DomainStartEndE-ValueType
Pfam:OCRL_clath_bd 18 118 1.5e-47 PFAM
low complexity region 168 189 N/A INTRINSIC
IPPc 237 538 1.16e-147 SMART
Blast:RhoGAP 673 704 2e-11 BLAST
RhoGAP 731 895 4.93e-39 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000115020
AA Change: V359A

PolyPhen 2 Score 0.440 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000110672
Gene: ENSMUSG00000001173
AA Change: V359A

DomainStartEndE-ValueType
PDB:2KIE|A 1 119 7e-69 PDB
low complexity region 168 189 N/A INTRINSIC
IPPc 237 538 1.16e-147 SMART
PDB:2QV2|A 561 722 1e-97 PDB
Predicted Effect noncoding transcript
Transcript: ENSMUST00000142719
Predicted Effect probably benign
Transcript: ENSMUST00000154732
SMART Domains Protein: ENSMUSP00000122084
Gene: ENSMUSG00000001173

DomainStartEndE-ValueType
Pfam:Exo_endo_phos 1 79 5.9e-6 PFAM
Blast:IPPc 139 175 5e-13 BLAST
PDB:3QBT|H 144 266 7e-83 PDB
Meta Mutation Damage Score 0.6454 question?
Coding Region Coverage
  • 1x: 88.8%
  • 3x: 72.5%
Validation Efficiency 88% (220/249)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] 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]
PHENOTYPE: Homozygous null mice do not develop and of the abnormalities associated with oculocerebrorenal syndrome of Lowe. [provided by MGI curators]
Allele List at MGI

All alleles(6) : Targeted, knock-out(2) Gene trapped(4)

Other mutations in this stock
Total: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
1110020G09Rik T A 15: 9,103,385 probably benign Homo
1700029J07Rik A G 8: 45,956,403 V293A probably damaging Het
Adam29 A T 8: 55,872,461 C319* probably null Het
Adgrg1 T C 8: 95,005,229 probably null Homo
Ago3 A T 4: 126,351,003 V630E probably damaging Het
Armc8 G T 9: 99,483,976 N628K probably benign Het
Chd7 A G 4: 8,862,650 D2579G probably damaging Het
Duox1 G A 2: 122,344,795 C1358Y probably benign Het
Fam208a A G 14: 27,471,992 I1050V probably benign Het
Ftsj3 C A 11: 106,254,808 M66I possibly damaging Homo
Iqub C T 6: 24,505,751 E53K possibly damaging Het
Kirrel T A 3: 87,083,203 T771S probably benign Het
Lrrc66 A T 5: 73,607,526 S725T probably benign Het
Mael T C 1: 166,236,886 I104M probably benign Homo
Mkks C T 2: 136,874,610 V457I probably benign Het
Npas1 T C 7: 16,463,244 probably null Het
Olfr1065 G A 2: 86,445,220 T254M probably damaging Het
Pde6b C T 5: 108,425,356 R531* probably null Het
Polr1a G A 6: 71,941,417 C653Y possibly damaging Het
Rbm26 A G 14: 105,152,540 V216A possibly damaging Het
Rin2 C A 2: 145,822,363 H52Q possibly damaging Het
Ssc5d C T 7: 4,943,983 T1112I possibly damaging Het
Sv2c C T 13: 96,088,481 V107M probably benign Het
Tulp3 G A 6: 128,324,150 S366L probably benign Het
Zfp831 T A 2: 174,645,266 V578E probably benign Homo
Other mutations in Ocrl
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00925:Ocrl APN X 47947097 missense probably benign 0.04
IGL02142:Ocrl APN X 47936118 missense probably damaging 0.98
IGL02494:Ocrl APN X 47933438 missense probably benign
IGL02496:Ocrl APN X 47933438 missense probably benign
R0599:Ocrl UTSW X 47936086 unclassified probably benign
R1834:Ocrl UTSW X 47962116 missense probably damaging 1.00
R1835:Ocrl UTSW X 47962116 missense probably damaging 1.00
R1836:Ocrl UTSW X 47962116 missense probably damaging 1.00
R3113:Ocrl UTSW X 47933427 missense probably benign
R3780:Ocrl UTSW X 47938303 missense probably benign 0.04
Nature of Mutation
DNA sequencing using the SOLiD technique identified a T to C transition at position 1273 of the Ocrl transcript in exon 12 of 24 total exons. Multiple transcripts of the Ocrl gene are displayed on Ensembl and Vega. The mutated nucleotide causes a valine to alanine substitution at amino acid 359 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
The Ocrl gene encodes a 900 amino acid protein that has mostly been characterized in humans (Uniprot Q6NVF0). In humans, the OCRL gene encodes a phosphatidylinositol 4,5-bisphosphate-5-phosphatase localized to the trans-Golgi network that is involved in actin polymerization. This protein may function in lysosomal membrane trafficking by regulating the specific pool of phosphatidylinositol 4,5-bisphosphate that is associated with lysosomes. OCRL contains a Rho-GAP domain at the C-terminus (Uniprot Q01968). Mutations in the OCRL gene cause Lowe syndrome (OCRL; OMIM 309000), an X-linked multisystem disorder affecting eyes, nervous system, and kidney. It is characterized by hydrophthalmia, cataract, mental retardation, vitamin D-resistant rickets, aminoaciduria, and reduced ammonia production by the kidney. OCRL mutations also cause Dent disease type (DD2; OMIM 300555) a renal disease characterized by proximal renal tubular defect, hypercalciuria, nephrocalcinosis, and renal insufficiency. Homozygous null mice do not develop the abnormalities associated with Lowe syndrome, but mice doubly homozygous for mutations in Ocrl and Inpp5b, which encodes a highly homologous protein, display early embryonic lethality.
 
The V359A change is predicted to be possibly damaging by the PolyPhen program.
Posted On 2010-08-10