INPP5E inositol polyphosphate-5-phosphatase E [Homo sapiens (human)] - Gene

Summary

Official Symbol: INPP5Eprovided by HGNC
Official Full Name: inositol polyphosphate-5-phosphatase Eprovided by HGNC
Primary source: HGNC:HGNC:21474
See related: Ensembl:ENSG00000148384 MIM:613037; AllianceGenome:HGNC:21474
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CPD4; CORS1; JBTS1; MORMS; PPI5PIV; pharbin
Summary: The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. Studies of the mouse counterpart suggest that this protein may hydrolyze phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,5-bisphosphate on the cytoplasmic Golgi membrane and thereby regulate Golgi-vesicular trafficking. Mutations in this gene cause Joubert syndrome; a clinically and genetically heterogenous group of disorders characterized by midbrain-hindbrain malformation and various associated ciliopathies that include retinal dystrophy, nephronophthisis, liver fibrosis and polydactyly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
Expression: Ubiquitous expression in testis (RPKM 7.5), spleen (RPKM 6.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9q34.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (136428619..136439845, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (148657963..148668937, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (139323071..139334297, complement)

Chromosome 9 - NC_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

TMEM67 is required for the gating function of the transition zone that controls entry of membrane-associated proteins ARL13B and INPP5E into primary cilia.
Title: TMEM67 is required for the gating function of the transition zone that controls entry of membrane-associated proteins ARL13B and INPP5E into primary cilia.
The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic hedgehog signaling.
Title: The ciliary gene INPP5E confers dorsal telencephalic identity to human cortical organoids by negatively regulating Sonic hedgehog signaling.
Interaction of INPP5E with ARL13B is essential for its ciliary membrane retention but dispensable for its ciliary entry.
Title: Interaction of INPP5E with ARL13B is essential for its ciliary membrane retention but dispensable for its ciliary entry.
The Major Ciliary Isoforms of RPGR Build Different Interaction Complexes with INPP5E and RPGRIP1L.
Title: The Major Ciliary Isoforms of RPGR Build Different Interaction Complexes with INPP5E and RPGRIP1L.
Formation of primary cilia is downregulated in TULP3-knockout (KO) RPE1 cells. ARL13B and INPP5E fail to localize to primary cilia in TULP3-KO cells.
Title: TULP3 is required for localization of membrane-associated proteins ARL13B and INPP5E to primary cilia.
miR598 contributed to cell proliferation and cell cycle progression in colorectal carcinoma by targeting INPP5E.
Title: Upregulation of miR‑598 promotes cell proliferation and cell cycle progression in human colorectal carcinoma by suppressing INPP5E expression.
INPP5E associates with the N-terminus of RPGR and trafficking of INPP5E to cilia is dependent upon the ciliary localization of RPGR.
Title: Prenylated retinal ciliopathy protein RPGR interacts with PDE6δ and regulates ciliary localization of Joubert syndrome-associated protein INPP5E.
we identify Inpp5e as an essential inhibitor of the PI3K/Akt/mTORC1 signaling axis in renal epithelial cells, and demonstrate a critical role for Inpp5e-dependent mTORC1 regulation in Polycystic kidney disease (PKD) suppression
Title: Inpp5e suppresses polycystic kidney disease via inhibition of PI3K/Akt-dependent mTORC1 signaling.
ARL13B regulates IFT-A-mediated retrograde protein trafficking within cilia through its interaction with INPP5E.
Title: Regulation of ciliary retrograde protein trafficking by the Joubert syndrome proteins ARL13B and INPP5E.
In neuronal cells, INPP5E knockdown strongly inhibited autophagy by impairing the autophagosome-lysosome fusion step.
Title: Autophagosome-lysosome fusion in neurons requires INPP5E, a protein associated with Joubert syndrome.

Submit: New GeneRIF Correction See all GeneRIFs (22)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Joubert syndrome 1 MedGen: C4551568 OMIM: 213300 GeneReviews: Joubert Syndrome	Compare labs
MORM syndrome MedGen: C1857802 OMIM: 610156 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 replication, specifically assembly, is restricted by over expression of INPP5E, which depletes monocyte derived macrophages of cellular PI(4,5)P2	PubMed
Knockdown of inositol polyphosphate-5-phosphatase, 72 kDa (INPP5E) by siRNA enhances the early stages of HIV-1 replication in HeLa-CD4 cells infected with viral pseudotypes HIV89.6R and HIV8.2N	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	Overexpression of phosphoinositide 5-phosphatase IV, an enzyme that depletes cellular PI(4,5)P2, severely reduces HIV-1 Gag virus production by retargeting Gag to late endosomes instead of the plasma membrane	PubMed
	gag	The chimeric HIV-1 Gag, in which MA is replaced with HTLV-1 MA, is less sensitive to 5ptaseIV overexpression compared to the wild type Gag, suggesting MA plays an important role of interaction between Gag and PI(4,5)P2	PubMed
	gag	The 74LR mutation in Gag increases virus infectivity and compensates for the inefficient virus release in T cells expressing polyphosphoinositide 5-phosphatase IV	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-F10030 (e-PCR)
- UniSTS:19719

RH77981 (e-PCR)
- UniSTS:4634

RH98963 (e-PCR)
- UniSTS:90464

RH104347 (e-PCR)
- UniSTS:98672

D9S158 (e-PCR)
- UniSTS:7075

WI-11990 (e-PCR)
- UniSTS:23744

RH70641 (e-PCR)
- UniSTS:29415

RH48856 (e-PCR)
- UniSTS:75755

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables inositol-polyphosphate 5-phosphatase activity	TAS Traceable Author Statement more info	PubMed
enables phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in biological_process	ND No biological Data available more info
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein localization to cilium	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of translation	IEA Inferred from Electronic Annotation more info
involved_in phosphatidylinositol biosynthetic process	TAS Traceable Author Statement more info
involved_in phosphatidylinositol dephosphorylation	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphatidylinositol-3-phosphate biosynthetic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in Golgi apparatus	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi cisterna membrane	IEA Inferred from Electronic Annotation more info
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
is_active_in axoneme	IBA Inferred from Biological aspect of Ancestor more info
located_in axoneme	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	TAS Traceable Author Statement more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in ruffle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: phosphatidylinositol polyphosphate 5-phosphatase type IV

Names: 72 kDa inositol polyphosphate 5-phosphatase; phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase; phosphatidylinositol-4,5-bisphosphate 5-phosphatase

NP_001305431.1

EC 3.1.3.36

EC 3.1.3.86

NP_063945.2

EC 3.1.3.36

EC 3.1.3.86

XP_016870415.1

EC 3.1.3.36

EC 3.1.3.86

XP_047279559.1

EC 3.1.3.36

EC 3.1.3.86

XP_054219279.1

EC 3.1.3.36

EC 3.1.3.86

XP_054219280.1

EC 3.1.3.36

EC 3.1.3.86

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016126.1 RefSeqGene

Range

4960..16186

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001318502.2 → NP_001305431.1 phosphatidylinositol polyphosphate 5-phosphatase type IV isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in an internal exon, compared to variant 1. It encodes isoform 2 which is shorter than isoform 1.

Source sequence(s)

AL592301, AL832846, BC028032

UniProtKB/Swiss-Prot

Q9NRR6

Conserved Domains (2) summary

cd09095
Location:295 → 592

INPP5c_INPP5E-like; Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol polyphosphate-5-phosphatase E and related proteins

PHA03247
Location:2 → 179

PHA03247; large tegument protein UL36; Provisional
NM_019892.6 → NP_063945.2 phosphatidylinositol polyphosphate 5-phosphatase type IV isoform 1

See identical proteins and their annotated locations for NP_063945.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL592301, AL832846, BC028032

Consensus CDS

CCDS7000.1

UniProtKB/Swiss-Prot

Q15734, Q6PIV5, Q9NRR6

Related

ENSP00000360777.3, ENST00000371712.4

Conserved Domains (2) summary

cd09095
Location:295 → 593

INPP5c_INPP5E-like; Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol polyphosphate-5-phosphatase E and related proteins

PHA03247
Location:2 → 179

PHA03247; large tegument protein UL36; Provisional

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

136428619..136439845 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047423603.1 → XP_047279559.1 phosphatidylinositol polyphosphate 5-phosphatase type IV isoform X2
XM_017014926.2 → XP_016870415.1 phosphatidylinositol polyphosphate 5-phosphatase type IV isoform X1

Conserved Domains (2) summary

cd09095
Location:295 → 593

INPP5c_INPP5E-like; Catalytic inositol polyphosphate 5-phosphatase (INPP5c) domain of Inositol polyphosphate-5-phosphatase E and related proteins

PHA03247
Location:2 → 244

PHA03247; large tegument protein UL36; Provisional

RNA

XR_929828.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060933.1 Alternate T2T-CHM13v2.0

Range

148657963..148668937 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054363305.1 → XP_054219280.1 phosphatidylinositol polyphosphate 5-phosphatase type IV isoform X2
XM_054363304.1 → XP_054219279.1 phosphatidylinositol polyphosphate 5-phosphatase type IV isoform X1