INPP5E

inositol polyphosphate-5-phosphatase E, the group of Phosphoinositide phosphatases

Basic information

Region (hg38): 9:136428618-136439845

Previous symbols: [ "JBTS1" ]

Links

ENSG00000148384 ∙ NCBI:56623 ∙ OMIM:613037 ∙ HGNC:21474 ∙ Uniprot:Q9NRR6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• MORM syndrome (Definitive), mode of inheritance: AR
• Joubert syndrome 1 (Definitive), mode of inheritance: AR
• MORM syndrome (Moderate), mode of inheritance: AR
• Joubert syndrome 1 (Strong), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• COACH syndrome 1 (Supportive), mode of inheritance: AR
• MORM syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with ocular defect (Supportive), mode of inheritance: AR
• MORM syndrome (Moderate), mode of inheritance: AR
• Joubert syndrome 1 (Strong), mode of inheritance: AR
• MORM syndrome (Moderate), mode of inheritance: AR
• Joubert syndrome 1 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 1; Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM syndrome)	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine; Genitourinary; Neurologic; Ophthalmologic; Renal	16493448; 19668216; 19668215
Individuals may have renal issues (though most reported individuals did not have evidence of compromised renal function)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the INPP5E gene.

• Familial aplasia of the vermis (594 variants)
• not provided (116 variants)
• Joubert syndrome 1 (96 variants)
• not specified (70 variants)
• INPP5E-related condition (39 variants)
• Inborn genetic diseases (36 variants)
• Rod-cone dystrophy (18 variants)
• Retinal dystrophy (10 variants)
• Joubert syndrome and related disorders (9 variants)
• MORM syndrome (7 variants)
• Joubert syndrome 1;MORM syndrome (2 variants)
• MORM syndrome;Joubert syndrome 1 (2 variants)
• INPP5E-related disorder (1 variants)
• 16 conditions (1 variants)
• Leber congenital amaurosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the INPP5E gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	142	12	158
missense	9	19	272	5	1	306
nonsense	7	2				9
start loss		1	1			2
frameshift	12	7	2			21
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)		1				1
splice region			14	21	4	39
non coding			24	70	33	127
Total	28	30	308	218	46

Highest pathogenic variant AF is 0.000158

Variants in INPP5E

This is a list of pathogenic ClinVar variants found in the INPP5E region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-136428749-A-G		Joubert syndrome 1	Likely benign (Apr 27, 2017)
9-136428762-A-G		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136428859-T-C		Joubert syndrome 1	Benign (Apr 27, 2017)
9-136428864-C-T		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136428912-C-G		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136428928-A-G		Joubert syndrome 1	Uncertain significance (Jan 12, 2018)
9-136428948-G-A		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136428954-G-A		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136428972-T-C		Joubert syndrome 1	Benign (Apr 27, 2017)
9-136429045-C-T		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136429093-G-A		Joubert syndrome 1	Uncertain significance (Jan 12, 2018)
9-136429116-G-A		Joubert syndrome 1	Uncertain significance (Jan 12, 2018)
9-136429191-G-C		Joubert syndrome 1	Uncertain significance (Jan 12, 2018)
9-136429347-A-G		Joubert syndrome 1	Benign (Jun 14, 2018)
9-136429440-T-C		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136429462-G-A		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136429577-C-T		Joubert syndrome 1	Benign/Likely benign (Jun 26, 2018)
9-136429662-C-T		Joubert syndrome 1	Uncertain significance (Jan 13, 2018)
9-136429670-A-C		INPP5E-related disorder	Likely benign (Jul 14, 2021)
9-136429684-G-A		Familial aplasia of the vermis	Likely benign (Feb 24, 2023)
9-136429687-GC-G		Familial aplasia of the vermis	Pathogenic (May 04, 2023)
9-136429691-A-G		Familial aplasia of the vermis	Uncertain significance (Aug 19, 2022)
9-136429700-G-C		Inborn genetic diseases	Uncertain significance (Aug 12, 2022)
9-136429703-TTC-T		not specified	Uncertain significance (Apr 12, 2022)
9-136429711-CTG-C		Familial aplasia of the vermis	Pathogenic (Feb 23, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
INPP5E	protein_coding	protein_coding	ENST00000371712	10	11204

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00310	0.995	125445	0	17	125462	0.0000678

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.507	355	383	0.927	0.0000243	4050
Missense in Polyphen		87	109.3	0.79598		1089
Synonymous	-0.988	196	179	1.09	0.0000118	1389
Loss of Function	2.68	8	21.4	0.374	0.00000101	244

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000636	0.0000618
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000102	0.0000971
Middle Eastern	0.000109	0.000109
South Asian	0.000104	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts phosphatidylinositol 3,4,5-trisphosphate (PtdIns 3,4,5-P3) to PtdIns-P2, and phosphatidylinositol 4,5- bisphosphate to phosphatidylinositol 4-phosphate. Specific for lipid substrates, inactive towards water soluble inositol phosphates. {ECO:0000269|PubMed:10764818}.
• Disease: DISEASE: Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORMS) [MIM:610156]: An autosomal recessive disorder characterized by moderate mental retardation, truncal obesity, congenital non-progressive retinal dystrophy, and micropenis in males. The phenotype is similar to Bardet-Biedl syndrome and Cohen syndrome Distinguishing features are the age of onset, the non-progressive nature of the visual impairment, lack of dysmorphic facies, skin or gingival infection, microcephaly, mottled retina, polydactyly, and testicular anomalies. {ECO:0000269|PubMed:19668215}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Metabolism of lipids;3-phosphoinositide degradation;Metabolism;Phosphatidylinositol phosphate metabolism;Synthesis of PIPs at the Golgi membrane;PI Metabolism;Phospholipid metabolism;ARL13B-mediated ciliary trafficking of INPP5E;Cargo trafficking to the periciliary membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.114

Haploinsufficiency Scores

• pHI: 0.174
• hipred: Y
• hipred_score: 0.699
• ghis: 0.565

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.659

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Inpp5e
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype; cellular phenotype; growth/size/body region phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: inpp5e
• Affected structure: pronephric glomerulus
• Phenotype tag: abnormal
• Phenotype quality: cystic

Gene ontology

• Biological process: phosphatidylinositol biosynthetic process;biological_process;inositol phosphate dephosphorylation;phosphatidylinositol dephosphorylation
• Cellular component: ruffle;cytosol;plasma membrane;cilium;axoneme;Golgi cisterna membrane
• Molecular function: phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity;inositol-polyphosphate 5-phosphatase activity