INPP5A

protein-coding

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

Gene summary

The protein encoded by this gene is a membrane-associated type I 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. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005539.5

Inheritance

—

ClinVar variants

U:61B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr10:132,537,787-132,783,480

External References & Databases

Ensembl (ENSG00000068383)

Transcript & Mutation Effects

hg38 • Region Span ~245.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to INPP5A variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 51

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005539.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	2 clinvar	2 clinvar	9
missense			51 clinvar			51
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	61	2	2	65

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005539.5	RefSeq	NP_005530.3	15	MANE Select
ENST00000368594.8	Ensembl	ENSP00000357583.3	15	MANE Select
NM_001321042.2	RefSeq	NP_001307971.1	12	Standard
ENST00000342652.6	Ensembl	ENSP00000340707.6	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Inositol phosphate metabolism - Homo sapiens (human)
Phosphatidylinositol signaling system - Homo sapiens (human)
D-myo-inositol (1,3,4)-trisphosphate biosynthesis
superpathway of D-myo-inositol (1,4,5)-trisphosphate metabolism
1D-myo-inositol hexakisphosphate biosynthesis II (mammalian)

Biological Process

inositol phosphate metabolic process
inositol phosphate dephosphorylation
phosphatidylinositol dephosphorylation
inositol phosphate-mediated signaling

Molecular Function

inositol-polyphosphate 5-phosphatase activity
protein binding
PH domain binding
inositol-1,4,5-trisphosphate 5-phosphatase activity
inositol-1,3,4,5-tetrakisphosphate 5-phosphatase activity

Cellular Component

plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368594
Coding exons: 15
Length: 245656
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125748
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.78	176	256	0.687	0.0000166	2739
Missense (PolyPhen)		42	82.86	0.50688		828
Synonymous	-0.781	112	102	1.10	0.00000730	721
Loss of Function	4.38	4	29.8	0.134	0.00000160	334

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Major isoenzyme hydrolyzing the calcium-mobilizing second messenger Ins(1,4,5)P3, this is a signal-terminating reaction.;

Recessive Scores

pRec: 0.205

Intolerance Scores

LoFtool: 0.178
RVIS EVS: -0.42
RVIS percentile EVS: 25.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.989

Gene Damage Prediction

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