INPP4B

protein-coding

inositol polyphosphate-4-phosphatase type II B, the group of C2 domain containing|Phosphoinositide phosphatases

Gene summary

INPP4B encodes the inositol polyphosphate 4-phosphatase type II, one of the enzymes involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 4 of the inositol ring from inositol 3,4-bisphosphate. There is limited data to suggest that the human type II enzyme is subject to alternative splicing, as has been established for the type I enzyme. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001101669.3

Inheritance

—

ClinVar variants

P:2U:99B:5

Top phenotype

Hypercholesterolemia, familial, 1

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr4:142,023,160-142,847,432

External References & Databases

Ensembl (ENSG00000109452)

Transcript & Mutation Effects

hg38 • Region Span ~824.3 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 INPP4B variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 3

Hypercholesterolemia, familial, 1Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001101669.3. 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			3 clinvar	1 clinvar		4
missense	2 clinvar		87 clinvar	4 clinvar		93
nonsense			4 clinvar			4
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	2	0	99	5	0	106

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 86 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001101669.3	RefSeq	NP_001095139.1	23	MANE Select
ENST00000262992.9	Ensembl	ENSP00000262992.4	23	MANE Select
NM_001331040.1	RefSeq	NP_001317969.1	23	Standard
NM_001385334.1	RefSeq	NP_001372263.1	23	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)
Inositol Phosphate Metabolism
Phosphatidylinositol Phosphate Metabolism
Joubert syndrome

Biological Process

phosphatidylinositol biosynthetic process
signal transduction
dephosphorylation
phosphatidylinositol-3-phosphate biosynthetic process
inositol phosphate metabolic process

Molecular Function

protein binding
phosphatidylinositol-3,4-bisphosphate 4-phosphatase activity
inositol-1,3,4-trisphosphate 4-phosphatase activity
phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity
inositol-3,4-bisphosphate 4-phosphatase activity

Cellular Component

cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000513000
Coding exons: 23
Length: 824273
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125748
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.13	410	480	0.855	0.0000233	6080
Missense (PolyPhen)		126	178.51	0.70584		2347
Synonymous	-0.139	181	179	1.01	0.00000930	1698
Loss of Function	5.37	12	55.0	0.218	0.00000308	647

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.000055	0.000054	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4- trisphosphate and inositol 1,4-bisphosphate.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.575
RVIS EVS: -0.44
RVIS percentile EVS: 24.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.911

Gene Damage Prediction

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