PPP1R9B

protein-coding

protein phosphatase 1 regulatory subunit 9B, the group of Protein phosphatase 1 regulatory subunits|PDZ domain containing

Gene summary

This gene encodes a scaffold protein that functions as a regulatory subunit of protein phosphatase 1a. Expression of this gene is particularly high in dendritic spines, suggesting that the encoded protein may play a role in receiving signals from the central nervous system. The encoded protein has putative tumor suppressor function and decreased expression has been observed in tumors. [provided by RefSeq, Feb 2014]

Previous symbols:

PPP1R6
PPP1R9

MANE transcript

NM_032595.5

Inheritance

—

ClinVar variants

U:50B:23

Top phenotype

PPP1R9B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr17:50,133,737-50,150,677

External References & Databases

Ensembl (ENSG00000108819)

Transcript & Mutation Effects

hg38 • Region Span ~16.9 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 PPP1R9B variants in ClinVar

3 Conditions Cataloged

not providedTotal: 35

PPP1R9B-related disorderTotal: 19

not specifiedTotal: 15

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032595.5. 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			20 clinvar	11 clinvar	2 clinvar	33
missense			24 clinvar	6 clinvar	2 clinvar	32
nonsense			1 clinvar			1
start loss						0
frameshift					2 clinvar	2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	50	17	6	73

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032595.5	RefSeq	NP_115984.3	10	MANE Select
ENST00000612501.2	Ensembl	ENSP00000478767.1	10	MANE Select
ENST00000962426.1	Ensembl	ENSP00000632485.1	9	Standard
ENST00000962427.1	Ensembl	ENSP00000632486.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of cell growth by extracellular stimulus
actin filament organization
cell cycle arrest
regulation of exit from mitosis
RNA splicing

Molecular Function

protein phosphatase inhibitor activity
protein binding
protein phosphatase 1 binding
actin filament binding

Cellular Component

protein phosphatase type 1 complex
nucleoplasm
cytoplasm
plasma membrane
adherens junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316878
Coding exons: 12
Length: 16888
Individuals with no LoFs: 121424
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 121444
p: 0.0000823

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.02	206	369	0.558	0.0000205	5148
Missense (PolyPhen)		20	85.235	0.23464		1011
Synonymous	-0.417	169	162	1.04	0.00000998	1626
Loss of Function	4.74	1	28.2	0.0355	0.00000128	364

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	0.0011	0.0011	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Seems to act as a scaffold protein in multiple signaling pathways. Modulates excitatory synaptic transmission and dendritic spine morphology. Binds to actin filaments (F-actin) and shows cross-linking activity. Binds along the sides of the F-actin. May play an important role in linking the actin cytoskeleton to the plasma membrane at the synaptic junction. Believed to target protein phosphatase 1/PP1 to dendritic spines, which are rich in F-actin, and regulates its specificity toward ion channels and other substrates, such as AMPA-type and NMDA-type glutamate receptors. Plays a role in regulation of G-protein coupled receptor signaling, including dopamine D2 receptors and alpha- adrenergic receptors. May establish a signaling complex for dopaminergic neurotransmission through D2 receptors by linking receptors downstream signaling molecules and the actin cytoskeleton. Binds to ADRA1B and RGS2 and mediates regulation of ADRA1B signaling. May confer to Rac signaling specificity by binding to both, RacGEFs and Rac effector proteins. Probably regulates p70 S6 kinase activity by forming a complex with TIAM1 (By similarity). Required for hepatocyte growth factor (HGF)- induced cell migration. {ECO:0000250, ECO:0000269|PubMed:19151759}.;

Recessive Scores

pRec: 0.251

Essentials

Indispensability pred.: E
Indispensability score: 0.766

Gene Damage Prediction

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