PPP1R18

protein-coding

protein phosphatase 1 regulatory subunit 18, the group of Protein phosphatase 1 regulatory subunits

Gene summary

Protein phosphatase-1 (PP1; see MIM 176875) interacts with regulatory subunits that target the enzyme to different cellular locations and change its activity toward specific substrates. Phostensin is a regulatory subunit that targets PP1 to F-actin (see MIM 102610) cytoskeleton (Kao et al., 2007 [PubMed 17374523]).[supplied by OMIM, Mar 2008]

Previous symbols:

KIAA1949

MANE transcript

NM_133471.4

Inheritance

—

ClinVar variants

U:89B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr6:30,676,389-30,687,895

External References & Databases

Ensembl (ENSG00000146112)

Transcript & Mutation Effects

hg38 • Region Span ~11.5 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 PPP1R18 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 88

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133471.4. 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			2 clinvar			2
missense			85 clinvar	6 clinvar	3 clinvar	94
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	89	6	3	98

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_133471.4	RefSeq	NP_597728.1	3	MANE Select
ENST00000274853.8	Ensembl	ENSP00000274853.3	3	MANE Select
NM_001134870.2	RefSeq	NP_001128342.1	3	Standard
ENST00000399199.7	Ensembl	ENSP00000382150.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TYROBP Causal Network

Molecular Function

actin binding
protein binding
phosphatase binding

Cellular Component

cytoplasm
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000274853
Coding exons: 3
Length: 11507
Individuals with no LoFs: 122612
Homozygous LoFs: 0
Heterozygous LoFs: 27
Defined: 122639
p: 0.000110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.01	275	326	0.843	0.0000184	3832
Missense (PolyPhen)		79	109.39	0.72218		1220
Synonymous	1.23	119	137	0.866	0.00000725	1359
Loss of Function	2.82	10	25.3	0.395	0.00000153	258

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00015	0.00014	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00010	0.000093	rare
European (Non-Finnish)	0.00017	0.00016	rare
South Asian	0.00010	0.000099	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 1: May target protein phosphatase 1 to F-actin cytoskeleton. {ECO:0000269|PubMed:24434620}.;

Intolerance Scores

RVIS EVS: 0.8
RVIS percentile EVS: 87.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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