PPP1R12C

protein-coding

protein phosphatase 1 regulatory subunit 12C, the group of Protein phosphatase 1 regulatory subunits|Myosin phosphatase targeting family|Ankyrin repeat domain containing

Gene summary

The gene encodes a subunit of myosin phosphatase. The encoded protein regulates the catalytic activity of protein phosphatase 1 delta and assembly of the actin cytoskeleton. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

Previous symbols:

LENG3

MANE transcript

NM_017607.4

Inheritance

—

ClinVar variants

U:139B:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr19:55,090,914-55,117,637

External References & Databases

Ensembl (ENSG00000125503)

Transcript & Mutation Effects

hg38 • Region Span ~26.7 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 PPP1R12C variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 123

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017607.4. 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			4 clinvar	9 clinvar	2 clinvar	15
missense			123 clinvar	4 clinvar	1 clinvar	128
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	0	0	139	13	3	155

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017607.4	RefSeq	NP_060077.1	22	MANE Select
ENST00000263433.8	Ensembl	ENSP00000263433.1	22	MANE Select
NM_001271618.2	RefSeq	NP_001258547.1	22	Standard
ENST00000435544.6	Ensembl	ENSP00000387833.2	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Focal adhesion - Homo sapiens (human)
Oxytocin signaling pathway - Homo sapiens (human)
Regulation of actin cytoskeleton - Homo sapiens (human)
Vascular smooth muscle contraction - Homo sapiens (human)
Proteoglycans in cancer - Homo sapiens (human)

Biological Process

signal transduction
negative regulation of catalytic activity

Molecular Function

enzyme inhibitor activity
protein binding
phosphatase regulator activity
protein kinase binding

Cellular Component

cytoplasm
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263433
Coding exons: 22
Length: 26647
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125747
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.63	343	439	0.781	0.0000306	4858
Missense (PolyPhen)		177	247.68	0.71463		2465
Synonymous	-0.427	198	191	1.04	0.0000136	1659
Loss of Function	4.34	10	39.3	0.254	0.00000210	449

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates myosin phosphatase activity. {ECO:0000269|PubMed:11399775}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.525
RVIS EVS: -1.04
RVIS percentile EVS: 7.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.781

Gene Damage Prediction

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