PPP1R12B

protein-coding

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

Gene summary

Myosin phosphatase is a protein complex comprised of three subunits: a catalytic subunit (PP1c-delta, protein phosphatase 1, catalytic subunit delta), a large regulatory subunit (MYPT, myosin phosphatase target) and small regulatory subunit (sm-M20). Two isoforms of MYPT have been isolated--MYPT1 and MYPT2, the first of which is widely expressed, and the second of which may be specific to heart, skeletal muscle, and brain. Each of the MYPT isoforms functions to bind PP1c-delta and increase phosphatase activity. This locus encodes both MYTP2 and M20. Alternatively spliced transcript variants encoding different isoforms have been identified. Related pseudogenes have been defined on the Y chromosome. [provided by RefSeq, Oct 2011]

Previous symbols:

MYPT2

MANE transcript

NM_002481.4

Inheritance

ClinVar variants

U:136B:7

Top phenotype

Congenital lactic acidosis

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr1:202,348,699-202,592,706

External References & Databases

Ensembl (ENSG00000077157)

Transcript & Mutation Effects

hg38 • Region Span ~244.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: LiferaOmics

Genetic evidence – Published PMID: 37644014 – Family 1 – one proband. Case-level (biallelic predicted null in AR model; canonical splice donor +1 variant; homozygous; no consanguinity information → no −0.5 applied) = 1.5; Segregation = 0; Case-control = 0 Family 1 total = 1.5 PMID: 37644014 total = 1.5 Published genetic evidence total = 1.5 / 12 Genetic evidence – Our case Family 1 – one proband. Case-level (biallelic predicted null in AR model; canonical splice donor +1 variant; homozygous scored once; consanguinity −0.5 applied) = (1.5 − 0.5) = 1.0; Segregation = 0; Case-control = 0 Family 1 total = 1.0 Our case contribution = 1.0 / 12 Total genetic evidence (published AR + our case) Published genetic evidence: 1.5 Our additional case: 1.0 Total genetic evidence = 2.5 / 12 Experimental evidence – Published No disease-specific experimental evidence (functional alteration in patient cells, model organism, rescue, etc.) has been identified for PPP1R12B in autosomal recessive neurodevelopmental disorder. Experimental evidence total = 0 / 6 Overall score Genetic evidence = 2.5 Experimental evidence = 0 Overall score = 2.5 / 18

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPP1R12B variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 123

not providedTotal: 4

Congenital lactic acidosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002481.4. 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			5 clinvar	2 clinvar		7
missense			125 clinvar	5 clinvar		130
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	136	7	0	143

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002481.4	RefSeq	NP_002472.2	24	MANE Select
ENST00000608999.6	Ensembl	ENSP00000476755.1	24	MANE Select
NM_001167857.2	RefSeq	NP_001161329.1	10	Standard
NM_001167858.2	RefSeq	NP_001161330.1	9	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

regulation of muscle contraction
signal transduction
positive regulation of catalytic activity
negative regulation of catalytic activity

Molecular Function

enzyme inhibitor activity
protein binding
enzyme activator activity
phosphatase regulator activity
protein kinase binding

Cellular Component

nucleoplasm
cytoplasm
cytosol
cytoskeleton
Z disc

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000608999
Coding exons: 24
Length: 244008
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 58
Defined: 125748
p: 0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.972	476	540	0.882	0.0000285	6373
Missense (PolyPhen)		143	180.81	0.79088		1994
Synonymous	1.54	169	196	0.860	0.00000967	1932
Loss of Function	4.77	18	56.8	0.317	0.00000309	656

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.00017	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates myosin phosphatase activity. Augments Ca(2+) sensitivity of the contractile apparatus. {ECO:0000269|PubMed:11067852, ECO:0000269|PubMed:9570949}.;

Recessive Scores

pRec: 0.108

Intolerance Scores

LoFtool: 0.896
RVIS EVS: -0.86
RVIS percentile EVS: 10.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.940

Gene Damage Prediction

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