PPP1R12A

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

Basic information

Region (hg38): 12:79773563-79935460

Previous symbols: [ "MYPT1" ]

Links

ENSG00000058272 ∙ NCBI:4659 ∙ OMIM:602021 ∙ HGNC:7618 ∙ Uniprot:O14974 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• genitourinary and/or brain malformation syndrome (Strong), mode of inheritance: AD
• genitourinary and/or brain malformation syndrome (Strong), mode of inheritance: AD
• genitourinary and/or brain malformation syndrome (Strong), mode of inheritance: AD
• genitourinary and/or brain malformation syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Genitourinary and/or/brain malformation syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Genitourinary; Gastrointestinal; Neurologic	31883643

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP1R12A gene.

• Genitourinary and/or brain malformation syndrome (4 variants)
• PPP1R12A-related disorder (2 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP1R12A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	7	8	21
missense			60	11	6	77
nonsense	3	3				6
start loss						0
frameshift	2	5	1			8
inframe indel			3	2		5
splice donor/acceptor (+/-2bp)		1	1			2
splice region			3	4	2	9
non coding			2	2	6	10
Total	5	9	73	22	20

Variants in PPP1R12A

This is a list of pathogenic ClinVar variants found in the PPP1R12A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-79775930-T-A		PPP1R12A-related disorder	Uncertain significance (Oct 01, 2022)
12-79775976-C-T			Likely pathogenic (May 23, 2024)
12-79779349-C-T			Benign (May 01, 2022)
12-79781840-C-A			Uncertain significance (Mar 29, 2021)
12-79781858-T-C			Uncertain significance (Sep 03, 2023)
12-79781867-A-G			Benign (Aug 30, 2023)
12-79781874-T-C			Likely benign (Nov 22, 2022)
12-79786420-T-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 02, 2023)
12-79786428-AT-A		Genitourinary and/or brain malformation syndrome	Likely pathogenic (-)
12-79786438-G-C		Inborn genetic diseases	Uncertain significance (Aug 04, 2022)
12-79788632-T-C			Uncertain significance (Nov 23, 2022)
12-79788648-CT-C		Genitourinary and/or brain malformation syndrome	Likely pathogenic (Aug 01, 2021)
12-79788655-A-C		Inborn genetic diseases	Uncertain significance (Dec 17, 2021)
12-79788661-G-C		Genitourinary and/or brain malformation syndrome	Uncertain significance (May 27, 2020)
12-79788667-T-A			Uncertain significance (Nov 25, 2020)
12-79788681-C-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Mar 07, 2023)
12-79788749-A-G		PPP1R12A-related disorder	Likely benign (Aug 12, 2024)
12-79788751-C-T		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
12-79788752-G-A		Genitourinary and/or brain malformation syndrome	Pathogenic (Feb 02, 2023)
12-79788772-CT-C		Genitourinary and/or brain malformation syndrome	Likely pathogenic (Jun 15, 2020)
12-79788773-TG-T		Genitourinary and/or brain malformation syndrome	Likely pathogenic (Sep 03, 2020)
12-79790482-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 15, 2024)
12-79793874-T-C			Uncertain significance (Mar 18, 2022)
12-79793882-GA-G		PPP1R12A-related disorder	Pathogenic (Dec 09, 2023)
12-79793893-T-C			Likely benign (Dec 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP1R12A	protein_coding	protein_coding	ENST00000450142	25	161898

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.82e-8	124534	0	28	124562	0.000112

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.64	342	509	0.671	0.0000254	6674
Missense in Polyphen		133	259.93	0.51167		3302
Synonymous	0.186	173	176	0.982	0.00000841	1942
Loss of Function	6.81	3	59.8	0.0501	0.00000338	772

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000198	0.000198
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000214	0.000213
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN- dependent suppression of HIF1A activity. {ECO:0000269|PubMed:18477460, ECO:0000269|PubMed:19245366, ECO:0000269|PubMed:20354225}.
• Pathway: Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Focal Adhesion;Regulation of Actin Cytoskeleton;Signal Transduction;RHO GTPases Activate ROCKs;RHO GTPases activate PAKs;RHO GTPases activate PKNs;RHO GTPases activate CIT;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of PLK1 Activity at G2/M Transition;G2/M Transition;Mitotic G2-G2/M phases;Cell Cycle;TNFalpha;Integrin-linked kinase signaling;Cell Cycle, Mitotic;PLK1 signaling events;RhoA signaling pathway (Consensus)

Recessive Scores

• pRec: 0.418

Intolerance Scores

• rvis_EVS: -0.86
• rvis_percentile_EVS: 10.85

Haploinsufficiency Scores

• pHI: 0.983
• hipred: Y
• hipred_score: 0.745
• ghis: 0.648

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.329

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppp1r12a
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; renal/urinary system phenotype; immune system phenotype; growth/size/body region phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: ppp1r12a
• Affected structure: neuroepithelial cell
• Phenotype tag: abnormal
• Phenotype quality: decreased accumulation

Gene ontology

• Biological process: mitotic cell cycle;protein dephosphorylation;centrosome cycle;signal transduction;regulation of cell adhesion;regulation of myosin-light-chain-phosphatase activity;positive regulation of myosin-light-chain-phosphatase activity;cellular response to drug;negative regulation of catalytic activity;positive regulation of transcription by RNA polymerase II;regulation of nucleocytoplasmic transport;regulation of establishment of endothelial barrier
• Cellular component: kinetochore;nucleoplasm;cytoplasm;centrosome;cytosol;focal adhesion;actin cytoskeleton;Z disc;A band;contractile fiber;PTW/PP1 phosphatase complex
• Molecular function: enzyme inhibitor activity;protein binding;phosphatase regulator activity;protein kinase binding;14-3-3 protein binding