PPP1R3A

protein phosphatase 1 regulatory subunit 3A, the group of Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 7:113876777-114075920

Previous symbols: [ "PPP1R3" ]

Links

ENSG00000154415 ∙ NCBI:5506 ∙ OMIM:600917 ∙ HGNC:9291 ∙ Uniprot:Q16821 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diabetes mellitus, noninsulin-dependent (No Known Disease Relationship), mode of inheritance: Unknown
• diabetes mellitus, noninsulin-dependent (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Insulin resistance, severe, digenic	Digenic	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	Endocrine	12118251
Severe digenic insulin resistance has been reported as resulting from digenic variants in PPP1R3A and PPARG

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP1R3A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP1R3A 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				2		2
missense			70	10	12	92
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					4	4
Total	0	0	71	12	16

Variants in PPP1R3A

This is a list of pathogenic ClinVar variants found in the PPP1R3A region.

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

Position	Type	Phenotype	Significance	ClinVar
7-113877258-AATTGA-CAGTGTTAAAT		Glycemia variation	association (Oct 01, 2009)
7-113877754-C-T		not specified	Uncertain significance (Mar 20, 2024)
7-113877775-G-A		not specified	Uncertain significance (Dec 21, 2022)
7-113877808-A-G			Uncertain significance (May 08, 2017)
7-113877832-A-C		Monogenic diabetes	Uncertain significance (Feb 09, 2018)
7-113877833-T-C		Monogenic diabetes	Benign (Dec 21, 2018)
7-113877877-G-C		not specified	Uncertain significance (Jan 10, 2022)
7-113877899-C-T		not specified	Uncertain significance (May 08, 2024)
7-113877923-C-T		not specified	Uncertain significance (Aug 02, 2022)
7-113877944-C-A		not specified	Uncertain significance (Mar 21, 2023)
7-113877949-C-T		not specified	Uncertain significance (Aug 21, 2023)
7-113877964-T-C		not specified	Uncertain significance (Aug 10, 2021)
7-113878048-T-C		Monogenic diabetes	Benign (Dec 21, 2018)
7-113878061-T-C		not specified	Uncertain significance (Apr 19, 2023)
7-113878066-C-G		not specified	Uncertain significance (May 28, 2024)
7-113878101-G-C		not specified	Uncertain significance (Mar 25, 2024)
7-113878102-A-C		Monogenic diabetes	Likely benign (Mar 10, 2017)
7-113878102-A-G		Monogenic diabetes	Uncertain significance (Sep 22, 2017)
7-113878120-C-T		Monogenic diabetes	Uncertain significance (Oct 05, 2018)
7-113878163-A-C		not specified	Uncertain significance (May 20, 2024)
7-113878192-G-T		not specified	Uncertain significance (May 05, 2023)
7-113878207-C-T		Monogenic diabetes	Likely benign (Jan 26, 2018)
7-113878249-G-A			Uncertain significance (-)
7-113878269-C-A		not specified	Uncertain significance (Jul 05, 2023)
7-113878270-A-G		Monogenic diabetes • not specified	Uncertain significance (Feb 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP1R3A	protein_coding	protein_coding	ENST00000284601	4	199144

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.31e-16	0.402	125018	5	705	125728	0.00283

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.300	567	547	1.04	0.0000269	7356
Missense in Polyphen		101	105.23	0.95979		1545
Synonymous	-1.10	219	199	1.10	0.0000104	2100
Loss of Function	1.52	29	39.3	0.738	0.00000214	571

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00294	0.00293
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000708	0.000707
Finnish	0.00143	0.00143
European (Non-Finnish)	0.00487	0.00482
Middle Eastern	0.000708	0.000707
South Asian	0.00140	0.00141
Other	0.00212	0.00196

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase (By similarity). {ECO:0000250}.
• Disease: DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:7926294}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Insulin resistance - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Insulin Signaling;Insulin-mediated glucose transport (Consensus)

Recessive Scores

• pRec: 0.184

Intolerance Scores

• loftool: 0.967
• rvis_EVS: 2.67
• rvis_percentile_EVS: 98.86

Haploinsufficiency Scores

• pHI: 0.0551
• hipred: N
• hipred_score: 0.172
• ghis: 0.392

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.477

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppp1r3a
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: glycogen metabolic process
• Cellular component: integral component of membrane