PHLPP2

PH domain and leucine rich repeat protein phosphatase 2, the group of Protein phosphatases, Mg2+/Mn2+ dependent|Pleckstrin homology domain containing|Small nucleolar RNA protein coding host genes

Basic information

Region (hg38): 16:71637835-71724701

Previous symbols: [ "PHLPPL" ]

Links

ENSG00000040199 ∙ NCBI:23035 ∙ OMIM:611066 ∙ HGNC:29149 ∙ Uniprot:Q6ZVD8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHLPP2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHLPP2 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	1	3
missense			75	6		81
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			2			2
Total	0	0	77	8	1

Variants in PHLPP2

This is a list of pathogenic ClinVar variants found in the PHLPP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-71640475-T-A		not specified	Uncertain significance (Oct 29, 2021)
16-71640944-G-A		not specified	Uncertain significance (Jun 18, 2021)
16-71648900-G-A		not specified	Uncertain significance (Apr 25, 2022)
16-71648993-T-A		not specified	Uncertain significance (Jul 25, 2023)
16-71649008-T-C		not specified	Likely benign (Aug 10, 2021)
16-71649009-G-T		not specified	Uncertain significance (Jul 11, 2023)
16-71649014-A-G		not specified	Uncertain significance (Jan 17, 2024)
16-71649182-T-C		not specified	Uncertain significance (Apr 27, 2024)
16-71649315-G-A		not specified	Uncertain significance (Feb 23, 2023)
16-71649341-C-A		not specified	Uncertain significance (Jun 13, 2023)
16-71649390-C-T		not specified	Uncertain significance (May 09, 2023)
16-71649414-C-G		not specified	Uncertain significance (Dec 27, 2023)
16-71649426-C-T		not specified	Uncertain significance (Dec 03, 2021)
16-71649436-C-A		not specified	Uncertain significance (Jan 23, 2023)
16-71649446-G-C			Likely benign (Mar 01, 2018)
16-71649488-G-T		not specified	Uncertain significance (Nov 17, 2022)
16-71649495-T-G		not specified	Uncertain significance (Feb 04, 2022)
16-71649515-C-T		not specified	Uncertain significance (Jul 12, 2022)
16-71649527-G-A		not specified	Uncertain significance (Jul 20, 2021)
16-71649597-C-A		not specified	Uncertain significance (Aug 22, 2023)
16-71649644-C-T		not specified	Uncertain significance (Apr 26, 2023)
16-71649690-T-C		not specified	Uncertain significance (Feb 28, 2024)
16-71649702-C-T		not specified	Uncertain significance (Dec 21, 2023)
16-71649803-T-C		not specified	Uncertain significance (Oct 12, 2022)
16-71649856-G-A			Benign (Mar 01, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHLPP2	protein_coding	protein_coding	ENST00000568954	18	86867

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000121	1.00	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.631	765	717	1.07	0.0000386	8641
Missense in Polyphen		270	286.29	0.9431		3515
Synonymous	-1.65	324	288	1.12	0.0000156	2688
Loss of Function	4.48	21	57.7	0.364	0.00000353	654

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000362	0.000300
Ashkenazi Jewish	0.00	0.00
East Asian	0.000489	0.000489
Finnish	0.000417	0.000416
European (Non-Finnish)	0.000238	0.000237
Middle Eastern	0.000489	0.000489
South Asian	0.000196	0.000196
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser- 473' of Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). {ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, ECO:0000269|PubMed:20513427, ECO:0000269|PubMed:21986499, ECO:0000269|PubMed:24530606}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;PIP3 activates AKT signaling;Negative regulation of the PI3K/AKT network;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.112

Intolerance Scores

• loftool: 0.658
• rvis_EVS: -1.23
• rvis_percentile_EVS: 5.56

Haploinsufficiency Scores

• pHI: 0.519
• hipred: N
• hipred_score: 0.495
• ghis: 0.583

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.433

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phlpp2
• Phenotype: growth/size/body region phenotype; immune system phenotype; digestive/alimentary phenotype

Gene ontology

• Biological process: protein dephosphorylation;hippocampus development
• Cellular component: photoreceptor inner segment;nucleus;cytoplasm;cytosol;photoreceptor outer segment membrane
• Molecular function: protein serine/threonine phosphatase activity;protein binding;metal ion binding