PHLPP1

PH domain and leucine rich repeat protein phosphatase 1, the group of Pleckstrin homology domain containing|Protein phosphatases, Mg2+/Mn2+ dependent

Basic information

Region (hg38): 18:62715541-62980433

Previous symbols: [ "PLEKHE1", "PHLPP" ]

Links

ENSG00000081913 ∙ NCBI:23239 ∙ OMIM:609396 ∙ HGNC:20610 ∙ Uniprot:O60346 ∙ 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 PHLPP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHLPP1 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				11	2	13
missense			102	2	1	105
nonsense						0
start loss						0
frameshift			1			1
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	104	13	4

Variants in PHLPP1

This is a list of pathogenic ClinVar variants found in the PHLPP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-62715760-C-A		not specified	Uncertain significance (Aug 02, 2022)
18-62715767-T-G			Likely benign (Jan 01, 2023)
18-62715770-G-T			Likely benign (Mar 01, 2023)
18-62715773-A-T			Likely benign (Mar 01, 2023)
18-62715776-A-T			Likely benign (Mar 01, 2023)
18-62715779-A-T			Likely benign (Mar 01, 2023)
18-62715782-A-C			Likely benign (Feb 01, 2023)
18-62715790-C-A		not specified	Uncertain significance (May 07, 2024)
18-62715810-G-A		not specified	Uncertain significance (Jun 22, 2023)
18-62715844-C-T		not specified	Uncertain significance (May 12, 2024)
18-62715847-T-G		not specified	Uncertain significance (Oct 25, 2022)
18-62715906-C-G		not specified	Uncertain significance (May 25, 2022)
18-62715910-G-C		not specified	Uncertain significance (Dec 26, 2023)
18-62715969-C-T		not specified	Uncertain significance (Aug 12, 2021)
18-62716014-G-A		not specified	Uncertain significance (Sep 20, 2023)
18-62716018-C-T		not specified	Uncertain significance (Jun 07, 2023)
18-62716074-TCCGCGGCCG-T			Uncertain significance (Jan 30, 2017)
18-62716162-C-G		not specified	Uncertain significance (Jun 22, 2023)
18-62716179-T-A		not specified	Uncertain significance (Jun 13, 2024)
18-62716189-C-G		not specified	Uncertain significance (Jan 08, 2024)
18-62716189-C-T		not specified	Uncertain significance (Apr 13, 2022)
18-62716203-A-T		not specified	Uncertain significance (Mar 14, 2023)
18-62716225-A-G		not specified	Uncertain significance (Dec 19, 2022)
18-62716234-C-T		not specified	Uncertain significance (Apr 07, 2023)
18-62716274-C-T			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHLPP1	protein_coding	protein_coding	ENST00000262719	17	264995

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000730	124669	0	14	124683	0.0000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.75	691	833	0.829	0.0000469	11022
Missense in Polyphen		260	358.41	0.72542		4223
Synonymous	-0.256	369	363	1.02	0.0000230	3642
Loss of Function	5.95	8	56.1	0.143	0.00000304	690

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000582	0.0000582
Ashkenazi Jewish	0.00	0.00
East Asian	0.000169	0.000167
Finnish	0.00	0.00
European (Non-Finnish)	0.0000463	0.0000442
Middle Eastern	0.000169	0.000167
South Asian	0.000100	0.0000980
Other	0.000165	0.000165

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 AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). 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 suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). 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 (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity). {ECO:0000250|UniProtKB:Q8CHE4, ECO:0000250|UniProtKB:Q9WTR8, ECO:0000269|PubMed:15808505, ECO:0000269|PubMed:17386267, ECO:0000269|PubMed:18162466, ECO:0000269|PubMed:19079341, 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;EGFR1;PIP3 activates AKT signaling;Negative regulation of the PI3K/AKT network;Intracellular signaling by second messengers (Consensus)

Recessive Scores

• pRec: 0.142

Haploinsufficiency Scores

• pHI: 0.542
• hipred: Y
• hipred_score: 0.639
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.715

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phlpp1
• Phenotype: growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; digestive/alimentary phenotype

Gene ontology

• Biological process: regulation of T cell anergy;protein dephosphorylation;apoptotic process;entrainment of circadian clock;regulation of apoptotic process;regulation of MAPK cascade;regulation of JNK cascade;negative regulation of protein kinase B signaling;regulation of p38MAPK cascade
• Cellular component: photoreceptor inner segment;cytoplasm;cytosol;nuclear membrane;photoreceptor outer segment membrane
• Molecular function: protein serine/threonine phosphatase activity;protein binding;metal ion binding