PRR5

proline rich 5, the group of MTOR complex 2

Basic information

Region (hg38): 22:44668546-44737681

Links

ENSG00000186654 ∙ NCBI:55615 ∙ OMIM:609406 ∙ HGNC:31682 ∙ Uniprot:P85299 ∙ 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 PRR5 gene.

• Inborn genetic diseases (17 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRR5 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						0
missense			16	2		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	2	0

Variants in PRR5

This is a list of pathogenic ClinVar variants found in the PRR5 region.

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

Position	Type	Phenotype	Significance	ClinVar
22-44679839-T-C		not specified	Uncertain significance (Sep 20, 2023)
22-44679840-C-T		not specified	Uncertain significance (Oct 22, 2021)
22-44679859-G-A		not specified	Uncertain significance (Dec 01, 2022)
22-44679875-G-T		not specified	Uncertain significance (Jan 03, 2024)
22-44702535-A-G		not specified	Uncertain significance (Jan 19, 2024)
22-44714622-C-A			not provided (-)
22-44726633-G-T		not specified	Uncertain significance (Dec 06, 2021)
22-44731768-T-G		not specified	Uncertain significance (Sep 14, 2022)
22-44731769-T-A		not specified	Uncertain significance (Sep 14, 2022)
22-44732278-G-A		not specified	Uncertain significance (Jan 23, 2024)
22-44732311-A-G		not specified	Uncertain significance (Jun 21, 2021)
22-44732312-G-A		not specified	Uncertain significance (Feb 16, 2023)
22-44732330-C-T		not specified	Uncertain significance (Dec 13, 2021)
22-44732339-G-A		not specified	Uncertain significance (Sep 29, 2022)
22-44732350-C-T		not specified	Uncertain significance (Nov 09, 2021)
22-44732359-C-G		not specified	Uncertain significance (Feb 27, 2024)
22-44732384-T-C		not specified	Uncertain significance (Dec 13, 2023)
22-44735048-G-A		not specified	Uncertain significance (Jan 20, 2023)
22-44736789-C-T		not specified	Uncertain significance (May 31, 2023)
22-44736832-G-A		not specified	Uncertain significance (Nov 09, 2021)
22-44736863-C-G		not specified	Uncertain significance (Apr 07, 2022)
22-44736882-G-C		not specified	Uncertain significance (Jan 31, 2024)
22-44736903-G-A		not specified	Uncertain significance (Nov 12, 2021)
22-44736951-G-A			Likely benign (Oct 01, 2023)
22-44736984-G-T		not specified	Uncertain significance (Jun 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRR5	protein_coding	protein_coding	ENST00000403581	9	68969

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0669	0.930	125693	0	37	125730	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.240	276	265	1.04	0.0000184	2596
Missense in Polyphen		91	94.502	0.96295		1000
Synonymous	-0.406	131	125	1.05	0.00000916	866
Loss of Function	2.63	5	16.6	0.302	7.06e-7	197

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000242
Ashkenazi Jewish	0.00	0.00
East Asian	0.000445	0.000435
Finnish	0.000100	0.0000924
European (Non-Finnish)	0.000127	0.000123
Middle Eastern	0.000445	0.000435
South Asian	0.000212	0.000196
Other	0.000169	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient- insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. PRR5 plays an important role in regulation of PDGFRB expression and in modulation of platelet-derived growth factor signaling. May act as a tumor suppressor in breast cancer. {ECO:0000269|PubMed:15718101, ECO:0000269|PubMed:17599906}.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Target Of Rapamycin (TOR) Signaling;Disease;Signal Transduction;Gene expression (Transcription);VEGFA-VEGFR2 Pathway;Generic Transcription Pathway;CD28 dependent PI3K/Akt signaling;CD28 co-stimulation;Costimulation by the CD28 family;RNA Polymerase II Transcription;Immune System;Adaptive Immune System;Regulation of TP53 Degradation;Regulation of TP53 Expression and Degradation;PIP3 activates AKT signaling;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Signaling by VEGF;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;mTOR signaling pathway;Diseases of signal transduction;VEGFR2 mediated vascular permeability (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.655
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.91

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.640
• ghis: 0.460

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.895

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prr5

Gene ontology

• Biological process: cell cycle;positive regulation of phosphatidylinositol 3-kinase signaling;activation of protein kinase B activity;TORC2 signaling
• Cellular component: cytosol;TORC2 complex
• Molecular function: protein binding