PPP2R5D

protein phosphatase 2 regulatory subunit B'delta, the group of Armadillo like helical domain containing|Protein phosphatase 2 regulatory subunits

Basic information

Region (hg38): 6:42984552-43012342

Links

ENSG00000112640 ∙ NCBI:5528 ∙ OMIM:601646 ∙ HGNC:9312 ∙ Uniprot:Q14738 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AD
• Hogue-Janssens syndrome 1 (Strong), mode of inheritance: AD
• Hogue-Janssens syndrome 1 (Strong), mode of inheritance: AD
• Hogue-Janssens syndrome 1 (Supportive), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hogue-Janssens syndrome 1	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	Craniofacial; Musculoskeletal; Neurologic	25533962; 25972378; 26168268

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP2R5D gene.

• not provided (378 variants)
• Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome (35 variants)
• Inborn genetic diseases (23 variants)
• not specified (4 variants)
• See cases (3 variants)
• Intellectual disability (2 variants)
• Neurodevelopmental delay (2 variants)
• PPP2R5D-related condition (2 variants)
• Global developmental delay (1 variants)
• Encephalopathy (1 variants)
• Neurodevelopmental disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP2R5D 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			3	75	4	82
missense	9	8	142	4	2	165
nonsense						0
start loss						0
frameshift						0
inframe indel		2	9			11
splice donor/acceptor (+/-2bp)			1	1		2
splice region			10	18	2	30
non coding			7	69	23	99
Total	9	10	162	149	29

Variants in PPP2R5D

This is a list of pathogenic ClinVar variants found in the PPP2R5D region.

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

Position	Type	Phenotype	Significance	ClinVar
6-42984641-G-T			Benign (Jul 28, 2021)
6-42984646-G-T			Benign (Jun 06, 2020)
6-42984673-C-T			Uncertain significance (Apr 01, 2021)
6-42984683-C-T			Uncertain significance (Oct 07, 2019)
6-42984685-A-T			Conflicting classifications of pathogenicity (Dec 16, 2023)
6-42984690-C-T			Uncertain significance (Nov 21, 2022)
6-42984703-A-C			Uncertain significance (Dec 02, 2021)
6-42984713-G-A			Likely benign (Sep 27, 2023)
6-42984714-G-T			Likely benign (Jan 24, 2024)
6-42984721-T-C			Benign (Jan 21, 2024)
6-42984723-C-A			Likely benign (Nov 18, 2023)
6-42984835-C-G			Likely benign (Aug 19, 2018)
6-42989576-C-T			Benign (Jul 10, 2020)
6-42989595-C-A			Likely benign (Jul 30, 2023)
6-42989600-T-C			Likely benign (Dec 03, 2023)
6-42989614-C-G			Uncertain significance (Dec 13, 2023)
6-42989619-C-A			Likely benign (Dec 01, 2023)
6-42989620-A-G			Uncertain significance (Apr 08, 2022)
6-42989621-A-G			Uncertain significance (Nov 01, 2022)
6-42989623-G-A			Uncertain significance (Dec 25, 2023)
6-42989640-C-T			Likely benign (Jan 19, 2024)
6-42989646-T-G			Likely benign (May 25, 2022)
6-42989648-G-A			Uncertain significance (Mar 23, 2023)
6-42989652-C-T			Likely benign (Oct 13, 2022)
6-42989654-C-T			Benign/Likely benign (Dec 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP2R5D	protein_coding	protein_coding	ENST00000485511	16	27844

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000719	125720	0	3	125723	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.65	155	346	0.448	0.0000215	3981
Missense in Polyphen		35	124.86	0.28031		1535
Synonymous	0.259	131	135	0.972	0.00000800	1141
Loss of Function	5.24	2	35.9	0.0557	0.00000193	408

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.
• Disease: DISEASE: Mental retardation, autosomal dominant 35 (MRD35) [MIM:616355]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:25533962, ECO:0000269|PubMed:26168268}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Oocyte meiosis - Homo sapiens (human);mRNA surveillance pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Glycogen Metabolism;Signaling by GPCR;Degradation of beta-catenin by the destruction complex;RAF activation;Toll Like Receptor 7/8 (TLR7/8) Cascade;Interleukin-17 signaling;Signaling by WNT;Signal Transduction;Signaling by Interleukins;mtor signaling pathway;telomeres telomerase cellular aging and immortality;wnt signaling pathway;regulation of ck1/cdk5 by type 1 glutamate receptors;deregulation of cdk5 in alzheimers disease;chrebp regulation by carbohydrates and camp;protein kinase a at the centrosome;multi-step regulation of transcription by pitx2;skeletal muscle hypertrophy is regulated via akt-mtor pathway;erk1/erk2 mapk signaling pathway;keratinocyte differentiation;ctcf: first multivalent nuclear factor;Metabolism of carbohydrates;Cytokine Signaling in Immune system;Toll Like Receptor 9 (TLR9) Cascade;PP2A-mediated dephosphorylation of key metabolic factors;GPCR Dopamine D1like receptor;MyD88 cascade initiated on plasma membrane;Toll Like Receptor 10 (TLR10) Cascade;Toll Like Receptor 3 (TLR3) Cascade;Toll Like Receptor 5 (TLR5) Cascade;Toll-Like Receptors Cascades;CTLA4 inhibitory signaling;Costimulation by the CD28 family;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;Innate Immune System;Immune System;Metabolism;Adaptive Immune System;insulin Mam;RHO GTPases Activate Formins;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Nuclear Events (kinase and transcription factor activation);Disassembly of the destruction complex and recruitment of AXIN to the membrane;Aurora A signaling;akap95 role in mitosis and chromosome dynamics;DARPP-32 events;Glycolysis;RHO GTPase Effectors;Signaling by Rho GTPases;ERKs are inactivated;Signaling by NTRK1 (TRKA);Signaling by NTRKs;ERK/MAPK targets;MAPK targets/ Nuclear events mediated by MAP kinases;MAP kinase activation;TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation;Hemostasis;MyD88 dependent cascade initiated on endosome;Negative regulation of MAPK pathway;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;Beta-catenin phosphorylation cascade;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Opioid Signalling;G alpha (i) signalling events;M Phase;Glucose metabolism;Cell Cycle;Resolution of Sister Chromatid Cohesion;TRIF(TICAM1)-mediated TLR4 signaling ;MyD88-independent TLR4 cascade ;Toll Like Receptor 4 (TLR4) Cascade;Signaling by Receptor Tyrosine Kinases;Integration of energy metabolism;Platelet sensitization by LDL;Platelet homeostasis;Cell Cycle, Mitotic;GPCR downstream signalling;Intracellular signaling by second messengers;MyD88:Mal cascade initiated on plasma membrane;Toll Like Receptor TLR1:TLR2 Cascade;Toll Like Receptor TLR6:TLR2 Cascade;Toll Like Receptor 2 (TLR2) Cascade;Aurora B signaling;TCF dependent signaling in response to WNT;Alpha-synuclein signaling;Lissencephaly gene (LIS1) in neuronal migration and development;Presenilin action in Notch and Wnt signaling;insulin (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.327
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.852
• hipred: Y
• hipred_score: 0.825
• ghis: 0.658

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppp2r5d
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: protein dephosphorylation;signal transduction;nervous system development;negative regulation of peptidyl-threonine phosphorylation;regulation of protein autophosphorylation;positive regulation of protein dephosphorylation;regulation of phosphoprotein phosphatase activity
• Cellular component: protein phosphatase type 2A complex;nucleus;nucleoplasm;cytosol
• Molecular function: phosphoprotein phosphatase activity;protein serine/threonine phosphatase activity;protein binding;protein phosphatase regulator activity;protein phosphatase activator activity