PPP2R3C

protein phosphatase 2 regulatory subunit B''gamma, the group of Protein phosphatase 2 regulatory subunits

Basic information

Region (hg38): 14:35085467-35122517

Previous symbols: [ "C14orf10" ]

Links

ENSG00000092020 ∙ NCBI:55012 ∙ OMIM:615902 ∙ HGNC:17485 ∙ Uniprot:Q969Q6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (Limited), mode of inheritance: AR
• spermatogenic failure 36 (Limited), mode of inheritance: AD
• gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spermatogenic failure 36; Myoectodermal gonadal dysgenesis syndrome	AD/AR	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	Audiologic/Otolaryngologic; Craniofacial; Dermatologic; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	30893644; 34750818; 35812758

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP2R3C gene.

• Spermatogenic failure 36 (3 variants)
• Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP2R3C 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	3		19	1		23
nonsense						0
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	3	0	21	1	2

Highest pathogenic variant AF is 0.00000657

Variants in PPP2R3C

This is a list of pathogenic ClinVar variants found in the PPP2R3C region.

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

Position	Type	Phenotype	Significance	ClinVar
14-35085605-G-T		not specified	Uncertain significance (May 18, 2023)
14-35085640-C-CCT		Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy	Uncertain significance (-)
14-35085673-A-T		not specified	Uncertain significance (Jan 31, 2022)
14-35085702-C-T		Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy	Pathogenic (Aug 31, 2022)
14-35085714-T-C		not specified	Uncertain significance (Jun 06, 2023)
14-35085787-G-GA		PPP2R3C-related disorder	Benign (Nov 25, 2019)
14-35087967-G-A		not specified	Uncertain significance (Mar 19, 2024)
14-35087992-T-C		not specified	Uncertain significance (Jul 15, 2021)
14-35091096-C-T		not specified	Uncertain significance (Jun 21, 2023)
14-35091134-A-G		Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy • Spermatogenic failure 36	Pathogenic (-)
14-35095085-C-T		not specified	Uncertain significance (Apr 22, 2022)
14-35095103-G-A		not specified	Uncertain significance (Jan 02, 2024)
14-35095118-C-G		not specified	Uncertain significance (Dec 26, 2023)
14-35095164-T-C		not specified	Uncertain significance (Jul 26, 2021)
14-35095167-C-T		not specified	Uncertain significance (Nov 17, 2022)
14-35095181-TG-T		Spermatogenic failure 36	Uncertain significance (Sep 17, 2024)
14-35096590-C-G		not specified	Uncertain significance (Nov 21, 2023)
14-35096597-T-C		not specified	Uncertain significance (Nov 29, 2023)
14-35096617-A-G		not specified	Uncertain significance (Jul 13, 2021)
14-35096756-TTA-T		not specified	Uncertain significance (Sep 08, 2023)
14-35099271-AAAG-A		Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy	Pathogenic (Aug 31, 2022)
14-35099280-G-C		not specified	Uncertain significance (Jan 06, 2023)
14-35099310-G-GGAGTAGAAA		Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy	Pathogenic (Aug 31, 2022)
14-35099380-A-G		Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy • Spermatogenic failure 36	Pathogenic (-)
14-35109847-C-T		not specified	Uncertain significance (Dec 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP2R3C	protein_coding	protein_coding	ENST00000261475	13	37051

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.82e-9	0.881	125697	0	50	125747	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.35	168	225	0.747	0.0000108	3008
Missense in Polyphen		51	72.51	0.70335		1015
Synonymous	-0.830	90	80.5	1.12	0.00000407	777
Loss of Function	1.72	17	26.6	0.640	0.00000112	374

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000279	0.000279
Ashkenazi Jewish	0.00	0.00
East Asian	0.000273	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000284	0.000281
Middle Eastern	0.000273	0.000272
South Asian	0.000215	0.000196
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate MCM3AP phosphorylation through phosphatase recruitment. May act as a negative regulator of ABCB1 expression and function through the dephosphorylation of ABCB1 by TFPI2/PPP2R3C complex. May play a role in the activation-induced cell death of B-cells. {ECO:0000250|UniProtKB:Q9JK24, ECO:0000269|PubMed:24333728}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Dopaminergic synapse - 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 (Consensus)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• loftool: 0.530
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.25

Haploinsufficiency Scores

• pHI: 0.177
• hipred: N
• hipred_score: 0.450
• ghis: 0.609

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.941

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppp2r3c
• Phenotype: immune system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: microtubule cytoskeleton organization;B cell homeostasis;regulation of antimicrobial humoral response;cortical cytoskeleton organization;activation of protein kinase activity;regulation of dephosphorylation;T cell homeostasis;positive regulation of B cell differentiation;spleen development;regulation of mitochondrial depolarization
• Cellular component: nucleus;Golgi apparatus;centrosome;spindle;cytosol
• Molecular function: protein binding;metal ion binding