PPP1R15B

protein phosphatase 1 regulatory subunit 15B, the group of Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 1:204396492-204411887

Links

ENSG00000158615 ∙ NCBI:84919 ∙ OMIM:613257 ∙ HGNC:14951 ∙ Uniprot:Q5SWA1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly, short stature, and impaired glucose metabolism 2 (Strong), mode of inheritance: AR
• primary microcephaly-mild intellectual disability-young-onset diabetes syndrome (Supportive), mode of inheritance: AR
• microcephaly, short stature, and impaired glucose metabolism 2 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, short stature, and impaired glucose metabolism 2	AR	Endocrine	Awareness of the risk of diabetes may allow prompt recognition and treatment	Craniofacial; Endocrine; Musculoskeletal; Neurologic	26159176; 26307080

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP1R15B gene.

• Microcephaly, short stature, and impaired glucose metabolism 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP1R15B 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				27	2	29
missense	1		90	5	6	102
nonsense			2			2
start loss			1			1
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				2	1	3
Total	1	0	96	34	9

Variants in PPP1R15B

This is a list of pathogenic ClinVar variants found in the PPP1R15B region.

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

Position	Type	Phenotype	Significance	ClinVar
1-204406097-A-G			Uncertain significance (Nov 02, 2022)
1-204406100-G-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
1-204406111-T-G			Uncertain significance (Jul 19, 2022)
1-204406134-C-G		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
1-204406236-T-C			Likely benign (Nov 28, 2022)
1-204406237-G-A		Inborn genetic diseases	Uncertain significance (Jul 14, 2022)
1-204406251-T-C			Likely benign (Feb 28, 2023)
1-204406261-C-A			Uncertain significance (Jun 29, 2023)
1-204406261-C-T			Conflicting classifications of pathogenicity (Nov 22, 2023)
1-204406262-G-A		Microcephaly, short stature, and impaired glucose metabolism 2	Pathogenic (May 22, 2022)
1-204406274-C-T		Inborn genetic diseases	Uncertain significance (Apr 15, 2024)
1-204406281-A-G			Likely benign (Nov 08, 2022)
1-204409480-C-T			Likely benign (Jul 01, 2023)
1-204409483-G-A			Likely benign (Oct 21, 2022)
1-204409499-C-G		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
1-204409526-G-C		not specified	Benign (Jan 23, 2024)
1-204409533-C-T			Uncertain significance (Nov 27, 2023)
1-204409544-A-G		Inborn genetic diseases	Uncertain significance (Dec 15, 2023)
1-204409546-C-T			Likely benign (Aug 02, 2023)
1-204409576-C-T			Likely benign (Nov 27, 2023)
1-204409583-T-A		Inborn genetic diseases	Uncertain significance (Nov 18, 2023)
1-204409620-T-C			Uncertain significance (May 29, 2023)
1-204409622-G-A			Uncertain significance (Nov 27, 2023)
1-204409645-CTTT-C			Uncertain significance (Nov 07, 2022)
1-204409647-T-C			Benign (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP1R15B	protein_coding	protein_coding	ENST00000367188	2	8405

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.151	0.849	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.35	431	359	1.20	0.0000164	4637
Missense in Polyphen		114	105.06	1.0851		1446
Synonymous	-0.790	154	142	1.08	0.00000655	1441
Loss of Function	3.33	6	23.4	0.257	0.00000109	291

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.000217	0.000217
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Maintains low levels of EIF2S1 phosphorylation in unstressed cells by promoting its dephosphorylation by PP1. {ECO:0000269|PubMed:26159176, ECO:0000269|PubMed:26307080}.
• Disease: DISEASE: Microcephaly, short stature, and impaired glucose metabolism 2 (MSSGM2) [MIM:616817]: A disease characterized by microcephaly, mental retardation, short stature, and disturbed glucose metabolism. {ECO:0000269|PubMed:26159176, ECO:0000269|PubMed:26307080}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in PPP1R15B has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.

Recessive Scores

• pRec: 0.0818

Intolerance Scores

• loftool: 0.349
• rvis_EVS: 0.73
• rvis_percentile_EVS: 86.3

Haploinsufficiency Scores

• pHI: 0.202
• hipred: N
• hipred_score: 0.233
• ghis: 0.417

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.235

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppp1r15b
• 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); growth/size/body region phenotype; homeostasis/metabolism phenotype; 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); hematopoietic system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of protein phosphorylation;ER overload response;positive regulation of phosphoprotein phosphatase activity;response to endoplasmic reticulum stress;response to hydrogen peroxide;peptidyl-serine dephosphorylation;negative regulation of PERK-mediated unfolded protein response;negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation
• Cellular component: protein phosphatase type 1 complex;cytoplasm;endoplasmic reticulum
• Molecular function: protein binding;protein phosphatase regulator activity