PPP1R21

protein phosphatase 1 regulatory subunit 21, the group of Protein phosphatase 1 regulatory subunits

Basic information

Region (hg38): 2:48440598-48515391

Previous symbols: [ "CCDC128", "KLRAQ1" ]

Links

ENSG00000162869 ∙ NCBI:129285 ∙ OMIM:618159 ∙ HGNC:30595 ∙ Uniprot:Q6ZMI0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (Strong), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (Strong), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	29808498; 32985083; 36692708; 34997808; 38356149

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPP1R21 gene.

• not provided (2 variants)
• Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (2 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPP1R21 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				7	2	9
missense			86	7	1	94
nonsense	4	2	2			8
start loss						0
frameshift	1	2				3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2	1			3
splice region			3	2		5
non coding						0
Total	5	6	90	14	3

Highest pathogenic variant AF is 0.0000197

Variants in PPP1R21

This is a list of pathogenic ClinVar variants found in the PPP1R21 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-48440961-C-T		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
2-48440982-A-G		Inborn genetic diseases	Uncertain significance (Jan 22, 2025)
2-48441006-C-G		Inborn genetic diseases	Uncertain significance (Aug 19, 2023)
2-48451036-AAG-A		Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities	Pathogenic (Jun 25, 2021)
2-48451059-A-T		Inborn genetic diseases	Uncertain significance (May 14, 2024)
2-48451078-T-C		Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities	Likely pathogenic (-)
2-48454592-T-C		Inborn genetic diseases	Uncertain significance (Sep 29, 2022)
2-48454605-A-G		Inborn genetic diseases	Uncertain significance (Dec 20, 2024)
2-48454611-A-G		Inborn genetic diseases	Uncertain significance (Aug 27, 2024)
2-48454619-T-G		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
2-48454622-T-C		PPP1R21-related disorder	Likely benign (Sep 10, 2019)
2-48454650-G-C		Inborn genetic diseases	Uncertain significance (Sep 29, 2022)
2-48454661-C-T		Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities	Pathogenic (Jun 25, 2021)
2-48454662-G-A		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
2-48454672-G-C		Inborn genetic diseases	Uncertain significance (Dec 08, 2023)
2-48454691-C-A		PPP1R21-related disorder	Uncertain significance (Dec 26, 2023)
2-48454691-C-G		Inborn genetic diseases	Uncertain significance (Mar 31, 2022)
2-48454692-T-G		Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities	Pathogenic (Dec 16, 2024)
2-48454699-A-G		PPP1R21-related disorder	Likely benign (May 02, 2019)
2-48454710-C-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2024)
2-48454711-T-C		PPP1R21-related disorder	Benign (Mar 25, 2019)
2-48454726-A-C		PPP1R21-related disorder	Likely benign (May 05, 2023)
2-48454729-C-G		PPP1R21-related disorder	Benign (Jan 27, 2021)
2-48454730-A-G		Inborn genetic diseases	Likely benign (Mar 25, 2022)
2-48458133-G-C		Inborn genetic diseases	Uncertain significance (Feb 14, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPP1R21	protein_coding	protein_coding	ENST00000294952	22	74789

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.30e-10	1.00	125699	0	48	125747	0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.92	506	398	1.27	0.0000200	5109
Missense in Polyphen		182	166.69	1.0918		2199
Synonymous	-0.991	163	148	1.10	0.00000759	1441
Loss of Function	3.37	25	50.9	0.491	0.00000277	604

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000539	0.000539
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000189	0.000185
European (Non-Finnish)	0.000233	0.000229
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000981	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Intolerance Scores

• rvis_EVS: -1.01
• rvis_percentile_EVS: 8.16

Haploinsufficiency Scores

• pHI: 0.210
• hipred: N
• hipred_score: 0.379
• ghis: 0.606

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppp1r21

Gene ontology

• Cellular component: membrane