PRKG2

protein kinase cGMP-dependent 2, the group of AGC family kinases

Basic information

Region (hg38): 4:81087370-81215222

Links

ENSG00000138669 ∙ NCBI:5593 ∙ OMIM:601591 ∙ HGNC:9416 ∙ Uniprot:Q13237 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• acromesomelic dysplasia 4 (Strong), mode of inheritance: AR
• acromesomelic dysplasia 4 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondylometaphyseal dysplasia, Pagnamenta type; Acromesomelic dysplasia 4	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	33106379; 34782440

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRKG2 gene.

• not provided (2 variants)
• Acromesomelic dysplasia 4 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKG2 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				4	3	7
missense		1	23	1		25
nonsense	2					2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region				2		2
non coding				2	2	4
Total	3	1	23	7	5

Variants in PRKG2

This is a list of pathogenic ClinVar variants found in the PRKG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-81089714-G-GT		Spondylometaphyseal dysplasia, pagnamenta type	Pathogenic (Oct 14, 2022)
4-81092426-C-A		Inborn genetic diseases	Uncertain significance (Nov 27, 2023)
4-81092465-A-AAAGG			Benign (Jan 08, 2024)
4-81092465-A-AAAGGAAGG			Likely benign (Jan 12, 2024)
4-81092465-A-AAAGGAAGGAAGG			Likely benign (Jan 08, 2024)
4-81104365-T-C		PRKG2-related disorder	Likely benign (Aug 01, 2022)
4-81105941-TAGAG-T		PRKG2-related disorder	Likely benign (Jun 19, 2019)
4-81110454-G-A		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
4-81110459-G-A		PRKG2-related disorder	Likely benign (Oct 28, 2019)
4-81110483-T-TTACGCTCTTAAAGTATATACACTTTATCACTAGTTAGGTTATTTTTGCATTTCTCTGAAGAGGTG			Pathogenic (Jul 05, 2022)
4-81110486-C-CGCTCTTAAAGTATATACACTTTATCACTAGTTAGGTTATTTTTGCATTTCTCTGAAGAGGTGGCTG			Pathogenic (Jul 05, 2022)
4-81110595-G-A		Inborn genetic diseases	Uncertain significance (Apr 22, 2022)
4-81135195-G-A		Inborn genetic diseases	Uncertain significance (Mar 21, 2024)
4-81135226-G-A		Acromesomelic dysplasia 4	Pathogenic (Oct 14, 2022)
4-81135289-A-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
4-81137475-G-A		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
4-81140534-T-G		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
4-81140627-T-C		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
4-81140668-A-C		Acromesomelic dysplasia 4	Likely pathogenic (-)
4-81142876-G-T		Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
4-81142936-G-A		Inborn genetic diseases	Uncertain significance (Dec 15, 2022)
4-81144235-G-A		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
4-81144312-G-A		PRKG2-related disorder	Likely benign (Jun 27, 2019)
4-81148883-C-T		Acromesomelic dysplasia 4	Pathogenic (May 11, 2023)
4-81151986-T-C		PRKG2-related disorder	Benign (Aug 12, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRKG2	protein_coding	protein_coding	ENST00000395578	18	126382

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.647	0.353	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.99	231	399	0.579	0.0000202	5006
Missense in Polyphen		60	146	0.41096		1851
Synonymous	-0.708	156	145	1.07	0.00000712	1416
Loss of Function	4.79	9	42.9	0.210	0.00000220	532

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000114	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000619	0.0000615
Middle Eastern	0.000114	0.000109
South Asian	0.000132	0.000131
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Crucial regulator of intestinal secretion and bone growth (By similarity). Phosphorylates and activates CFTR on the plasma membrane. Plays a key role in intestinal secretion by regulating cGMP-dependent translocation of CFTR in jejunum (By similarity). Acts downstream of NMDAR to activate the plasma membrane accumulation of GRIA1/GLUR1 in synapse and increase synaptic plasticity. Phosphorylates GRIA1/GLUR1 at Ser-863 (By similarity). Acts as regulator of gene expression and activator of the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2 in mechanically stimulated osteoblasts. Under fluid shear stress, mediates ERK activation and subsequent induction of FOS, FOSL1/FRA1, FOSL2/FRA2 and FOSB that play a key role in the osteoblast anabolic response to mechanical stimulation (By similarity). {ECO:0000250|UniProtKB:Q61410, ECO:0000250|UniProtKB:Q64595}.
• Pathway: Platelet activation - Homo sapiens (human);Regulation of lipolysis in adipocytes - Homo sapiens (human);Long-term depression - Homo sapiens (human);Gap junction - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Renin secretion - Homo sapiens (human);Salivary secretion - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Olfactory transduction - Homo sapiens (human);NO-cGMP-PKG mediated Neuroprotection;Signaling by WNT;Signal Transduction;ion channels and their functional role in vascular endothelium;Metabolism;actions of nitric oxide in the heart;Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation;Metabolism of cofactors;Metabolism of vitamins and cofactors;IL-7 signaling;Ca2+ pathway;Beta-catenin independent WNT signaling;Hemostasis;JAK STAT pathway and regulation;EPO signaling;cGMP effects;Nitric oxide stimulates guanylate cyclase;VEGF;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.219
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.18

Haploinsufficiency Scores

• pHI: 0.277
• hipred: Y
• hipred_score: 0.756
• ghis: 0.530

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.834

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prkg2
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype

Gene ontology

• Biological process: protein phosphorylation;signal transduction;peptidyl-serine autophosphorylation;cofactor metabolic process;protein localization to plasma membrane;negative regulation of chloride transport
• Cellular component: cytosol;apical plasma membrane;nuclear membrane
• Molecular function: protein kinase activity;cGMP-dependent protein kinase activity;ATP binding;cGMP binding;protein homodimerization activity