PRKCSH

protein kinase C substrate 80K-H, the group of MRH domain containing |EF-hand domain containing

Basic information

Region (hg38): 19:11435283-11450968

Previous symbols: [ "G19P1", "PCLD", "PLD1" ]

Links

ENSG00000130175 ∙ NCBI:5589 ∙ OMIM:177060 ∙ HGNC:9411 ∙ Uniprot:P14314 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• polycystic liver disease 1 (Strong), mode of inheritance: AD
• polycystic liver disease 1 (Strong), mode of inheritance: AD
• polycystic liver disease 1 (Definitive), mode of inheritance: AD
• polycystic liver disease 1 (Supportive), mode of inheritance: AD
• polycystic liver disease 1 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Polycystic liver disease 1 with or without kidney cysts	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	Gastrointestinal; Renal	11047756; 12577059; 12529853; 16835903; 20095989; 22415584
Though some individuals may require treatment, it is unclear if early (genetic) diagnosis would be beneficial; Liver transplantion has been described

ClinVar

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

• not provided (212 variants)
• Polycystic liver disease 1 (95 variants)
• Inborn genetic diseases (32 variants)
• not specified (15 variants)
• Autosomal dominant polycystic liver disease (3 variants)
• PRKCSH-related condition (1 variants)
• Primary ciliary dyskinesia 30 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRKCSH 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			11	41	4	56
missense			66	12	2	80
nonsense	2	2				4
start loss						0
frameshift	6	1				7
inframe indel			11	4	2	17
splice donor/acceptor (+/-2bp)		3	1		1	5
splice region			7	8	4	19
non coding			9	41	26	76
Total	8	6	98	98	35

Highest pathogenic variant AF is 0.00000658

Variants in PRKCSH

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

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

Position	Type	Phenotype	Significance	ClinVar
19-11435448-G-A		Polycystic liver disease 1	Benign (Jun 14, 2016)
19-11435484-CCTCT-C		Polycystic liver disease 1	Likely benign (Jun 14, 2016)
19-11435591-G-A		Polycystic liver disease 1	Uncertain significance (Jun 14, 2016)
19-11435616-G-A		Polycystic liver disease 1	Uncertain significance (Jun 14, 2016)
19-11435641-G-A		Polycystic liver disease 1	Likely benign (Jun 14, 2016)
19-11435654-C-T		Polycystic liver disease 1	Benign (Jan 12, 2018)
19-11435665-C-G		Polycystic liver disease 1	Benign (Jan 13, 2018)
19-11435679-T-C		Polycystic liver disease 1	Uncertain significance (Jan 12, 2018)
19-11435744-T-C		Primary ciliary dyskinesia 30 • ODAD3-related disorder	Benign (Mar 09, 2022)
19-11435780-G-A		ODAD3-related disorder	Likely benign (Dec 29, 2023)
19-11436039-A-C		Polycystic liver disease 1	Uncertain significance (Mar 04, 2022)
19-11436129-G-C			Likely benign (Oct 08, 2021)
19-11436128-C-CGCT			Uncertain significance (Jan 02, 2024)
19-11436132-G-A			Likely benign (Jan 30, 2023)
19-11436139-C-A		Polycystic liver disease 1	Uncertain significance (Aug 07, 2022)
19-11436153-C-T			Likely benign (Jun 27, 2023)
19-11436154-T-C		Polycystic liver disease 1	Benign/Likely benign (Dec 15, 2023)
19-11436155-G-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 31, 2023)
19-11436177-C-T		Polycystic liver disease 1	Likely benign (Nov 10, 2021)
19-11436184-G-C		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
19-11436188-C-T		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
19-11436192-C-CACCAGTGA		Autosomal dominant polycystic liver disease	Likely pathogenic (Sep 01, 2021)
19-11436197-G-C			Likely pathogenic (Nov 11, 2022)
19-11436201-GTCC-G		not specified • Polycystic liver disease 1	Benign (Jan 31, 2024)
19-11436202-T-TCCTCCTGTTCAC			Benign (Jan 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRKCSH	protein_coding	protein_coding	ENST00000252455	16	15675

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.01e-7	0.997	125701	0	47	125748	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.532	286	312	0.915	0.0000213	3448
Missense in Polyphen		91	116.17	0.78336		1278
Synonymous	-2.64	178	138	1.29	0.0000114	964
Loss of Function	2.64	17	33.5	0.508	0.00000169	389

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000219	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000754	0.000739
European (Non-Finnish)	0.000147	0.000141
Middle Eastern	0.000109	0.000109
South Asian	0.000197	0.000196
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulatory subunit of glucosidase II that cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins (PubMed:10929008). Required for efficient PKD1/Polycystin-1 biogenesis and trafficking to the plasma membrane of the primary cilia (By similarity). {ECO:0000250|UniProtKB:O08795, ECO:0000269|PubMed:10929008}.
• Disease: DISEASE: Polycystic liver disease 1 with or without kidney cysts (PCLD1) [MIM:174050]: An autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts. A subset of patients may develop kidney cysts that usually do not result in clinically significant renal disease. {ECO:0000269|PubMed:12529853, ECO:0000269|PubMed:12577059, ECO:0000269|PubMed:28375157}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Post-translational protein phosphorylation;Calnexin/calreticulin cycle;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;Fibroblast growth factor-1;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Asparagine N-linked glycosylation;Advanced glycosylation endproduct receptor signaling;N-glycan trimming in the ER and Calnexin/Calreticulin cycle (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.445
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.46

Haploinsufficiency Scores

• pHI: 0.165
• hipred: N
• hipred_score: 0.414
• ghis: 0.581

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.927

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prkcsh
• Phenotype: homeostasis/metabolism phenotype; cellular 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); renal/urinary system phenotype; liver/biliary system phenotype

Zebrafish Information Network

• Gene name: prkcsh
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: kinked

Gene ontology

• Biological process: N-glycan processing;intracellular signal transduction;post-translational protein modification;cellular protein metabolic process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum lumen;glucosidase II complex;intracellular membrane-bounded organelle
• Molecular function: protein kinase C binding;calcium ion binding;protein binding;ion channel binding;phosphoprotein binding