PRKCSH

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

Basic information

Region (hg38): 19:11435284-11450968

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 (272 variants)
Polycystic_liver_disease_1 (169 variants)
Inborn_genetic_diseases (85 variants)
Autosomal_dominant_polycystic_liver_disease (14 variants)
PRKCSH-related_disorder (11 variants)
not_specified (10 variants)
Primary_ciliary_dyskinesia_30 (2 variants)
ODAD3-related_disorder (2 variants)
See_cases (1 variants)
Biliary_tract_abnormality (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. These statistics are base on transcript: NM_001289104.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			13 clinvar	67 clinvar	5 clinvar	85
missense	1 clinvar	4 clinvar	146 clinvar	40 clinvar		191
nonsense	7 clinvar	4 clinvar				11
start loss						0
frameshift	9 clinvar	4 clinvar	1 clinvar			14
splice donor/acceptor (+/-2bp)	4 clinvar	8 clinvar	2 clinvar		1 clinvar	15
Total	21	20	162	107	6

Highest pathogenic variant AF is 0.000119709

Loading clinvar variants...

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
essential_gene_gene_trap
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