PIGK
protein-codingphosphatidylinositol glycan anchor biosynthesis class K, the group of Phosphatidylinositol glycan anchor biosynthesis|Glycosylphosphatidylinositol transamidase complex
Gene summary
This gene encodes a member of the cysteine protease family C13 that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is a member of the multisubunit enzyme, GPI transamidase and is thought to be its enzymatic component. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~130.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030037
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0030037
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0030037
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0030037
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PIGK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005482.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 8 | 1 | 11 | ||
| missense | 5 | 3 | 54 | 2 | 64 | |
| nonsense | 1 | 1 | 2 | 4 | ||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 5 | 6 | |||
| Total | 9 | 4 | 63 | 10 | 1 | 87 |
Highest pathogenic variant AF is 0.000018062481
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005473.1 | 11 | MANE Select | |
| Ensembl | ENSP00000359848.3 | 11 | MANE Select | |
| Ensembl | ENSP00000352041.1 | 9 | Standard | |
| Ensembl | ENSP00000352041.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pigk | Danio rerio | Structure: retinal ganglion cell Quality: organization quality abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human)
- Attachment of GPI anchor to uPAR
- Post-translational modification: synthesis of GPI-anchored proteins
- Post-translational protein modification
- Metabolism of proteins
Biological Process
- proteolysis
- attachment of GPI anchor to protein
- protein localization to cell surface
Molecular Function
- protein disulfide isomerase activity
- GPI-anchor transamidase activity
- protein binding
- cysteine-type peptidase activity
- GPI anchor binding
Cellular Component
- endoplasmic reticulum membrane
- membrane
- integral component of endoplasmic reticulum membrane
- GPI-anchor transamidase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370812
- Coding exons
- 11
- Length
- 130441
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 33
- Defined
- 125746
- p
- 0.000131
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.553 | 193 | 216 | 0.894 | 0.0000108 | 2637 |
| Missense (PolyPhen) | 67 | 94.328 | 0.71029 | 1121 | ||
| Synonymous | -0.463 | 74 | 69.1 | 1.07 | 0.00000313 | 711 |
| Loss of Function | 2.36 | 10 | 21.9 | 0.457 | 0.00000118 | 250 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.00028 | 0.00028 | rare |
| European (Non-Finnish) | 0.00014 | 0.00013 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates GPI anchoring in the endoplasmic reticulum, by replacing a protein's C-terminal GPI attachment signal peptide with a pre-assembled GPI. During this transamidation reaction, the GPI transamidase forms a carbonyl intermediate with the substrate protein.;
Recessive Scores
- pRec
- 0.120
Intolerance Scores
- LoFtool
- 0.823
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.69
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.694
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |