PIGK

phosphatidylinositol glycan anchor biosynthesis class K, the group of Phosphatidylinositol glycan anchor biosynthesis|Glycosylphosphatidylinositol transamidase complex

Basic information

Region (hg38): 1:77088989-77219430

Links

ENSG00000142892 ∙ NCBI:10026 ∙ OMIM:605087 ∙ HGNC:8965 ∙ Uniprot:Q92643 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures (Strong), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures (Strong), mode of inheritance: AR
• neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures	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	31353022

ClinVar

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

• Inborn_genetic_diseases (45 variants)
• not_provided (14 variants)
• Neurodevelopmental_disorder_with_hypotonia_and_cerebellar_atrophy,_with_or_without_seizures (10 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005482.3. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6		6
missense	5	2	45	2		54
nonsense	1					1
start loss						0
frameshift	2					2
splice donor/acceptor (+/-2bp)	1					1
Total	9	2	45	8	0

Highest pathogenic variant AF is 0.0000164282

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGK	protein_coding	protein_coding	ENST00000370812	11	130441

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000138	0.992	125713	0	33	125746	0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.553	193	216	0.894	0.0000108	2637
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000212	0.000211
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.000282	0.000277
European (Non-Finnish)	0.000135	0.000132
Middle Eastern	0.000110	0.000109
South Asian	0.000168	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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.
• Pathway: 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 (Consensus)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.823
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

• pHI: 0.126
• hipred: N
• hipred_score: 0.237
• ghis: 0.590

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.694

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigk

Zebrafish Information Network

• Gene name: pigk
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: organization quality

Gene ontology

• Biological process: proteolysis;attachment of GPI anchor to protein;protein localization to cell surface
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of endoplasmic reticulum membrane;GPI-anchor transamidase complex
• Molecular function: protein disulfide isomerase activity;GPI-anchor transamidase activity;protein binding;cysteine-type peptidase activity;GPI anchor binding