PIGC

phosphatidylinositol glycan anchor biosynthesis class C, the group of Phosphatidylinositol glycan anchor biosynthesis|Glycosylphosphatidylinositol-N-acetylglucosaminyltransferase complex

Basic information

Region (hg38): 1:172370189-172444086

Links

ENSG00000135845 ∙ NCBI:5279 ∙ OMIM:601730 ∙ HGNC:8960 ∙ Uniprot:Q92535 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycosylphosphatidylinositol biosynthesis defect 16 (Limited), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 16 (Strong), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycosylphosphatidylinositol biosynthesis defect 16	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	Neurologic	27694521

ClinVar

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

• not_specified (37 variants)
• not_provided (32 variants)
• Glycosylphosphatidylinositol_biosynthesis_defect_16 (19 variants)
• Non-immune_hydrops_fetalis (1 variants)
• Global_developmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000153747.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	2	10
missense	2	3	54	1		60
nonsense	1	2	1			4
start loss						0
frameshift	1					1
splice donor/acceptor (+/-2bp)						0
Total	4	5	55	9	2

Highest pathogenic variant AF is 0.0000724925

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGC	protein_coding	protein_coding	ENST00000367728	1	73902

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00551	0.905	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.788	137	166	0.828	0.00000880	1915
Missense in Polyphen		37	50.25	0.73632		650
Synonymous	2.34	40	63.8	0.627	0.00000293	626
Loss of Function	1.46	5	9.95	0.502	5.91e-7	105

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in GPI anchor biosynthesis (PubMed:8806613, PubMed:27694521). Part of the complex catalyzing the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, the first step of GPI biosynthesis (ECO:0000269|PubMed:27694521). {ECO:0000269|PubMed:27694521, ECO:0000269|PubMed:8806613}.
• Disease: DISEASE: Glycosylphosphatidylinositol biosynthesis defect 16 (GPIBD16) [MIM:617816]: An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, and seizures. {ECO:0000269|PubMed:27694521}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human);Synthesis of glycosylphosphatidylinositol (GPI);Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins;Phosphatidylinositol phosphate metabolism (Consensus)

Recessive Scores

• pRec: 0.157

Intolerance Scores

• loftool: 0.918
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.22

Haploinsufficiency Scores

• pHI: 0.313
• hipred: N
• hipred_score: 0.350
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: E
• gene_indispensability_score: 0.917

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigc

Gene ontology

• Biological process: GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane
• Cellular component: glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex;endoplasmic reticulum membrane;integral component of membrane
• Molecular function: catalytic activity;phosphatidylinositol N-acetylglucosaminyltransferase activity