PIGG

phosphatidylinositol glycan anchor biosynthesis class G, the group of Phosphatidylinositol glycan anchor biosynthesis

Basic information

Region (hg38): 4:499210-540200

Links

ENSG00000174227 ∙ NCBI:54872 ∙ OMIM:616918 ∙ HGNC:25985 ∙ Uniprot:Q5H8A4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 53 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Blood group, EMM system; Neurodevelopmental disorder with or without hypotonia, seizures, and cerebellar atrophy	BG/AR	Hematologic	Variants associated with a blood group may be important in specific situations (eg, related to transfusion)	Hematologic; Neurologic	26996948; 33763700; 34535746

ClinVar

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

• Intellectual disability, autosomal recessive 53 (45 variants)
• not provided (7 variants)
• Emm-null phenotype (2 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGG 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			6	243	6	255
missense			393	24	7	424
nonsense	15	5	1			21
start loss		1				1
frameshift	32	9	2			43
inframe indel			9			9
splice donor/acceptor (+/-2bp)	1	10				11
splice region			11	27	1	39
non coding		1	7	106	31	145
Total	48	26	418	373	44

Highest pathogenic variant AF is 0.0000197

Variants in PIGG

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

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

Position	Type	Phenotype	Significance	ClinVar
4-499336-A-G		Seizure	Likely pathogenic (Dec 11, 2018)
4-499339-C-A		Intellectual disability, autosomal recessive 53	Likely benign (Sep 13, 2022)
4-499340-G-A		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
4-499343-T-G		Intellectual disability, autosomal recessive 53	Uncertain significance (Nov 22, 2022)
4-499349-C-A		Intellectual disability, autosomal recessive 53	Uncertain significance (Aug 23, 2021)
4-499352-G-A		Intellectual disability, autosomal recessive 53	Uncertain significance (Jan 02, 2022)
4-499357-T-C		Inborn genetic diseases	Uncertain significance (Mar 07, 2024)
4-499358-T-C		Intellectual disability, autosomal recessive 53	Uncertain significance (Sep 30, 2021)
4-499359-C-G		Intellectual disability, autosomal recessive 53	Conflicting classifications of pathogenicity (Jan 04, 2024)
4-499364-C-A		Intellectual disability, autosomal recessive 53	Uncertain significance (Jul 19, 2022)
4-499365-C-T		Intellectual disability, autosomal recessive 53	Likely benign (Dec 08, 2023)
4-499368-T-C		Intellectual disability, autosomal recessive 53	Likely benign (Sep 24, 2022)
4-499370-G-A		Intellectual disability, autosomal recessive 53	Uncertain significance (Aug 15, 2022)
4-499370-G-C		Intellectual disability, autosomal recessive 53	Uncertain significance (Jul 05, 2022)
4-499371-C-T		Intellectual disability, autosomal recessive 53	Likely benign (Apr 17, 2023)
4-499374-A-G		Intellectual disability, autosomal recessive 53	Likely benign (Feb 11, 2022)
4-499377-G-T		Intellectual disability, autosomal recessive 53	Likely benign (Aug 05, 2021)
4-499379-T-C		Intellectual disability, autosomal recessive 53	Uncertain significance (Dec 31, 2021)
4-499382-A-C		Intellectual disability, autosomal recessive 53	Uncertain significance (Jul 18, 2022)
4-499391-G-A			Uncertain significance (Feb 10, 2022)
4-499393-A-G		Intellectual disability, autosomal recessive 53	Uncertain significance (Apr 03, 2019)
4-499401-C-T		Intellectual disability, autosomal recessive 53	Likely benign (Oct 13, 2022)
4-499412-G-T		Intellectual disability, autosomal recessive 53	Uncertain significance (Dec 11, 2019)
4-499420-C-G		Intellectual disability, autosomal recessive 53 • Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
4-499429-G-T		Intellectual disability, autosomal recessive 53	Uncertain significance (Jul 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGG	protein_coding	protein_coding	ENST00000453061	13	40997

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.43e-15	0.533	125458	0	290	125748	0.00115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.168	574	563	1.02	0.0000325	6303
Missense in Polyphen		191	205.27	0.9305		2457
Synonymous	-0.600	266	254	1.05	0.0000176	2090
Loss of Function	1.61	28	38.9	0.720	0.00000189	470

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00115	0.00115
Ashkenazi Jewish	0.00	0.00
East Asian	0.000491	0.000489
Finnish	0.000416	0.000416
European (Non-Finnish)	0.00177	0.00176
Middle Eastern	0.000491	0.000489
South Asian	0.00118	0.00118
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers ethanolamine phosphate to the GPI second mannose. {ECO:0000269|PubMed:15632136}.
• Disease: DISEASE: Mental retardation, autosomal recessive 53 (MRT53) [MIM:616917]: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Most MRT53 patients manifest severely delayed psychomotor development, hypotonia, and early-onset seizures. Additional features, such as cerebellar hypoplasia and ataxia have been observed in some patients. Note=The disease is caused by mutations affecting the gene represented in this entry. Cells from patients carrying PIGG disease-causing mutations show abnormal accumulation of the GPI precursors H7 and H7' and absence of mature GPI precursor H8, consistent with a loss of function. However, GPI-anchored proteins, including CD59, CD55, CD24 and CD16, are normally expressed at the cell surface of lymphocytes and granulocytes and CD59 exhibits sensitivity to bacterial phosphatidylinositol- specific phospholipase C, suggesting a normal structure. The role of PIGG in MRT53 etiology is not clear. {ECO:0000269|PubMed:26996948}.
• 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 (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.852
• rvis_EVS: 1.79
• rvis_percentile_EVS: 96.87

Haploinsufficiency Scores

• pHI: 0.202
• hipred: N
• hipred_score: 0.331
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.397

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigg

Gene ontology

• Biological process: GPI anchor biosynthetic process;preassembly of GPI anchor in ER membrane
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of endoplasmic reticulum membrane
• Molecular function: phosphotransferase activity, for other substituted phosphate groups;CP2 mannose-ethanolamine phosphotransferase activity