PIGT

phosphatidylinositol glycan anchor biosynthesis class T, the group of Phosphatidylinositol glycan anchor biosynthesis|Glycosylphosphatidylinositol transamidase complex|MicroRNA protein coding host genes

Basic information

Region (hg38): 20:45416084-45456934

Links

ENSG00000124155 ∙ NCBI:51604 ∙ OMIM:610272 ∙ HGNC:14938 ∙ Uniprot:Q969N2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multiple congenital anomalies-hypotonia-seizures syndrome 3 (Definitive), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 3 (Strong), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 3 (Strong), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 3 (Supportive), mode of inheritance: AR
• multiple congenital anomalies-hypotonia-seizures syndrome 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Multiple congenital anomalies-hypotonia-seizures syndrome 3	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; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal	23636107; 24906948; 25943031; 28728837

ClinVar

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

• Multiple congenital anomalies-hypotonia-seizures syndrome 3 (10 variants)
• not provided (6 variants)
• PIGT-related disorder (2 variants)
• Inborn genetic diseases (2 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGT 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	1			60	2	63
missense		5	121	11	1	138
nonsense	4	1	1			6
start loss						0
frameshift	7	2	2			11
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			5	7		12
non coding			2	31	10	43
Total	12	9	126	102	13

Highest pathogenic variant AF is 0.0000592

Variants in PIGT

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

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

Position	Type	Phenotype	Significance	ClinVar
20-45416162-G-C		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Likely benign (Jan 28, 2020)
20-45416164-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Uncertain significance (Sep 27, 2022)
20-45416168-T-C		Multiple congenital anomalies-hypotonia-seizures syndrome 3 • PIGT-related disorder	Benign/Likely benign (Jan 18, 2024)
20-45416169-A-G		Inborn genetic diseases	Likely benign (Feb 27, 2024)
20-45416170-T-C			Likely benign (-)
20-45416175-C-G			Uncertain significance (Jan 15, 2023)
20-45416175-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Uncertain significance (Jul 11, 2022)
20-45416178-G-C		Inborn genetic diseases	Uncertain significance (Feb 01, 2023)
20-45416178-G-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Uncertain significance (Oct 06, 2023)
20-45416179-C-G		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Uncertain significance (Aug 16, 2022)
20-45416179-C-T		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)
20-45416181-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Likely benign (Aug 23, 2022)
20-45416189-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3 • PIGT-related disorder	Benign (Apr 11, 2023)
20-45416197-T-G			Uncertain significance (Jan 19, 2023)
20-45416202-G-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Uncertain significance (Jan 22, 2024)
20-45416212-GC-G		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Pathogenic (Apr 19, 2019)
20-45416216-G-C		Inborn genetic diseases	Uncertain significance (May 31, 2023)
20-45416217-T-G		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Uncertain significance (Nov 08, 2022)
20-45416226-G-A		Multiple congenital anomalies-hypotonia-seizures syndrome 3 • Inborn genetic diseases	Uncertain significance (Jan 19, 2024)
20-45416230-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Uncertain significance (Aug 06, 2022)
20-45416237-C-G		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Likely benign (Jun 08, 2022)
20-45416238-G-A			Uncertain significance (Jan 10, 2022)
20-45416264-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Likely benign (Jul 30, 2022)
20-45416269-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Uncertain significance (Jul 07, 2023)
20-45416291-C-T		Multiple congenital anomalies-hypotonia-seizures syndrome 3	Likely benign (Nov 08, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGT	protein_coding	protein_coding	ENST00000279036	12	10168

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.30e-10	0.880	125641	0	107	125748	0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.277	326	340	0.958	0.0000200	3660
Missense in Polyphen		145	158.52	0.9147		1622
Synonymous	-1.25	169	150	1.13	0.00000870	1234
Loss of Function	1.78	19	29.4	0.646	0.00000158	306

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000478	0.000478
Ashkenazi Jewish	0.00	0.00
East Asian	0.00147	0.00141
Finnish	0.000278	0.000277
European (Non-Finnish)	0.000409	0.000404
Middle Eastern	0.00147	0.00141
South Asian	0.000465	0.000457
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the GPI transamidase complex. Essential for transfer of GPI to proteins, particularly for formation of carbonyl intermediates. {ECO:0000269|PubMed:11483512}.
• Disease: DISEASE: Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) [MIM:615398]: An autosomal recessive syndrome characterized by distinct facial features, intellectual disability, hypotonia and seizures, in combination with abnormal skeletal, endocrine, and ophthalmologic findings including impaired vision, as well as abnormal motility of the eyes. {ECO:0000269|PubMed:23636107}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Paroxysmal nocturnal hemoglobinuria 2 (PNH2) [MIM:615399]: A disorder characterized by hemolytic anemia with hemoglobinuria, thromboses in large vessels, and a deficiency in hematopoiesis. Red blood cell breakdown with release of hemoglobin into the urine is manifested most prominently by dark-colored urine in the morning. {ECO:0000269|PubMed:23733340}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• 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: 0.114

Intolerance Scores

• loftool: 0.941
• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.23

Haploinsufficiency Scores

• pHI: 0.175
• hipred: N
• hipred_score: 0.282
• ghis: 0.556

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.832

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigt
• 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)

Zebrafish Information Network

• Gene name: pigt
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: shortened

Gene ontology

• Biological process: attachment of GPI anchor to protein;neuron differentiation;neuron apoptotic process
• Cellular component: endoplasmic reticulum membrane;membrane;integral component of endoplasmic reticulum membrane;cytoplasmic vesicle;GPI-anchor transamidase complex
• Molecular function: GPI-anchor transamidase activity;protein binding