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 (224 variants)
not_provided (124 variants)
Inborn_genetic_diseases (93 variants)
PIGT-related_disorder (11 variants)
Paroxysmal_nocturnal_hemoglobinuria_2 (9 variants)
not_specified (7 variants)
Neurodevelopmental_delay (2 variants)
High_myopia (1 variants)
Paroxysmal_nocturnal_hemoglobinuria_1 (1 variants)
Seizure (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 PIGT gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015937.6. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				71 clinvar	1 clinvar	72
missense	1 clinvar	9 clinvar	166 clinvar	14 clinvar	1 clinvar	191
nonsense	4 clinvar	1 clinvar	1 clinvar			6
start loss						0
frameshift	7 clinvar	7 clinvar	4 clinvar			18
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	13	18	172	85	2

Highest pathogenic variant AF is 0.000113467

Loading clinvar variants...

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