PIGT

Chr 20ADSomaticAR

phosphatidylinositol glycan anchor biosynthesis class T

Also known as: CGI-06, MCAHS3, NDAP, PIG-T, PNH2

NCBI Gene: 51604ENSG00000124155UniProt: Q969N2

This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is an essential component of the multisubunit enzyme, GPI transamidase. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

Primary Disease Associations & Inheritance

?Paroxysmal nocturnal hemoglobinuria 2MIM #615399
ADSomatic
Multiple congenital anomalies-hypotonia-seizures syndrome 3MIM #615398
AR
388
ClinVar variants
37
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— PIGT
🧬
Gene-Disease Validity (ClinGen)
multiple congenital anomalies-hypotonia-seizures syndrome 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
37 Pathogenic / Likely Pathogenic· 186 VUS of 388 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.000
Z-score 1.78
OE 0.65 (0.45–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.28Z-score
OE missense 0.96 (0.87–1.05)
326 obs / 340.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.65 (0.45–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.87–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.13
0≤1.21.6
LoF obs/exp: 19 / 29.4Missense obs/exp: 326 / 340.4Syn Z: -1.25

ClinVar Variant Classifications

388 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic16
VUS186
Likely Benign131
Benign16
Conflicting18
21
Pathogenic
16
Likely Pathogenic
186
VUS
131
Likely Benign
16
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
13
0
21
Likely Pathogenic
7
7
2
0
16
VUS
2
174
10
0
186
Likely Benign
0
7
47
77
131
Benign
0
1
12
3
16
Conflicting
—18
Total171898480388

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PIGT · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PIGT-related multiple congenital anomalies-hypotonia-seizures syndrome

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Paroxysmal nocturnal hemoglobinuria 2

MIM #615399

Molecular basis of disorder known

Autosomal dominantSomatic mutation

Multiple congenital anomalies-hypotonia-seizures syndrome 3

MIM #615398

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.
Conte F et al.·Int J Mol Sci
2023Review
A Novel Homozygous Missense Variant of PIGT Related to Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 with Elevated of Serum ALP Level in a Thai Newborn Patient.
Klangjorhor J et al.·Int J Mol Sci
2025Case report
Expanding the clinical and molecular characteristics of PIGT-CDG, a disorder of glycosylphosphatidylinositol anchors.
Lam C et al.·Mol Genet Metab
2015Case report
PIGT-CDG, a disorder of the glycosylphosphatidylinositol anchor: description of 13 novel patients and expansion of the clinical characteristics.
Bayat A et al.·Genet Med
2019Case report
Paroxysmal nocturnal hemoglobinuria without GPI-anchor deficiency.
Brodsky RA·J Clin Invest
2019
Complement and inflammasome overactivation mediates paroxysmal nocturnal hemoglobinuria with autoinflammation.
Höchsmann B et al.·J Clin Invest
2019Case report
Analyzing clinical and genetic characteristics of a cohort with multiple congenital anomalies-hypotonia-seizures syndrome (MCAHS).
Jiao X et al.·Orphanet J Rare Dis
2020Cohort
Expression of the IL-18-related gene PTX3 correlates with clinicopathological features and prognosis in glioma patients.
Wang D et al.·PeerJ
2025Cohort
Evidence of the milder phenotypic spectrum of c.1582G>A PIGT variant: Delineation based on seven novel Polish patients.
Jezela-Stanek A et al.·Clin Genet
2020Cohort
[Genetic analysis and prenatal diagnosis of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 due to variants of PIGT gene].
Hua Y et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2023Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet

External Resources

Links to major genomics databases and tools