PIGT

Chr 20ADSomaticAR

phosphatidylinositol glycan anchor biosynthesis class T

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

NCBI Gene: 51604 ENSG00000124155 UniProt: Q969N2 OMIM: 610272

The encoded protein serves as an essential component of GPI transamidase, which catalyzes the transfer of glycosylphosphatidylinositol anchors to proteins in the endoplasmic reticulum for cell surface attachment. Mutations cause multiple congenital anomalies-hypotonia-seizures syndrome 3 through autosomal recessive inheritance and paroxysmal nocturnal hemoglobinuria 2 through somatic mutations or autosomal dominant inheritance. The pathogenicity results from defective GPI-anchor biosynthesis, disrupting normal protein anchoring to cell membranes.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

AD/Somatic/ARLOEUF 0.952 OMIM phenotypes

Clinical Summary— PIGT

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Gene-Disease Validity (ClinGen)

multiple congenital anomalies-hypotonia-seizures syndrome 3 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

25 unique Pathogenic / Likely Pathogenic· 186 VUS of 389 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.000

Z-score 1.78

OE 0.65 (0.45–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.28Z-score

OE missense 0.96 (0.87–1.05)

326 obs / 340.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.45–0.95)

0≤0.351.4

Missense OE?0.96 (0.87–1.05)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 19 / 29.4Missense obs/exp: 326 / 340.4Syn Z: -1.25

ClinVar Variant Classifications

389 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic14

VUS186

Likely Benign132

Benign16

Conflicting18

Pathogenic

Likely Pathogenic

186

VUS

132

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	0	0	0	11
Likely Pathogenic	9	5	0	0	14
VUS	3	175	8	0	186
Likely Benign	0	6	49	77	132
Benign	0	1	12	3	16
Conflicting	—				18
Total	23	187	69	80	377

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

View in ClinVar →

7 pathogenic / likely-pathogenic (of 9) ClinVar copy-number / structural variants overlap PIGT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →