PIGQ

Chr 16AR

phosphatidylinositol glycan anchor biosynthesis class Q

Also known as: DEE77, EIEE77, GPI1, GPIBD19, MCAHS4, c407A10.1

NCBI Gene: 9091 ENSG00000007541 UniProt: Q9BRB3 OMIM: 605754

The PIGQ protein is a N-acetylglucosaminyl transferase component that catalyzes the first step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis, transferring N-acetylglucosamine from UDP-GlcNAc to phosphatidylinositol to create anchors that attach proteins to cell surfaces. Mutations cause multiple congenital anomalies-hypotonia-seizures syndrome 4 through an autosomal recessive inheritance pattern. The pathogenic mechanism involves gain-of-function mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is involved in the first step 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 gene encodes a N-acetylglucosaminyl transferase component that is part of the complex that catalyzes transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.901 OMIM phenotype

Clinical Summary— PIGQ

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Gene-Disease Validity (ClinGen)

developmental and epileptic encephalopathy, 77 · 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

50 unique Pathogenic / Likely Pathogenic· 344 VUS of 816 total submissions

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?

0.90LOEUF

pLI 0.000

Z-score 1.91

OE 0.57 (0.37–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.09Z-score

OE missense 1.01 (0.94–1.09)

488 obs / 482.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.57 (0.37–0.90)

0≤0.351.4

Missense OE?1.01 (0.94–1.09)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 13 / 22.9Missense obs/exp: 488 / 482.1Syn Z: -1.91

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPIGQ-related severe early-onset epilepsyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6649th %ile

GOF

0.73top 25%

LOF

0.3259th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

816 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39

Likely Pathogenic11

VUS344

Likely Benign327

Benign55

Conflicting25

Pathogenic

Likely Pathogenic

344

VUS

327

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	35	0	4	0	39
Likely Pathogenic	8	3	0	0	11
VUS	12	305	18	9	344
Likely Benign	1	34	85	207	327
Benign	0	8	40	7	55
Conflicting	—				25
Total	56	350	147	223	801

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

View in ClinVar →

50 pathogenic / likely-pathogenic (of 72) ClinVar copy-number / structural variants overlap PIGQ — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →