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…

Primary Disease Associations & Inheritance

Multiple congenital anomalies-hypotonia-seizures syndrome 4MIM #618548

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · developmental and epileptic encephalopathy, 77 · AR · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in PIGQ?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 33

1,321 rare PASS variants

Rare truncating (LoF)

1 in 590

192 rare PASS variants

Rare synonymous (reference)

1 in 58

630 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PIGQ. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 41	1 in 780
South Asian	~43k	1 in 27	1 in 390
Remaining (unassigned)	~30k	1 in 28	1 in 390
European (Finnish)	~27k	1 in 88	1 in 1,600
Admixed American	~22k	1 in 38	1 in 210
African / African American	~21k	1 in 28	1 in 240
East Asian	~20k	1 in 32	1 in 490
Ashkenazi Jewish	~13k	1 in 170	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 31	≈ 1 in 960

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 9 of 10 coding exons well covered in gnomAD exomes; exon 9 marginal. Genomes: all 10.? see exons ↓