PIGU

Chr 20AR

phosphatidylinositol glycan anchor biosynthesis class U

Also known as: CDC91L1, GAB1, GPIBD21, NEDBSS, PIG-U

NCBI Gene: 128869 ENSG00000101464 UniProt: Q9H490 OMIM: 608528

The protein functions as the fifth subunit of GPI transamidase complex, which catalyzes the attachment of GPI-anchors to proteins and is essential for GPI-anchored protein biosynthesis. Mutations cause autosomal recessive neurodevelopmental disorder with brain anomalies, seizures, and scoliosis. This disorder involves the central nervous system and musculoskeletal system, with neurodevelopmental impairment as a key feature.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Cdc91, a predicted integral membrane protein that may function in cell division control. The protein encoded by this gene is the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismARLOEUF 0.861 OMIM phenotype

Clinical Summary— PIGU

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Gene-Disease Validity (ClinGen)

glycosylphosphatidylinositol biosynthesis defect 21 · ARLimited

Limited evidence — not for standalone diagnostic reporting

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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

3 unique Pathogenic / Likely Pathogenic· 48 VUS of 142 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?

0.86LOEUF

pLI 0.000

Z-score 2.03

OE 0.52 (0.33–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.72Z-score

OE missense 0.87 (0.78–0.97)

208 obs / 239.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.52 (0.33–0.86)

0≤0.351.4

Missense OE?0.87 (0.78–0.97)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 11 / 21.1Missense obs/exp: 208 / 239.4Syn Z: -0.55

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongPIGU-related intellectual disability, central nervous system anomalies and scoliosisOTHERAR

This gene — mechanism propensity

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

0.6550th %ile

GOF

0.5758th %ile

LOF

0.2581th %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

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic1

VUS48

Likely Benign67

Benign10

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	0	2
Likely Pathogenic	1	0	0	0	1
VUS	1	40	4	3	48
Likely Benign	0	3	28	36	67
Benign	0	1	7	2	10
Total	2	46	39	41	128

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap PIGU — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →