PIGO

Chr 9

phosphatidylinositol glycan anchor biosynthesis class O

Also known as: HPMRS2, hGPCR43

NCBI Gene: 84720 ENSG00000165282 UniProt: Q8TEQ8

The protein transfers ethanolaminephosphate to the third mannose in glycosylphosphatidylinositol (GPI) anchor biosynthesis, which anchors proteins to cell surfaces including blood cells. Autosomal recessive mutations cause hyperphosphatasia with impaired intellectual development syndrome 2. The pathogenic mechanism involves loss of function leading to defective GPI anchor formation.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid which contains three mannose molecules in its core backbone. The GPI-anchor is found on many blood cells and serves to anchor proteins to the cell surface. This protein is involved in the transfer of ethanolaminephosphate (EtNP) to the third mannose in GPI. At least three alternatively spliced transcripts encoding two distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.81

Clinical Summary— PIGO

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Gene-Disease Validity (ClinGen)

complex neurodevelopmental disorder · 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

81 unique Pathogenic / Likely Pathogenic· 550 VUS of 1071 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.81LOEUF

pLI 0.000

Z-score 2.50

OE 0.57 (0.41–0.81)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.96Z-score

OE missense 0.89 (0.83–0.96)

549 obs / 615.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.41–0.81)

0≤0.351.4

Missense OE?0.89 (0.83–0.96)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 23 / 40.1Missense obs/exp: 549 / 615.8Syn Z: -0.94

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitivePIGO-related hyperphosphatasia with intellectual developmental disorder syndromeLOFAR

This gene — mechanism propensity

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

0.7133th %ile

GOF

0.5760th %ile

LOF

0.2969th %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

1071 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic55

Likely Pathogenic26

VUS550

Likely Benign367

Benign23

Conflicting34

Pathogenic

Likely Pathogenic

550

VUS

367

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	54	1	0	0	55
Likely Pathogenic	20	5	1	0	26
VUS	4	516	18	12	550
Likely Benign	0	8	87	272	367
Benign	0	3	15	5	23
Conflicting	—				34
Total	78	533	121	289	1,055

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

View in ClinVar →

72 pathogenic / likely-pathogenic (of 79) ClinVar copy-number / structural variants overlap PIGO — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →