PIGV

Chr 1AR

phosphatidylinositol glycan anchor biosynthesis class V

Also known as: GPI-MT-II, HPMRS1, PIG-V

The protein is a mannosyltransferase enzyme localized to the endoplasmic reticulum that transfers the second mannose to the glycosylphosphatidylinositol (GPI) backbone during GPI biosynthesis, where GPI serves as a membrane anchor for many proteins. Autosomal recessive mutations cause hyperphosphatasia with impaired intellectual development syndrome 1 through loss of function. The pathogenic mechanism involves disrupted GPI anchor biosynthesis leading to defective protein anchoring to cell membranes.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.241 OMIM phenotype
Clinical SummaryPIGV
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Gene-Disease Validity (ClinGen)
hyperphosphatasia with intellectual disability syndrome 1 · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.24LOEUF
pLI 0.000
Z-score 0.81
OE 0.79 (0.521.24)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.40Z-score
OE missense 0.93 (0.841.03)
240 obs / 258.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.79 (0.521.24)
00.351.4
Missense OE0.93 (0.841.03)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 14 / 17.7Missense obs/exp: 240 / 258.0Syn Z: 0.20
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePIGV-related hyperphosphatasia with intellectual developmental disorderLOFAR

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

DN
0.6743th %ile
GOF
0.5170th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PIGV · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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