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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PGAP2
post-GPI attachment to proteins 2
Chromosome 11 Β· 11p15.4
NCBI Gene: 27315Ensembl: ENSG00000148985.20HGNC: HGNC:17893UniProt: A0A024RCD5
23PubMed Papers
21Diseases
0Drugs
15Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingGPI anchor biosynthetic processendoplasmic reticulum membraneGolgi membranehyperphosphatasia-intellectual disability syndromeIntellectual disabilitygenetic disordergenetic developmental and epileptic encephalopathy
✦AI Summary

PGAP2 encodes a protein involved in the fatty acid remodeling steps of GPI-anchor maturation, where it may catalyze the second step by reacylating lyso-GPI intermediates at sn-2 of inositol phosphate with saturated fatty acid chains 1. This remodeling process is critical for proper integration of GPI-anchored proteins into lipid rafts and their surface expression 1. The protein functions in the Golgi membrane during GPI-anchor processing 2. Biallelic pathogenic variants in PGAP2 cause hyperphosphatasia with impaired intellectual development syndrome 3 (HPMRS3), an autosomal recessive disorder characterized by severe intellectual disability, developmental delay, epilepsy, microcephaly, and elevated alkaline phosphatase 34. Recent case reports have expanded the phenotypic spectrum to include digital anomalies such as brachydactyly, camptodactyly, and syndactyly, as well as macrocephaly in some patients 5. The clinical presentation often includes drug-resistant epilepsy and developmental encephalopathy 4. PGAP2 deficiency disrupts proper GPI-anchored protein processing, leading to their secretion rather than membrane anchoring, which can be exploited for biotechnological applications in cell line selection 2. The disorder belongs to the inherited GPI deficiencies (IGDs) group of diseases 6.

Sources cited
1
PGAP2 involvement in fatty acid remodeling of GPI-anchor maturation and critical role for lipid raft integration
PMID: 23561846
2
PGAP2 function in GPI-anchored protein processing and Golgi membrane localization
PMID: 28642584
3
PGAP2 mutations causing HPMRS3 with intellectual disability, epilepsy, and microcephaly
PMID: 27871432
4
Expanded phenotype including developmental epileptic encephalopathy and drug-resistant seizures
PMID: 38365198
5
Novel phenotypic features including digital anomalies and macrocephaly
PMID: 40225942
6
Classification as inherited GPI deficiency and autosomal recessive inheritance pattern
PMID: 31805394
Disease Associationsβ“˜21
hyperphosphatasia-intellectual disability syndromeOpen Targets
0.64Moderate
Intellectual disabilityOpen Targets
0.60Moderate
genetic disorderOpen Targets
0.34Weak
Dysequilibrium syndromeOpen Targets
0.27Weak
genetic developmental and epileptic encephalopathyOpen Targets
0.27Weak
familial hemolytic anemiaOpen Targets
0.13Weak
Hypoplasia of the corpus callosumOpen Targets
0.12Weak
MicrognathiaOpen Targets
0.12Weak
omphaloceleOpen Targets
0.12Weak
Ankyloblepharon filiforme adnatum - cleft palateOpen Targets
0.06Suggestive
ankyloblepharon filiforme adnatum-cleft palate syndromeOpen Targets
0.06Suggestive
van der Woude syndromeOpen Targets
0.05Suggestive
anencephaly 2Open Targets
0.05Suggestive
familial median cleft of the upper and lower lipsOpen Targets
0.05Suggestive
orofacial cleft 1Open Targets
0.05Suggestive
orofacial cleft 10Open Targets
0.05Suggestive
orofacial cleft 11Open Targets
0.05Suggestive
orofacial cleft 5Open Targets
0.05Suggestive
cleft palate-lateral synechia syndromeOpen Targets
0.05Suggestive
van der Woude syndrome 1Open Targets
0.05Suggestive
Hyperphosphatasia with impaired intellectual development syndrome 3UniProt
Pathogenic Variants15
NM_014489.4(PGAP2):c.713G>C (p.Arg238Pro)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 3|Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 3
β˜…β˜…β˜†β˜†2023β†’ Residue 238
NM_014489.4(PGAP2):c.380C>T (p.Ala127Val)Likely pathogenic
not provided|Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜…β˜†β˜†2022β†’ Residue 127
NM_014489.4(PGAP2):c.881C>T (p.Thr294Met)Likely pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜…β˜†β˜†2022β†’ Residue 294
NM_001256236.2(PGAP2):c.-60_-57delPathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜†β˜†β˜†2024
NM_014489.4(PGAP2):c.737G>T (p.Arg246Leu)Likely pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜†β˜†β˜†2024β†’ Residue 246
NM_014489.4(PGAP2):c.642_645del (p.Leu215fs)Likely pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜†β˜†β˜†2023β†’ Residue 215
NM_014489.4(PGAP2):c.732dup (p.Gln245fs)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2023β†’ Residue 245
NM_014489.4(PGAP2):c.1A>G (p.Met1Val)Likely pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜†β˜†β˜†2022β†’ Residue 1
NM_014489.4(PGAP2):c.479A>G (p.Tyr160Cys)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜†β˜†β˜†2020β†’ Residue 160
NM_014489.4(PGAP2):c.391G>T (p.Glu131Ter)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜†β˜†β˜†2019β†’ Residue 131
NM_014489.4(PGAP2):c.449T>C (p.Phe150Ser)Likely pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜†β˜†β˜†2019β†’ Residue 150
NM_014489.4(PGAP2):c.509A>G (p.Tyr170Cys)Likely pathogenic
Genetic developmental and epileptic encephalopathy
β˜…β˜†β˜†β˜†2019β†’ Residue 170
NM_014489.4(PGAP2):c.2T>G (p.Met1Arg)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜…β˜†β˜†β˜†β†’ Residue 1
NM_014489.4(PGAP2):c.491C>T (p.Thr164Ile)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜†β˜†β˜†β˜†2013β†’ Residue 164
NM_014489.4(PGAP2):c.46C>T (p.Arg16Trp)Pathogenic
Hyperphosphatasia with intellectual disability syndrome 3
β˜†β˜†β˜†β˜†2013β†’ Residue 16
View on ClinVar β†—
Related Genes
PGAP4Shared pathway100%PIGZShared pathway100%CWH43Shared pathway100%PIGXShared pathway100%PIGGShared pathway100%PIGPShared pathway100%
Tissue Expression6 tissues
Liver
100%
Lung
56%
Bone Marrow
56%
Heart
52%
Ovary
45%
Brain
19%
Gene Interaction Network
Click a node to explore
PGAP2PGAP4PIGZCWH43PIGXPIGGPIGP
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9UHJ9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.87LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.60 [0.43–0.87]
RankingsWhere PGAP2 stands among ~20K protein-coding genes
  • #13,479of 20,598
    Most Researched23
  • #2,484of 5,498
    Most Pathogenic Variants15
  • #7,689of 17,882
    Most Constrained (LOEUF)0.87
Genes detectedPGAP2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
New perspective in diagnostics of mitochondrial disorders: two years' experience with whole-exome sequencing at a national paediatric centre.
PMID: 27290639
J Transl Med Β· 2016
1.00
2
A novel mutation in PGAP2 gene causes developmental delay, intellectual disability, epilepsy and microcephaly in consanguineous Saudi family.
PMID: 27871432
J Neurol Sci Β· 2016
0.90
3
Molecular switching system using glycosylphosphatidylinositol to select cells highly expressing recombinant proteins.
PMID: 28642584
Sci Rep Β· 2017
0.80
4
PGAP2-Related Hyperphosphatasia-Mental Retardation Syndrome: Report of a Novel Patient, Toward a Broadening of Phenotypic Spectrum and Therapeutic Perspectives.
PMID: 38365198
Neuropediatrics Β· 2024
0.70
5
Macrocephaly and Digital Anomalies Expand the Phenotypic Spectrum of
PMID: 40225942
Hum Mutat Β· 2024
0.60