PGAP3

post-GPI attachment to proteins phospholipase 3

Basic information

Region (hg38): 17:39671122-39696797

Previous symbols: [ "PERLD1" ]

Links

ENSG00000161395 ∙ NCBI:93210 ∙ OMIM:611801 ∙ HGNC:23719 ∙ Uniprot:Q96FM1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperphosphatasia with intellectual disability syndrome 4 (Definitive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 4 (Strong), mode of inheritance: AR
• hyperphosphatasia-intellectual disability syndrome (Supportive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 4 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperphosphatasia with impaired intellectual development syndrome 4	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	22315194; 24439110; 29620724; 30217754; 30345601

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PGAP3 gene.

• Hyperphosphatasia with intellectual disability syndrome 4 (9 variants)
• not provided (5 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PGAP3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	40	2	43
missense	1	5	57	8		71
nonsense	6	1				7
start loss						0
frameshift	3	4				7
inframe indel						0
splice donor/acceptor (+/-2bp)	2					2
splice region			1	4		5
non coding		1	2	18	14	35
Total	12	11	60	66	16

Highest pathogenic variant AF is 0.0000197

Variants in PGAP3

This is a list of pathogenic ClinVar variants found in the PGAP3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-39672243-T-C			Benign (Jan 22, 2024)
17-39672243-TG-CA			Uncertain significance (Oct 23, 2022)
17-39672244-G-A		Hyperphosphatasia with intellectual disability syndrome 4	Uncertain significance (Aug 26, 2021)
17-39672492-A-G			Benign (Jul 27, 2018)
17-39672534-G-A			Benign (Jul 27, 2018)
17-39672828-G-A		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
17-39672845-C-T			Likely benign (Nov 08, 2023)
17-39672847-G-C			Uncertain significance (Jun 11, 2022)
17-39672852-T-C		Hyperphosphatasia with intellectual disability syndrome 4	Pathogenic/Likely pathogenic (Oct 23, 2023)
17-39672876-A-G		Hyperphosphatasia with intellectual disability syndrome 4	Benign (Feb 01, 2024)
17-39672884-A-G			Benign (Jan 25, 2024)
17-39672885-G-C			Likely benign (Oct 13, 2023)
17-39673053-G-GA		Hyperphosphatasia with intellectual disability syndrome 4	Likely pathogenic (Mar 16, 2022)
17-39673089-C-A		Hyperphosphatasia with intellectual disability syndrome 4	Pathogenic (Mar 01, 2016)
17-39673094-T-C		Hyperphosphatasia with intellectual disability syndrome 4	Uncertain significance (Jan 09, 2022)
17-39673099-T-C		10 conditions • Hyperphosphatasia with intellectual disability syndrome 4 • See cases	Pathogenic/Likely pathogenic (Dec 03, 2024)
17-39673100-G-A		Hyperphosphatasia with intellectual disability syndrome 4	Pathogenic/Likely pathogenic (Mar 17, 2024)
17-39673100-G-C		Hyperphosphatasia with intellectual disability syndrome 4	Conflicting classifications of pathogenicity (Sep 01, 2022)
17-39673105-T-C		Hyperphosphatasia with intellectual disability syndrome 4	Pathogenic (Oct 04, 2016)
17-39673108-A-G		Hyperphosphatasia with intellectual disability syndrome 4	Pathogenic (Mar 01, 2016)
17-39673111-A-G		Inborn genetic diseases	Uncertain significance (Mar 18, 2024)
17-39673122-C-T			Likely benign (Oct 04, 2023)
17-39673123-G-A		Inborn genetic diseases • PGAP3-related disorder • Hyperphosphatasia with intellectual disability syndrome 4	Pathogenic/Likely pathogenic (Mar 20, 2024)
17-39673128-G-A			Likely benign (Nov 22, 2022)
17-39673131-G-T		Inborn genetic diseases	Uncertain significance (Aug 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PGAP3	protein_coding	protein_coding	ENST00000300658	8	25676

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00194	0.978	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.685	154	180	0.856	0.0000109	2019
Missense in Polyphen		53	59.847	0.88559		748
Synonymous	0.671	73	80.7	0.905	0.00000514	650
Loss of Function	2.05	7	15.8	0.444	6.77e-7	167

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000455	0.0000439
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the lipid remodeling steps of GPI-anchor maturation. Lipid remodeling steps consist in the generation of 2 saturated fatty chains at the sn-2 position of GPI-anchors proteins. Required for phospholipase A2 activity that removes an acyl-chain at the sn-2 position of GPI-anchors during the remodeling of GPI (Probable). {ECO:0000305|PubMed:17021251}.

Recessive Scores

• pRec: 0.132

Intolerance Scores

• loftool: 0.177
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.41

Haploinsufficiency Scores

• pHI: 0.325
• hipred: N
• hipred_score: 0.369
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.339

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pgap3
• Phenotype: limbs/digits/tail phenotype; immune system phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); growth/size/body region phenotype

Gene ontology

• Biological process: GPI anchor metabolic process;GPI anchor biosynthetic process
• Cellular component: Golgi membrane;integral component of membrane;intrinsic component of endoplasmic reticulum membrane
• Molecular function: hydrolase activity, acting on ester bonds