PGAP2

post-GPI attachment to proteins 2

Basic information

Region (hg38): 11:3797723-3826371

Previous symbols: [ "MRT21", "MRT17" ]

Links

ENSG00000148985 ∙ NCBI:27315 ∙ OMIM:615187 ∙ HGNC:17893 ∙ Uniprot:Q9UHJ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Definitive), mode of inheritance: AR
• hyperphosphatasia with intellectual disability syndrome 3 (Strong), mode of inheritance: AR
• hyperphosphatasia-intellectual disability syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperphosphatasia with impaired intellectual development syndrome 3	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	Musculoskeletal; Neurologic	21629298; 21643797; 23561846; 23561847

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PGAP2 gene.

• not provided (51 variants)
• Inborn genetic diseases (22 variants)
• Hyperphosphatasia with intellectual disability syndrome 3 (20 variants)
• Autism spectrum disorder (2 variants)
• Congenital omphalocele;Hypoplasia of the corpus callosum;Micrognathia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PGAP2 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	6		7
missense	1	4	23	4	2	34
nonsense	1		1			2
start loss	1	1				2
frameshift		1	1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	2		5
non coding	1		3	4	19	27
Total	4	6	29	14	21

Highest pathogenic variant AF is 0.0000131

Variants in PGAP2

This is a list of pathogenic ClinVar variants found in the PGAP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-3797878-G-C			Likely benign (Mar 01, 2023)
11-3797940-A-T		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
11-3797989-A-G		Hyperphosphatasia with intellectual disability syndrome 3	Uncertain significance (Aug 08, 2019)
11-3798037-C-T			Benign (May 26, 2021)
11-3798189-T-A			Benign (Jul 27, 2018)
11-3807993-A-C			Benign (Sep 11, 2018)
11-3807994-C-T			Benign (Sep 11, 2018)
11-3808066-CCGG-C			Benign (Sep 11, 2018)
11-3808189-G-C			Benign (Jul 27, 2018)
11-3808296-A-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Apr 01, 2022)
11-3808299-T-C			Benign (May 01, 2023)
11-3808313-G-A			Likely benign (Jan 01, 2023)
11-3808632-C-G			Benign (Sep 11, 2018)
11-3811027-G-T			Benign (Jul 27, 2018)
11-3811260-A-G		Hyperphosphatasia with intellectual disability syndrome 3	Likely pathogenic (Apr 01, 2022)
11-3811261-T-G		Hyperphosphatasia with intellectual disability syndrome 3	Pathogenic (-)
11-3811269-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2022)
11-3811289-G-T			Likely benign (Oct 09, 2018)
11-3811305-C-T		Hyperphosphatasia with intellectual disability syndrome 3	Pathogenic (Apr 04, 2013)
11-3811306-G-A		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
11-3811311-C-T			Likely benign (Nov 03, 2023)
11-3811312-G-A		Inborn genetic diseases	Uncertain significance (Mar 01, 2024)
11-3811356-G-A		Hypoplasia of the corpus callosum;Micrognathia;Congenital omphalocele • Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
11-3811371-A-G		Autism spectrum disorder	Likely benign (Apr 12, 2022)
11-3811388-C-A			Likely benign (Jun 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PGAP2	protein_coding	protein_coding	ENST00000278243	6	28648

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.935	0.0654	125668	0	80	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.933	168	206	0.817	0.0000138	2058
Missense in Polyphen		51	66.192	0.77049		688
Synonymous	-0.211	91	88.5	1.03	0.00000634	632
Loss of Function	3.09	1	13.1	0.0765	5.59e-7	147

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000304
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000554	0.000554
European (Non-Finnish)	0.000519	0.000519
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the lipid remodeling steps of GPI-anchor maturation. Required for stable expression of GPI-anchored proteins at the cell surface (By similarity). {ECO:0000250}.

Intolerance Scores

• loftool: 0.327
• rvis_EVS: -0.29
• rvis_percentile_EVS: 33.2

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.385
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.457

Mouse Genome Informatics

• Gene name: Pgap2
• Phenotype: skeleton 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)

Gene ontology

• Biological process: GPI anchor biosynthetic process;protein transport
• Cellular component: Golgi membrane;endoplasmic reticulum membrane;integral component of membrane
• Molecular function: protein binding;protein transporter activity