PGAP1

post-GPI attachment to proteins inositol deacylase 1

Basic information

Region (hg38): 2:196833004-196927796

Links

ENSG00000197121

∙ NCBI:80055 ∙ OMIM:611655 ∙ HGNC:25712 ∙ Uniprot:Q75T13 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
autosomal recessive spastic paraplegia type 67 (Supportive), mode of inheritance: AR
intellectual disability, autosomal recessive 42 (Strong), mode of inheritance: AR
intellectual disability, autosomal recessive 42 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with dysmorphic features, spasticity, and brain abnormalities	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; Neurologic	24784135

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PGAP1 gene.

Intellectual_disability,_autosomal_recessive_42 (284 variants)
Inborn_genetic_diseases (97 variants)
not_provided (66 variants)
Hereditary_spastic_paraplegia (29 variants)
not_specified (16 variants)
PGAP1-related_disorder (6 variants)
See_cases (3 variants)
Neurodevelopmental_disorder (2 variants)
Cerebral_visual_impairment_and_intellectual_disability (2 variants)
High_myopia (1 variants)
Intellectual_disability,_autosomal_recessive_58 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PGAP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024989.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	4 clinvar	62 clinvar	3 clinvar	70
missense			167 clinvar	15 clinvar		182
nonsense	4 clinvar	12 clinvar				16
start loss						0
frameshift	9 clinvar	4 clinvar	1 clinvar			14
splice donor/acceptor (+/-2bp)	6 clinvar	5 clinvar	1 clinvar			12
Total	19	22	173	77	3

Highest pathogenic variant AF is 0.0000173551

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PGAP1	protein_coding	protein_coding	ENST00000354764	27	94793

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.16e-8	1.00	125689	0	59	125748	0.000235

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.26	379	455	0.834	0.0000221	5990
Missense in Polyphen		95	131.68	0.72145		1727
Synonymous	0.799	146	159	0.919	0.00000778	1729
Loss of Function	3.89	22	52.4	0.420	0.00000244	711

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000456	0.000442
Ashkenazi Jewish	0.000399	0.000397
East Asian	0.000280	0.000272
Finnish	0.000234	0.000231
European (Non-Finnish)	0.000233	0.000229
Middle Eastern	0.000280	0.000272
South Asian	0.000245	0.000196
Other	0.000519	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in inositol deacylation of GPI-anchored proteins. GPI inositol deacylation may important for efficient transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi (By similarity). {ECO:0000250}.;
Disease: DISEASE: Mental retardation, autosomal recessive 42 (MRT42) [MIM:615802]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:24482476, ECO:0000269|PubMed:24784135}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human);Attachment of GPI anchor to uPAR;Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins (Consensus)

Intolerance Scores

loftool: 0.219
rvis_EVS: -0.67
rvis_percentile_EVS: 15.86

Haploinsufficiency Scores

pHI: 0.243
hipred: N
hipred_score: 0.492
ghis: 0.552

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.334

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pgap1
Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; respiratory system phenotype; embryo phenotype; reproductive 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); vision/eye phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; skeleton phenotype;

Zebrafish Information Network

Gene name: pgap1
Affected structure: ceratobranchial cartilage
Phenotype tag: abnormal
Phenotype quality: shortened

Gene ontology

Biological process: GPI anchor metabolic process;endoplasmic reticulum to Golgi vesicle-mediated transport;sensory perception of sound;embryonic pattern specification;anterior/posterior axis specification;protein transport;myo-inositol transport;attachment of GPI anchor to protein;forebrain regionalization;nucleic acid phosphodiester bond hydrolysis
Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane
Molecular function: nuclease activity;hydrolase activity, acting on ester bonds;phosphoric ester hydrolase activity;phosphatidylinositol deacylase activity