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

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 (17 variants)
• Inborn genetic diseases (3 variants)
• not provided (2 variants)
• Cerebral visual impairment and intellectual disability (2 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.

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			3	46	3	52
missense			133	8		141
nonsense	4	10				14
start loss						0
frameshift	9	3	1			13
inframe indel	1	2				3
splice donor/acceptor (+/-2bp)	4	5	1			10
splice region	1	1	13	10	3	28
non coding			3	46	41	90
Total	18	20	141	100	44

Highest pathogenic variant AF is 0.0000197

Variants in PGAP1

This is a list of pathogenic ClinVar variants found in the PGAP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-196841029-C-G			Benign (Jun 20, 2019)
2-196841061-T-C			Uncertain significance (Apr 22, 2021)
2-196841239-T-C		Intellectual disability, autosomal recessive 42	Uncertain significance (Oct 24, 2022)
2-196841260-G-A		Intellectual disability, autosomal recessive 42	Uncertain significance (-)
2-196841269-G-A		Intellectual disability, autosomal recessive 42 • Hereditary spastic paraplegia • Inborn genetic diseases	Benign/Likely benign (Jan 30, 2024)
2-196841279-A-G		Intellectual disability, autosomal recessive 42	Likely benign (Sep 27, 2022)
2-196841294-A-G		Intellectual disability, autosomal recessive 42	Likely benign (Jun 24, 2022)
2-196841313-A-G		Intellectual disability, autosomal recessive 42	Uncertain significance (Jul 19, 2018)
2-196841348-T-C		Intellectual disability, autosomal recessive 42	Likely benign (Nov 27, 2023)
2-196841356-T-C		Intellectual disability, autosomal recessive 42 • Hereditary spastic paraplegia	Likely benign (Jan 06, 2024)
2-196841360-C-G		Intellectual disability, autosomal recessive 42	Uncertain significance (Sep 29, 2017)
2-196841361-T-C		Intellectual disability, autosomal recessive 42	Uncertain significance (Nov 01, 2022)
2-196841379-A-G		Intellectual disability, autosomal recessive 42	Likely benign (Apr 20, 2022)
2-196842521-G-GA			Likely benign (Jul 27, 2020)
2-196842701-G-T		Intellectual disability, autosomal recessive 42	Likely benign (Apr 24, 2023)
2-196842706-A-G		Intellectual disability, autosomal recessive 42	Benign (Dec 01, 2023)
2-196842737-C-T		Intellectual disability, autosomal recessive 42	Uncertain significance (Aug 31, 2022)
2-196842740-TGTAA-T		Intellectual disability, autosomal recessive 42	Pathogenic (Jul 11, 2024)
2-196842740-T-TGTAA		Intellectual disability, autosomal recessive 42	Uncertain significance (Jan 14, 2022)
2-196842747-A-G		Intellectual disability, autosomal recessive 42 • Hereditary spastic paraplegia • PGAP1-related disorder	Benign/Likely benign (Jan 15, 2024)
2-196842760-G-A		Inborn genetic diseases	Uncertain significance (Jun 16, 2024)
2-196842764-T-C		Intellectual disability, autosomal recessive 42	Uncertain significance (Dec 02, 2021)
2-196842800-G-A		Intellectual disability, autosomal recessive 42	Uncertain significance (Jul 05, 2022)
2-196842803-C-A		Intellectual disability, autosomal recessive 42	Uncertain significance (Dec 02, 2021)
2-196842814-T-A		Inborn genetic diseases • Intellectual disability, autosomal recessive 42	Uncertain significance (Aug 13, 2022)

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