GPAA1

glycosylphosphatidylinositol anchor attachment 1, the group of Glycosylphosphatidylinositol transamidase complex

Basic information

Region (hg38): 8:144082337-144093149

Links

ENSG00000197858 ∙ NCBI:8733 ∙ OMIM:603048 ∙ HGNC:4446 ∙ Uniprot:O43292 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycosylphosphatidylinositol biosynthesis defect 15 (Strong), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 15 (Strong), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 15 (Supportive), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 15 (Strong), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 15 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glycosylphosphatidylinositol biosynthesis defect 15	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	29100095

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GPAA1 gene.

• not provided (15 variants)
• Glycosylphosphatidylinositol biosynthesis defect 15 (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GPAA1 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	145	4	150
missense	1	4	208	5	4	222
nonsense	5	3	1			9
start loss			1			1
frameshift	12	1				13
inframe indel			3			3
splice donor/acceptor (+/-2bp)		13	3			16
splice region			12	14	3	29
non coding			3	72	4	79
Total	18	21	220	222	12

Highest pathogenic variant AF is 0.0000329

Variants in GPAA1

This is a list of pathogenic ClinVar variants found in the GPAA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-144082731-A-C		Glycosylphosphatidylinositol biosynthesis defect 15	Uncertain significance (Mar 22, 2022)
8-144082736-C-G			Likely benign (Oct 03, 2022)
8-144082737-C-G			Uncertain significance (Sep 29, 2022)
8-144082747-A-G		Inborn genetic diseases	Uncertain significance (Sep 22, 2022)
8-144082749-C-T			Uncertain significance (Jul 28, 2022)
8-144082750-C-T			Uncertain significance (Jul 10, 2023)
8-144082756-G-A			Uncertain significance (Jul 03, 2022)
8-144082759-G-A		Glycosylphosphatidylinositol biosynthesis defect 15 • Inborn genetic diseases	Uncertain significance (Sep 06, 2022)
8-144082763-C-A			Likely benign (Nov 12, 2023)
8-144082765-C-T			Uncertain significance (Aug 16, 2022)
8-144082766-G-A			Likely benign (Dec 22, 2022)
8-144082770-GC-G		Glycosylphosphatidylinositol biosynthesis defect 15	Pathogenic/Likely pathogenic (May 28, 2024)
8-144082775-C-T			Likely benign (Jan 13, 2022)
8-144082779-G-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2022)
8-144082781-G-A			Likely benign (Aug 30, 2023)
8-144082781-G-T			Likely benign (Dec 13, 2023)
8-144082782-C-G			Uncertain significance (Feb 27, 2022)
8-144082788-C-T			Uncertain significance (Dec 14, 2022)
8-144082792-A-G			Uncertain significance (Jun 27, 2023)
8-144082793-C-T			Likely benign (Jun 27, 2023)
8-144082801-TGTG-T			Uncertain significance (Dec 14, 2021)
8-144082805-G-A			Likely pathogenic (May 13, 2023)
8-144082808-A-G			Uncertain significance (Jun 03, 2022)
8-144082813-A-G			Likely benign (Jul 19, 2022)
8-144082819-C-G			Likely benign (Oct 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GPAA1	protein_coding	protein_coding	ENST00000355091	12	3627

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.50e-9	0.851	124713	0	108	124821	0.000433

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.868	324	371	0.873	0.0000220	3880
Missense in Polyphen		97	105.51	0.91936		1138
Synonymous	-0.431	180	173	1.04	0.0000105	1423
Loss of Function	1.65	17	26.1	0.652	0.00000120	279

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00100	0.000986
Ashkenazi Jewish	0.000497	0.000497
East Asian	0.00106	0.00106
Finnish	0.0000467	0.0000464
European (Non-Finnish)	0.000418	0.000415
Middle Eastern	0.00106	0.00106
South Asian	0.000328	0.000327
Other	0.000339	0.000330

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential for GPI-anchoring of precursor proteins but not for GPI synthesis. Acts before or during formation of the carbonyl intermediate. {ECO:0000269|PubMed:29100095, ECO:0000269|PubMed:9468317}.
• 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)

Recessive Scores

• pRec: 0.120

Intolerance Scores

• loftool: 0.215
• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.49

Haploinsufficiency Scores

• pHI: 0.0944
• hipred: N
• hipred_score: 0.335
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.819

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gpaa1

Gene ontology

• Biological process: protein retention in ER lumen;attachment of GPI anchor to protein;protein-containing complex assembly
• Cellular component: endoplasmic reticulum membrane;membrane;GPI-anchor transamidase complex
• Molecular function: GPI-anchor transamidase activity;protein binding;tubulin binding;GPI anchor binding