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 (534 variants)
• Inborn_genetic_diseases (93 variants)
• Glycosylphosphatidylinositol_biosynthesis_defect_15 (36 variants)
• GPAA1-related_disorder (18 variants)
• not_specified (3 variants)
• See_cases (1 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. These statistics are base on transcript: NM_000003801.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	166	5	173
missense	2	8	236	8	4	258
nonsense	9	3	1			13
start loss			1			1
frameshift	11	4				15
splice donor/acceptor (+/-2bp)		13	3			16
Total	22	28	243	174	9

Highest pathogenic variant AF is 0.0000756052

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