GPAA1 (glycosylphosphatidylinositol anchor attachment 1)

Gene

• Entrez ID: 8733
• Gene name: Glycosylphosphatidylinositol anchor attachment 1
• Gene symbol: GPAA1
• Synonyms (NCBI Gene): GAA1, GPIBD15, hGAA1
• Chromosome: 8
• Chromosome location: 8q24.3
• Summary: Posttranslational glycosylphosphatidylinositol (GPI) anchor attachment serves as a general mechanism for linking proteins to the cell surface membrane. The protein encoded by this gene presumably functions in GPI anchoring at the GPI transfer step. The mR

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs782220208	G>C	Likely-pathogenic	Coding sequence variant, missense variant
rs782339984	AG>-	Pathogenic	Frameshift variant, coding sequence variant
rs782615259	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs782768127	G>A,C	Likely-pathogenic	Coding sequence variant, missense variant
rs922800309	A>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1010907740	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1554763770	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1554764058	T>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1554764067	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1554764080	GTACAAGTATGAC>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023933	hsa-miR-1-3p	Proteomics	18668040
MIRT025943	hsa-miR-7-5p	Microarray	19073608
MIRT051180	hsa-miR-16-5p	CLASH	23622248
MIRT1028068	hsa-miR-1827	CLIP-seq
MIRT1028069	hsa-miR-2355-5p	CLIP-seq
MIRT1028070	hsa-miR-3173-3p	CLIP-seq
MIRT1028071	hsa-miR-3612	CLIP-seq
MIRT1028072	hsa-miR-3679-3p	CLIP-seq
MIRT1028073	hsa-miR-4695-5p	CLIP-seq
MIRT1028074	hsa-miR-650	CLIP-seq
MIRT1028068	hsa-miR-1827	CLIP-seq
MIRT2004965	hsa-miR-2110	CLIP-seq
MIRT1028069	hsa-miR-2355-5p	CLIP-seq
MIRT2004966	hsa-miR-3150a-3p	CLIP-seq
MIRT1028070	hsa-miR-3173-3p	CLIP-seq
MIRT2004967	hsa-miR-3175	CLIP-seq
MIRT2004968	hsa-miR-3189-3p	CLIP-seq
MIRT1028071	hsa-miR-3612	CLIP-seq
MIRT1028072	hsa-miR-3679-3p	CLIP-seq
MIRT2004969	hsa-miR-4294	CLIP-seq
MIRT1028073	hsa-miR-4695-5p	CLIP-seq
MIRT2004970	hsa-miR-4729	CLIP-seq
MIRT2004971	hsa-miR-593	CLIP-seq
MIRT2004972	hsa-miR-615-5p	CLIP-seq
MIRT1028074	hsa-miR-650	CLIP-seq
MIRT2004973	hsa-miR-939	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003923	Function	GPI-anchor transamidase activity	NAS	9468317
GO:0005515	Function	Protein binding	IPI	10793132, 11483512, 12802054, 15713669, 28514442, 32814053, 33961781
GO:0005739	Component	Mitochondrion	IDA
GO:0005783	Component	Endoplasmic reticulum	IDA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	NAS	12802054
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005813	Component	Centrosome	IDA
GO:0005829	Component	Cytosol	IDA
GO:0006506	Process	GPI anchor biosynthetic process	IEA
GO:0006621	Process	Protein retention in ER lumen	NAS	12052837
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IEA
GO:0016255	Process	Attachment of GPI anchor to protein	IBA
GO:0016255	Process	Attachment of GPI anchor to protein	IDA	9468317, 12802054, 29100095, 34576938, 35165458, 35551457, 37684232
GO:0016255	Process	Attachment of GPI anchor to protein	IMP	14660601
GO:0016255	Process	Attachment of GPI anchor to protein	NAS	9468317, 12802054
GO:0016255	Process	Attachment of GPI anchor to protein	TAS	11483512
GO:0034235	Function	GPI anchor binding	IDA	37684232
GO:0034235	Function	GPI anchor binding	IMP	14660601
GO:0042765	Component	GPI-anchor transamidase complex	IBA
GO:0042765	Component	GPI-anchor transamidase complex	IDA	9468317, 11483512, 12582175, 12802054, 14660601, 34576938, 35165458, 35551457, 37684232
GO:0042765	Component	GPI-anchor transamidase complex	IEA
GO:0042765	Component	GPI-anchor transamidase complex	IPI	12802054
GO:0042765	Component	GPI-anchor transamidase complex	TAS	15713669
GO:0180046	Process	GPI anchored protein biosynthesis	IDA	9468317, 29100095, 34576938, 35165458, 35551457, 37684232

Other IDs

• MIM: 603048
• HGNC: 4446
• e!Ensembl: ENSG00000197858

Protein

• UniProt ID: O43292
• Protein name: GPI-anchor transamidase component GPAA1 (GAA1 protein homolog) (hGAA1) (Glycosylphosphatidylinositol anchor attachment 1 protein) (GPI anchor attachment protein 1)
• Protein function: Component of the glycosylphosphatidylinositol-anchor (GPI-anchor) transamidase (GPI-T) complex that catalyzes the formation of the linkage between a proprotein and a GPI-anchor and participates in GPI anchored protein biosynthesis (PubMed:114835
• PDB: 7W72, 7WLD, 8IMX, 8IMY
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF04114	Gaa1	125 → 615	Gaa1-like, GPI transamidase component	Family

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitously expressed in fetal and adult tissues. Expressed at higher levels in fetal tissues than adult tissues. {ECO:0000269|PubMed:9468317}.
• Sequence:

  MGLLSDPVRRRALARLVLRLNAPLCVLSYVAGIAWFLALVFPPLTQRTYMSENAMGSTMV
  EEQFAGGDRARAFARDFAAHRKKSGALPVAWLERTMRSVGLEVYTQSFSRKLPFPDETHE
  RYMVSGTNVYGILRAPRAASTESLVLTVPCGSDSTNSQAVGLLLALAAHFRGQIYWAKDI
  VFLVTEHDLLGTEAWLEAYHDVNVTGMQSSPLQGRAGAIQAAVALELSSDVVTSLDVAVE
  GLNGQLPNLDLLNLFQTFCQKGGLLCTLQGKLQPEDWTSLDGPLQGLQTLLLMVLRQASG
  RPHGSHGLFLRYRVEALTLRGINSFRQYKYDLVAVGKALEGMFRKLNHLLERLHQSFFLY
  LLPGLSRFVSIGLYMPAVGFLLLVLGLKALELWMQLHEAGMGLEEPGGAPGPSVPLPPSQ
  GVGLASLVAPLLISQAMGLALYVLPVLGQHVATQHFPVAEAEAVVLTLLAIYAAGLALPH
  NTHRVVSTQAPDRGWMALKLVALIYLALQLGCIALTNFSLGFLLATTMVPTAALAKPHGP
  RTLYAALLVLTSPAATLLGSLFLWRELQEAPLSLAEGWQLFLAALAQGVLEHHTYGALLF
  PLLSLGLYPCWLLFWNVLFWK

• Sequence length: 621

Pathways

KEGG:

Glycosylphosphatidylinositol (GPI)-anchor biosynthesis
Metabolic pathways

Reactome:

Attachment of GPI anchor to uPAR

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Glycosylphosphatidylinositol biosynthesis defect 15	Pathogenic; Likely pathogenic	rs1835941699, rs782498857, rs1554763955, rs187027021, rs2129936761, rs868951923, rs113583033, rs368192144, rs1010907740, rs1554764080, rs1554764067, rs782768127, rs782220208, rs782615259, rs1554763770	RCV001329755 RCV001782221 RCV005630288 RCV002051976 RCV004698863 RCV002250026 RCV002290396 RCV002471506 RCV000521887 RCV000523072 RCV000519589 RCV000521850 RCV000523649 RCV002272309 RCV000755735	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GPAA1-related disorder	Likely pathogenic; Pathogenic	rs781908018, rs782615259, rs372939605	RCV003982630 RCV004754509 RCV003409907	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DELAY, SEIZURES, OPHTHALMIC ANOMALIES, OSTEOPENIA, CEREBELLAR ATROPHY SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DELAY-SEIZURES-OPHTHALMIC ANOMALIES-OSTEOPENIA-CEREBELLAR ATROPHY SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Papillary renal cell carcinoma type 1	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Apraxias	Apraxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Auditory Perceptual Disorders	Auditory perceptual disorder	Pubtator	33599954	Associate	★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	18487995		★☆☆☆☆ Found in Text Mining only
Bone Diseases Metabolic	Bone disease	Pubtator	29100095	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	31353022	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	17047043, 18487995		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	18487995, 22654114	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	18487995		★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	BEFREE	14653855		★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	29100095, 37510348	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar Hypoplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cirrhosis	Cirrhosis	BEFREE	16642471		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	24535878		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	24535878	Associate	★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	29100095, 37510348	Associate	★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	29100095	Associate	★☆☆☆☆ Found in Text Mining only
Friedreich Ataxia	Friedreich Ataxia	BEFREE	10825709, 16092110		★☆☆☆☆ Found in Text Mining only
FRIEDREICH ATAXIA 1	Friedreich Ataxia	BEFREE	21412413, 21771600, 30596685, 31721791		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	GENOMICS_ENGLAND_DG	24896178		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 15	Glycosylphosphatidylinositol deficiency	GENOMICS_ENGLAND_DG	24896178, 29100095		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 15	Glycosylphosphatidylinositol deficiency	CLINVAR_DG	29100095		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 15	Glycosylphosphatidylinositol deficiency	UNIPROT_DG	29100095		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
GLYCOSYLPHOSPHATIDYLINOSITOL BIOSYNTHESIS DEFECT 15	Glycosylphosphatidylinositol deficiency	ORPHANET_DG	29100095		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Intellectual Disability	Intellectual developmental disorder	Pubtator	31353022, 37510348	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	16642471		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	LHGDN	16642471		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	16642471		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	17047043, 18487995		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	31118109		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	18487995		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	31118109		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	32462000	Associate	★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	17047043, 31118109		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental delay-seizures-ophthalmic anomalies-osteopenia-cerebellar atrophy syndrome	Neurodevelopmental Delay, Seizures, Ophthalmic Anomalies, Osteopenia, Cerebellar Atrophy Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oculomotor apraxia	Oculomotor apraxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oculovestibuloauditory syndrome	Oculovestibuloauditory Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	29100095, 31353022, 37510348	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	LHGDN	18028549		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	18028549	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	BEFREE	18028549		★☆☆☆☆ Found in Text Mining only
Status Epilepticus	Status Epilepticus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	31118109		★☆☆☆☆ Found in Text Mining only
Tonic - clonic seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only