PIGU

phosphatidylinositol glycan anchor biosynthesis class U, the group of Phosphatidylinositol glycan anchor biosynthesis|Glycosylphosphatidylinositol transamidase complex

Basic information

Region (hg38): 20:34560542-34698790

Previous symbols: [ "CDC91L1" ]

Links

ENSG00000101464 ∙ NCBI:128869 ∙ OMIM:608528 ∙ HGNC:15791 ∙ Uniprot:Q9H490 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• glycosylphosphatidylinositol biosynthesis defect 21 (Strong), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 21 (Moderate), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 21 (Strong), mode of inheritance: AR
• glycosylphosphatidylinositol biosynthesis defect 21 (Limited), mode of inheritance: AD
• glycosylphosphatidylinositol biosynthesis defect 21 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with brain anomalies, seizures, and scoliosis	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	Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	31353022

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIGU 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			2	27	2	31
missense			35	3	1	39
nonsense			1			1
start loss			1			1
frameshift		1				1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			3	5	1	9
non coding			1	14	4	19
Total	0	1	41	44	7

Variants in PIGU

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

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

Position	Type	Phenotype	Significance	ClinVar
20-34560872-G-C			Likely benign (Apr 12, 2022)
20-34560877-C-T			Uncertain significance (Aug 22, 2022)
20-34560887-CT-C		Glycosylphosphatidylinositol biosynthesis defect 21	Likely pathogenic (Jun 23, 2021)
20-34560896-A-G			Likely benign (Sep 23, 2022)
20-34560901-T-C			Uncertain significance (Oct 21, 2022)
20-34560900-T-TTGGCGGTCAAGTAGAGGCCATGTG			Uncertain significance (Feb 21, 2022)
20-34560904-C-T			Uncertain significance (Nov 08, 2022)
20-34560911-G-A			Likely benign (Apr 25, 2022)
20-34560917-G-C			Likely benign (Jul 23, 2022)
20-34560929-G-C		Glycosylphosphatidylinositol biosynthesis defect 21	Uncertain significance (Dec 14, 2022)
20-34560930-T-C			Uncertain significance (Dec 03, 2021)
20-34560938-C-T			Likely benign (Oct 31, 2022)
20-34560954-T-C			Uncertain significance (Jul 06, 2022)
20-34560965-A-G			Likely benign (Jul 29, 2023)
20-34560989-G-A			Likely benign (Jul 12, 2022)
20-34562555-C-T		Glycosylphosphatidylinositol biosynthesis defect 21	Uncertain significance (Aug 06, 2019)
20-34575101-T-C		Glycosylphosphatidylinositol biosynthesis defect 21	Uncertain significance (Jun 23, 2021)
20-34575149-G-T		Glycosylphosphatidylinositol biosynthesis defect 21	Pathogenic (May 18, 2020)
20-34575198-A-G		Inborn genetic diseases	Uncertain significance (Oct 06, 2021)
20-34575208-C-T			Uncertain significance (Jul 19, 2022)
20-34575211-T-C		Inborn genetic diseases	Uncertain significance (May 27, 2022)
20-34575236-G-A			Likely benign (Oct 02, 2021)
20-34575266-C-T			Likely benign (Jul 28, 2023)
20-34581533-G-A			Likely benign (Feb 09, 2023)
20-34581535-C-T			Likely benign (Apr 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIGU	protein_coding	protein_coding	ENST00000217446	12	116565

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000190	0.975	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.721	208	239	0.869	0.0000126	2838
Missense in Polyphen		73	91.345	0.79917		1180
Synonymous	-0.546	104	97.2	1.07	0.00000558	857
Loss of Function	2.03	11	21.1	0.522	8.92e-7	268

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000324	0.000324
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.000109	0.000109
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000270	0.0000264
Middle Eastern	0.000109	0.000109
South Asian	0.000132	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the GPI transamidase complex. May be involved in the recognition of either the GPI attachment signal or the lipid portion of GPI. {ECO:0000269|PubMed:12802054}.
• 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: 0.111

Intolerance Scores

• loftool: 0.145
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.178
• hipred: Y
• hipred_score: 0.530
• ghis: 0.609

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.634

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pigu
• 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); 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)

Zebrafish Information Network

• Gene name: pigu
• Affected structure: Rohon-Beard neuron
• Phenotype tag: abnormal
• Phenotype quality: increased age

Gene ontology

• Biological process: GPI anchor biosynthetic process;attachment of GPI anchor to protein;protein localization to cell surface;regulation of JAK-STAT cascade
• Cellular component: endoplasmic reticulum membrane;plasma membrane;membrane;integral component of endoplasmic reticulum membrane;GPI-anchor transamidase complex
• Molecular function: GPI-anchor transamidase activity;GPI anchor binding