PIGZ

protein-coding

phosphatidylinositol glycan anchor biosynthesis class Z, the group of Dolichyl D-mannosyl phosphate dependent mannosyltransferases|Phosphatidylinositol glycan anchor biosynthesis

Gene summary

The glycosylphosphatidylinositol (GPI) anchor is a glycolipid found on many blood cells that serves to anchor proteins to the cell surface. This gene encodes a protein that is localized to the endoplasmic reticulum, and is involved in GPI anchor biosynthesis. As shown for the yeast homolog, which is a member of a family of dolichol-phosphate-mannose (Dol-P-Man)-dependent mannosyltransferases, this protein can also add a side-branching fourth mannose to GPI precursors during the assembly of GPI anchors. [provided by RefSeq, Jul 2008]

MANE transcript

NM_025163.4

Inheritance

—

ClinVar variants

U:108B:24

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr3:196,946,356-196,969,060

External References & Databases

Ensembl (ENSG00000119227)

Transcript & Mutation Effects

hg38 • Region Span ~22.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PIGZ variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025163.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar	2 clinvar	9
missense			107 clinvar	15 clinvar		122
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	108	22	2	132

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025163.4	RefSeq	NP_079439.2	2	MANE Select
ENST00000412723.6	Ensembl	ENSP00000413405.1	2	MANE Select
ENST00000413127.1	Ensembl	ENSP00000405341.1	2	Standard
ENST00000443835.1	Ensembl	ENSP00000389327.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycosylphosphatidylinositol (GPI)-anchor biosynthesis - Homo sapiens (human)
Synthesis of glycosylphosphatidylinositol (GPI)
Post-translational modification: synthesis of GPI-anchored proteins
Post-translational protein modification
Metabolism of proteins

Biological Process

GPI anchor biosynthetic process
preassembly of GPI anchor in ER membrane
mannosylation

Molecular Function

alpha-1,2-mannosyltransferase activity
mannosyltransferase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000412723
Coding exons: 2
Length: 22718
Individuals with no LoFs: 125593
Homozygous LoFs: 0
Heterozygous LoFs: 155
Defined: 125748
p: 0.000616

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0441	337	335	1.01	0.0000197	3628
Missense (PolyPhen)		103	111.4	0.92463		1327
Synonymous	-2.15	192	158	1.22	0.00000962	1348
Loss of Function	1.38	10	16.0	0.627	8.19e-7	147

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00068	0.00068	rare
Latino/Admixed American	0.00078	0.00078	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.0014	0.0014	notable
Finnish	0.000095	0.000092	rare
European (Non-Finnish)	0.00058	0.00057	rare
South Asian	0.00049	0.00049	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers a fourth mannose to some trimannosyl-GPIs during GPI precursor assembly. The presence of a fourth mannose in GPI is facultative and only scarcely detected, suggesting that it only exists in some tissues. {ECO:0000269|PubMed:15208306}.;

Recessive Scores

pRec: 0.0973

Intolerance Scores

LoFtool: 0.805
RVIS EVS: 0.29
RVIS percentile EVS: 71.62

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0494

Gene Damage Prediction

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