PIGZ

Summary

PIGZ (phosphatidylinositol glycan anchor biosynthesis class Z (Gwada blood group), HGNC:30596) is a protein-coding gene on chromosome 3q29, encoding GPI alpha-1,2-mannosyltransferase 4 (Q86VD9). Alpha-1,2-mannosyltransferase that catalyzes the transfer of the fourth mannose, via an alpha-1,2 bond, from a dolichol-phosphate-mannose (Dol-P-Man) to a 2-acyl-6-[alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl….

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.

Source: NCBI Gene 80235 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 134 total — 1 pathogenic
• MANE Select transcript: NM_025163

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30596
Approved symbol	PIGZ
Name	phosphatidylinositol glycan anchor biosynthesis class Z (Gwada blood group)
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12768, MGC52163, SMP3, hSMP3, PIG-Z, GPI-MT-IV
Ensembl gene	ENSG00000119227
Ensembl biotype	protein_coding
OMIM	611671
Entrez	80235

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 retained_intron

ENST00000238138, ENST00000412723, ENST00000413127, ENST00000443835, ENST00000910248, ENST00000910249, ENST00000910250, ENST00000958080, ENST00000958081, ENST00000958082

RefSeq mRNA: 1 — MANE Select: NM_025163 NM_025163

CCDS: CCDS3324

Canonical transcript exons

ENST00000412723 — 3 exons

Exon	Start	End
ENSE00001364646	196968687	196968833
ENSE00001642096	196951821	196952031
ENSE00001700079	196946356	196948685

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 93.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.2838 / max 61.8816, expressed in 1345 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46392	2.8037	1263
46393	0.4802	254

Top tissues by expression

268 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	93.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.30	gold quality
transverse colon	UBERON:0001157	90.84	gold quality
rectum	UBERON:0001052	90.51	gold quality
ileal mucosa	UBERON:0000331	89.65	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.31	gold quality
colonic mucosa	UBERON:0000317	88.95	gold quality
cerebellar hemisphere	UBERON:0002245	88.76	gold quality
cerebellar cortex	UBERON:0002129	88.66	gold quality
cerebellum	UBERON:0002037	87.70	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.86	gold quality
large intestine	UBERON:0000059	84.93	gold quality
colon	UBERON:0001155	84.89	gold quality
right frontal lobe	UBERON:0002810	84.33	gold quality
anterior cingulate cortex	UBERON:0009835	82.74	gold quality
cingulate cortex	UBERON:0003027	82.68	gold quality
intestine	UBERON:0000160	82.59	gold quality
apex of heart	UBERON:0002098	82.45	gold quality
middle temporal gyrus	UBERON:0002771	82.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.43	gold quality
endothelial cell	CL:0000115	81.18	silver quality
nucleus accumbens	UBERON:0001882	80.73	gold quality
prefrontal cortex	UBERON:0000451	80.47	gold quality
primary visual cortex	UBERON:0002436	80.36	gold quality
frontal cortex	UBERON:0001870	80.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	80.18	gold quality
neocortex	UBERON:0001950	80.12	gold quality
stromal cell of endometrium	CL:0002255	79.93	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	23.05
E-ANND-3	yes	8.39
E-MTAB-6058	no	90.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting PIGZ, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4709-3P	98.88	68.04	1594

Literature-anchored findings (GeneRIF, showing 1)

• publication also discusses human SMP3 (PMID:11356840)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

GPI alpha-1,2-mannosyltransferase 4 — Q86VD9 (reviewed: Q86VD9)

Alternative names: GPI mannosyltransferase IV, Phosphatidylinositol-glycan biosynthesis class Z protein, SMP3 homolog

All UniProt accessions (3): C9JQX2, Q86VD9, H7C2E0

UniProt curated annotations — full annotation on UniProt →

Function. Alpha-1,2-mannosyltransferase that catalyzes the transfer of the fourth mannose, via an alpha-1,2 bond, from a dolichol-phosphate-mannose (Dol-P-Man) to a 2-acyl-6-[alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol (also termed H6) intermediate to generate a 2-acyl-6-[alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol (also termed M4C) and participates in the twelfth step of the glycosylphosphatidylinositol-anchor biosynthesis. The presence of a fourth mannose in GPI is facultative, suggesting that it only exists in some tissues.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed at low level, with highest level in brain and colon.

Pathway. Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.

Similarity. Belongs to the glycosyltransferase 22 family. PIGZ subfamily.

RefSeq proteins (1): NP_079439* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005599	GPI_mannosylTrfase	Family

Pfam: PF03901

Catalyzed reactions (Rhea), 1 shown:

• a 2-acyl-6-[alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol + a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate = a 2-acyl-6-[alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:61024)

UniProt features (13 total): transmembrane region 8, sequence variant 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VD9-F1	87.63	0.65

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-162710	Synthesis of glycosylphosphatidylinositol (GPI)

MSigDB gene sets: 93 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, REACTOME_SYNTHESIS_OF_GLYCOSYLPHOSPHATIDYLINOSITOL_GPI, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, KEGG_GLYCOSYLPHOSPHATIDYLINOSITOL_GPI_ANCHOR_BIOSYNTHESIS, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (1): GPI anchor biosynthetic process (GO:0006506)

GO Molecular Function (5): alpha-1,2-mannosyltransferase activity (GO:0000026), mannosyltransferase activity (GO:0000030), dol-P-Man:Man(3)GlcN-acyl-PI alpha-1,2-mannosyltransferase activity (GO:0120565), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational modification: synthesis of GPI-anchored proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GPI anchor metabolic process	1
glycolipid biosynthetic process	1
glycerophospholipid biosynthetic process	1
GPI anchored protein biosynthesis	1
mannosyltransferase activity	1
hexosyltransferase activity	1
alpha-1,2-mannosyltransferase activity	1
GPI mannosyltransferase activity	1
catalytic activity	1
transferase activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIGZ	PIGV	Q9NUD9	805
PIGZ	PIGM	Q9H3S5	773
PIGZ	PIGG	Q5H8A4	742
PIGZ	PIGW	Q7Z7B1	734
PIGZ	PIGK	Q92643	730
PIGZ	PIGO	Q8TEQ8	716
PIGZ	PIGY	Q3MUY2	716
PIGZ	PIGN	O95427	693
PIGZ	PIGQ	Q9BRB3	681
PIGZ	GPAA1	O43292	681
PIGZ	PIGC	Q92535	674
PIGZ	WDR53	Q7Z5U6	670
PIGZ	PIGL	Q9Y2B2	664
PIGZ	PGAP4	Q9BRR3	664
PIGZ	ALG12	Q9BV10	647

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PIGZ	HSPA5	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): PIGZ (Affinity Capture-RNA), HSPA5 (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, B0BNG2, O60725, O75908, O77759, O88269, O88908, O95255, Q0P4J9, Q290J8, Q3T1L5, Q3TAE8, Q3UV71, Q499P8, Q49LS7, Q4R4E1, Q4VV71, Q5F380, Q5KR61, Q5R8F6, Q5RAH7, Q5RKL5, Q6AZ83, Q6NVG1, Q7SXZ1, Q7T310, Q7TPN3, Q7TQM4, Q86VD9, Q8AVI9, Q8BTP0, Q8C0T0, Q8C3X8, Q8CI59, Q8IUR5, Q8K2A8, Q8L638, Q8R1J1, Q8R4P9

Diamond homologs: Q04174, Q2UTP0, Q4I785, Q4WTT7, Q5A0L9, Q5BAX7, Q6BJ96, Q6CDD0, Q6CU99, Q6FMA9, Q753C1, Q86VD9, Q8BTP0, Q09837, Q8MT80

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

134 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	20
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
562857	GRCh37/hg19 3q28-29(chr3:191593619-197851986)x3	Pathogenic

SpliceAI

718 predictions. Top by Δscore:

Variant	Effect	Δscore
3:196948473:C:CT	acceptor_gain	0.9900
3:196948473:C:T	acceptor_gain	0.9900
3:196948477:C:CT	acceptor_gain	0.9900
3:196948683:CCT:C	acceptor_gain	0.9900
3:196948684:CTC:C	acceptor_gain	0.9900
3:196948685:TCT:T	acceptor_gain	0.9900
3:196948686:C:CC	acceptor_gain	0.9900
3:196951853:T:C	donor_gain	0.9900
3:196948477:C:T	acceptor_gain	0.9800
3:196948684:CT:C	acceptor_gain	0.9800
3:196948686:C:G	acceptor_gain	0.9800
3:196951913:C:CT	donor_gain	0.9800
3:196948682:TCCT:T	acceptor_gain	0.9700
3:196948683:CCTC:C	acceptor_gain	0.9700
3:196948686:C:CG	acceptor_loss	0.9700
3:196948687:T:G	acceptor_loss	0.9700
3:196968683:T:TC	donor_loss	0.9700
3:196968684:CACCC:C	donor_loss	0.9700
3:196968685:AC:A	donor_gain	0.9700
3:196968686:C:A	donor_loss	0.9700
3:196968686:CC:C	donor_gain	0.9700
3:196951866:AG:A	donor_gain	0.9600
3:196951866:AGC:A	donor_gain	0.9600
3:196968681:ACT:A	donor_loss	0.9600
3:196968685:A:AC	donor_gain	0.9600
3:196968686:C:CC	donor_gain	0.9600
3:196968686:CCCG:C	donor_gain	0.9600
3:196948478:A:T	acceptor_gain	0.9500
3:196948681:GTCCT:G	acceptor_gain	0.9500
3:196951823:G:A	donor_gain	0.9500

AlphaMissense

3678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:196947724:G:C	F391L	0.996
3:196947724:G:T	F391L	0.996
3:196947726:A:G	F391L	0.996
3:196948645:A:C	F84L	0.995
3:196948645:A:T	F84L	0.995
3:196948647:A:G	F84L	0.995
3:196948363:G:C	N178K	0.993
3:196948363:G:T	N178K	0.993
3:196947734:T:A	E388V	0.991
3:196948376:C:A	R174M	0.990
3:196948651:C:A	W82C	0.990
3:196948651:C:G	W82C	0.990
3:196947725:A:G	F391S	0.989
3:196951846:G:C	F62L	0.987
3:196951846:G:T	F62L	0.987
3:196951848:A:G	F62L	0.987
3:196947725:A:C	F391C	0.986
3:196948353:C:G	G182R	0.986
3:196948353:C:T	G182R	0.986
3:196948355:T:A	E181V	0.986
3:196947997:G:C	N300K	0.985
3:196947997:G:T	N300K	0.985
3:196948217:C:G	R227P	0.984
3:196951853:T:A	D60V	0.984
3:196948207:A:C	F230L	0.983
3:196948207:A:T	F230L	0.983
3:196948209:A:G	F230L	0.983
3:196948198:A:C	F233L	0.981
3:196948198:A:T	F233L	0.981
3:196948200:A:G	F233L	0.981

dbSNP variants (sampled 300 via entrez): RS1000199592 (3:196961607 A>G), RS1000261185 (3:196955647 G>A), RS1000420460 (3:196949878 G>A,C), RS1000476997 (3:196967955 G>A,C), RS1000533790 (3:196959626 A>G), RS1000538891 (3:196949388 G>A), RS1000688995 (3:196954492 G>A), RS1001212124 (3:196958719 G>T), RS1001228924 (3:196956246 G>A), RS1001264348 (3:196958436 G>C), RS1001618353 (3:196952179 A>G), RS1001632086 (3:196950343 G>A), RS1001660643 (3:196946874 T>G), RS1001867930 (3:196968863 C>G,T), RS1001899791 (3:196959025 T>G)

Disease associations

OMIM: gene MIM:611671 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_204	Night sleep phenotypes	9.000000e-06
GCST008758_42	Pre-treatment viral load in HIV-1 infection	2.000000e-17
GCST010725_2	Malaria	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010125	viral load

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, decreases reaction	4
Nickel	decreases expression	2
Cyclosporine	decreases expression	2
afuresertib	increases expression	1
dicrotophos	increases expression	1
bufotalin	decreases expression	1
bisphenol A	affects expression	1
chlorophyllin	decreases reaction, increases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
ochratoxin A	decreases expression	1
dinophysistoxin 1	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Allergens	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases methylation	1
Vehicle Emissions	affects cotreatment, decreases expression, increases abundance	1
Cisplatin	increases expression, affects cotreatment	1
Hydrogen Peroxide	affects expression	1
Lead	affects expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Sodium Selenite	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.