PIGX

Summary

PIGX (phosphatidylinositol glycan anchor biosynthesis class X, HGNC:26046) is a protein-coding gene on chromosome 3q29, encoding GPI alpha-1,4-mannosyltransferase I, stabilizing subunit (Q8TBF5). Stabilizing subunit of the glycosylphosphatidylinositol-mannosyltransferase I complex which catalyzes the transfer of the first mannose, via an alpha-1,4 bond from a dolichol-phosphate-mannose (Dol-P-Man) to the glucosaminyl acyl phosphatidylinositol (GlcN-(acyl)PI) intermediate….

This gene encodes a type I transmembrane protein in the endoplasmic reticulum (ER). The protein is an essential component of glycosylphosphatidylinositol-mannosyltransferase I, which transfers the first of the four mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis. Studies in rat indicate that the protein is translated from a non-AUG translation initiation site. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 54965 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_017861

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26046
Approved symbol	PIGX
Name	phosphatidylinositol glycan anchor biosynthesis class X
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20522, PIG-X
Ensembl gene	ENSG00000163964
Ensembl biotype	protein_coding
OMIM	610276
Entrez	54965

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000296333, ENST00000392391, ENST00000415832, ENST00000421265, ENST00000426755, ENST00000451319, ENST00000453218, ENST00000457284, ENST00000495440

RefSeq mRNA: 2 — MANE Select: NM_017861 NM_001166304, NM_017861

CCDS: CCDS3320, CCDS54701

Canonical transcript exons

ENST00000392391 — 6 exons

Exon	Start	End
ENSE00001921521	196712377	196712644
ENSE00001927884	196733759	196736007
ENSE00003522685	196716858	196716921
ENSE00003556956	196727923	196728136
ENSE00003598777	196730992	196731092
ENSE00003641212	196722415	196722556

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 90.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7113 / max 369.5182, expressed in 969 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40742	13.7479	1793
40739	11.7113	969
40743	3.7164	1493
40741	0.0460	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	90.42	gold quality
prefrontal cortex	UBERON:0000451	89.66	gold quality
palpebral conjunctiva	UBERON:0001812	89.49	gold quality
anterior cingulate cortex	UBERON:0009835	89.14	gold quality
embryo	UBERON:0000922	88.99	gold quality
ganglionic eminence	UBERON:0004023	88.99	gold quality
cortical plate	UBERON:0005343	88.99	gold quality
islet of Langerhans	UBERON:0000006	88.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.79	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.45	gold quality
secondary oocyte	CL:0000655	88.35	gold quality
hypothalamus	UBERON:0001898	88.20	gold quality
nucleus accumbens	UBERON:0001882	88.13	gold quality
eye	UBERON:0000970	88.02	gold quality
caudate nucleus	UBERON:0001873	87.90	gold quality
monocyte	CL:0000576	87.87	gold quality
leukocyte	CL:0000738	87.73	gold quality
putamen	UBERON:0001874	87.54	gold quality
amygdala	UBERON:0001876	87.48	gold quality
spinal cord	UBERON:0002240	87.28	gold quality
gastrocnemius	UBERON:0001388	87.09	gold quality
neocortex	UBERON:0001950	87.00	gold quality
muscle of leg	UBERON:0001383	86.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	86.90	gold quality
right frontal lobe	UBERON:0002810	86.76	gold quality
smooth muscle tissue	UBERON:0001135	86.64	gold quality
blood	UBERON:0000178	86.47	gold quality
frontal cortex	UBERON:0001870	86.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.43

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting PIGX, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-3182	99.40	68.15	2454

Literature-anchored findings (GeneRIF, showing 1)

• mammalian PIG-X and yeast Pbn1p are the essential components of glycosylphosphatidylinositol-mannosyltransferase I (PMID:15635094)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pigx	ENSDARG00000063559
mus_musculus	Pigx	ENSMUSG00000023791
rattus_norvegicus	Pigx	ENSRNOG00000033623
drosophila_melanogaster	PIG-X	FBGN0050381

Protein

Protein identifiers

GPI alpha-1,4-mannosyltransferase I, stabilizing subunit — Q8TBF5 (reviewed: Q8TBF5)

Alternative names: Phosphatidylinositol-glycan biosynthesis class X protein

All UniProt accessions (9): A0A1X7SBT4, C9JF71, C9JFU3, Q8TBF5, C9JLT7, F8WEJ3, H0Y2P9, H7C081, H7C0F2

UniProt curated annotations — full annotation on UniProt →

Function. Stabilizing subunit of the glycosylphosphatidylinositol-mannosyltransferase I complex which catalyzes the transfer of the first mannose, via an alpha-1,4 bond from a dolichol-phosphate-mannose (Dol-P-Man) to the glucosaminyl acyl phosphatidylinositol (GlcN-(acyl)PI) intermediate to generate alpha-D-Man-(1->4)-alpha-D-GlcN-(1->6)-(1-radyl,2-acyl-sn-glycero-3-phospho)-2-acyl-inositol and participates in the sixth step of the glycosylphosphatidylinositol-anchor biosynthesis. Probably acts by stabilizing the mannosyltransferase PIGM.

Subunit / interactions. Part of the glycosylphosphatidylinositol-mannosyltransferase I complex that is composed of PIGM and PIGX. Interacts with PIGM; PIGX stabilizes PIGM.

Subcellular location. Endoplasmic reticulum membrane.

Pathway. Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.

Similarity. Belongs to the PIGX family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TBF5-1	1	yes
Q8TBF5-2	2

RefSeq proteins (2): NP_001159776, NP_060331* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013233	PIG-X/PBN1	Family
IPR040039	PIGX	Family

Pfam: PF08320

UniProt features (10 total): topological domain 2, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBF5-F1	85.23	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 103

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 133 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, 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, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS

GO Biological Process (2): GPI anchor biosynthetic process (GO:0006506), GPI anchor metabolic process (GO:0006505)

GO Molecular Function (0):

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), 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
glycerophospholipid metabolic process	1
glycolipid metabolic process	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1510 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIGX	PIGM	Q9H3S5	954
PIGX	ANKRD36B	Q8N2N9	487
PIGX	PIGY	Q3MUY2	452
PIGX	PIGC	Q92535	399
PIGX	CHPF2	Q9P2E5	398
PIGX	DPM2	O94777	371
PIGX	DPM3	Q9P2X0	354
PIGX	EPRS1	P07814	353
PIGX	YARS1	P54577	352
PIGX	MYH15	Q9Y2K3	350
PIGX	VARS1	P26640	349
PIGX	SMCO1	Q147U7	349
PIGX	WDR53	Q7Z5U6	349
PIGX	PIGZ	Q86VD9	349
PIGX	MARS1	P56192	340

IntAct

9 interactions, top by confidence:

A	B	Type	Score
PIGX		psi-mi:“MI:0915”(physical association)	0.560
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
M		psi-mi:“MI:0914”(association)	0.350
M	TM9SF1	psi-mi:“MI:0914”(association)	0.350
SLC2A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC6A12	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): PIGX (Affinity Capture-MS), PIGX (Affinity Capture-MS), PIGX (Proximity Label-MS), PIGX (Proximity Label-MS), PIGX (Proximity Label-MS), PIGX (Affinity Capture-MS), PIGX (Affinity Capture-MS), PIGX (Affinity Capture-MS), PIGX (Positive Genetic), PIGX (Proximity Label-MS), PIGX (Affinity Capture-MS), PIGX (Affinity Capture-MS), PIGX (Affinity Capture-MS)

ESM2 similar proteins: A2RT67, A2RUS2, B0CM32, B0KW86, E1B8U2, E7F240, F1MDL2, O94955, O95456, P48553, Q05AX3, Q0P5F2, Q1JQA1, Q1RMS8, Q1RMZ1, Q2HJ90, Q2TBA3, Q3T0J1, Q3TLI0, Q568M3, Q5FVM6, Q5R989, Q5RAQ5, Q5RFG8, Q60GF7, Q641X7, Q6VNB8, Q7Z7H3, Q80TA6, Q8BXK4, Q8CHQ0, Q8IZQ1, Q8NFZ0, Q8TBF5, Q91W96, Q91Z62, Q92902, Q96QE5, Q99LV7, Q9BTF0

Diamond homologs: Q60GF7, Q8TBF5, Q99LV7, O94472

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

812 predictions. Top by Δscore:

Variant	Effect	Δscore
3:196639873:GCC:G	donor_gain	1.0000
3:196639876:G:GG	donor_gain	1.0000
3:196654521:CCACA:C	acceptor_loss	1.0000
3:196654522:CACA:C	acceptor_loss	1.0000
3:196654524:CAGG:C	acceptor_loss	1.0000
3:196654525:A:AG	acceptor_gain	1.0000
3:196654525:A:G	acceptor_loss	1.0000
3:196654525:AG:A	acceptor_gain	1.0000
3:196654526:G:GA	acceptor_gain	1.0000
3:196654526:GG:G	acceptor_gain	1.0000
3:196654526:GGGC:G	acceptor_gain	1.0000
3:196654526:GGGCT:G	acceptor_gain	1.0000
3:196654644:GTTG:G	donor_gain	1.0000
3:196707909:CAAT:C	acceptor_gain	1.0000
3:196707910:AATC:A	acceptor_loss	1.0000
3:196707913:C:CA	acceptor_loss	1.0000
3:196707913:C:CC	acceptor_gain	1.0000
3:196639871:GAGCC:G	donor_gain	0.9900
3:196639872:AGCC:A	donor_gain	0.9900
3:196639872:AGCCG:A	donor_loss	0.9900
3:196639873:GCCG:G	donor_gain	0.9900
3:196639874:CC:C	donor_gain	0.9900
3:196639875:CG:C	donor_loss	0.9900
3:196639876:G:GA	donor_loss	0.9900
3:196639877:T:TA	donor_loss	0.9900
3:196639878:GAGT:G	donor_loss	0.9900
3:196639879:A:AC	donor_loss	0.9900
3:196639880:G:C	donor_loss	0.9900
3:196654523:ACAG:A	acceptor_gain	0.9900
3:196654525:AGG:A	acceptor_gain	0.9900

AlphaMissense

1674 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:196731071:G:C	W204C	0.995
3:196731071:G:T	W204C	0.995
3:196731069:T:A	W204R	0.988
3:196731069:T:C	W204R	0.988
3:196722420:T:C	L61P	0.982
3:196728055:C:A	R151S	0.981
3:196728059:A:G	Y152C	0.981
3:196728049:C:G	H149D	0.980
3:196728058:T:C	Y152H	0.980
3:196733849:T:C	C242R	0.976
3:196722513:A:G	D92G	0.972
3:196728047:T:A	V148E	0.972
3:196722504:T:C	L89P	0.971
3:196722415:A:C	R59S	0.970
3:196722415:A:T	R59S	0.970
3:196728056:G:C	R151P	0.969
3:196728116:T:C	L171S	0.969
3:196716914:T:C	F57L	0.968
3:196716916:C:A	F57L	0.968
3:196716916:C:G	F57L	0.968
3:196722513:A:T	D92V	0.967
3:196727955:G:C	E117D	0.967
3:196727955:G:T	E117D	0.967
3:196728051:C:A	H149Q	0.967
3:196728051:C:G	H149Q	0.967
3:196728058:T:G	Y152D	0.964
3:196716917:C:G	H58D	0.963
3:196733792:G:A	G223R	0.962
3:196733792:G:C	G223R	0.962
3:196722467:T:C	C77R	0.959

dbSNP variants (sampled 300 via entrez): RS1000058493 (3:196720368 T>C), RS1000201572 (3:196720179 A>G), RS1000208651 (3:196722948 A>G), RS1000373958 (3:196711475 A>G), RS1000381929 (3:196717124 C>A,T), RS1000541827 (3:196714955 A>G), RS1000640865 (3:196727290 A>G), RS1000690537 (3:196714449 G>GT), RS1000691498 (3:196720643 A>G), RS1000727267 (3:196723232 T>C,G), RS1000858487 (3:196733834 C>G), RS1000949741 (3:196721626 G>A), RS1001099934 (3:196728386 C>G,T), RS1001166602 (3:196714785 G>T), RS1001345049 (3:196723807 G>T)

Disease associations

OMIM: gene MIM:610276 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST009391_1237	Metabolite levels	5.000000e-06
GCST009798_34	Asthma	4.000000e-12
GCST90002381_200	Eosinophil count	4.000000e-17
GCST90002382_589	Eosinophil percentage of white cells	2.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0010422	triacylglycerol 54:4 measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lead	affects splicing, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
sodium arsenite	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Acetaminophen	increases expression	1
Vehicle Emissions	decreases expression, decreases reaction	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Diethylstilbestrol	decreases expression	1
Doxorubicin	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, decreases reaction	1

Clinical trials (associated diseases)

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