PIGS

Summary

PIGS (phosphatidylinositol glycan anchor biosynthesis class S, HGNC:14937) is a protein-coding gene on chromosome 17q11.2, encoding GPI-anchor transamidase component PIGS (Q96S52). 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. It is a selective cancer dependency (DepMap: 12.0% of cell lines).

This gene encodes a protein that is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (GPI) anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene encodes an essential component of the multisubunit enzyme, GPI transamidase. GPI transamidase mediates GPI anchoring in the endoplasmic reticulum, by catalyzing the transfer of fully assembled GPI units to proteins.

Source: NCBI Gene 94005 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycosylphosphatidylinositol biosynthesis defect 18 (Definitive, ClinGen)
• Clinical variants (ClinVar): 145 total — 8 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 64
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 12.0% of screened cell lines
• MANE Select transcript: NM_033198

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14937
Approved symbol	PIGS
Name	phosphatidylinositol glycan anchor biosynthesis class S
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	PIG-S
Ensembl gene	ENSG00000087111
Ensembl biotype	protein_coding
OMIM	610271
Entrez	94005

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 16 nonsense_mediated_decay, 10 protein_coding, 10 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000268758, ENST00000308360, ENST00000395346, ENST00000465444, ENST00000484580, ENST00000487231, ENST00000492429, ENST00000577594, ENST00000577620, ENST00000580968, ENST00000582615, ENST00000582721, ENST00000583631, ENST00000584080, ENST00000584413, ENST00000706175, ENST00000706176, ENST00000706177, ENST00000706178, ENST00000706179, ENST00000706180, ENST00000706181, ENST00000706182, ENST00000706183, ENST00000706184, ENST00000706185, ENST00000706186, ENST00000706187, ENST00000706188, ENST00000706189, ENST00000706190, ENST00000706191, ENST00000706192, ENST00000706193, ENST00000706194, ENST00000896504, ENST00000931672, ENST00000931673, ENST00000954253

RefSeq mRNA: 1 — MANE Select: NM_033198 NM_033198

CCDS: CCDS11235

Canonical transcript exons

ENST00000308360 — 12 exons

Exon	Start	End
ENSE00002695279	28571463	28571524
ENSE00003474353	28563431	28563522
ENSE00003514926	28561422	28561629
ENSE00003540786	28553387	28554495
ENSE00003544800	28570852	28570963
ENSE00003586015	28563818	28563907
ENSE00003600846	28556166	28556266
ENSE00003623061	28554851	28555061
ENSE00003656403	28571049	28571188
ENSE00003657808	28556827	28556972
ENSE00003665850	28560049	28560191
ENSE00003680101	28558476	28558590

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 94.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.4930 / max 155.4419, expressed in 1817 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165031	39.5259	1817
165024	0.2924	127
165030	0.2808	129
165029	0.2510	136
165025	0.0538	10
165027	0.0480	16
165026	0.0335	6
165028	0.0076	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	94.71	gold quality
granulocyte	CL:0000094	93.92	gold quality
islet of Langerhans	UBERON:0000006	93.07	gold quality
mucosa of transverse colon	UBERON:0004991	92.92	gold quality
rectum	UBERON:0001052	92.66	gold quality
duodenum	UBERON:0002114	92.20	gold quality
leukocyte	CL:0000738	92.11	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.11	gold quality
monocyte	CL:0000576	91.94	gold quality
heart left ventricle	UBERON:0002084	91.93	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.92	gold quality
metanephros cortex	UBERON:0010533	91.88	gold quality
cerebellum	UBERON:0002037	91.83	gold quality
cerebellar hemisphere	UBERON:0002245	91.82	gold quality
cerebellar cortex	UBERON:0002129	91.80	gold quality
blood	UBERON:0000178	91.79	gold quality
small intestine	UBERON:0002108	91.78	gold quality
apex of heart	UBERON:0002098	91.75	gold quality
skin of leg	UBERON:0001511	91.73	gold quality
transverse colon	UBERON:0001157	91.71	gold quality
adult mammalian kidney	UBERON:0000082	91.53	gold quality
zone of skin	UBERON:0000014	91.44	gold quality
esophagus mucosa	UBERON:0002469	91.29	gold quality
gastrocnemius	UBERON:0001388	91.23	gold quality
bone element	UBERON:0001474	91.18	gold quality
bone marrow	UBERON:0002371	91.18	gold quality
spleen	UBERON:0002106	91.12	gold quality
skin of abdomen	UBERON:0001416	91.10	gold quality
body of stomach	UBERON:0001161	90.90	gold quality
kidney	UBERON:0002113	90.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-CURD-10	no	151.18
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting PIGS, 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-8485	100.00	77.57	4731
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 12.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• By describing the consequences of PIGS disruption in humans and extending the family of IGDs. (PMID:30269814)
• Expanding the phenotype of PIGS-associated early onset epileptic developmental encephalopathy. (PMID:33410539)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pigs	ENSDARG00000017813
mus_musculus	Pigs	ENSMUSG00000041958
rattus_norvegicus	Pigs	ENSRNOG00000011366
drosophila_melanogaster	PIG-S	FBGN0265190
caenorhabditis_elegans		WBGENE00011776

Protein

Protein identifiers

GPI-anchor transamidase component PIGS — Q96S52 (reviewed: Q96S52)

Alternative names: Phosphatidylinositol-glycan biosynthesis class S protein

All UniProt accessions (21): Q96S52, A0A994J546, A0A994J550, A0A994J555, A0A994J5E2, A0A994J5E6, A0A994J5F0, A0A994J5F5, A0A994J5S0, A0A994J5S5, A0A994J5S7, A0A994J7M3, A0A994J7M6, A0A994J7M9, A0A994J801, A0A994J804, A0A994J808, A0A994J810, H0Y2N5, J3QL67, K7EN97

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Heteropentamer. Part of the GPI-anchor transamidase complex, consisting of PIGK, PIGT, PIGS, PIGU and GAA1.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Glycosylphosphatidylinositol biosynthesis defect 18 (GPIBD18) [MIM:618143] An autosomal recessive disorder with onset in utero or early infancy and characterized by severe global developmental delay, seizures, hypotonia, weakness, ataxia, and dysmorphic facial features. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.

Similarity. Belongs to the PIGS family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96S52-1	1	yes
Q96S52-2	2

RefSeq proteins (1): NP_149975* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019540	PtdIno-glycan_biosynth_class_S	Family

Pfam: PF10510

UniProt features (85 total): helix 24, strand 23, mutagenesis site 11, turn 9, sequence variant 6, topological domain 3, glycosylation site 2, transmembrane region 2, binding site 2, initiator methionine 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7WLD	ELECTRON MICROSCOPY	2.53
8IMX	ELECTRON MICROSCOPY	2.85
7W72	ELECTRON MICROSCOPY	3.1
8IMY	ELECTRON MICROSCOPY	3.22

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96S52-F1	85.48	0.43

Functional residue map

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

Ligand- & substrate-binding residues (2): 15; 18

Glycosylation sites (2): 370, 267

Mutagenesis-validated functional residues (11):

Position	Phenotype
43	no effect on function in gpi-anchor attachment to protein.
47	no effect on function in gpi-anchor attachment to protein.
267	no effect on function in gpi-anchor attachment to protein.
272	no effect on function in gpi-anchor attachment to protein.
276	no effect on function in gpi-anchor attachment to protein.
301	no effect on function in gpi-anchor attachment to protein.
335	no effect on function in gpi-anchor attachment to protein.
370	no effect on function in gpi-anchor attachment to protein.
444	no effect on function in gpi-anchor attachment to protein.
459–460	no effect on function in gpi-anchor attachment to protein.
515–516	no effect on function in gpi-anchor attachment to protein.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-162791	Attachment of GPI anchor to uPAR

MSigDB gene sets: 276 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, chr17q11, 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 (3): GPI anchor biosynthetic process (GO:0006506), attachment of GPI anchor to protein (GO:0016255), GPI anchored protein biosynthesis (GO:0180046)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), GPI-anchor transamidase complex (GO:0042765), endoplasmic reticulum (GO:0005783)

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 anchored protein biosynthesis	2
protein maturation	2
GPI anchor metabolic process	1
glycolipid biosynthetic process	1
glycerophospholipid biosynthetic process	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
endoplasmic reticulum membrane	1
caspase complex	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
transferase complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIGS	GPAA1	O43292	914
PIGS	PIGT	Q969N2	901
PIGS	PIGK	Q92643	887
PIGS	PIGO	Q8TEQ8	596
PIGS	PIGU	Q9H490	592
PIGS	PIGB	Q92521	572
PIGS	PIGC	Q92535	539
PIGS	PIGQ	Q9BRB3	526
PIGS	PIGV	Q9NUD9	524
PIGS	PGAP1	Q75T13	507
PIGS	PIGM	Q9H3S5	500
PIGS	TMEM223	A0PJW6	484
PIGS	PIGP	P57054	479
PIGS	PIGW	Q7Z7B1	474
PIGS	PIGL	Q9Y2B2	472

IntAct

179 interactions, top by confidence:

A	B	Type	Score
GPAA1	PIGK	psi-mi:“MI:0914”(association)	0.860
PIGK	GPAA1	psi-mi:“MI:0914”(association)	0.860
PIGK	PIGT	psi-mi:“MI:0914”(association)	0.820
PIGT	PIGK	psi-mi:“MI:0914”(association)	0.820
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
PIGT	GPAA1	psi-mi:“MI:0914”(association)	0.790
GPAA1	PIGT	psi-mi:“MI:0914”(association)	0.790
PIGS	PIGT	psi-mi:“MI:0915”(physical association)	0.770
PIGS	GPAA1	psi-mi:“MI:0914”(association)	0.760
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
PIGS	PIGK	psi-mi:“MI:0914”(association)	0.690

BioGRID (194): KRT40 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), PIGS (Affinity Capture-MS), PIGS (Affinity Capture-MS), PIGS (Affinity Capture-MS), PIGS (Affinity Capture-MS), PIGS (Affinity Capture-MS), PIGS (Co-fractionation), PIGS (Proximity Label-MS), PIGS (Proximity Label-MS), FANCD2 (Affinity Capture-MS), PPM1A (Affinity Capture-MS), SF3A2 (Affinity Capture-MS)

ESM2 similar proteins: A0JMH0, A2ARP1, A5PK74, A7Z050, A9JTG5, B5DE73, B5DFG1, D3YY23, D3ZU57, O00562, O35954, O43304, P0C644, P0CB42, P16386, Q01433, Q02356, Q09200, Q10468, Q32P28, Q3SZL5, Q3U308, Q3V1T4, Q4KLM6, Q5HZW3, Q5RDF1, Q5RF50, Q5U2N3, Q5ZMM1, Q68J42, Q6ICH7, Q6JHU7, Q6PD26, Q6PFW1, Q6YRM6, Q80VP9, Q86TL0, Q8BGV9, Q8BGW1, Q8CG71

Diamond homologs: Q3SZL5, Q5XI31, Q6PD26, Q96S52

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PIGS	“up-regulates activity”	GPAA1	binding
PIGS	“up-regulates activity”	PIGK	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
cholesterol transport	5	27.1×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	5
Uncertain significance	86
Likely benign	27
Benign	5

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1119953	NM_033198.4(PIGS):c.174G>C (p.Gln58His)	Pathogenic
1119954	NM_033198.4(PIGS):c.1070G>A (p.Gly357Asp)	Pathogenic
1119955	NM_033198.4(PIGS):c.986C>G (p.Pro329Arg)	Pathogenic
1119956	NM_033198.4(PIGS):c.1141_1164dup (p.Asp381_Val388dup)	Pathogenic
1119957	NM_033198.4(PIGS):c.734G>A (p.Trp245Ter)	Pathogenic
3769036	NM_033198.4(PIGS):c.662_663del (p.Leu221fs)	Pathogenic
585255	NM_033198.4(PIGS):c.1316_1352delinsGGTTGCT (p.Thr439_Lys451delinsArgLeuLeu)	Pathogenic
585257	NM_033198.4(PIGS):c.468+1G>C	Pathogenic
2683019	NM_033198.4(PIGS):c.398del (p.Glu133fs)	Likely pathogenic
3338277	NM_033198.4(PIGS):c.1436T>A (p.Leu479Ter)	Likely pathogenic
585253	NM_033198.4(PIGS):c.108G>A (p.Trp36Ter)	Likely pathogenic
585254	NM_033198.4(PIGS):c.101T>C (p.Leu34Pro)	Likely pathogenic
585256	NM_033198.4(PIGS):c.923A>G (p.Glu308Gly)	Likely pathogenic

SpliceAI

1805 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28554491:TACAC:T	acceptor_gain	1.0000
17:28554492:ACAC:A	acceptor_gain	1.0000
17:28554493:CAC:C	acceptor_gain	1.0000
17:28554493:CACC:C	acceptor_gain	1.0000
17:28554494:AC:A	acceptor_gain	1.0000
17:28554495:CC:C	acceptor_gain	1.0000
17:28554496:C:CC	acceptor_gain	1.0000
17:28554496:C:CG	acceptor_loss	1.0000
17:28554846:CTTA:C	donor_loss	1.0000
17:28554847:TTA:T	donor_loss	1.0000
17:28554848:TACC:T	donor_loss	1.0000
17:28554849:A:AC	donor_gain	1.0000
17:28554849:A:AT	donor_loss	1.0000
17:28554850:C:CC	donor_gain	1.0000
17:28554850:CCT:C	donor_gain	1.0000
17:28556834:C:CT	donor_gain	1.0000
17:28556882:T:TA	donor_gain	1.0000
17:28558460:AT:A	donor_gain	1.0000
17:28558461:T:TA	donor_gain	1.0000
17:28558475:CCCAG:C	donor_gain	1.0000
17:28558588:AATCT:A	acceptor_loss	1.0000
17:28558589:ATCT:A	acceptor_loss	1.0000
17:28558590:TCT:T	acceptor_loss	1.0000
17:28558591:C:CC	acceptor_gain	1.0000
17:28558591:CT:C	acceptor_loss	1.0000
17:28558592:T:A	acceptor_loss	1.0000
17:28560045:TCAC:T	donor_loss	1.0000
17:28560046:CA:C	donor_loss	1.0000
17:28560048:C:CA	donor_loss	1.0000
17:28560192:C:CC	acceptor_gain	1.0000

AlphaMissense

3586 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28554329:G:T	A520D	0.999
17:28554349:G:C	F513L	0.999
17:28554349:G:T	F513L	0.999
17:28554350:A:C	F513C	0.999
17:28554351:A:G	F513L	0.999
17:28554486:C:G	A468P	0.999
17:28554900:A:G	L448P	0.999
17:28554408:C:G	A494P	0.998
17:28554305:G:T	P528H	0.997
17:28554326:A:T	I521N	0.997
17:28554359:A:G	L510P	0.997
17:28554368:A:G	L507P	0.997
17:28554382:G:C	F502L	0.997
17:28554382:G:T	F502L	0.997
17:28554384:A:G	F502L	0.997
17:28554415:G:C	S491R	0.997
17:28554415:G:T	S491R	0.997
17:28554417:T:G	S491R	0.997
17:28554909:A:G	L445P	0.997
17:28554918:A:G	L442P	0.997
17:28556839:C:A	W356C	0.997
17:28556839:C:G	W356C	0.997
17:28560172:A:C	S232R	0.997
17:28560172:A:T	S232R	0.997
17:28560174:T:G	S232R	0.997
17:28554305:G:C	P528R	0.996
17:28554317:G:T	P524Q	0.996
17:28554386:G:T	A501D	0.996
17:28554873:A:T	I457N	0.996
17:28556854:G:C	F351L	0.996

dbSNP variants (sampled 300 via entrez): RS1000000703 (17:28567948 T>C), RS1000527173 (17:28555753 G>A), RS1000786829 (17:28561955 G>C), RS1000891287 (17:28560735 G>A), RS1000892716 (17:28569073 G>A,C), RS1001060460 (17:28553947 G>A), RS1001374510 (17:28561224 C>T), RS1001765644 (17:28569061 C>T), RS1002039697 (17:28556029 T>C), RS1002239693 (17:28562455 A>C), RS1002476740 (17:28569910 T>C), RS1002889512 (17:28557405 T>C,G), RS1002904561 (17:28565352 A>C), RS1003138681 (17:28573377 T>C), RS1003160844 (17:28562988 C>T)

Disease associations

OMIM: gene MIM:610271 | disease phenotypes: MIM:618143

GenCC curated gene-disease

Disease	Classification	Inheritance
glycosylphosphatidylinositol biosynthesis defect 18	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
glycosylphosphatidylinositol biosynthesis defect 18	Definitive	AR

Mondo (1): glycosylphosphatidylinositol biosynthesis defect 18 (MONDO:0029140)

Orphanet (0):

HPO phenotypes

64 total (30 of 64 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000158	Macroglossia
HP:0000212	Gingival overgrowth
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000331	Short chin
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000384	Preauricular skin tag
HP:0000391	Thickened helices
HP:0000476	Cystic hygroma
HP:0000505	Visual impairment
HP:0000639	Nystagmus
HP:0000687	Widely spaced teeth
HP:0000729	Autistic behavior
HP:0000748	Inappropriate laughter
HP:0000768	Pectus carinatum
HP:0000954	Single transverse palmar crease
HP:0001156	Brachydactyly
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001344	Absent speech
HP:0001382	Joint hypermobility
HP:0001537	Umbilical hernia

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067379 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.53	Kd	29.79	nM	CHEMBL3752910
7.53	ED50	29.79	nM	CHEMBL3752910
6.59	Kd	254.7	nM	CHEMBL5653589
6.59	ED50	254.7	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149006: Binding affinity to human PIGS incubated for 45 mins by Kinobead based pull down assay	kd	0.0298	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149006: Binding affinity to human PIGS incubated for 45 mins by Kinobead based pull down assay	kd	0.2547	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
bisphenol A	affects cotreatment, increases methylation, increases expression	3
sodium arsenite	affects binding, increases reaction, decreases expression	2
Silicon Dioxide	decreases expression, decreases methylation	2
sodium arsenate	increases expression	1
titanium dioxide	decreases methylation	1
butyraldehyde	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Lead	increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Vanadates	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652048	Binding	Binding affinity to human PIGS incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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