PIGT

Summary

PIGT (phosphatidylinositol glycan anchor biosynthesis class T, HGNC:14938) is a protein-coding gene on chromosome 20q13.12, encoding GPI-anchor transamidase component PIGT (Q969N2). 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.

This gene encodes a protein that is involved in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This protein is 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. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 51604 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multiple congenital anomalies-hypotonia-seizures syndrome 3 (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 391 total — 12 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 113
• Druggable target: yes
• MANE Select transcript: NM_015937

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14938
Approved symbol	PIGT
Name	phosphatidylinositol glycan anchor biosynthesis class T
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	PIG-T
Ensembl gene	ENSG00000124155
Ensembl biotype	protein_coding
OMIM	610272
Entrez	51604

Gene structure

Transcript identifiers

Ensembl transcripts: 96 — 38 protein_coding, 38 nonsense_mediated_decay, 16 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000279035, ENST00000279036, ENST00000372689, ENST00000424705, ENST00000432270, ENST00000455050, ENST00000543458, ENST00000545755, ENST00000595203, ENST00000638241, ENST00000638246, ENST00000638277, ENST00000638353, ENST00000638383, ENST00000638387, ENST00000638415, ENST00000638445, ENST00000638478, ENST00000638489, ENST00000638537, ENST00000638594, ENST00000638612, ENST00000638641, ENST00000638671, ENST00000638689, ENST00000638691, ENST00000638710, ENST00000638714, ENST00000638745, ENST00000638864, ENST00000638927, ENST00000638938, ENST00000638953, ENST00000638962, ENST00000638967, ENST00000638978, ENST00000639058, ENST00000639194, ENST00000639235, ENST00000639239, ENST00000639250, ENST00000639286, ENST00000639292, ENST00000639382, ENST00000639417, ENST00000639499, ENST00000639664, ENST00000639783, ENST00000639872, ENST00000639932, ENST00000639984, ENST00000640107, ENST00000640108, ENST00000640123, ENST00000640175, ENST00000640194, ENST00000640210, ENST00000640253, ENST00000640272, ENST00000640324, ENST00000640364, ENST00000640542, ENST00000640549, ENST00000640585, ENST00000640638, ENST00000640649, ENST00000640666, ENST00000640691, ENST00000640692, ENST00000640940, ENST00000640986, ENST00000640996, ENST00000687237, ENST00000689203, ENST00000690376, ENST00000690879, ENST00000692236, ENST00000854442, ENST00000854443, ENST00000854444, ENST00000854445, ENST00000854446, ENST00000911909, ENST00000911910, ENST00000911911, ENST00000911912, ENST00000956767, ENST00000956768, ENST00000956769, ENST00000956770, ENST00000956771, ENST00000956772, ENST00000956773, ENST00000956774, ENST00000956775, ENST00000956776

RefSeq mRNA: 4 — MANE Select: NM_015937 NM_001184728, NM_001184729, NM_001184730, NM_015937

CCDS: CCDS13353, CCDS54464, CCDS54465, CCDS54466

Canonical transcript exons

ENST00000279036 — 12 exons

Exon	Start	End
ENSE00001125356	45421383	45421583
ENSE00001125412	45424496	45424579
ENSE00001125422	45424216	45424381
ENSE00003514500	45419504	45419590
ENSE00003525793	45418852	45418979
ENSE00003548129	45416517	45416694
ENSE00003696725	45416141	45416343
ENSE00003696960	45420332	45420429
ENSE00003698735	45420528	45420693
ENSE00003699603	45420136	45420223
ENSE00003701895	45419295	45419395
ENSE00003701896	45425574	45426241

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 98.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 145.1793 / max 767.2998, expressed in 1826 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184912	140.3074	1826
184913	1.8059	1042
184917	1.5046	976
184914	0.7541	439
184918	0.4557	250
184919	0.3397	160
184915	0.0119	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardia of stomach	UBERON:0001162	98.23	gold quality
stromal cell of endometrium	CL:0002255	98.14	gold quality
pylorus	UBERON:0001166	98.12	gold quality
right coronary artery	UBERON:0001625	98.09	gold quality
descending thoracic aorta	UBERON:0002345	98.00	gold quality
thoracic aorta	UBERON:0001515	97.91	gold quality
ascending aorta	UBERON:0001496	97.89	gold quality
right atrium auricular region	UBERON:0006631	97.78	gold quality
cardiac atrium	UBERON:0002081	97.75	gold quality
coronary artery	UBERON:0001621	97.56	gold quality
left coronary artery	UBERON:0001626	97.50	gold quality
aorta	UBERON:0000947	97.45	gold quality
apex of heart	UBERON:0002098	97.44	gold quality
islet of Langerhans	UBERON:0000006	97.38	gold quality
renal medulla	UBERON:0000362	97.37	gold quality
trachea	UBERON:0003126	97.35	gold quality
nipple	UBERON:0002030	97.34	gold quality
ventral tegmental area	UBERON:0002691	97.29	gold quality
heart left ventricle	UBERON:0002084	97.25	gold quality
smooth muscle tissue	UBERON:0001135	97.17	gold quality
mucosa of transverse colon	UBERON:0004991	97.14	gold quality
popliteal artery	UBERON:0002250	97.13	gold quality
tibial artery	UBERON:0007610	97.13	gold quality
transverse colon	UBERON:0001157	97.09	gold quality
vena cava	UBERON:0004087	97.06	silver quality
rectum	UBERON:0001052	97.02	gold quality
cardiac ventricle	UBERON:0002082	97.02	gold quality
body of stomach	UBERON:0001161	96.89	gold quality
left uterine tube	UBERON:0001303	96.84	gold quality
body of tongue	UBERON:0011876	96.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-75367	no	443.58
E-GEOD-124858	no	247.61
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting PIGT, 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-3692-3P	99.98	70.27	2139
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-3654	96.43	66.55	646

Literature-anchored findings (GeneRIF, showing 8)

• GPI8 and PIG-T form a functionally important intermolecular disulfide bridge (PMID:12582175)
• ER-localized because of information in its transmembrane span (PMID:15713669)
• mutations in PIGT as the cause of a novel autosomal recessive intellectual disability syndrome (PMID:23636107)
• Germline mutation and a somatic mutation in PIGT is associated with paroxysmal nocturnal hemoglobinuria. (PMID:23733340)
• PIGT-knockout HEK293 cells showed that p.(E237Q) results in a small reduction in the amount of CD59 anchored to the cell membrane. (PMID:28327575)
• Whole-exome sequencing revealed compound heterozygous mutations (c.250G > T, p.Glu84X and c.1096G > T, p.Gly366Trp) in PIGT (NM_015937.5), which were confirmed using Sanger sequencing. Thus inherited GPI anchor deficiency associated with these PIGT mutations was diagnosed (PMID:28728837)
• Evidence of the milder phenotypic spectrum of c.1582G>A PIGT variant: Delineation based on seven novel Polish patients. (PMID:32725661)
• Bilateral anterior segment dysgenesis and peripheral avascular retina with tractional retinal detachment in an infant with multiple congenital anomalies-hypotony-seizures syndrome 3. (PMID:33620284)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pigt	ENSDARG00000075842
mus_musculus	Pigt	ENSMUSG00000017721
rattus_norvegicus	Pigt	ENSRNOG00000014690
drosophila_melanogaster	PIG-T	FBGN0030035
caenorhabditis_elegans		WBGENE00008918

Protein

Protein identifiers

GPI-anchor transamidase component PIGT — Q969N2 (reviewed: Q969N2)

Alternative names: Phosphatidylinositol-glycan biosynthesis class T protein

All UniProt accessions (40): A0A1W2PNP0, A0A1W2PNS2, A0A1W2PNW9, A0A1W2PNZ5, A0A1W2PP03, A0A1W2PP13, Q969N2, A0A1W2PP53, A0A1W2PP57, A0A1W2PP91, A0A1W2PP98, A0A1W2PPC3, A0A1W2PPI8, A0A1W2PPK4, A0A1W2PPQ7, A0A1W2PPR6, A0A1W2PPS0, A0A1W2PPU8, A0A1W2PQ29, A0A1W2PQ50, A0A1W2PQ52, A0A1W2PQI9, A0A1W2PQL3, A0A1W2PQL9, A0A1W2PQY1, A0A1W2PR22, A0A1W2PR34, A0A1W2PR70, A0A1W2PR73, A0A1W2PR92, A0A1W2PRB4, A0A1W2PRG1, A0A1W2PRH2, A0A1W2PRH8, A0A1W2PRL6, A0A1W2PRV7, A0A1W2PRZ8, A0A1W2PSC5, B7Z7C5, H7C2Y2

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. May play a crucial role in GPI-T complex assembly in the luminal layer. Binds GPI-anchor.

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

Subcellular location. Endoplasmic reticulum membrane.

Post-translational modifications. The disulfide bond between PIGK/GPI8 and PIGT is important for normal enzyme activity.

Disease relevance. Multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) [MIM:615398] An autosomal recessive syndrome characterized by distinct facial features, intellectual disability, hypotonia and seizures, in combination with abnormal skeletal, endocrine, and ophthalmologic findings including impaired vision, as well as abnormal motility of the eyes. The disease is caused by variants affecting the gene represented in this entry. Paroxysmal nocturnal hemoglobinuria 2 (PNH2) [MIM:615399] A disorder characterized by hemolytic anemia with hemoglobinuria, thromboses in large vessels, and a deficiency in hematopoiesis. Red blood cell breakdown with release of hemoglobin into the urine is manifested most prominently by dark-colored urine in the morning. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Pathway. Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.

Miscellaneous. May be due to intron retention.

Similarity. Belongs to the PIGT family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q969N2-1	1	yes
Q969N2-2	2
Q969N2-3	3
Q969N2-4	4
Q969N2-5	5
Q969N2-6	6

RefSeq proteins (4): NP_001171657, NP_001171658, NP_001171659, NP_057021* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007245	PIG-T	Family

Pfam: PF04113

UniProt features (113 total): strand 30, sequence variant 21, mutagenesis site 21, helix 14, turn 6, splice variant 6, binding site 4, glycosylation site 3, disulfide bond 3, topological domain 2, signal peptide 1, chain 1, transmembrane region 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-Q969N2-F1	87.71	0.65

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 (4): 461; 521; 523; 527

Disulfide bonds (3): 182, 195–272, 226–231

Glycosylation sites (3): 291, 327, 164

Mutagenesis-validated functional residues (21):

Position	Phenotype
38	no effect on function in gpi-anchor attachment to protein.
92	no effect on function in gpi-anchor attachment to protein.
129	no effect on function in gpi-anchor attachment to protein.
135–136	no effect on function in gpi-anchor attachment to protein.
139	no effect on function in gpi-anchor attachment to protein.
146	no effect on function in gpi-anchor attachment to protein.
164	no effect on function in gpi-anchor attachment to protein.
182	decreased function in gpi-anchor attachment to protein.
184	no effect on function in gpi-anchor attachment to protein.
190–191	no effect on function in gpi-anchor attachment to protein.
291	no effect on function in gpi-anchor attachment to protein.
327	no effect on function in gpi-anchor attachment to protein.
396	no effect on function in gpi-anchor attachment to protein.
429	decreased function in gpi-anchor attachment to protein.
455	no effect on function in gpi-anchor attachment to protein.
459	no effect on function in gpi-anchor attachment to protein.
521	decreases the gpi-anchor transamidase activity to 28.9%,.
521	decreases the gpi-anchor transamidase activity to 18.8%. almost abolishes the gpi-anchor transamidase activity to 6.2%;
523	decreases the gpi-anchor transamidase activity to 76.5% almost abolishes the gpi-anchor transamidase activity to 6.2%; w
523	decreases the gpi-anchor transamidase activity to 76.8%.
528–529	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: 366 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, CCAWYNNGAAR_UNKNOWN, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CHANDRAN_METASTASIS_DN, 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

GO Biological Process (5): GPI anchor biosynthetic process (GO:0006506), attachment of GPI anchor to protein (GO:0016255), neuron differentiation (GO:0030182), neuron apoptotic process (GO:0051402), GPI anchored protein biosynthesis (GO:0180046)

GO Molecular Function (2): GPI anchor binding (GO:0034235), protein binding (GO:0005515)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410), GPI-anchor transamidase complex (GO:0042765), cytoplasm (GO:0005737), 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
cellular anatomical structure	2
cytoplasm	2
GPI anchor metabolic process	1
glycolipid biosynthetic process	1
glycerophospholipid biosynthetic process	1
cell differentiation	1
generation of neurons	1
apoptotic process	1
phospholipid binding	1
glycolipid binding	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular vesicle	1
endoplasmic reticulum membrane	1
caspase complex	1
membrane protein complex	1
endoplasmic reticulum protein-containing complex	1
transferase complex	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIGT	GPAA1	O43292	999
PIGT	PIGK	Q92643	999
PIGT	PIGS	Q96S52	901
PIGT	PIGU	Q9H490	858
PIGT	PIGV	Q9NUD9	842
PIGT	PIGO	Q8TEQ8	841
PIGT	PIGA	P37287	840
PIGT	PIGL	Q9Y2B2	813
PIGT	PIGM	Q9H3S5	810
PIGT	PIGW	Q7Z7B1	808
PIGT	PGAP2	Q9UHJ9	791
PIGT	PIGB	Q92521	768
PIGT	PIGP	P57054	735
PIGT	PIGG	Q5H8A4	735
PIGT	PIGH	Q14442	734

IntAct

130 interactions, top by confidence:

A	B	Type	Score
PIGK	GPAA1	psi-mi:“MI:0914”(association)	0.860
GPAA1	PIGK	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
PIGK	PIGT	psi-mi:“MI:0915”(physical association)	0.820
PIGT	GPAA1	psi-mi:“MI:0914”(association)	0.790
GPAA1	PIGT	psi-mi:“MI:0914”(association)	0.790
GPAA1	PIGT	psi-mi:“MI:0915”(physical 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
PIGS	PIGK	psi-mi:“MI:0914”(association)	0.690
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640

BioGRID (279): PIGT (Affinity Capture-MS), PIGT (Affinity Capture-MS), PIGT (Affinity Capture-MS), ERLEC1 (Co-fractionation), PIGT (Proximity Label-MS), PIGT (Affinity Capture-MS), PIGT (Affinity Capture-MS), PIGT (Affinity Capture-MS), USP54 (Affinity Capture-MS), TNIP1 (Affinity Capture-MS), CEP85L (Affinity Capture-MS), HOXC9 (Affinity Capture-MS), RMND5B (Affinity Capture-MS), PIGT (Affinity Capture-MS), PIGT (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NGV2, A2VE47, A4IG72, A7E2V1, D3Z2R5, F1PCT7, O43909, P02786, P04844, P25235, P57716, Q07891, Q0VCN6, Q28120, Q28DV7, Q2V905, Q5R9Q9, Q5RBM1, Q5RDH6, Q5XIA1, Q5ZJH2, Q5ZL00, Q62351, Q64255, Q6DDX8, Q6NZ07, Q7TMC8, Q8BXQ2, Q8C7X2, Q8CGU6, Q8K224, Q8N766, Q8N961, Q8R553, Q8VCM8, Q8VDL4, Q92542, Q969N2, Q969V3, Q99JH7

Diamond homologs: O94380, P38875, Q8BXQ2, Q969N2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	8
Uncertain significance	187
Likely benign	122
Benign	15

Top pathogenic / likely-pathogenic (20)

Variant ID	HGVS	Classification
1418074	NM_015937.6(PIGT):c.271C>T (p.Gln91Ter)	Pathogenic
143195	NM_015937.6(PIGT):c.918_919insT (p.Val307fs)	Pathogenic
1700185	NM_015937.6(PIGT):c.910dup (p.Tyr304fs)	Pathogenic
2030623	NM_015937.6(PIGT):c.564del (p.Trp189fs)	Pathogenic
225546	NM_015937.6(PIGT):c.250G>T (p.Glu84Ter)	Pathogenic
2995955	NM_015937.6(PIGT):c.1043del (p.Pro348fs)	Pathogenic
372986	NM_015937.6(PIGT):c.988C>T (p.Arg330Ter)	Pathogenic
452443	NM_015937.6(PIGT):c.608_609del (p.Val203fs)	Pathogenic
503770	NM_015937.6(PIGT):c.918dup (p.Val307fs)	Pathogenic
576071	NM_015937.6(PIGT):c.57del (p.Trp20fs)	Pathogenic
583283	NM_015937.6(PIGT):c.494-2A>G	Pathogenic
660514	NM_015937.6(PIGT):c.835C>T (p.Arg279Ter)	Pathogenic
1301736	NM_015937.6(PIGT):c.1724_1725insA (p.Leu578fs)	Likely pathogenic
1331559	NM_015937.6(PIGT):c.245_246del (p.Leu82fs)	Likely pathogenic
2585406	NM_015937.6(PIGT):c.709G>C (p.Glu237Gln)	Likely pathogenic
3359139	NM_015937.6(PIGT):c.17del (p.Pro6fs)	Likely pathogenic
3390855	NM_015937.6(PIGT):c.1520_1521insCTCTACA (p.Leu508fs)	Likely pathogenic
3780121	NM_015937.6(PIGT):c.1465_1466del (p.Phe492fs)	Likely pathogenic
619956	NM_015937.6(PIGT):c.1096G>T (p.Gly366Trp)	Likely pathogenic
64649	NM_015937.6(PIGT):c.547A>C (p.Thr183Pro)	Likely pathogenic

SpliceAI

1948 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45416337:G:GT	donor_gain	1.0000
20:45416340:GGAG:G	donor_gain	1.0000
20:45416341:G:GT	donor_gain	1.0000
20:45416342:AGG:A	donor_loss	1.0000
20:45416344:G:C	donor_loss	1.0000
20:45416345:T:A	donor_loss	1.0000
20:45418850:A:AG	acceptor_gain	1.0000
20:45418851:G:GG	acceptor_gain	1.0000
20:45418851:GT:G	acceptor_gain	1.0000
20:45419289:CCTCA:C	acceptor_loss	1.0000
20:45419290:CTCA:C	acceptor_loss	1.0000
20:45419291:TCAG:T	acceptor_loss	1.0000
20:45419292:CAGAC:C	acceptor_loss	1.0000
20:45419293:A:AC	acceptor_loss	1.0000
20:45419293:A:AG	acceptor_gain	1.0000
20:45419294:G:GT	acceptor_gain	1.0000
20:45419294:GA:G	acceptor_gain	1.0000
20:45419294:GAC:G	acceptor_gain	1.0000
20:45419294:GACA:G	acceptor_gain	1.0000
20:45419294:GACAC:G	acceptor_gain	1.0000
20:45419392:CAAG:C	donor_loss	1.0000
20:45419393:AAGG:A	donor_loss	1.0000
20:45419394:AGGTG:A	donor_loss	1.0000
20:45419396:GTGA:G	donor_loss	1.0000
20:45419564:G:GT	donor_gain	1.0000
20:45419586:GCAGA:G	donor_gain	1.0000
20:45419589:GA:G	donor_gain	1.0000
20:45419591:G:GG	donor_gain	1.0000
20:45419602:G:T	donor_gain	1.0000
20:45420328:TCAGA:T	acceptor_loss	1.0000

AlphaMissense

3710 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:45416257:T:C	L34P	1.000
20:45419346:G:A	C182Y	1.000
20:45419347:C:G	C182W	1.000
20:45419352:A:T	E184V	1.000
20:45419353:A:C	E184D	1.000
20:45419353:A:T	E184D	1.000
20:45419356:C:A	N185K	1.000
20:45419356:C:G	N185K	1.000
20:45419358:T:C	L186P	1.000
20:45419366:T:A	W189R	1.000
20:45419366:T:C	W189R	1.000
20:45425656:A:C	S523R	1.000
20:45425658:C:A	S523R	1.000
20:45425658:C:G	S523R	1.000
20:45416257:T:A	L34H	0.999
20:45416305:T:C	F50S	0.999
20:45416664:T:C	L112P	0.999
20:45418902:G:A	C139Y	0.999
20:45419345:T:A	C182S	0.999
20:45419345:T:C	C182R	0.999
20:45419346:G:C	C182S	0.999
20:45419346:G:T	C182F	0.999
20:45419352:A:C	E184A	0.999
20:45419368:G:C	W189C	0.999
20:45419368:G:T	W189C	0.999
20:45419376:T:C	L192P	0.999
20:45419507:G:C	G200R	0.999
20:45419508:G:A	G200D	0.999
20:45419558:T:C	S217P	0.999
20:45420167:T:C	L238P	0.999

dbSNP variants (sampled 300 via entrez): RS1000197828 (20:45421165 C>G,T), RS1000802864 (20:45422559 A>C,T), RS1000868966 (20:45423660 G>A), RS1000898374 (20:45422750 A>T), RS1001136356 (20:45423017 G>A), RS1001846454 (20:45417050 G>A), RS1002241566 (20:45423756 T>C), RS1002408665 (20:45423126 G>A), RS1002479835 (20:45417444 G>A), RS1002517078 (20:45420011 G>A,C), RS1002577041 (20:45425435 A>G), RS1002609573 (20:45425095 A>G), RS1003220333 (20:45418715 C>G), RS1003309397 (20:45414311 A>T), RS1003843073 (20:45426238 C>T)

Disease associations

OMIM: gene MIM:610272 | disease phenotypes: MIM:603530, MIM:615398, MIM:615399, MIM:300818

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple congenital anomalies-hypotonia-seizures syndrome 3	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
multiple congenital anomalies-hypotonia-seizures syndrome 3	Definitive	AR

Mondo (3): multiple congenital anomalies-hypotonia-seizures syndrome 3 (MONDO:0014165), paroxysmal nocturnal hemoglobinuria 2 (MONDO:0014166), paroxysmal nocturnal hemoglobinuria 1 (MONDO:0010438)

Orphanet (2): Intellectual disability-seizures-hypophosphatasia-ophthalmic-skeletal anomalies syndrome (Orphanet:369837), Paroxysmal nocturnal hemoglobinuria (Orphanet:447)

HPO phenotypes

113 total (30 of 113 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000071	Ureteral stenosis
HP:0000072	Hydroureter
HP:0000079	Abnormality of the urinary system
HP:0000107	Renal cyst
HP:0000110	Renal dysplasia
HP:0000121	Nephrocalcinosis
HP:0000164	Abnormality of the dentition
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000256	Macrocephaly
HP:0000272	Malar flattening
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000496	Abnormality of eye movement
HP:0000505	Visual impairment
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000565	Esotropia
HP:0000582	Upslanted palpebral fissure

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010725_40	Malaria	1.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566367	Light Fixation Seizure Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067339 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.27	Kd	540.4	nM	CHEMBL5653589
6.27	ED50	540.4	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149007: Binding affinity to human PIGT incubated for 45 mins by Kinobead based pull down assay	kd	0.5404	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	decreases expression, increases expression	1
sodium arsenite	increases abundance, increases expression	1
perfluorooctanoic acid	decreases expression	1
ICG 001	increases expression	1
bisphenol S	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Smoke	decreases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	decreases expression	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
CHEMBL5652049	Binding	Binding affinity to human PIGT 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

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3DU	Abcam HEK293T PIGT KO	Transformed cell line	Female
CVCL_TD53	HAP1 PIGT (-) 1	Cancer cell line	Male
CVCL_TD54	HAP1 PIGT (-) 2	Cancer cell line	Male
CVCL_TD55	HAP1 PIGT (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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