PIGU

Summary

PIGU (phosphatidylinositol glycan anchor biosynthesis class U, HGNC:15791) is a protein-coding gene on chromosome 20q11.22, encoding GPI-anchor transamidase component PIGU (Q9H490). 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.

The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Cdc91, a predicted integral membrane protein that may function in cell division control. The protein encoded by this gene is the fifth subunit of GPI transamidase that attaches GPI-anchors to proteins.

Source: NCBI Gene 128869 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glycosylphosphatidylinositol biosynthesis defect 21 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 38
• Clinical variants (ClinVar): 255 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 52
• MANE Select transcript: NM_080476

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15791
Approved symbol	PIGU
Name	phosphatidylinositol glycan anchor biosynthesis class U
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	bA346K17.2, GAB1, PIG-U
Ensembl gene	ENSG00000101464
Ensembl biotype	protein_coding
OMIM	608528
Entrez	128869

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000217446, ENST00000374820, ENST00000438215, ENST00000462389, ENST00000480175, ENST00000628281, ENST00000897591, ENST00000897592, ENST00000897593, ENST00000897594, ENST00000897595, ENST00000940068, ENST00000940069, ENST00000940070, ENST00000940071, ENST00000940072, ENST00000940073, ENST00000949703, ENST00000949704, ENST00000949705

RefSeq mRNA: 1 — MANE Select: NM_080476 NM_080476

CCDS: CCDS13239

Canonical transcript exons

ENST00000217446 — 12 exons

Exon	Start	End
ENSE00000860124	34575104	34575246
ENSE00000860125	34585437	34585580
ENSE00000860127	34616042	34616139
ENSE00000860128	34634615	34634715
ENSE00000860129	34637876	34637985
ENSE00000860130	34644164	34644226
ENSE00001414279	34560542	34560979
ENSE00003467670	34645275	34645334
ENSE00003530337	34657180	34657244
ENSE00003676008	34588453	34588607
ENSE00003684954	34581548	34581672
ENSE00003900529	34676956	34677092

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 90.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.3680 / max 167.6156, expressed in 1809 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186991	33.3680	1809

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	90.34	gold quality
ganglionic eminence	UBERON:0004023	90.14	gold quality
ventricular zone	UBERON:0003053	89.85	gold quality
islet of Langerhans	UBERON:0000006	89.79	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.72	gold quality
oocyte	CL:0000023	89.68	gold quality
tibialis anterior	UBERON:0001385	89.28	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.24	gold quality
rectum	UBERON:0001052	88.93	gold quality
right uterine tube	UBERON:0001302	88.84	gold quality
cortical plate	UBERON:0005343	88.09	gold quality
secondary oocyte	CL:0000655	87.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.80	gold quality
spinal cord	UBERON:0002240	87.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.47	gold quality
smooth muscle tissue	UBERON:0001135	87.26	gold quality
adrenal tissue	UBERON:0018303	86.95	gold quality
ileal mucosa	UBERON:0000331	86.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.58	gold quality
tibial nerve	UBERON:0001323	86.26	gold quality
stromal cell of endometrium	CL:0002255	86.19	gold quality
left testis	UBERON:0004533	86.04	gold quality
esophagus mucosa	UBERON:0002469	85.82	gold quality
lower esophagus mucosa	UBERON:0035834	85.60	gold quality
prefrontal cortex	UBERON:0000451	85.57	gold quality
right testis	UBERON:0004534	85.46	gold quality
left adrenal gland	UBERON:0001234	85.40	gold quality
right adrenal gland	UBERON:0001233	85.33	gold quality
right adrenal gland cortex	UBERON:0035827	85.32	gold quality
muscle of leg	UBERON:0001383	85.30	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

18 targeting PIGU, 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-4447	99.85	67.81	2900
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-449B-3P	99.20	67.24	1047
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-1263	98.13	69.18	459
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-9851-5P	97.57	67.49	1067
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-7973	96.48	65.54	502
HSA-MIR-3690	96.44	65.18	737
HSA-MIR-6835-5P	95.81	64.27	500

Literature-anchored findings (GeneRIF, showing 8)

• CDC91L1 is an oncogene in bladder cancer, and implicate the GPI anchoring system as a potential oncogenic pathway and therapeutic target in human cancers (PMID:15034568)
• Function of a membrane-embedded domain evolutionarily multiplied in the GPI lipid anchor pathway proteins PIG-B, PIG-M, PIG-U, PIG-W, PIG-V, and PIG-Z has been described. (PMID:29764287)
• Low PIG-U expression is associated with Papillary Thyroid Carcinoma. (PMID:30053080)
• our findings suggest that PIGU overexpression provides independent and complementary prognostic information in hepatocellular carcinoma patients (PMID:30171988)
• Mutations in PIGU Impair the Function of the glycosylphosphatidylinositol Transamidase Complex, Causing Severe Intellectual Disability, Epilepsy, and Brain Anomalies. (PMID:31353022)
• Identification of PIGU as the Hub Gene Associated with KRAS Mutation in Colorectal Cancer by Coexpression Analysis. (PMID:32552000)
• PIGU promotes hepatocellular carcinoma progression through activating NF-kappaB pathway and increasing immune escape. (PMID:32971102)
• Functional Analysis of the GPI Transamidase Complex by Screening for Amino Acid Mutations in Each Subunit. (PMID:34576938)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pigu	ENSDARG00000075530
mus_musculus	Pigu	ENSMUSG00000038383
rattus_norvegicus	Pigu	ENSRNOG00000025181
drosophila_melanogaster	PIG-U	FBGN0032052
caenorhabditis_elegans	pigu-1	WBGENE00011914

Protein

Protein identifiers

GPI-anchor transamidase component PIGU — Q9H490 (reviewed: Q9H490)

Alternative names: Cell division cycle protein 91-like 1, GPI transamidase component PIG-U, Phosphatidylinositol glycan anchor biosynthesis class U protein

All UniProt accessions (2): Q9H490, Q5JWU1

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. Binds the lipid portion of GPI-anchor. May act as an organizer in the transmembrane layer to recruit other subunits, and thus is essential for assembly of the complex.

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. Neurodevelopmental disorder with brain anomalies, seizures, and scoliosis (NEDBSS) [MIM:618590] An autosomal recessive disorder characterized by global developmental delay, severe-to-profound intellectual disability, muscular hypotonia, seizures, brain anomalies, including thin corpus callosum and cerebellar atrophy, scoliosis, and mild facial dysmorphism. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.

Similarity. Belongs to the PIGU family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H490-1	1	yes
Q9H490-2	2

RefSeq proteins (1): NP_536724* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009600	PIG-U	Family

Pfam: PF06728

UniProt features (77 total): helix 22, mutagenesis site 13, transmembrane region 12, topological domain 9, strand 6, binding site 5, turn 4, sequence variant 2, initiator methionine 1, chain 1, splice variant 1, sequence conflict 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-Q9H490-F1	92.75	0.85

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 (5): 216; 217; 309; 383; 385

Mutagenesis-validated functional residues (13):

Position	Phenotype
67	no effect on function in gpi-anchor attachment to protein.
95	no effect on function in gpi-anchor attachment to protein.
144	no effect on function in gpi-anchor attachment to protein.
150	no effect on function in gpi-anchor attachment to protein.
153	no effect on function in gpi-anchor attachment to protein.
167	no effect on function in gpi-anchor attachment to protein.
225	no effect on function in gpi-anchor attachment to protein.
237	no effect on function in gpi-anchor attachment to protein.
283	no effect on function in gpi-anchor attachment to protein.
285	no effect on function in gpi-anchor attachment to protein.
375–376	decreased function in gpi-anchor attachment to protein.
406	no effect on function in gpi-anchor attachment to protein.
411	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: 614 (showing top): PID_SHP2_PATHWAY, GCACCTT_MIR18A_MIR18B, TGGTGCT_MIR29A_MIR29B_MIR29C, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, ZHAN_MULTIPLE_MYELOMA_PR_DN, REACTOME_GAB1_SIGNALOSOME, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (4): GPI anchor biosynthetic process (GO:0006506), attachment of GPI anchor to protein (GO:0016255), regulation of receptor signaling pathway via JAK-STAT (GO:0046425), GPI anchored protein biosynthesis (GO:0180046)

GO Molecular Function (3): GPI anchor binding (GO:0034235), GPI-anchor transamidase activity (GO:0003923), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), 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
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via STAT	1
phospholipid binding	1
glycolipid binding	1
cysteine-type endopeptidase activity	1
transferase activity, transferring nitrogenous groups	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	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

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIGU	PIGK	Q92643	978
PIGU	GPAA1	O43292	866
PIGU	PIGT	Q969N2	858
PIGU	MYH7B	A7E2Y1	797
PIGU	PIGV	Q9NUD9	664
PIGU	PIGB	Q92521	663
PIGU	MC1R	Q01726	609
PIGU	PIGS	Q96S52	592
PIGU	PIGW	Q7Z7B1	564
PIGU	PIGZ	Q86VD9	559
PIGU	PIGO	Q8TEQ8	537
PIGU	PIGM	Q9H3S5	534
PIGU	MPDU1	O75352	503
PIGU	PIGC	Q92535	493
PIGU	DPM3	Q9P2X0	474

IntAct

81 interactions, top by confidence:

A	B	Type	Score
PIGK	GPAA1	psi-mi:“MI:0914”(association)	0.860
PIGS	GPAA1	psi-mi:“MI:0914”(association)	0.760
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
KASH5	PIGU	psi-mi:“MI:0915”(physical association)	0.560
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
NECTIN4	EIF2B2	psi-mi:“MI:0914”(association)	0.530
GPR17	IPO8	psi-mi:“MI:0914”(association)	0.530
PIGT	ZNF609	psi-mi:“MI:0914”(association)	0.530
STOM	EI24	psi-mi:“MI:0914”(association)	0.510
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
PIGU	F2RL1	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
CFTR	MYH7B	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
CRELD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMTM5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SCN4A	C2CD4B	psi-mi:“MI:0914”(association)	0.350

BioGRID (155): PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS), PIGU (Affinity Capture-MS)

ESM2 similar proteins: A6X919, A8MR93, A8Y3M2, D4AD75, O43053, O80505, O82244, P34413, P47088, P54002, Q0P5D9, Q23361, Q2PZI1, Q2UB20, Q3T1L5, Q3TAE8, Q4IJT0, Q4R4E1, Q4V7R2, Q500W7, Q5EA10, Q5NVS8, Q5RAH7, Q5RCJ4, Q66IJ4, Q6CRE7, Q6FXQ5, Q6P8H8, Q6ZPD9, Q71B07, Q7RXP5, Q7SXZ1, Q802T2, Q8C2R7, Q8CHJ0, Q8CHJ1, Q8K358, Q8L638, Q8VDB2, Q94A15

Diamond homologs: O13883, P41733, Q8CHJ0, Q8CHJ1, Q8K358, Q9H490

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 95 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
G alpha (q) signalling events	7	6.5×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
GPI anchor biosynthetic process	5	28.5×	1e-04
positive regulation of cytosolic calcium ion concentration	8	10.8×	1e-04
G protein-coupled receptor signaling pathway	12	5.0×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	127
Likely benign	73
Benign	28

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
545492	NM_002039.4(GAB1):c.347G>A (p.Gly116Glu)	Pathogenic
689723	NM_080476.5(PIGU):c.209T>A (p.Ile70Lys)	Pathogenic
689724	NM_080476.5(PIGU):c.1149C>A (p.Asn383Lys)	Pathogenic
1696481	NM_080476.5(PIGU):c.1286del (p.Glu429fs)	Likely pathogenic

SpliceAI

2893 predictions. Top by Δscore:

Variant	Effect	Δscore
4:143394924:G:GG	donor_gain	1.0000
4:143415468:T:A	acceptor_gain	1.0000
4:143415472:TCTAG:T	acceptor_loss	1.0000
4:143415473:CTAGG:C	acceptor_loss	1.0000
4:143415474:TAGGC:T	acceptor_loss	1.0000
4:143415475:A:AC	acceptor_loss	1.0000
4:143415475:A:AG	acceptor_gain	1.0000
4:143415475:AG:A	acceptor_gain	1.0000
4:143415476:G:GT	acceptor_gain	1.0000
4:143415476:GG:G	acceptor_gain	1.0000
4:143415476:GGC:G	acceptor_gain	1.0000
4:143415476:GGCAT:G	acceptor_gain	1.0000
4:143415768:GAAG:G	donor_gain	1.0000
4:143415769:AAGG:A	donor_loss	1.0000
4:143415770:AGGTA:A	donor_loss	1.0000
4:143415771:GGTA:G	donor_loss	1.0000
4:143415772:G:GA	donor_loss	1.0000
4:143415772:G:GG	donor_gain	1.0000
4:143438838:G:GT	donor_gain	1.0000
4:143439888:G:GG	donor_gain	1.0000
4:143459382:CA:C	acceptor_loss	1.0000
4:143459383:A:AG	acceptor_gain	1.0000
4:143459384:G:GA	acceptor_gain	1.0000
4:143459384:GT:G	acceptor_gain	1.0000
4:143459384:GTC:G	acceptor_gain	1.0000
4:143459384:GTCA:G	acceptor_gain	1.0000
4:143459384:GTCAA:G	acceptor_gain	1.0000
4:143459474:CGAGA:C	donor_gain	1.0000
4:143459475:GAGA:G	donor_gain	1.0000
4:143459475:GAGAG:G	donor_gain	1.0000

AlphaMissense

2856 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:34585517:A:C	F282L	1.000
20:34585517:A:T	F282L	1.000
20:34585518:A:C	F282C	1.000
20:34585519:A:G	F282L	1.000
20:34560939:C:G	R412P	0.999
20:34575123:A:G	L392P	0.999
20:34575140:G:C	F386L	0.999
20:34575140:G:T	F386L	0.999
20:34575142:A:G	F386L	0.999
20:34575143:A:C	N385K	0.999
20:34575143:A:T	N385K	0.999
20:34575172:A:G	W376R	0.999
20:34575172:A:T	W376R	0.999
20:34575174:A:G	L375P	0.999
20:34585508:G:C	F285L	0.999
20:34585508:G:T	F285L	0.999
20:34585510:A:G	F285L	0.999
20:34585537:A:G	Y276H	0.999
20:34585540:A:G	W275R	0.999
20:34585540:A:T	W275R	0.999
20:34657236:C:G	G47R	0.999
20:34575149:G:C	N383K	0.998
20:34575149:G:T	N383K	0.998
20:34575170:C:A	W376C	0.998
20:34575170:C:G	W376C	0.998
20:34585455:G:C	P303R	0.998
20:34585496:A:C	F289L	0.998
20:34585496:A:T	F289L	0.998
20:34585498:A:G	F289L	0.998
20:34585519:A:C	F282V	0.998

dbSNP variants (sampled 300 via entrez): RS1000004525 (20:34636422 T>C), RS1000010683 (20:34662103 C>T), RS1000023719 (20:34617038 A>C), RS1000049494 (20:34577292 A>G), RS1000092129 (20:34671188 C>T), RS1000123816 (20:34624317 G>C), RS1000144641 (20:34671404 G>A), RS1000146167 (20:34661786 C>T), RS1000206419 (20:34563237 T>A), RS1000235902 (20:34632628 G>A), RS1000291683 (20:34603447 C>T), RS1000343304 (20:34584254 A>T), RS1000377881 (20:34645960 T>C), RS1000392508 (20:34561145 T>C), RS1000395792 (20:34569524 A>G)

Disease associations

OMIM: gene MIM:608528 | disease phenotypes: MIM:618590, MIM:616898, MIM:605428

GenCC curated gene-disease

Disease	Classification	Inheritance
glycosylphosphatidylinositol biosynthesis defect 21	Strong	Autosomal recessive
autosomal recessive nonsyndromic hearing loss 26	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
glycosylphosphatidylinositol biosynthesis defect 21	Limited	AR

Mondo (3): glycosylphosphatidylinositol biosynthesis defect 21 (MONDO:0032824), 15q14 microdeletion syndrome (MONDO:0014822), autosomal recessive nonsyndromic hearing loss 26 (MONDO:0011553)

Orphanet (2): Cleft palate-congenital heart defect-intellectual disability syndrome due to 15q14 microdeletion (Orphanet:261190), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636)

HPO phenotypes

52 total (30 of 52 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000319	Smooth philtrum
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000506	Telecanthus
HP:0000540	Hypermetropia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000767	Pectus excavatum
HP:0000938	Osteopenia
HP:0000998	Hypertrichosis
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001272	Cerebellar atrophy
HP:0001320	Cerebellar vermis hypoplasia

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST000198_1	Melanoma	1.000000e-15
GCST001183_2	Asthma	7.000000e-08
GCST004142_28	Melanoma	1.000000e-15
GCST005956_30	Waist-to-hip ratio adjusted for BMI	9.000000e-06
GCST005956_31	Waist-to-hip ratio adjusted for BMI	8.000000e-08
GCST005958_16	Waist-to-hip ratio adjusted for BMI (age >50)	6.000000e-06
GCST005959_30	Waist-to-hip ratio adjusted for BMI x sex interaction	7.000000e-06
GCST005962_40	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-08
GCST006190_16	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	2.000000e-11
GCST006190_57	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-11
GCST006192_36	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	3.000000e-11
GCST006192_86	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	4.000000e-13
GCST006193_48	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-10
GCST006193_86	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-09
GCST006195_37	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	6.000000e-12
GCST006195_78	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-10
GCST006666_19	Lipid traits (pleiotropy) (HIPO component 1)	1.000000e-09
GCST006989_55	Brown vs. black hair color	1.000000e-65
GCST007094_128	Diastolic blood pressure	1.000000e-07
GCST007099_48	Systolic blood pressure	2.000000e-09
GCST007327_31	Smoking status (ever vs never smokers)	3.000000e-08
GCST007856_83	Colorectal cancer or advanced adenoma	3.000000e-07
GCST008059_125	Estimated glomerular filtration rate	2.000000e-37
GCST008103_149	Bipolar disorder	3.000000e-06
GCST008152_123	Weight	4.000000e-06
GCST008152_28	Weight	2.000000e-07
GCST008745_48	Estimated glomerular filtration rate in non-diabetics	3.000000e-08
GCST008839_139	Height	5.000000e-10
GCST010135_33	Oily fish consumption	7.000000e-09
GCST010140_23	Pork consumption	7.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008343	sex interaction measurement
EFO:0008007	age at assessment
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006335	systolic blood pressure
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0003924	hair color
EFO:0004318	smoking behavior
EFO:0004338	body weight
EFO:0008111	diet measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565329	Deafness, Autosomal Recessive 26 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
corosolic acid	decreases expression	1
abrine	decreases expression	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
Acrolein	affects cotreatment, increases expression, increases abundance	1
Arsenic	increases expression, increases abundance	1
Coal	decreases expression, increases abundance	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Folic Acid	decreases expression	1
Ozone	affects cotreatment, increases expression, increases abundance	1
Selenomethionine	affects expression	1
Smoke	decreases expression, increases abundance	1
Thiram	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	decreases expression	1
beta-Naphthoflavone	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1
Volatile Organic Compounds	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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