PIGB

Summary

PIGB (phosphatidylinositol glycan anchor biosynthesis class B, HGNC:8959) is a protein-coding gene on chromosome 15q21.3, encoding GPI alpha-1,2-mannosyltransferase 3 (Q92521). Alpha-1,2-mannosyltransferase that catalyzes the transfer of the third mannose, via an alpha-1,2 bond, from a dolichol-phosphate-mannose (Dol-P-Man) to a 2-acyl-6-[alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-gl….

This gene encodes a transmembrane protein that is located in the endoplasmic reticulum and 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 is thought to encode a member of a family of dolichol-phosphate-mannose (Dol-P-Man) dependent mannosyltransferases.

Source: NCBI Gene 9488 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 80 (Strong, GenCC)
• Clinical variants (ClinVar): 370 total — 24 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 47
• MANE Select transcript: NM_004855

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8959
Approved symbol	PIGB
Name	phosphatidylinositol glycan anchor biosynthesis class B
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	PIG-B, GPI-MT-III
Ensembl gene	ENSG00000069943
Ensembl biotype	protein_coding
OMIM	604122
Entrez	9488

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 13 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000164305, ENST00000539642, ENST00000562751, ENST00000563742, ENST00000565367, ENST00000565402, ENST00000565502, ENST00000566072, ENST00000566999, ENST00000569823, ENST00000569909, ENST00000570059, ENST00000858251, ENST00000858252, ENST00000858253, ENST00000858254, ENST00000858255, ENST00000858256, ENST00000858257, ENST00000919400, ENST00000919401, ENST00000946972

RefSeq mRNA: 1 — MANE Select: NM_004855 NM_004855

CCDS: CCDS61641

Canonical transcript exons

ENST00000164305 — 12 exons

Exon	Start	End
ENSE00002601319	55355286	55355648
ENSE00003465949	55321273	55321390
ENSE00003466646	55327531	55327635
ENSE00003484437	55340612	55340823
ENSE00003512291	55341738	55341802
ENSE00003549971	55320275	55320410
ENSE00003588278	55350699	55350912
ENSE00003616323	55354798	55354978
ENSE00003644956	55339267	55339318
ENSE00003751905	55329724	55329854
ENSE00003787075	55333867	55334007
ENSE00003844862	55319222	55319413

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 89.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.9282 / max 167.3708, expressed in 1791 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146760	7.0027	1759
146758	3.4592	1232
146759	0.3727	127
146761	0.0936	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	89.94	gold quality
blood	UBERON:0000178	88.83	gold quality
calcaneal tendon	UBERON:0003701	88.81	gold quality
monocyte	CL:0000576	88.71	gold quality
mononuclear cell	CL:0000842	88.57	gold quality
leukocyte	CL:0000738	88.51	gold quality
adenohypophysis	UBERON:0002196	88.50	gold quality
left lobe of thyroid gland	UBERON:0001120	87.65	gold quality
right lobe of thyroid gland	UBERON:0001119	87.51	gold quality
body of pancreas	UBERON:0001150	87.38	gold quality
thyroid gland	UBERON:0002046	87.21	gold quality
pituitary gland	UBERON:0000007	87.15	gold quality
mucosa of stomach	UBERON:0001199	86.95	gold quality
spleen	UBERON:0002106	86.78	gold quality
metanephros cortex	UBERON:0010533	86.68	gold quality
right uterine tube	UBERON:0001302	85.51	gold quality
descending thoracic aorta	UBERON:0002345	85.44	gold quality
epithelium of nasopharynx	UBERON:0001951	84.93	gold quality
ascending aorta	UBERON:0001496	84.83	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.83	gold quality
thoracic aorta	UBERON:0001515	84.79	gold quality
tibia	UBERON:0000979	84.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.69	gold quality
bone marrow	UBERON:0002371	84.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.59	gold quality
bone marrow cell	CL:0002092	84.51	gold quality
mucosa of transverse colon	UBERON:0004991	84.31	gold quality
caudate nucleus	UBERON:0001873	84.29	gold quality
body of stomach	UBERON:0001161	84.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting PIGB, 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-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052
HSA-MIR-3130-5P	98.14	66.00	711
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-4799-3P	97.78	65.97	893

Literature-anchored findings (GeneRIF, showing 4)

• Downregulation of the gene for phosphatidylinositol glycan class B (PIGB) by siRNA confers resistance to methylmercury in HEK293 cells. (PMID:18198489)
• 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)
• Mutations in PIGB Cause an Inherited GPI Biosynthesis Defect with an Axonal Neuropathy and Metabolic Abnormality. (PMID:31256876)
• A novel intronic variant in PIGB in Acrofrontofacionasal dysostosis type 1 patients expands the spectrum of phenotypes associated with GPI biosynthesis defects. (PMID:34400385)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pigb	ENSDARG00000105011
mus_musculus	Pigb	ENSMUSG00000079469
rattus_norvegicus	Pigb	ENSRNOG00000059622
drosophila_melanogaster	PIG-B	FBGN0035464
caenorhabditis_elegans		WBGENE00194986

Paralogs (2): ALG9 (ENSG00000086848), ALG12 (ENSG00000182858)

Protein

Protein identifiers

GPI alpha-1,2-mannosyltransferase 3 — Q92521 (reviewed: Q92521)

Alternative names: GPI mannosyltransferase III, Phosphatidylinositol-glycan biosynthesis class B protein

All UniProt accessions (6): Q92521, F5H1S1, H3BNW7, H3BQU3, H3BRK6, H3BS45

UniProt curated annotations — full annotation on UniProt →

Function. Alpha-1,2-mannosyltransferase that catalyzes the transfer of the third mannose, via an alpha-1,2 bond, from a dolichol-phosphate-mannose (Dol-P-Man) to a 2-acyl-6-[alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol intermediate to generate a 2-acyl-6-[alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol (also termed H6) and participates in the nineth step of the glycosylphosphatidylinositol-anchor biosynthesis. May also add the third mannose to a 2-acyl-6-[alpha-D-mannosyl-(1->6)-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol (also termed H3) intermediate generating a 2-acyl-6-(alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl)-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol (also termed H4).

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Developmental and epileptic encephalopathy 80 (DEE80) [MIM:618580] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE80 is an autosomal recessive form characterized by onset of refractory seizures in the first year of life, severe global developmental delay and/or intellectual disability. Additional variable features include polyneuropathy, hearing loss, visual impairment, dysmorphic or coarse facial features, and distal skeletal abnormalities. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.

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

RefSeq proteins (1): NP_004846* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005599	GPI_mannosylTrfase	Family

Pfam: PF03901

Catalyzed reactions (Rhea), 2 shown:

• a 2-acyl-6-[alpha-D-mannosyl-(1->6)-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol + a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate = a 2-acyl-6-(alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl)-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:61000)
• a 2-acyl-6-[alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol + a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate = a 2-acyl-6-[alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(1->6)-2-phosphoethanolamine-alpha-D-mannosyl-(1->4)-alpha-D-glucosaminyl]-1-(1-radyl,2-acyl-sn-glycero-3-phospho)-1D-myo-inositol + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:61004)

UniProt features (29 total): sequence variant 16, transmembrane region 9, glycosylation site 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92521-F1	88.48	0.81

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 (2): 26, 427

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 261 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8A_DC_DN, MORF_RAGE, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, MORF_FLT1, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, REACTOME_SYNTHESIS_OF_GLYCOSYLPHOSPHATIDYLINOSITOL_GPI, MORF_ATRX, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_ESR1, MODULE_16, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS

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

GO Molecular Function (5): alpha-1,2-mannosyltransferase activity (GO:0000026), GPI mannosyltransferase activity (GO:0004376), dol-P-Man:Man(2)GlcN-acyl-PI alpha-1,2-mannosyltransferase activity (GO:0120564), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), 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
mannosyltransferase activity	2
GPI anchor metabolic process	1
glycolipid biosynthetic process	1
glycerophospholipid biosynthetic process	1
GPI anchored protein biosynthesis	1
alpha-1,2-mannosyltransferase activity	1
GPI mannosyltransferase activity	1
catalytic activity	1
transferase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

634 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIGB	PIGM	Q9H3S5	854
PIGB	PIGH	Q14442	848
PIGB	PIGV	Q9NUD9	847
PIGB	PIGG	Q5H8A4	816
PIGB	PIGC	Q92535	814
PIGB	PIGA	P37287	811
PIGB	PIGL	Q9Y2B2	811
PIGB	PIGW	Q7Z7B1	810
PIGB	PIGK	Q92643	806
PIGB	PIGO	Q8TEQ8	796
PIGB	PIGP	P57054	769
PIGB	PIGT	Q969N2	768
PIGB	PIGQ	Q9BRB3	747
PIGB	PIGN	O95427	746
PIGB	GPAA1	O43292	723

IntAct

27 interactions, top by confidence:

A	B	Type	Score
TCTN2	CLGN	psi-mi:“MI:0914”(association)	0.780
POMK	TMEM120B	psi-mi:“MI:0914”(association)	0.530
FUT1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TMPRSS12	FZD6	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
HFE	ADAM10	psi-mi:“MI:0914”(association)	0.530
WTAP	DDX39A	psi-mi:“MI:0914”(association)	0.350
MPPE1	ADAM10	psi-mi:“MI:0914”(association)	0.350
GGT7	ENTPD6	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350
MPPE1	FAM234B	psi-mi:“MI:0914”(association)	0.350
TCTN2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
CRLF2	METTL15	psi-mi:“MI:0914”(association)	0.350
CHRNB4	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC3A2	GET1	psi-mi:“MI:0914”(association)	0.350
KLRC2	CLGN	psi-mi:“MI:0914”(association)	0.350
KLRK1	NRDC	psi-mi:“MI:0914”(association)	0.350
LRRC52	CANX	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): PIGB (Affinity Capture-MS), PIGB (Synthetic Growth Defect), PIGB (Affinity Capture-MS), PIGB (Affinity Capture-MS), PIGB (Affinity Capture-MS), PIGB (Affinity Capture-MS), PIGB (Affinity Capture-MS), PIGB (Affinity Capture-MS), PIGB (Affinity Capture-MS), PIGB (Affinity Capture-RNA), PIGB (Proximity Label-MS), PIGB (Affinity Capture-MS), PIGB (Proximity Label-MS), PIGB (Affinity Capture-MS), PIGB (Affinity Capture-MS)

ESM2 similar proteins: A4IID1, B4F753, C5H5C4, E9PTA2, O77485, O77486, O77487, O95453, O95803, P37287, P42694, P69341, Q05B63, Q08C93, Q08DW9, Q10981, Q10984, Q1LZA0, Q1PET6, Q3U2J5, Q4R766, Q5F383, Q5F407, Q5F477, Q5M854, Q5RC51, Q5U4X8, Q5ZIN0, Q6AYT7, Q6DFV5, Q6GQI7, Q6GQK9, Q6IS24, Q6P4H8, Q6YJI5, Q7TT15, Q812G0, Q8MIQ9, Q8N2K0, Q8VDG3

Diamond homologs: Q1LZA0, Q23361, Q4V7R2, Q4WPG0, Q5AK24, Q5BCB9, Q6BH65, Q6CAB8, Q7SXZ1, Q92521, Q94A15, Q9JJQ0, Q9USN0, Q9VZM5, A8MR93, P53730, Q8VDB2, Q9BV10, Q9USD4, Q9VH78, Q2UH15, Q4IB63, Q75BG9, P30777, Q6CN76, Q6FTY5, P86935, C6Y4A9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	8
Uncertain significance	143
Likely benign	160
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1896849	NM_004855.5(PIGB):c.840dup (p.Gly281fs)	Pathogenic
1912356	NM_004855.5(PIGB):c.913_920del (p.Ser305fs)	Pathogenic
1943029	NM_004855.5(PIGB):c.91A>T (p.Lys31Ter)	Pathogenic
2088596	NM_004855.5(PIGB):c.1014C>G (p.Tyr338Ter)	Pathogenic
2180209	NM_004855.5(PIGB):c.970_973del (p.Leu324fs)	Pathogenic
2710308	NM_004855.5(PIGB):c.1151G>A (p.Trp384Ter)	Pathogenic
2715941	NM_004855.5(PIGB):c.663C>G (p.Tyr221Ter)	Pathogenic
2716626	NM_004855.5(PIGB):c.482del (p.Ser160_Leu161insTer)	Pathogenic
2797321	NM_004855.5(PIGB):c.303T>G (p.Tyr101Ter)	Pathogenic
2833250	NM_004855.5(PIGB):c.1172del (p.Phe391fs)	Pathogenic
2869209	NM_004855.5(PIGB):c.318G>A (p.Trp106Ter)	Pathogenic
2874430	NM_004855.5(PIGB):c.502C>T (p.Gln168Ter)	Pathogenic
2992843	NM_004855.5(PIGB):c.812T>A (p.Leu271Ter)	Pathogenic
3243872	NC_000015.9:g.(?55611449)(55613608_?)del	Pathogenic
3243873	NC_000015.9:g.(?55611449)(55619853_?)del	Pathogenic
3243874	NC_000015.9:g.(?55611449)(55622072_?)del	Pathogenic
3610423	NM_004855.5(PIGB):c.840del (p.Phe280fs)	Pathogenic
3699577	NM_004855.5(PIGB):c.1152G>A (p.Trp384Ter)	Pathogenic
4693847	NM_004855.5(PIGB):c.211C>T (p.Arg71Ter)	Pathogenic
689514	NM_004855.5(PIGB):c.212G>A (p.Arg71Gln)	Pathogenic
689515	NM_004855.5(PIGB):c.1162G>C (p.Ala388Pro)	Pathogenic
689516	NM_004855.5(PIGB):c.856G>C (p.Val286Leu)	Pathogenic
689519	NM_004855.5(PIGB):c.847-10A>G	Pathogenic
976714	NM_004855.5(PIGB):c.392T>G (p.Leu131Ter)	Pathogenic
1098618	NM_004855.5(PIGB):c.795-1G>C	Likely pathogenic
2005289	NM_004855.5(PIGB):c.795-19T>G	Likely pathogenic
2099514	NM_004855.5(PIGB):c.654-2A>G	Likely pathogenic
2181336	NM_004855.5(PIGB):c.523-2A>G	Likely pathogenic
2671585	Single allele	Likely pathogenic
2769741	NM_004855.5(PIGB):c.1337+1G>A	Likely pathogenic

SpliceAI

1931 predictions. Top by Δscore:

Variant	Effect	Δscore
15:55319410:GGGG:G	donor_gain	1.0000
15:55319411:GGG:G	donor_gain	1.0000
15:55319411:GGGG:G	donor_gain	1.0000
15:55319412:GG:G	donor_gain	1.0000
15:55319412:GGG:G	donor_gain	1.0000
15:55319412:GGGTG:G	donor_loss	1.0000
15:55319413:GG:G	donor_gain	1.0000
15:55319415:T:A	donor_loss	1.0000
15:55319698:A:G	donor_gain	1.0000
15:55324451:A:T	donor_gain	1.0000
15:55327520:A:AG	acceptor_gain	1.0000
15:55327520:AACT:A	acceptor_gain	1.0000
15:55327521:A:AG	acceptor_gain	1.0000
15:55327523:T:A	acceptor_gain	1.0000
15:55327618:G:GT	donor_gain	1.0000
15:55329722:A:AG	acceptor_gain	1.0000
15:55329723:G:GG	acceptor_gain	1.0000
15:55340603:C:CA	acceptor_gain	1.0000
15:55340752:T:TA	acceptor_gain	1.0000
15:55341737:GCAT:G	acceptor_gain	1.0000
15:55341800:GTG:G	donor_gain	1.0000
15:55354794:A:AG	acceptor_gain	1.0000
15:55354795:T:G	acceptor_gain	1.0000
15:55354796:A:AG	acceptor_gain	1.0000
15:55354797:G:GA	acceptor_gain	1.0000
15:55354797:GCC:G	acceptor_gain	1.0000
15:55354797:GCCA:G	acceptor_gain	1.0000
15:55354797:GCCAT:G	acceptor_gain	1.0000
15:55354976:GAGGT:G	donor_loss	1.0000
15:55354978:GGT:G	donor_loss	1.0000

AlphaMissense

3653 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:55341752:A:T	K358I	0.993
15:55341753:A:C	K358N	0.993
15:55341753:A:T	K358N	0.993
15:55329770:G:C	R190T	0.991
15:55329771:A:C	R190S	0.991
15:55329771:A:T	R190S	0.991
15:55329770:G:T	R190I	0.990
15:55341763:T:C	F362L	0.989
15:55341765:T:A	F362L	0.989
15:55341765:T:G	F362L	0.989
15:55333928:T:A	W239R	0.988
15:55333928:T:C	W239R	0.988
15:55321295:T:A	W108R	0.986
15:55321295:T:C	W108R	0.986
15:55341761:G:T	R361M	0.986
15:55320323:G:C	R71P	0.985
15:55329748:T:C	F183L	0.985
15:55329750:C:A	F183L	0.985
15:55329750:C:G	F183L	0.985
15:55320350:C:T	T80I	0.983
15:55341787:T:C	C370R	0.982
15:55329754:T:A	W185R	0.981
15:55329754:T:C	W185R	0.981
15:55321297:G:C	W108C	0.980
15:55321297:G:T	W108C	0.980
15:55329745:T:A	W182R	0.979
15:55329745:T:C	W182R	0.979
15:55340754:G:A	G330D	0.979
15:55341761:G:C	R361T	0.979
15:55320406:T:C	F99L	0.978

dbSNP variants (sampled 300 via entrez): RS1000029758 (15:55352203 C>T), RS1000110993 (15:55342321 G>A,C), RS1000211247 (15:55339705 C>T), RS1000215987 (15:55333102 A>G), RS1000242432 (15:55340061 C>G,T), RS1000434861 (15:55323882 G>T), RS1000440719 (15:55332883 C>A,T), RS1000549486 (15:55352430 C>T), RS1000550248 (15:55334853 G>A), RS1000612505 (15:55341075 A>C), RS1000688306 (15:55327108 A>G), RS1000786544 (15:55347406 C>A,T), RS1000852523 (15:55346066 C>A), RS1000965121 (15:55323513 G>T), RS1000965712 (15:55322002 G>A,C,T)

Disease associations

OMIM: gene MIM:604122 | disease phenotypes: MIM:618580, MIM:239300

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 80	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 80	Moderate	AR

Mondo (2): developmental and epileptic encephalopathy, 80 (MONDO:0032822), hyperphosphatasia with intellectual disability syndrome 1 (MONDO:0009398)

Orphanet (1): Hyperphosphatasia-intellectual disability syndrome (Orphanet:247262)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000280	Coarse facial features
HP:0000293	Full cheeks
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000396	Overfolded helix
HP:0000431	Wide nasal bridge
HP:0000505	Visual impairment
HP:0000520	Proptosis
HP:0000543	Optic disc pallor
HP:0000582	Upslanted palpebral fissure
HP:0001182	Tapered finger
HP:0001199	Triphalangeal thumb
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001284	Areflexia
HP:0001290	Generalized hypotonia
HP:0001508	Failure to thrive
HP:0001510	Growth delay

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs12050587	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Leukopenia;Neutropenia

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs12050587	PIGB, PIGBOS1	3	0.50	1	cyclophosphamide;epirubicin;fluorouracil
rs2290344	PIGB, PIGBOS1		0.00	0
rs8024695	PIGB, PIGBOS1		0.00	0

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
MT19c compound	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Doxorubicin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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