PIGQ

Summary

PIGQ (phosphatidylinositol glycan anchor biosynthesis class Q, HGNC:14135) is a protein-coding gene on chromosome 16p13.3, encoding Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q (Q9BRB3). Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis.

This gene is involved in the first step 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 gene encodes a N-acetylglucosaminyl transferase component that is part of the complex that catalyzes transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9091 — RefSeq curated summary.

At a glance

• Gene–disease (curated): developmental and epileptic encephalopathy, 77 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 818 total — 39 pathogenic, 6 likely-pathogenic
• Phenotypes (HPO): 97
• MANE Select transcript: NM_004204

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14135
Approved symbol	PIGQ
Name	phosphatidylinositol glycan anchor biosynthesis class Q
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	hGPI1, GPI1
Ensembl gene	ENSG00000007541
Ensembl biotype	protein_coding
OMIM	605754
Entrez	9091

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 20 protein_coding, 8 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 4 retained_intron

ENST00000026218, ENST00000293874, ENST00000321878, ENST00000409527, ENST00000420990, ENST00000422307, ENST00000439574, ENST00000443147, ENST00000470411, ENST00000476438, ENST00000480424, ENST00000537901, ENST00000540241, ENST00000540548, ENST00000544860, ENST00000634341, ENST00000635205, ENST00000635909, ENST00000635935, ENST00000636005, ENST00000636657, ENST00000637468, ENST00000637701, ENST00000638143, ENST00000638152, ENST00000854221, ENST00000854222, ENST00000854223, ENST00000854224, ENST00000854225, ENST00000854226, ENST00000854227, ENST00000854228, ENST00000968575, ENST00000968576, ENST00000968577, ENST00000968578

RefSeq mRNA: 2 — MANE Select: NM_004204 NM_004204, NM_148920

CCDS: CCDS10411, CCDS10412

Canonical transcript exons

ENST00000321878 — 11 exons

Exon	Start	End
ENSE00000664270	580183	580263
ENSE00000664272	578785	578938
ENSE00000664275	575839	575970
ENSE00001242883	580858	580972
ENSE00001855685	582883	584109
ENSE00003519048	576134	576254
ENSE00003547450	579069	579180
ENSE00003584364	578379	578505
ENSE00003616336	582248	582309
ENSE00003786870	574066	574763
ENSE00003900421	569968	570096

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 97.27.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9811 / max 24.7684, expressed in 437 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151947	11.1561	1785
151944	0.9811	437
151948	0.1087	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	97.27	gold quality
right uterine tube	UBERON:0001302	97.10	gold quality
left lobe of thyroid gland	UBERON:0001120	96.79	gold quality
metanephros cortex	UBERON:0010533	96.68	gold quality
right testis	UBERON:0004534	96.63	gold quality
adenohypophysis	UBERON:0002196	96.57	gold quality
left testis	UBERON:0004533	96.46	gold quality
right frontal lobe	UBERON:0002810	96.08	gold quality
body of pancreas	UBERON:0001150	95.54	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.41	gold quality
thyroid gland	UBERON:0002046	94.98	gold quality
right adrenal gland cortex	UBERON:0035827	94.88	gold quality
right adrenal gland	UBERON:0001233	94.86	gold quality
cerebellar hemisphere	UBERON:0002245	94.48	gold quality
left adrenal gland cortex	UBERON:0035825	94.46	gold quality
pituitary gland	UBERON:0000007	94.30	gold quality
left adrenal gland	UBERON:0001234	94.29	gold quality
cerebellar cortex	UBERON:0002129	94.26	gold quality
apex of heart	UBERON:0002098	93.35	gold quality
peripheral nervous system	UBERON:0000010	93.11	gold quality
tibial nerve	UBERON:0001323	93.11	gold quality
cingulate cortex	UBERON:0003027	92.97	gold quality
anterior cingulate cortex	UBERON:0009835	92.90	gold quality
lower esophagus mucosa	UBERON:0035834	92.87	gold quality
mucosa of transverse colon	UBERON:0004991	92.85	gold quality
right ovary	UBERON:0002118	92.83	gold quality
nucleus accumbens	UBERON:0001882	92.79	gold quality
right lobe of liver	UBERON:0001114	92.74	gold quality
adrenal cortex	UBERON:0001235	92.74	gold quality
endocervix	UBERON:0000458	92.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.18
E-HCAD-10	no	1.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, FOXO1

miRNA regulators (miRDB)

19 targeting PIGQ, 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-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-203A-5P	96.33	65.03	714

Literature-anchored findings (GeneRIF, showing 3)

• Genetic studies reveal two novel genes for Ohtahara Syndrome: KCNT1 and PIGQ. (PMID:24463883)
• Genome-wide association analyses identified four suggestive loci (PAX3, CCRN4L, PIGQ, and ADAM19)determinants of disease progression in Alzheimer’s disease (PMID:25114068)
• Identifying novel risk conferring genes involved in glycosylation processes with familial schizophrenia in an Indian cohort: Prediction of ADAMTS9 gene variant for structural stability. (PMID:37105505)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pigq	ENSDARG00000038097
mus_musculus	Pigq	ENSMUSG00000025728
rattus_norvegicus	Pigq	ENSRNOG00000020140
drosophila_melanogaster	PIG-Q	FBGN0086448
caenorhabditis_elegans		WBGENE00008504

Protein

Protein identifiers

Phosphatidylinositol N-acetylglucosaminyltransferase subunit Q — Q9BRB3 (reviewed: Q9BRB3)

Alternative names: N-acetylglucosamyl transferase component GPI1, Phosphatidylinositol-glycan biosynthesis class Q protein

All UniProt accessions (13): Q9BRB3, A0A0U1RQX6, A0A1B0GUF6, A0A1B0GUW1, A0A1B0GVF8, A0A1B0GVV7, A0A1B0GVY0, B8ZZ29, B8ZZ31, E7ERP4, H0YFM9, H7C336, J3QTH6

UniProt curated annotations — full annotation on UniProt →

Function. Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis.

Subunit / interactions. Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2. Interacts with PIGA, PIGH and PIGC.

Subcellular location. Membrane.

Disease relevance. Multiple congenital anomalies-hypotonia-seizures syndrome 4 (MCAHS4) [MIM:618548] An autosomal recessive syndrome characterized by onset of refractory seizures in the first months of life. Additional clinical features include severe global developmental delay, dysmorphic facial features, and skeletal, renal and ophthalmic anomalies. At the cellular level, the disorder is caused by a defect in the synthesis of glycosylphosphatidylinositol (GPI). The disease is caused by variants affecting the gene represented in this entry.

Pathway. Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.

Similarity. Belongs to the PIGQ family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BRB3-1	1	yes
Q9BRB3-2	2
Q9BRB3-3	3

RefSeq proteins (2): NP_004195, NP_683721 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007720	PigQ/GPI1	Family

Pfam: PF05024

Enzyme classification (BRENDA):

• EC 2.4.1.198 — phosphatidylinositol N-acetylglucosaminyltransferase (BRENDA: 42 organisms, 12 substrates, 7 inhibitors, 0 Km, 0 kcat entries)

UniProt features (18 total): sequence variant 6, transmembrane region 5, splice variant 4, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRB3-F1	64.70	0.21

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 345 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_SYNTHESIS_OF_GLYCOSYLPHOSPHATIDYLINOSITOL_GPI, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, MARTINEZ_RB1_TARGETS_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS

GO Biological Process (2): carbohydrate metabolic process (GO:0005975), GPI anchor biosynthetic process (GO:0006506)

GO Molecular Function (2): phosphatidylinositol N-acetylglucosaminyltransferase activity (GO:0017176), protein binding (GO:0005515)

GO Cellular Component (4): glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex (GO:0000506), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational modification: synthesis of GPI-anchored proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIGQ	PIGH	Q14442	999
PIGQ	PIGC	Q92535	999
PIGQ	PIGA	P37287	998
PIGQ	PIGP	P57054	998
PIGQ	PIGY	Q3MUY2	998
PIGQ	DPM2	O94777	995
PIGQ	PIGL	Q9Y2B2	965
PIGQ	PIGW	Q7Z7B1	823
PIGQ	PYURF	Q96I23	807
PIGQ	PIGV	Q9NUD9	791
PIGQ	ERI1	Q8IV48	785
PIGQ	GPI	P06744	771
PIGQ	PIGM	Q9H3S5	767
PIGQ	PIGK	Q92643	765
PIGQ	PIGO	Q8TEQ8	764

IntAct

66 interactions, top by confidence:

A	B	Type	Score
PIGA	PIGQ	psi-mi:“MI:0915”(physical association)	0.710
PIGA	PIGP	psi-mi:“MI:0914”(association)	0.710
PIGH	PIGQ	psi-mi:“MI:0915”(physical association)	0.670
PIGA	DPM2	psi-mi:“MI:0914”(association)	0.660
DPM2	PIGA	psi-mi:“MI:0914”(association)	0.660
TNFSF13B	IPO8	psi-mi:“MI:0914”(association)	0.640
PIGC	PIGA	psi-mi:“MI:0914”(association)	0.640
PIGA	PIGY	psi-mi:“MI:0914”(association)	0.560
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
TCTN2	TPST2	psi-mi:“MI:0914”(association)	0.530
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530
ELP2	DNAJA2	psi-mi:“MI:0914”(association)	0.530
CREB3	MYO9A	psi-mi:“MI:0914”(association)	0.530
PIGC	PIGQ	psi-mi:“MI:0915”(physical association)	0.500
PIGQ	DPM2	psi-mi:“MI:0915”(physical association)	0.500
AP2B1	PIGQ	psi-mi:“MI:0407”(direct interaction)	0.440
PIGQ	PIGP	psi-mi:“MI:0915”(physical association)	0.400
PA	PIGQ	psi-mi:“MI:0915”(physical association)	0.370
PIGQ	TSG101	psi-mi:“MI:0915”(physical association)	0.370
PIGQ	SMAD1	psi-mi:“MI:0915”(physical association)	0.370
PCDHAC2	TMEM223	psi-mi:“MI:0914”(association)	0.350
DPEP1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
TMCO3	POTEF	psi-mi:“MI:0914”(association)	0.350
IL17RC	C2CD2L	psi-mi:“MI:0914”(association)	0.350
PMEL	MAN1A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (53): PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-MS), PIGQ (Affinity Capture-RNA), PIGQ (Affinity Capture-Western), PIGQ (Affinity Capture-MS), PIGH (Affinity Capture-Western), PIGC (Affinity Capture-Western)

ESM2 similar proteins: A1L3T7, A6NGW2, A6NJZ7, A6NNM3, O15287, O43593, O94761, O94927, P03972, P0C7N4, P27106, P49000, P79295, Q13671, Q15572, Q17RM4, Q1LZD1, Q2M3G4, Q3UPH7, Q3ZBU3, Q49AM3, Q58EX7, Q5JYT7, Q5M844, Q6P773, Q6ZS11, Q6ZS72, Q7L2K0, Q7M733, Q7RTU9, Q7Z3H0, Q7Z6P3, Q810H6, Q811T9, Q8BG26, Q8BWG4, Q8CAI1, Q8CII8, Q8IXR5, Q8N205

Diamond homologs: O14357, Q9BRB3, Q9QYT7, P53306

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
Synthesis of glycosylphosphatidylinositol (GPI)	6	77.7×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
GPI anchor biosynthetic process	7	53.4×	2e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	39
Likely pathogenic	6
Uncertain significance	346
Likely benign	322
Benign	55

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070292	NM_004204.5(PIGQ):c.211C>T (p.Gln71Ter)	Pathogenic
1365801	NM_004204.5(PIGQ):c.1024C>T (p.Gln342Ter)	Pathogenic
1369604	NM_004204.5(PIGQ):c.91_106del (p.Val31fs)	Pathogenic
1387773	NM_004204.5(PIGQ):c.551del (p.Gly184fs)	Pathogenic
140458	NM_004204.5(PIGQ):c.690-2A>G	Pathogenic
1416208	NM_004204.5(PIGQ):c.52_70dup (p.Val24fs)	Pathogenic
1452468	NM_004204.5(PIGQ):c.161_174del (p.Gln54fs)	Pathogenic
1453534	NM_004204.5(PIGQ):c.733_734del (p.Ser245fs)	Pathogenic
1457001	NM_004204.5(PIGQ):c.449del (p.Arg150fs)	Pathogenic
1457615	NM_004204.5(PIGQ):c.942+1G>C	Pathogenic
1459251	NC_000016.9:g.(?624589)(626254_?)del	Pathogenic
183339	NM_004204.5(PIGQ):c.619C>T (p.Arg207Ter)	Pathogenic
1992066	NM_004204.5(PIGQ):c.68G>A (p.Trp23Ter)	Pathogenic
2067066	NM_004204.5(PIGQ):c.254dup (p.Ala86fs)	Pathogenic
2115834	NM_004204.5(PIGQ):c.1521C>G (p.Tyr507Ter)	Pathogenic
2127429	NM_004204.5(PIGQ):c.909del (p.His304fs)	Pathogenic
2296530	NM_004204.5(PIGQ):c.572G>A (p.Trp191Ter)	Pathogenic
2425035	NC_000016.9:g.(?622268)(632290_?)del	Pathogenic
2831080	NM_004204.5(PIGQ):c.223G>T (p.Glu75Ter)	Pathogenic
2901493	NM_004204.5(PIGQ):c.573G>A (p.Trp191Ter)	Pathogenic
2976561	NM_004204.5(PIGQ):c.220G>T (p.Glu74Ter)	Pathogenic
3008372	NM_004204.5(PIGQ):c.255dup (p.Ala86fs)	Pathogenic
3031382	NM_004204.5(PIGQ):c.1134_1143del (p.Ala377_Cys378insTer)	Pathogenic
3243221	NC_000016.9:g.(?624075)(633035_?)del	Pathogenic
3611634	NM_004204.5(PIGQ):c.961C>T (p.Gln321Ter)	Pathogenic
3617283	NM_004204.5(PIGQ):c.637del (p.Cys213fs)	Pathogenic
3662397	NM_004204.5(PIGQ):c.69G>A (p.Trp23Ter)	Pathogenic
3666464	NM_004204.5(PIGQ):c.532del (p.Ser178fs)	Pathogenic
3670452	NM_004204.5(PIGQ):c.1165_1166del (p.Ser389fs)	Pathogenic
3685725	NM_004204.5(PIGQ):c.1333C>T (p.Gln445Ter)	Pathogenic

SpliceAI

2819 predictions. Top by Δscore:

Variant	Effect	Δscore
16:567076:G:C	donor_loss	1.0000
16:567076:GTAA:G	donor_loss	1.0000
16:567077:T:G	donor_loss	1.0000
16:575837:A:AG	acceptor_gain	1.0000
16:575838:G:GG	acceptor_gain	1.0000
16:575869:C:CA	acceptor_gain	1.0000
16:576252:GAC:G	donor_gain	1.0000
16:576255:G:GG	donor_gain	1.0000
16:578375:GCA:G	acceptor_loss	1.0000
16:578376:CAGC:C	acceptor_loss	1.0000
16:578377:A:AG	acceptor_gain	1.0000
16:578378:G:GG	acceptor_gain	1.0000
16:578378:GC:G	acceptor_gain	1.0000
16:578378:GCAC:G	acceptor_gain	1.0000
16:578501:GATCA:G	donor_gain	1.0000
16:578503:TCA:T	donor_gain	1.0000
16:578506:G:GG	donor_gain	1.0000
16:579068:GGCT:G	acceptor_gain	1.0000
16:579118:C:CA	acceptor_gain	1.0000
16:580269:C:G	donor_gain	1.0000
16:580856:A:AG	acceptor_gain	1.0000
16:580857:G:GG	acceptor_gain	1.0000
16:580857:GCTCC:G	acceptor_gain	1.0000
16:580968:GGCGG:G	donor_gain	1.0000
16:580969:GCGG:G	donor_gain	1.0000
16:580969:GCGGG:G	donor_gain	1.0000
16:580970:CGG:C	donor_gain	1.0000
16:580970:CGGGT:C	donor_loss	1.0000
16:580971:GG:G	donor_gain	1.0000
16:580971:GGG:G	donor_gain	1.0000

AlphaMissense

3704 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:578499:T:A	W355R	0.999
16:578499:T:C	W355R	0.999
16:579135:C:A	N430K	0.998
16:579135:C:G	N430K	0.998
16:579142:C:A	R433S	0.998
16:580193:G:A	G449E	0.998
16:580255:T:C	F470L	0.998
16:580257:C:A	F470L	0.998
16:580257:C:G	F470L	0.998
16:578416:T:C	L327P	0.997
16:578441:G:C	K335N	0.997
16:578441:G:T	K335N	0.997
16:578497:T:C	L354P	0.997
16:579115:T:C	F424L	0.997
16:579117:C:A	F424L	0.997
16:579117:C:G	F424L	0.997
16:579154:G:C	D437H	0.997
16:580192:G:A	G449R	0.997
16:580192:G:C	G449R	0.997
16:580229:C:A	P461H	0.997
16:578447:C:A	N337K	0.996
16:578447:C:G	N337K	0.996
16:578475:T:C	F347L	0.996
16:578477:C:A	F347L	0.996
16:578477:C:G	F347L	0.996
16:578883:G:C	D390H	0.996
16:578916:T:C	C401R	0.996
16:579106:T:A	W421R	0.996
16:579106:T:C	W421R	0.996
16:579116:T:C	F424S	0.996

dbSNP variants (sampled 300 via entrez): RS1000162198 (16:573522 C>T), RS1000198093 (16:578834 G>A,T), RS1000457863 (16:571804 G>A,C), RS1000483000 (16:579103 C>A,G), RS1000510150 (16:571660 C>T), RS1000563832 (16:570945 T>C), RS1000808224 (16:576765 C>T), RS1000857074 (16:580112 A>C,T), RS1001044517 (16:584163 G>GA,GC,GT), RS1001165187 (16:574377 C>T), RS1001396476 (16:577927 G>A), RS1001522315 (16:582039 A>G), RS1001843812 (16:575023 T>A), RS1001888416 (16:578087 G>A), RS1001896244 (16:574828 G>A,T)

Disease associations

OMIM: gene MIM:605754 | disease phenotypes: MIM:618548

GenCC curated gene-disease

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 77	Strong	Autosomal recessive
genetic developmental and epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
developmental and epileptic encephalopathy, 77	Definitive	AR

Mondo (5): epilepsy (MONDO:0005027), developmental and epileptic encephalopathy, 77 (MONDO:0032808), optic atrophy (MONDO:0003608), developmental and epileptic encephalopathy (MONDO:0100620), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (0):

HPO phenotypes

97 total (30 of 97 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000054	Micropenis
HP:0000070	Ureterocele
HP:0000076	Vesicoureteral reflux
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000260	Wide anterior fontanel
HP:0000280	Coarse facial features
HP:0000293	Full cheeks
HP:0000319	Smooth philtrum
HP:0000340	Sloping forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000522	Alacrima
HP:0000729	Autistic behavior
HP:0000752	Hyperactivity
HP:0000767	Pectus excavatum
HP:0000803	Renal cortical cysts
HP:0000826	Precocious puberty
HP:0000977	Soft skin
HP:0001249	Intellectual disability

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001687_9	Disc degeneration (lumbar)	4.000000e-06
GCST004605_15	Mean corpuscular hemoglobin concentration	2.000000e-09
GCST004605_16	Mean corpuscular hemoglobin concentration	2.000000e-09
GCST004619_188	Reticulocyte fraction of red cells	4.000000e-12
GCST004622_37	Reticulocyte count	9.000000e-13
GCST012227_277	Hip circumference adjusted for BMI	3.000000e-08
GCST90002385_70	High light scatter reticulocyte count	5.000000e-13
GCST90002386_278	High light scatter reticulocyte percentage of red cells	2.000000e-11
GCST90002391_73	Mean corpuscular hemoglobin concentration	1.000000e-32
GCST90002396_647	Mean reticulocyte volume	1.000000e-10
GCST90002396_648	Mean reticulocyte volume	3.000000e-18
GCST90002397_227	Mean spheric corpuscular volume	6.000000e-49
GCST90002405_354	Reticulocyte count	4.000000e-24
GCST90002406_429	Reticulocyte fraction of red cells	2.000000e-21

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007986	reticulocyte count
EFO:0008039	BMI-adjusted hip circumference
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D009896	Optic Atrophy	C10.292.700.225; C11.640.451

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
kojic acid	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
ICG 001	increases expression	1
MT19c compound	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
Temozolomide	increases expression	1
Arbutin	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cadmium	increases expression	1
Copper	affects binding, increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Diazinon	increases methylation	1
Disulfiram	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy