GPC4

Summary

GPC4 (glypican 4, HGNC:4452) is a protein-coding gene on chromosome Xq26.2, encoding Glypican-4 (O75487). Cell surface proteoglycan that bears heparan sulfate.

Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. The GPC4 gene is adjacent to the 3’ end of GPC3 and may also play a role in Simpson-Golabi-Behmel syndrome.

Source: NCBI Gene 2239 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Keipert syndrome (Definitive, GenCC)
• Clinical variants (ClinVar): 255 total — 7 pathogenic, 9 likely-pathogenic
• Phenotypes (HPO): 169
• MANE Select transcript: NM_001448

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4452
Approved symbol	GPC4
Name	glypican 4
Location	Xq26.2
Locus type	gene with protein product
Status	Approved
Aliases	K-glypican
Ensembl gene	ENSG00000076716
Ensembl biotype	protein_coding
OMIM	300168
Entrez	2239

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000370828, ENST00000887818, ENST00000887819, ENST00000887820, ENST00000887821, ENST00000931828, ENST00000931829, ENST00000931830, ENST00000952996, ENST00000952997

RefSeq mRNA: 1 — MANE Select: NM_001448 NM_001448

CCDS: CCDS14637

Canonical transcript exons

ENST00000370828 — 9 exons

Exon	Start	End
ENSE00000676747	133324145	133324536
ENSE00000676749	133311258	133311423
ENSE00000676751	133304725	133304861
ENSE00000676752	133303166	133303341
ENSE00000841621	133305772	133305918
ENSE00001453718	133300103	133303069
ENSE00001453724	133414806	133415489
ENSE00001753407	133306024	133306154
ENSE00003598355	133339183	133339341

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.7829 / max 1747.3189, expressed in 1357 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200556	40.6441	1297
200554	5.8147	916
200557	3.7875	904
200555	1.3598	585
200558	0.8845	497
200552	0.2465	132
200559	0.0457	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.79	gold quality
ganglionic eminence	UBERON:0004023	92.07	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.14	gold quality
lower esophagus	UBERON:0013473	91.05	gold quality
embryo	UBERON:0000922	90.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.92	gold quality
mucosa of stomach	UBERON:0001199	89.57	gold quality
right lung	UBERON:0002167	89.49	gold quality
thoracic aorta	UBERON:0001515	89.35	gold quality
ascending aorta	UBERON:0001496	89.30	gold quality
aorta	UBERON:0000947	89.09	gold quality
popliteal artery	UBERON:0002250	89.03	gold quality
tibial artery	UBERON:0007610	89.01	gold quality
descending thoracic aorta	UBERON:0002345	88.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.52	gold quality
left coronary artery	UBERON:0001626	86.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.80	gold quality
biceps brachii	UBERON:0001507	86.60	gold quality
right coronary artery	UBERON:0001625	86.27	gold quality
blood vessel layer	UBERON:0004797	86.21	gold quality
tibia	UBERON:0000979	86.19	gold quality
adrenal tissue	UBERON:0018303	85.78	gold quality
coronary artery	UBERON:0001621	85.74	gold quality
sigmoid colon	UBERON:0001159	85.00	gold quality
upper lobe of left lung	UBERON:0008952	84.98	gold quality
upper lobe of lung	UBERON:0008948	84.85	gold quality
metanephros	UBERON:0000081	84.63	gold quality
nephron tubule	UBERON:0001231	84.59	gold quality
metanephric glomerulus	UBERON:0004736	84.47	gold quality
lung	UBERON:0002048	84.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.49
E-GEOD-93593	yes	13.78
E-MTAB-9388	yes	12.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, SP3

miRNA regulators (miRDB)

126 targeting GPC4, 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-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394

Literature-anchored findings (GeneRIF, showing 16)

• new function of miR-125a by targeting gene glypican-4 in cell growth process (PMID:22644326)
• Findings establish that Gpc4 acts at the interface of extrinsic and intrinsic signal regulation to fine tune stem cell fate. (PMID:22761013)
• Data suggest gender difference in circulating GPC4 levels in nonalcoholic fatty liver disease; GPC4 levels in women appear to correlate with cardiometabolic risk factors (adiposity/body fat distribution, insulin resistance, and arterial stiffness). (PMID:23633195)
• serum level elevated in polycystic ovary syndrome and correlated with fat distribution and cardiovascular risk (PMID:26486309)
• The T allele of GPC4 may represent a risk factor for Epstein-Barr virus-associated gastric carcinoma. (PMID:27071854)
• According to behavioral studies, downregulation of Gpc4 by Gpc4 siRNA decreased spontaneous seizure frequency, while upregulation of Gpc4 by recombinant Gpc4 overexpression led to a converse result. These findings support the hypothesis that increased expression of Gpc4 in the brain is associated with epileptic seizures. (PMID:27425250)
• Pathogenic variants in GPC4 gene are associated with Keipert Syndrome. (PMID:30982611)
• serum concentrations significantly increased in metabolic syndrome patients (PMID:31217057)
• Results indicate a CD36-glypcian 4 (GPC4)-beta-catenin-c-myc signaling axis that regulates glycolysis in colorectal cancer (CRC) development and may provide an intervention strategy for CRC prevention. (PMID:31484922)
• The GPC4 gene polymorphism is associated with susceptibility to EBV-positive NPC. The CC genotype of GPC4 may represent a risk factor for NPC in Northern China. (PMID:31522169)
• Downregulation of glypican-4 facilitates breast cancer progression by inducing cell migration and proliferation. (PMID:32199612)
• Serum glypican-4 is a marker of future vascular risk and mortality in coronary angiography patients. (PMID:35202959)
• Serum glypican-4 is associated with the 10-year clinical outcome of patients with peripheral artery disease. (PMID:35944770)
• The Shear Stress-Regulated Expression of Glypican-4 in Endothelial Dysfunction In Vitro and Its Clinical Significance in Atherosclerosis. (PMID:37511353)
• Circulating glypican-4 is a new predictor of all-cause mortality in patients with heart failure. (PMID:37844682)
• Glypican-4 serum levels are associated with cognitive dysfunction and vascular risk factors in Parkinson’s disease. (PMID:38424123)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpc4	ENSDARG00000015472
mus_musculus	Gpc4	ENSMUSG00000031119
rattus_norvegicus	Gpc4	ENSRNOG00000002413
drosophila_melanogaster	dlp	FBGN0041604

Paralogs (5): GPC1 (ENSG00000063660), GPC3 (ENSG00000147257), GPC5 (ENSG00000179399), GPC6 (ENSG00000183098), GPC2 (ENSG00000213420)

Protein

Protein identifiers

Glypican-4 — O75487 (reviewed: O75487)

Alternative names: K-glypican

All UniProt accessions (1): O75487

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface proteoglycan that bears heparan sulfate. May be involved in the development of kidney tubules and of the central nervous system.

Subcellular location. Cell membrane Secreted. Extracellular space.

Disease relevance. Keipert syndrome (KPTS) [MIM:301026] An X-linked recessive syndrome characterized by craniofacial and digital abnormalities. Clinical features include a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and widening of all distal phalanges. Additional variable features are cognitive impairment and sensorineural deafness. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the glypican family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75487-1	1	yes
O75487-2	2

RefSeq proteins (1): NP_001439* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001863	Glypican	Family
IPR019803	Glypican_CS	Conserved_site

Pfam: PF01153

UniProt features (16 total): sequence variant 5, glycosylation site 4, chain 2, signal peptide 1, splice variant 1, propeptide 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75487-F1	83.68	0.71

Functional residue map

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

Post-translational modifications (2): 357, 529

Glycosylation sites (4): 494, 498, 500, 514

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1971475	Glycosaminoglycan-protein linkage region biosynthesis
R-HSA-2022928	HS-GAG biosynthesis
R-HSA-2024096	HS-GAG degradation
R-HSA-3560783	Defective B4GALT7 causes EDS, progeroid type
R-HSA-3560801	Defective B3GAT3 causes JDSSDHD
R-HSA-3656237	Defective EXT2 causes exostoses 2
R-HSA-3656253	Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-4420332	Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-9694614	Attachment and Entry
R-HSA-975634	Retinoid metabolism and transport
R-HSA-9769735	Initiation of coagulation cascade
R-HSA-9769739	Regulation of clotting cascade
R-HSA-9820960	Respiratory syncytial virus (RSV) attachment and entry
R-HSA-9833110	RSV-host interactions
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 681 (showing top): RNGTGGGC_UNKNOWN, SHEPARD_BMYB_MORPHOLINO_UP, KAAB_FAILED_HEART_ATRIUM_DN, GOBP_SYNAPSE_ASSEMBLY, NKX25_02, CMYB_01, GOZGIT_ESR1_TARGETS_DN, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, MEF2_02, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGGTGGRR_PAX4_03, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, ATGTTAA_MIR302C, GOBP_CELL_CELL_ADHESION

GO Biological Process (6): regulation of signal transduction (GO:0009966), Wnt signaling pathway (GO:0016055), cell migration (GO:0016477), regulation of neurotransmitter receptor localization to postsynaptic specialization membrane (GO:0098696), synaptic membrane adhesion (GO:0099560), regulation of presynapse assembly (GO:1905606)

GO Molecular Function (2): coreceptor activity (GO:0015026), protein binding (GO:0005515)

GO Cellular Component (13): nucleus (GO:0005634), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), lysosomal lumen (GO:0043202), synapse (GO:0045202), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), extracellular region (GO:0005576), membrane (GO:0016020), obsolete collagen-containing extracellular matrix (GO:0062023), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Diseases associated with glycosaminoglycan metabolism	5
Heparan sulfate/heparin (HS-GAG) metabolism	2
Coagulation pathway	2
Respiratory Syncytial Virus Infection Pathway	2
Dengue Virus Infection	2
Glycosaminoglycan metabolism	1
Early SARS-CoV-2 Infection Events	1
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
membrane	2
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
cell surface receptor signaling pathway	1
cell motility	1
regulation of biological quality	1
neurotransmitter receptor localization to postsynaptic specialization membrane	1
regulation of protein localization to synapse	1
regulation of receptor localization to synapse	1
regulation of protein localization to cell periphery	1
regulation of protein localization to membrane	1
synapse organization	1
cell-cell adhesion	1
regulation of synapse assembly	1
presynapse assembly	1
regulation of presynapse organization	1
signaling receptor activity	1
binding	1
intracellular membrane-bounded organelle	1
Golgi apparatus	1
intracellular organelle lumen	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
lysosome	1
vacuolar lumen	1
cell junction	1
extracellular vesicle	1
synapse	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1142 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPC4	LRRTM4	Q86VH4	947
GPC4	COL18A1	P39060	840
GPC4	COL15A1	P39059	807
GPC4	WNT3A	P56704	744
GPC4	PTPRS	Q13332	658
GPC4	GPR158	Q5T848	656
GPC4	SDC2	P34741	622
GPC4	GPC3	P51654	605
GPC4	WNT5A	P41221	590
GPC4	FGF2	P09038	573
GPC4	FGF13	Q92913	561
GPC4	SPARCL1	Q14515	558
GPC4	SDC3	O75056	553
GPC4	BMP4	P12644	530
GPC4	LRRTM2	O43300	529

IntAct

101 interactions, top by confidence:

A	B	Type	Score
GPC6	GPC4	psi-mi:“MI:0915”(physical association)	0.710
GPC6	GPC4	psi-mi:“MI:0914”(association)	0.710
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
GPC4	PICK1	psi-mi:“MI:0915”(physical association)	0.560
GPR183	NRP1	psi-mi:“MI:0914”(association)	0.530
GPC4	SPCS2	psi-mi:“MI:0914”(association)	0.530
PDPK1	AGRN	psi-mi:“MI:0914”(association)	0.530
MINK1	CNOT1	psi-mi:“MI:0914”(association)	0.530
LRRTM4	AP3B1	psi-mi:“MI:0914”(association)	0.530
HADHA	AGRN	psi-mi:“MI:0914”(association)	0.530
HADHA	GPC4	psi-mi:“MI:0914”(association)	0.530
ALK	PIK3R2	psi-mi:“MI:0914”(association)	0.420
GPC1	SNAP23	psi-mi:“MI:0915”(physical association)	0.400
GPC1	GANAB	psi-mi:“MI:0915”(physical association)	0.400
GPC4	CCNC	psi-mi:“MI:0915”(physical association)	0.370
GPC4	ABHD17A	psi-mi:“MI:0915”(physical association)	0.370
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
vIRF	GPC4	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
SCGB2A2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (118): GPC4 (Affinity Capture-MS), GPC4 (Co-fractionation), GPC4 (Reconstituted Complex), GPC4 (Proximity Label-MS), GPC4 (Two-hybrid), ABHD17A (Two-hybrid), CCNC (Two-hybrid), GPC6 (Affinity Capture-MS), GPC4 (Affinity Capture-MS), GPC4 (Affinity Capture-MS), SPCS2 (Affinity Capture-MS), GPC4 (Affinity Capture-MS), GPC4 (Affinity Capture-MS), GPC4 (Affinity Capture-MS), GPC4 (Affinity Capture-MS)

ESM2 similar proteins: A2BDP1, A4IFM1, A4IHZ3, A5A6P7, B1AL88, F1QCC6, G3X745, L7VG99, O14525, O75487, O75949, O93279, P05067, P12023, P13265, P15943, P35052, P35053, P50593, P51653, P51654, P51655, P53601, P78333, P79307, P86009, Q06335, Q06481, Q0V9W0, Q14DG7, Q24114, Q32LT7, Q568B8, Q5EGE1, Q5IS80, Q5RE54, Q60495, Q61137, Q6P1U2, Q6V9Y8

Diamond homologs: F1QCC6, G3X745, O75487, P35052, P35053, P50593, P51653, P51655, Q0V9W0, Q5RE54, Q8BKV1, Q8N158, Q9QZF2, Q9R087, Q9Y625

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GPC4	up-regulates	WNT3A	binding
GPC4	up-regulates	WNT5A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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
Protein-protein interactions at synapses	5	14.9×	5e-03
Neurexins and neuroligins	5	11.1×	8e-03
PIP3 activates AKT signaling	8	6.0×	8e-03
Infectious disease	14	3.9×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	9
Uncertain significance	92
Likely benign	17
Benign	8

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1701612	NM_001448.3(GPC4):c.654_656delinsTTAC (p.Arg219fs)	Pathogenic
547175	NM_001448.3(GPC4):c.1516C>T (p.Gln506Ter)	Pathogenic
547176	NM_001448.3(GPC4):c.701dup (p.Val235fs)	Pathogenic
547177	NM_001448.3(GPC4):c.1486G>T (p.Glu496Ter)	Pathogenic
547178	NM_001448.3(GPC4):c.316del (p.Asp106fs)	Pathogenic
626360	NM_001448.3(GPC4):c.1518_1521dup (p.Pro508fs)	Pathogenic
626361	NM_001448.3(GPC4):c.742del (p.Leu248fs)	Pathogenic
1299207	NM_001448.3(GPC4):c.1183C>T (p.Gln395Ter)	Likely pathogenic
1344686	NM_001448.3(GPC4):c.455del (p.Val152fs)	Likely pathogenic
2628071	NM_001448.3(GPC4):c.1051C>T (p.Arg351Ter)	Likely pathogenic
3061373	NM_001448.3(GPC4):c.1032del (p.Lys345fs)	Likely pathogenic
3242585	NM_001448.3(GPC4):c.1506_1507del (p.Cys502_Glu503delinsTer)	Likely pathogenic
3776172	NM_001448.3(GPC4):c.1512T>G (p.Tyr504Ter)	Likely pathogenic
4082055	NM_001448.3(GPC4):c.1496dup (p.Ser500fs)	Likely pathogenic
4813675	NM_001448.3(GPC4):c.1513C>T (p.Gln505Ter)	Likely pathogenic
488053	NM_001448.3(GPC4):c.1235G>A (p.Arg412Lys)	Likely pathogenic

SpliceAI

1493 predictions. Top by Δscore:

Variant	Effect	Δscore
X:133303069:CCTAG:C	acceptor_loss	1.0000
X:133303070:CT:C	acceptor_loss	1.0000
X:133303071:T:G	acceptor_loss	1.0000
X:133303164:A:AC	donor_gain	1.0000
X:133303165:C:CG	donor_gain	1.0000
X:133303337:GGTAC:G	acceptor_gain	1.0000
X:133303338:GTAC:G	acceptor_gain	1.0000
X:133303339:TAC:T	acceptor_gain	1.0000
X:133303340:AC:A	acceptor_gain	1.0000
X:133303341:CC:C	acceptor_gain	1.0000
X:133303342:C:CC	acceptor_gain	1.0000
X:133303347:A:AC	acceptor_gain	1.0000
X:133303349:G:C	acceptor_gain	1.0000
X:133303349:G:GC	acceptor_gain	1.0000
X:133304723:A:AC	donor_gain	1.0000
X:133304723:A:C	donor_loss	1.0000
X:133304723:ACCTG:A	donor_gain	1.0000
X:133304724:C:CA	donor_loss	1.0000
X:133304724:C:CC	donor_gain	1.0000
X:133304724:CCTG:C	donor_gain	1.0000
X:133304724:CCTGC:C	donor_gain	1.0000
X:133304738:T:A	donor_gain	1.0000
X:133304755:T:TA	donor_gain	1.0000
X:133304857:GTAAC:G	acceptor_gain	1.0000
X:133304858:TAAC:T	acceptor_gain	1.0000
X:133304859:AAC:A	acceptor_gain	1.0000
X:133304860:AC:A	acceptor_gain	1.0000
X:133304861:CC:C	acceptor_gain	1.0000
X:133304862:C:CC	acceptor_gain	1.0000
X:133304862:C:T	acceptor_gain	1.0000

AlphaMissense

3721 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:133304745:C:A	W424C	0.999
X:133304745:C:G	W424C	0.999
X:133304817:C:A	W400C	0.999
X:133304817:C:G	W400C	0.999
X:133304819:A:G	W400R	0.999
X:133304819:A:T	W400R	0.999
X:133305905:C:G	C341S	0.999
X:133305905:C:T	C341Y	0.999
X:133305906:A:G	C341R	0.999
X:133305906:A:T	C341S	0.999
X:133306068:C:G	A322P	0.999
X:133306074:A:G	S320P	0.999
X:133311271:C:A	W288C	0.999
X:133311271:C:G	W288C	0.999
X:133311273:A:G	W288R	0.999
X:133311273:A:T	W288R	0.999
X:133324256:G:C	F200L	0.999
X:133324256:G:T	F200L	0.999
X:133324258:A:G	F200L	0.999
X:133324291:A:G	C189R	0.999
X:133324353:A:G	L168P	0.999
X:133324363:A:G	W165R	0.999
X:133324363:A:T	W165R	0.999
X:133324484:A:C	F124L	0.999
X:133324484:A:T	F124L	0.999
X:133324486:A:G	F124L	0.999
X:133324497:A:G	L120P	0.999
X:133303231:A:G	L468P	0.998
X:133304794:C:G	C408S	0.998
X:133304795:A:T	C408S	0.998

dbSNP variants (sampled 300 via entrez): RS1000090591 (X:133362554 T>C), RS1000102601 (X:133310762 G>A), RS1000128392 (X:133408739 TAAA>T,TAA,TAAAA), RS1000157034 (X:133373166 A>G), RS1000264687 (X:133316814 T>C), RS1000313556 (X:133353931 G>A), RS1000324674 (X:133396771 C>T), RS1000354260 (X:133333786 G>A), RS1000362120 (X:133305360 C>A), RS1000383602 (X:133384513 T>C), RS1000433267 (X:133353327 T>C), RS1000473779 (X:133406418 T>C), RS1000508119 (X:133388549 T>C), RS1000551834 (X:133324140 C>G), RS1000572440 (X:133405915 C>T)

Disease associations

OMIM: gene MIM:300168 | disease phenotypes: MIM:255980, MIM:301026, MIM:194070, MIM:312870, MIM:123100

GenCC curated gene-disease

Disease	Classification	Inheritance
Keipert syndrome	Definitive	X-linked

Mondo (4): Keipert syndrome (MONDO:0009720), Wilms tumor 1 (MONDO:0008679), Simpson-Golabi-Behmel syndrome type 1 (MONDO:0020602), craniosynostosis (MONDO:0015469)

Orphanet (4): Keipert syndrome (Orphanet:2662), Simpson-Golabi-Behmel syndrome (Orphanet:373), Nephroblastoma (Orphanet:654), Craniosynostosis (Orphanet:1531)

HPO phenotypes

169 total (30 of 169 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000072	Hydroureter
HP:0000073	Ureteral duplication
HP:0000098	Tall stature
HP:0000105	Enlarged kidney
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000175	Cleft palate
HP:0000189	Narrow palate
HP:0000204	Cleft upper lip
HP:0000212	Gingival overgrowth
HP:0000215	Thick upper lip vermilion
HP:0000238	Hydrocephalus
HP:0000243	Trigonocephaly
HP:0000256	Macrocephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000337	Broad forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
C538337	Nasodigitoacoustic syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	5
bisphenol A	decreases expression, increases expression, increases methylation	4
methylmercuric chloride	increases expression, affects cotreatment	3
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	increases expression, affects methylation, decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cisplatin	affects expression, increases expression	2
Estradiol	affects binding, increases reaction, affects cotreatment, increases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
aristolochic acid I	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
salinomycin	decreases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
nickel sulfate	increases expression	1
pentabromodiphenyl ether	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
incobotulinumtoxinA	increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Dasatinib	increases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 1 transformed cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B2Y4	Abcam HEK293T GPC4 KO	Transformed cell line	Female
CVCL_B6RJ	ATCi002-A	Induced pluripotent stem cell	Male
CVCL_SQ37	HAP1 GPC4 (-) 1	Cancer cell line	Male
CVCL_SQ38	HAP1 GPC4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT00038207	PHASE2	COMPLETED	Liposomal Vincristine for Pediatric and Adolescent Patients With Relapsed Malignancies
NCT00335556	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and/or Surgery in Treating Patients With High-Risk Kidney Tumors
NCT02229968	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery
NCT00011414	PHASE1	COMPLETED	Phase I Trial of Tariquidar (XR9576) in Combination With Doxorubicin, Vinorelbine, or Docetaxel in Pediatric Patients With Solid Tumors
NCT02164097	PHASE1	TERMINATED	ODSH + ICE Chemotherapy in Pediatric Solid Tumors
NCT00912119	PHASE1	COMPLETED	Amicar Pharmacokinetics of Children Having Craniofacial Surgery
NCT00503893	Not specified	UNKNOWN	Genetics of Wilms’ Tumor and/or the Associated Conditions of Aniridia, Hemihypertrophy, and Genitourinary Anomalies
NCT05179850	Not specified	UNKNOWN	Computer Aided Diagnostic Tool on Computed Tomography Images for Diagnosis of Retroperitoneal Tumor in Children
NCT00077831	Not specified	COMPLETED	Child and Infant Learning Project
NCT00106977	Not specified	COMPLETED	Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)
NCT00367796	Not specified	COMPLETED	Genetic Analysis of Craniosynostosis, Philadelphia Type
NCT00769847	Not specified	WITHDRAWN	Endoscopic Treatment for Isolated, Single Suture Craniosynostosis
NCT00773643	Not specified	COMPLETED	Osteogenic Profiling of Tissue From Children With Craniosynostosis
NCT01898650	Not specified	COMPLETED	MRI for Non-invasive Evaluation of Brain Stress
NCT02287805	Not specified	COMPLETED	Qualitative and Quantitative Study Which Aims to Determine the Specifics of the Announcement for the Diagnosis of Patients With Craniosynostosis and Their Parents to Better Support Them in Their Care
NCT02561728	Not specified	WITHDRAWN	Hanger Helmet Study
NCT03025763	Not specified	ACTIVE_NOT_RECRUITING	Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones
NCT03231085	Not specified	COMPLETED	Comparison of the Rate of Preoperative Haemoglobin After Administration of Epoetin Alpha Associated With an Oral Medical Supplementation Versus Intravenous Before Surgery of Craniosynostosis at the Child
NCT04704284	Not specified	COMPLETED	Comparing MRI to CT on Pediatric Craniosynostosis.
NCT05911139	Not specified	ENROLLING_BY_INVITATION	Influence of General Anesthesia on the Dynamic Changes in Brain Damage Markers During and After Craniosynostosis Operations in Infancy
NCT06928727	Not specified	RECRUITING	Ocular Characteristics in Patients With Craniosynostosis