GPC5

Summary

GPC5 (glypican 5, HGNC:4453) is a protein-coding gene on chromosome 13q31.3, encoding Glypican-5 (P78333). 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.

Source: NCBI Gene 2262 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 157 total — 3 pathogenic, 3 likely-pathogenic
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4453
Approved symbol	GPC5
Name	glypican 5
Location	13q31.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000179399
Ensembl biotype	protein_coding
OMIM	602446
Entrez	2262

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000377067, ENST00000483422, ENST00000618283

RefSeq mRNA: 1 — MANE Select: NM_004466 NM_004466

CCDS: CCDS9468

Canonical transcript exons

ENST00000377067 — 8 exons

Exon	Start	End
ENSE00001259354	91907937	91908057
ENSE00001310581	92144830	92144989
ENSE00001313134	91693187	91693881
ENSE00001320810	91448761	91448922
ENSE00001327788	91756295	91756420
ENSE00001472677	92866282	92867237
ENSE00001472693	91398621	91399209
ENSE00003569600	91728532	91728665

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 87.03.

FANTOM5 (CAGE): breadth broad, TPM avg 1.4337 / max 56.8913, expressed in 269 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
135629	1.0673	222
135628	0.1922	90
135630	0.1742	84

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.03	gold quality
caudate nucleus	UBERON:0001873	84.04	gold quality
putamen	UBERON:0001874	83.85	gold quality
endothelial cell	CL:0000115	83.84	gold quality
nucleus accumbens	UBERON:0001882	83.57	gold quality
entorhinal cortex	UBERON:0002728	83.36	gold quality
pons	UBERON:0000988	83.23	gold quality
temporal lobe	UBERON:0001871	80.06	gold quality
superior vestibular nucleus	UBERON:0007227	79.53	gold quality
amygdala	UBERON:0001876	79.19	gold quality
lateral globus pallidus	UBERON:0002476	79.14	gold quality
substantia nigra pars compacta	UBERON:0001965	77.29	gold quality
substantia nigra	UBERON:0002038	76.97	gold quality
midbrain	UBERON:0001891	76.71	gold quality
nephron tubule	UBERON:0001231	76.43	gold quality
Brodmann (1909) area 46	UBERON:0006483	76.36	gold quality
telencephalon	UBERON:0001893	76.32	gold quality
postcentral gyrus	UBERON:0002581	76.09	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	76.02	gold quality
superior frontal gyrus	UBERON:0002661	76.01	gold quality
hypothalamus	UBERON:0001898	75.49	gold quality
medial globus pallidus	UBERON:0002477	75.27	gold quality
globus pallidus	UBERON:0001875	75.00	gold quality
forebrain	UBERON:0001890	74.98	gold quality
prefrontal cortex	UBERON:0000451	74.76	gold quality
right frontal lobe	UBERON:0002810	74.61	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.48	gold quality
parietal lobe	UBERON:0001872	74.41	gold quality
cingulate cortex	UBERON:0003027	74.14	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.12	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	8103.41
E-HCAD-35	yes	6787.84
E-GEOD-131882	yes	6550.19
E-HCAD-30	yes	5951.70
E-HCAD-25	yes	5163.97
E-GEOD-180759	yes	3706.87
E-ANND-3	no	4.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting GPC5, 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-4673	100.00	66.64	1490
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-297	99.40	69.58	1418

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 30)

• GPC5 is a possible target for the 13q31-q32 amplification detected in lymphoma cell lines. (PMID:12721791)
• Independent replication confirms GPC5 as a genetic risk factor for multiple sclerosis. (PMID:19010793)
• ZIC2, SPRY2, and GPC5 genes are candidate genes suspected to explain the malformations associated with cerebral anomalies in the hypothesis of a contiguous gene syndrome in 13q deletion syndrome (PMID:19022413)
• Confirm the association of polymorphisms within GPC5 with response to interferon-beta therapy in patients with multiple sclerosis. (PMID:19556317)
• GPC5 polymorphism associated with susceptibility to lung cancer in never smokers (PMID:20304703)
• GPC5 is a novel genetic locus protective against sudden cardiac arrest (PMID:20360844)
• No association between GPC5rs2352028 variant and lung cancer in never smokers in meta-analysis of 7 genome-wide association studies under the random effects model. (PMID:20688270)
• This study supports that multiple sclerosis susceptibility at 13q31-32 may localize to the Glypican-5 gene. (PMID:20692050)
• GPC5 stimulates Hh signaling by facilitating/stabilizing the interaction between Hh and Ptc1. (PMID:21339334)
• findings suggested that SNP rs2352028 in GPC5 might confer a slight risk to lung cancer/adenocarcinoma (PMID:22236185)
• GPC5 is a gene required for normal neural tube development. (PMID:23223018)
• Shh binds to HSPG co-receptors containing a glypican 5 core and 2-O-sulfo-iduronic acid to promote neural precursor proliferation. (PMID:23867465)
• Data suggest that glypican-5 (GPC5) is a metastasis suppressor gene in non-small cell lung cancer (NSCLC) and may be a potential biomarker that predicts NSCLC metastasis. (PMID:23962560)
• The IL7R, TNFRSF1A, and GPC5 polymorphisms tended to be associated with having a second event of Multiple sclerosis within a year. (PMID:24130709)
• These results indicate that GPC5 polymorphisms would be useful genetic indicators for Inflammatory demyelinating diseasess, including neuromyelitis optica and multiple sclerosis . (PMID:24135429)
• Variants in the 50-upstream region of GPC5 confer risk of lung cancer in never smokers (PMID:24456789)
• GPC5, a tumor suppressor, is regulated by miR-620 in lung adenocarcinoma. (PMID:24682381)
• gene variants in IRF5, IRF8 and GPC5 were not associated with risk of relapse or disease progression in multiple sclerosis (PMID:24943672)
• Results suggest a potential association between CRP and GPC5 variants with lung cancer risk; variation in GKN1 is associated with chemotherapy response in the Chinese Han population. (PMID:25999661)
• GPC5 protein expression showed a close correlation with the tumorigenesis and tumor progression of prostate cancer, and that might be applied as a novel biomarker for the prediction of diagnosis and prognosis of prostate cancer. (PMID:26631038)
• GPC5 is a novel epigenetically silenced tumor suppressor, which inhibits tumor growth by suppressing Wnt/beta-catenin signaling in lung adenocarcinoma. (PMID:27157618)
• These results suggest that miR-297 acted as an oncogenic miRNA, partly by targeting GPC5, adenocarcinoma of the lung. (PMID:27554041)
• Suggest that GPC5 is able to suppress the lung adenocarcinoma metastasis by competitively binding to Wnt3a and inactivating the Wnt/beta-catenin signaling pathway. (PMID:27806326)
• Our results showed that GPC5 was lowly expressed in PCa cell lines. (PMID:28893348)
• Taken together, our results suggest GPC5 as a tumor suppressor in PDAC and its expression is possibly regulated by miR-4295. Our study indicates that the miR-4295/GPC5 axis may play an important role in the pathogenesis of PADC and has potential applications for the development of PDAC therapy. (PMID:29407175)
• Hotair promoted Gastric Cancer development by promoting GCP5 expression via sponging miR-217. (PMID:30557546)
• miR-301b represses the proliferation and invasion of glioma cells by up-regulating GPC5 expression (PMID:30951720)
• Glypican-1, -3, -5 (GPC1, GPC3, GPC5) and Hedgehog Pathway Expression in Oral Squamous Cell Carcinoma. (PMID:33512817)
• Subcellular localization of glypican-5 is associated with dynamic motility of the human mesenchymal stem cell line U3DT. (PMID:33606708)
• GPC5 suppresses lung cancer progression and metastasis via intracellular CTDSP1/AhR/ARNT signaling axis and extracellular exosome secretion. (PMID:34079082)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gpc5a	ENSDARG00000103647
mus_musculus	Gpc5	ENSMUSG00000022112
rattus_norvegicus	Gpc5	ENSRNOG00000071105
drosophila_melanogaster	dally	FBGN0263930
caenorhabditis_elegans		WBGENE00001687

Paralogs (5): GPC1 (ENSG00000063660), GPC4 (ENSG00000076716), GPC3 (ENSG00000147257), GPC6 (ENSG00000183098), GPC2 (ENSG00000213420)

Protein

Protein identifiers

Glypican-5 — P78333 (reviewed: P78333)

All UniProt accessions (2): P78333, A0A087WX13

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface proteoglycan that bears heparan sulfate.

Subcellular location. Cell membrane Secreted. Extracellular space.

Tissue specificity. In adult, primarily expressed in the brain. Also detected in fetal brain, lung and liver.

Similarity. Belongs to the glypican family.

RefSeq proteins (1): NP_004457* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001863	Glypican	Family
IPR019803	Glypican_CS	Conserved_site

Pfam: PF01153

UniProt features (16 total): glycosylation site 8, chain 2, sequence conflict 2, signal peptide 1, sequence variant 1, propeptide 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78333-F1	78.66	0.61

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 (8): 507, 509, 527, 120, 237, 441, 486, 495

Function

Pathways and Gene Ontology

Reactome pathways

17 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-5362798	Release of Hh-Np from the secreting cell
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: 135 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, MODULE_99, GOBP_POSITIVE_REGULATION_OF_CANONICAL_WNT_SIGNALING_PATHWAY, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GOBP_POSITIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_LOCALIZATION_WITHIN_MEMBRANE, MODULE_48, MODULE_95, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, GOCC_LYSOSOMAL_LUMEN, LEIN_MIDBRAIN_MARKERS

GO Biological Process (4): cell migration (GO:0016477), positive regulation of canonical Wnt signaling pathway (GO:0090263), regulation of protein localization to membrane (GO:1905475), regulation of signal transduction (GO:0009966)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), Golgi lumen (GO:0005796), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), lysosomal lumen (GO:0043202), side of membrane (GO:0098552), obsolete collagen-containing extracellular matrix (GO:0062023)

Reactome top-level categories

Rollup of top-10 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
Hedgehog ligand biogenesis	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
cell motility	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
regulation of protein localization	1
regulation of cellular localization	1
protein localization to membrane	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
binding	1
Golgi apparatus	1
intracellular organelle lumen	1
cell periphery	1
lysosome	1
vacuolar lumen	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1124 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GPC5	SLC10A1	Q14973	670
GPC5	WNT3A	P56704	655
GPC5	AKAP11	Q9UKA4	607
GPC5	IRX4	P78413	601
GPC5	PTCH1	Q13635	579
GPC5	CD58	P19256	578
GPC5	CLEC16A	Q2KHT3	576
GPC5	GPC6	Q9Y625	559
GPC5	IRX2	Q9BZI1	557
GPC5	IRX3	P78415	551
GPC5	SHH	Q15465	550
GPC5	CD6	P30203	536
GPC5	TRIM15	Q9C019	517
GPC5	IRX1	P78414	509
GPC5	SDC3	O75056	506

IntAct

42 interactions, top by confidence:

A	B	Type	Score
GPC5	RYBP	psi-mi:“MI:0915”(physical association)	0.560
GPC5	BOD1	psi-mi:“MI:0915”(physical association)	0.560
GPC5	MAGEC3	psi-mi:“MI:0915”(physical association)	0.560
GPC5	FAM117B	psi-mi:“MI:0915”(physical association)	0.560
GPC5	SMAD4	psi-mi:“MI:0915”(physical association)	0.550
SMAD4	GPC5	psi-mi:“MI:2364”(proximity)	0.550
GPC5	BRAF	psi-mi:“MI:2364”(proximity)	0.470
GPC5	BRAF	psi-mi:“MI:0915”(physical association)	0.470
APP	GPC5	psi-mi:“MI:0407”(direct interaction)	0.440
Shcbp1	PDIA4	psi-mi:“MI:0915”(physical association)	0.400
Gpr158	GPC5	psi-mi:“MI:0915”(physical association)	0.400
GPR179	GPC5	psi-mi:“MI:0915”(physical association)	0.400
DCPS	GPC5	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
GPC5	HSPA5	psi-mi:“MI:0914”(association)	0.350
GPC5	HSPG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): GPC5 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), FXYD6 (Affinity Capture-MS), HSPG2 (Affinity Capture-MS), SPCS2 (Affinity Capture-MS), GPC5 (Proximity Label-MS), GPC5 (Proximity Label-MS), GPC5 (Proximity Label-MS), GPC5 (Proximity Label-MS), GPC5 (Affinity Capture-MS), GPC5 (Two-hybrid)

ESM2 similar proteins: A2A699, A2ALI5, A2AWH2, A2BDP1, A4IFM1, A4IHZ3, A8MVW0, B0BN44, B1AL88, D3ZZP4, O35144, O35451, O75129, O75949, O94983, P0C7U0, P13265, P51693, P78333, Q03157, Q15554, Q1XFL1, Q2F7Z7, Q3T0Q2, Q3U4N7, Q4W8E7, Q5EGE1, Q5F267, Q5R800, Q5RA50, Q60943, Q61137, Q6H9L7, Q6P9J5, Q6UWH4, Q766D5, Q80Y50, Q80Z10, Q810F0, Q86V42

Diamond homologs: A5A6P7, P13265, P51654, P78333, Q6V9Y8, Q8CAL5, Q8CFZ4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of ERK1 and ERK2 cascade	5	25.0×	2e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — CHOL, OVT.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	3
Uncertain significance	116
Likely benign	19
Benign	5

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
242850	GRCh37/hg19 13q31.3(chr13:90644219-92557099)x1	Pathogenic
395407	GRCh37/hg19 13q31.1-31.3(chr13:86963003-93390362)x3	Pathogenic
4279323	GRCh37/hg19 13q31.1-31.3(chr13:86942417-92631762)x1	Pathogenic
148197	GRCh38/hg38 13q31.1-31.3(chr13:84005264-92784013)x1	Likely pathogenic
560158	Single allele	Likely pathogenic
815605	GRCh37/hg19 13q31.3(chr13:91460305-92069153)x3	Likely pathogenic

SpliceAI

4939 predictions. Top by Δscore:

Variant	Effect	Δscore
13:91448758:CA:C	acceptor_loss	1.0000
13:91448759:A:AG	acceptor_gain	1.0000
13:91448760:G:GG	acceptor_gain	1.0000
13:91448920:AAG:A	donor_gain	1.0000
13:91448921:AG:A	donor_gain	1.0000
13:91448921:AGG:A	donor_loss	1.0000
13:91448922:GG:G	donor_gain	1.0000
13:91448923:G:GC	donor_loss	1.0000
13:91448923:G:GG	donor_gain	1.0000
13:91521633:A:AG	acceptor_gain	1.0000
13:91693881:GGTA:G	donor_loss	1.0000
13:91693882:G:GG	donor_gain	1.0000
13:91693882:GTAA:G	donor_loss	1.0000
13:91693883:T:A	donor_loss	1.0000
13:91728662:GAAA:G	donor_gain	1.0000
13:91728663:A:T	donor_gain	1.0000
13:91728666:G:GG	donor_gain	1.0000
13:91756289:A:AG	acceptor_gain	1.0000
13:91756290:T:G	acceptor_gain	1.0000
13:91756290:TTTA:T	acceptor_loss	1.0000
13:91756293:A:AG	acceptor_gain	1.0000
13:91756293:A:C	acceptor_loss	1.0000
13:91756294:G:GG	acceptor_gain	1.0000
13:91756294:GA:G	acceptor_gain	1.0000
13:91756294:GAGA:G	acceptor_gain	1.0000
13:91756294:GAGAA:G	acceptor_gain	1.0000
13:91756416:AAAAG:A	donor_gain	1.0000
13:91756418:AAGGT:A	donor_loss	1.0000
13:91756422:T:G	donor_loss	1.0000
13:91907931:T:A	acceptor_gain	1.0000

AlphaMissense

3767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:91756397:G:C	W419C	0.994
13:91756397:G:T	W419C	0.994
13:91448778:T:A	C61S	0.993
13:91448779:G:C	C61S	0.993
13:91693213:G:C	A118P	0.993
13:91908041:T:C	L462P	0.992
13:91448778:T:C	C61R	0.991
13:91693543:G:C	A228P	0.990
13:91693702:T:C	C281R	0.989
13:91693683:C:G	C274W	0.988
13:91693735:T:A	W292R	0.987
13:91693735:T:C	W292R	0.987
13:91693737:G:C	W292C	0.987
13:91693737:G:T	W292C	0.987
13:91693642:T:A	C261S	0.986
13:91693643:G:C	C261S	0.986
13:91448780:C:G	C61W	0.985
13:91448802:T:A	C69S	0.984
13:91448803:G:C	C69S	0.984
13:91693471:T:C	F204L	0.984
13:91693473:T:A	F204L	0.984
13:91693473:T:G	F204L	0.984
13:91693633:T:C	C258R	0.984
13:91448779:G:A	C61Y	0.983
13:91693635:C:G	C258W	0.983
13:91693671:T:G	C270W	0.983
13:91448802:T:C	C69R	0.982
13:91693547:T:C	L229P	0.982
13:91693644:C:G	C261W	0.982
13:91693837:G:C	A326P	0.982

dbSNP variants (sampled 300 via entrez): RS1000000371 (13:92852310 T>G), RS1000001180 (13:92763155 A>G), RS1000005704 (13:92180968 C>T), RS1000006714 (13:92429662 A>G), RS1000009889 (13:91863622 A>G), RS1000011684 (13:92144223 A>T), RS1000012337 (13:92029231 G>A), RS1000012968 (13:92668338 T>C), RS1000015556 (13:92386109 T>C), RS1000022432 (13:91565530 A>T), RS1000027488 (13:92022806 C>A), RS1000027495 (13:91774231 C>G), RS1000028391 (13:92063982 T>A), RS1000034662 (13:91649287 G>T), RS1000034887 (13:92391783 C>A,G,T)

Disease associations

OMIM: gene MIM:602446 | disease phenotypes: MIM:192350

GenCC curated gene-disease

Mondo (1): VACTERL/vater association (MONDO:0008642)

Orphanet (1): VACTERL/VATER association (Orphanet:887)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000269_4	Multiple sclerosis	1.000000e-06
GCST000274_13	Metabolite levels	1.000000e-07
GCST000611_3	Height	3.000000e-06
GCST000633_1	Lung cancer	6.000000e-06
GCST000656_1	HIV-1 viral setpoint	5.000000e-06
GCST000817_147	Height	1.000000e-11
GCST001018_1	Nephrotic syndrome (acquired)	3.000000e-07
GCST001762_82	Obesity-related traits	4.000000e-07
GCST001762_948	Obesity-related traits	5.000000e-06
GCST001807_4	Tetralogy of Fallot	3.000000e-09
GCST002001_3	Adverse response to chemotherapy (neutropenia/leucopenia) (all antimicrotubule drugs)	1.000000e-06
GCST002587_22	Blood pressure (smoking interaction)	6.000000e-07
GCST002587_23	Blood pressure (smoking interaction)	2.000000e-06
GCST002647_104	Height	8.000000e-15
GCST002702_76	Height	1.000000e-10
GCST003431_1	Incident coronary heart disease	6.000000e-06
GCST005142_33	Cognitive ability	2.000000e-08
GCST006291_71	Spherical equivalent or myopia (age of diagnosis)	4.000000e-10
GCST006585_1114	Blood protein levels	2.000000e-218
GCST006959_186	Rheumatoid arthritis	3.000000e-09
GCST006959_189	Rheumatoid arthritis	3.000000e-06
GCST007160_23	Refractive astigmatism	8.000000e-06
GCST007470_15	Rapid automatized naming of letters	8.000000e-06
GCST007576_399	Chronotype	3.000000e-09
GCST008161_39	Waist circumference adjusted for body mass index	3.000000e-06
GCST008478_39	Neurological blood protein biomarker levels	1.000000e-36
GCST008478_40	Neurological blood protein biomarker levels	1.000000e-10
GCST008595_77	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-08
GCST009391_627	Metabolite levels	5.000000e-06
GCST012198_6	Interleukin-6 levels	1.000000e-05

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004529	lipid measurement
EFO:0000180	HIV-1 infection
EFO:0003940	physical activity
EFO:0005260	response to antimicrotubule agent
EFO:0006335	systolic blood pressure
EFO:0006525	cigarettes per day measurement
EFO:0006526	pack-years measurement
EFO:0004337	intelligence
EFO:0004847	age at onset
EFO:0005301	reading and spelling ability
EFO:0008328	chronotype measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004784	self reported educational attainment
EFO:0010502	indoxyl sulfate measurement
EFO:0004810	interleukin-6 measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	6
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Aflatoxin B1	decreases expression, decreases methylation, affects methylation	3
bisphenol A	increases methylation, affects cotreatment, affects methylation, decreases expression	2
Acetaminophen	affects cotreatment, increases expression	2
OTX015	increases expression	1
bisphenol F	increases methylation	1
methyleugenol	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
sulforaphane	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
evodiamine	increases expression	1
dinophysistoxin 1	decreases expression	1
CGP 52608	affects binding, increases reaction	1
azaspiracid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
tricetin	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Atrazine	increases expression	1
Chenodeoxycholic Acid	increases expression, affects cotreatment	1
Daunorubicin	affects response to substance	1
Deoxycholic Acid	affects cotreatment, increases expression	1
Folic Acid	decreases expression	1
Glycochenodeoxycholic Acid	affects cotreatment, increases expression	1
Glycocholic Acid	affects cotreatment, increases expression	1
Glycodeoxycholic Acid	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03799705	Not specified	COMPLETED	Genetic Variants in Nicotinamide Adenine Dinucleotide (NAD) Synthesis Pathway