SEMA3D

Summary

SEMA3D (semaphorin 3D, HGNC:10726) is a protein-coding gene on chromosome 7q21.11, encoding Semaphorin-3D (O95025). Induces the collapse and paralysis of neuronal growth cones.

This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development.

Source: NCBI Gene 223117 — RefSeq curated summary.

At a glance

• Gene–disease (curated): skeletal dysplasia (Limited, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 242 total — 1 pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_001384900

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10726
Approved symbol	SEMA3D
Name	semaphorin 3D
Location	7q21.11
Locus type	gene with protein product
Status	Approved
Aliases	coll-2, Sema-Z2
Ensembl gene	ENSG00000153993
Ensembl biotype	protein_coding
OMIM	609907
Entrez	223117

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000284136, ENST00000444867, ENST00000463315, ENST00000484038, ENST00000916323

RefSeq mRNA: 5 — MANE Select: NM_001384900 NM_001384900, NM_001384901, NM_001384902, NM_001384903, NM_152754

CCDS: CCDS34676

Canonical transcript exons

ENST00000284136 — 19 exons

Exon	Start	End
ENSE00001013430	85081517	85081579
ENSE00001013452	85065424	85065552
ENSE00001121003	84995553	84999865
ENSE00001300109	85042171	85042285
ENSE00001303103	85068191	85068284
ENSE00001324530	85072962	85073081
ENSE00001400663	85097805	85097965
ENSE00001401229	85121741	85121931
ENSE00001505589	85055717	85055859
ENSE00001685028	85153608	85153739
ENSE00003463948	85006802	85006941
ENSE00003476108	85012782	85012846
ENSE00003480093	85040673	85040742
ENSE00003481442	85036889	85037033
ENSE00003519292	85020233	85020321
ENSE00003603141	85022391	85022613
ENSE00003604603	85018252	85018293
ENSE00003631985	85015059	85015216
ENSE00003921551	85186678	85187056

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 96.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.6553 / max 588.8334, expressed in 960 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84684	2.4625	828
84689	0.6918	245
84686	0.5909	186
84683	0.3804	212
84688	0.2234	74
84687	0.1739	71
84685	0.1325	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.22	gold quality
tendon of biceps brachii	UBERON:0008188	85.53	gold quality
spleen	UBERON:0002106	83.14	gold quality
left lobe of thyroid gland	UBERON:0001120	82.39	gold quality
thyroid gland	UBERON:0002046	82.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.82	gold quality
right lobe of thyroid gland	UBERON:0001119	81.80	gold quality
calcaneal tendon	UBERON:0003701	80.83	gold quality
adrenal tissue	UBERON:0018303	79.05	gold quality
descending thoracic aorta	UBERON:0002345	78.94	gold quality
tendon	UBERON:0000043	77.84	gold quality
thoracic aorta	UBERON:0001515	76.78	gold quality
ascending aorta	UBERON:0001496	76.53	gold quality
right lung	UBERON:0002167	74.77	gold quality
colonic epithelium	UBERON:0000397	74.07	gold quality
mucosa of stomach	UBERON:0001199	73.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.16	gold quality
rectum	UBERON:0001052	73.03	gold quality
right coronary artery	UBERON:0001625	72.92	gold quality
left coronary artery	UBERON:0001626	72.44	gold quality
sural nerve	UBERON:0015488	72.43	gold quality
aorta	UBERON:0000947	71.59	gold quality
tibia	UBERON:0000979	70.81	gold quality
coronary artery	UBERON:0001621	70.74	gold quality
lymph node	UBERON:0000029	70.54	gold quality
germinal epithelium of ovary	UBERON:0001304	69.28	gold quality
gall bladder	UBERON:0002110	68.65	gold quality
artery	UBERON:0001637	68.15	gold quality
popliteal artery	UBERON:0002250	67.86	gold quality
tibial artery	UBERON:0007610	67.83	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-11268	yes	1024.08
E-GEOD-130148	yes	4.78
E-MTAB-6058	no	11.27
E-ANND-3	no	5.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

193 targeting SEMA3D, 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-3646	100.00	73.56	5283
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Literature-anchored findings (GeneRIF, showing 14)

• Sema3D inhibits tumor development from MDA-MB-231 and MDA-MB-435 cancer cells. It inhibits tumor angiogenesis in all of the formed tumors. (PMID:18818766)
• This study provided strong evidence that SEMA3D confers susceptibility to schizophrenia, which could contribute to the neurodevelopmental impairments in the disorder. (PMID:20684831)
• in this study we have analyzed three aminoacidic substitutions, A131T-SEMA3A, S598G-SEMA3A and E198K-SEMA3D. These variants result in an increase of SEMA proteins levels in the HSCR colon tissue. (PMID:23372769)
• In the absence of Sema3d, endothelial tubes form in a region that is normally avascular (PMID:23685842)
• Semaphorin 3d requires neuropilin 1 or PI3K/Akt, whereas semaphorin 3e requires plexin D1 in directing endothelial motility. (PMID:24825896)
• Functional loss of semaphorin 3C and/or semaphorin 3D and their epistatic interaction with ret are critical to Hirschsprung disease liability. (PMID:25839327)
• CTNNA3 and SEMA3D: Promising loci for asthma exacerbation identified through multiple genome-wide association studies (PMID:26073756)
• Data show significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. (PMID:26286962)
• Novel mutation in SEMA3D segregates with the complete phenotype with variable expressivity in two pedigrees with autosomal dominant familial Meniere’s disease. (PMID:27876815)
• Low SEMA3D expression is associated with colorectal cancer. (PMID:28320475)
• SEMA3D mRNA is expressed mainly in the cytoplasm of the endometrial cancer cells. (PMID:29074988)
• Semaphorin 3D inhibits proliferation and migration of papillary thyroid carcinoma by regulating MAPK/ERK signaling pathway. (PMID:35190928)
• Tumor-derived semaphorin 3D promoting cancer cachexia via regulating hypothalamic pro-opiomelanocortin neurons. (PMID:37219490)
• Semaphorin 3D promotes pancreatic ductal adenocarcinoma progression and metastasis through macrophage reprogramming. (PMID:39413197)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sema3d	ENSDARG00000017369
mus_musculus	Sema3d	ENSMUSG00000040254
rattus_norvegicus	Sema3d	ENSRNOG00000007202

Paralogs (19): SEMA3F (ENSG00000001617), SEMA3G (ENSG00000010319), SEMA3B (ENSG00000012171), SEMA3A (ENSG00000075213), SEMA3C (ENSG00000075223), SEMA5B (ENSG00000082684), SEMA6A (ENSG00000092421), SEMA4G (ENSG00000095539), SEMA5A (ENSG00000112902), SEMA4F (ENSG00000135622), SEMA6D (ENSG00000137872), SEMA7A (ENSG00000138623), SEMA6C (ENSG00000143434), SEMA6B (ENSG00000167680), SEMA4C (ENSG00000168758), SEMA3E (ENSG00000170381), SEMA4B (ENSG00000185033), SEMA4D (ENSG00000187764), SEMA4A (ENSG00000196189)

Protein

Protein identifiers

Semaphorin-3D — O95025 (reviewed: O95025)

All UniProt accessions (2): O95025, C9JYT6

UniProt curated annotations — full annotation on UniProt →

Function. Induces the collapse and paralysis of neuronal growth cones. Could potentially act as repulsive cues toward specific neuronal populations. Binds to neuropilin.

Subcellular location. Secreted.

Domain organisation. Strong binding to neuropilin is mediated by the carboxy third of the protein.

Similarity. Belongs to the semaphorin family.

RefSeq proteins (5): NP_001371829, NP_001371830, NP_001371831, NP_001371832, NP_689967 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR027231	Semaphorin	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036352	Semap_dom_sf	Homologous_superfamily
IPR041416	IL-1RAcP-like_ig	Domain
IPR042582	Sema3D_Sema	Domain

Pfam: PF01403, PF18452

UniProt features (18 total): disulfide bond 6, glycosylation site 3, domain 3, compositionally biased region 2, signal peptide 1, chain 1, sequence variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95025-F1	84.10	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.

Disulfide bonds (6): 117–128, 146–155, 286–398, 310–358, 534–552, 665–731

Glycosylation sites (3): 724, 139, 607

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_NEUROGENESIS, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_TAXIS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, DELYS_THYROID_CANCER_DN, GOBP_HEAD_DEVELOPMENT, GOBP_MESENCHYME_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_STEM_CELL_DIFFERENTIATION, GOBP_SEMAPHORIN_PLEXIN_SIGNALING_PATHWAY

GO Biological Process (8): neural crest cell migration (GO:0001755), axon guidance (GO:0007411), positive regulation of cell migration (GO:0030335), forebrain development (GO:0030900), negative chemotaxis (GO:0050919), semaphorin-plexin signaling pathway (GO:0071526), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (4): semaphorin receptor binding (GO:0030215), neuropilin binding (GO:0038191), chemorepellent activity (GO:0045499), protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), extracellular region (GO:0005576), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signaling receptor binding	2
cellular anatomical structure	2
neural crest cell development	1
mesenchymal cell migration	1
axonogenesis	1
neuron projection guidance	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
brain development	1
anatomical structure development	1
chemotaxis	1
cell surface receptor signaling pathway	1
system development	1
cellular developmental process	1
receptor ligand activity	1
negative chemotaxis	1
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMA3D	NRP1	O14786	986
SEMA3D	PLXNA3	P51805	813
SEMA3D	PLXND1	Q9Y4D7	769
SEMA3D	NRP2	O60462	739
SEMA3D	PLXNA1	Q9UIW2	737
SEMA3D	E7EQY1	E7EQY1	614
SEMA3D	TBX18	O95935	605
SEMA3D	PLXNA4	Q9HCM2	562
SEMA3D	TCF21	O43680	542
SEMA3D	SCX	Q7RTU7	482
SEMA3D	PCDHGA12	O60330	479
SEMA3D	WT1	P19544	451
SEMA3D	ERBB2	P04626	436
SEMA3D	TNC	P24821	425
SEMA3D	SLIT2	O94813	425

IntAct

5 interactions, top by confidence:

A	B	Type	Score
SEMA3D	HNRNPM	psi-mi:“MI:0915”(physical association)	0.400
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
SEMA3C	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): SEMA3D (Synthetic Lethality), HNRNPM (Proximity Label-MS), SEMA3D (Affinity Capture-RNA), SEMA3D (Affinity Capture-MS), SEMA3D (Affinity Capture-MS), SEMA3D (Proximity Label-MS), SEMA3D (Proximity Label-MS)

ESM2 similar proteins: A0M8R7, A0M8S8, A7MB70, O08665, O09126, O42236, O88632, O95025, P08581, P16056, P97523, Q07DV8, Q07DY1, Q07DZ1, Q07E24, Q07E37, Q07E48, Q09YH7, Q09YK0, Q09YL1, Q108U6, Q13275, Q14563, Q24323, Q26473, Q2IBA6, Q2IBD8, Q2IBF2, Q2IBG7, Q2QL89, Q2QLA9, Q2QLC0, Q2QLE0, Q2QLF1, Q2QLG5, Q2QLH6, Q5RE75, Q62181, Q63548, Q75ZY9

Diamond homologs: A7MB70, D3ZTD8, O08665, O09126, O15041, O35464, O42236, O42237, O88632, O95025, O95754, P70275, Q13214, Q13275, Q13591, Q14563, Q17330, Q24322, Q24323, Q26473, Q26972, Q4LFA9, Q5EA85, Q5R7F5, Q5RE75, Q60519, Q62177, Q62178, Q62179, Q62181, Q62217, Q63548, Q64151, Q76KF0, Q8BH34, Q8NFY4, Q90607, Q90663, Q90665, Q92854

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	136
Likely benign	69
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
224833	NM_001384900.1(SEMA3D):c.1738C>T (p.Pro580Ser)	Pathogenic

SpliceAI

2457 predictions. Top by Δscore:

Variant	Effect	Δscore
7:85012776:A:AC	donor_gain	1.0000
7:85012777:C:CC	donor_gain	1.0000
7:85012777:CTTA:C	donor_gain	1.0000
7:85012778:TTA:T	donor_loss	1.0000
7:85012779:TA:T	donor_loss	1.0000
7:85012780:A:AC	donor_gain	1.0000
7:85012780:ACTGT:A	donor_gain	1.0000
7:85012781:C:CA	donor_gain	1.0000
7:85012781:CT:C	donor_gain	1.0000
7:85012781:CTG:C	donor_gain	1.0000
7:85012781:CTGT:C	donor_gain	1.0000
7:85012781:CTGTC:C	donor_gain	1.0000
7:85012842:CTCTC:C	acceptor_gain	1.0000
7:85012844:CTC:C	acceptor_gain	1.0000
7:85012845:TC:T	acceptor_gain	1.0000
7:85012846:CC:C	acceptor_gain	1.0000
7:85012847:C:CC	acceptor_gain	1.0000
7:85012850:C:CT	acceptor_gain	1.0000
7:85012851:G:T	acceptor_gain	1.0000
7:85015053:TCTTA:T	donor_loss	1.0000
7:85015054:CTTA:C	donor_loss	1.0000
7:85015055:TTA:T	donor_loss	1.0000
7:85015056:TA:T	donor_loss	1.0000
7:85015057:A:AC	donor_gain	1.0000
7:85015058:C:CC	donor_gain	1.0000
7:85015058:C:CG	donor_loss	1.0000
7:85015212:TGTTG:T	acceptor_gain	1.0000
7:85015213:GTTG:G	acceptor_gain	1.0000
7:85015214:TTG:T	acceptor_gain	1.0000
7:85015215:TG:T	acceptor_gain	1.0000

AlphaMissense

5152 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:84999779:G:C	C665W	1.000
7:85006840:A:G	W624R	1.000
7:85006840:A:T	W624R	1.000
7:85015085:G:C	C559W	1.000
7:85015086:C:G	C559S	1.000
7:85015087:A:G	C559R	1.000
7:85015087:A:T	C559S	1.000
7:85015100:C:A	W554C	1.000
7:85015100:C:G	W554C	1.000
7:85015102:A:G	W554R	1.000
7:85015102:A:T	W554R	1.000
7:85015106:A:C	C552W	1.000
7:85015107:C:G	C552S	1.000
7:85015107:C:T	C552Y	1.000
7:85015108:A:G	C552R	1.000
7:85015108:A:T	C552S	1.000
7:85015116:T:C	D549G	1.000
7:85015127:A:C	C545W	1.000
7:85015130:A:C	C544W	1.000
7:85015131:C:G	C544S	1.000
7:85015132:A:G	C544R	1.000
7:85015132:A:T	C544S	1.000
7:85015160:G:C	C534W	1.000
7:85015161:C:T	C534Y	1.000
7:85015162:A:G	C534R	1.000
7:85042249:A:G	W300R	1.000
7:85042249:A:T	W300R	1.000
7:84999780:C:G	C665S	0.999
7:84999780:C:T	C665Y	0.999
7:84999781:A:G	C665R	0.999

dbSNP variants (sampled 300 via entrez): RS1000000361 (7:85209766 T>C), RS1000002855 (7:85002583 A>C,G), RS1000056013 (7:85209477 T>G), RS1000069554 (7:85044452 ATTTG>A), RS1000086197 (7:85199955 C>A), RS1000114827 (7:85242281 AT>A,ATT), RS1000127364 (7:85239735 G>A), RS1000138569 (7:85213432 G>A), RS1000150626 (7:85108698 C>T), RS1000165200 (7:85076078 C>T), RS1000179142 (7:85201047 T>C), RS1000181821 (7:85021971 T>C), RS1000184453 (7:85040286 C>G,T), RS1000194229 (7:85203645 T>G), RS1000208341 (7:85058589 T>C)

Disease associations

OMIM: gene MIM:609907 | disease phenotypes: MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
skeletal dysplasia	Limited	Autosomal dominant

Mondo (4): Hirschsprung disease, susceptibility to, 1 (MONDO:0007723), CHARGE syndrome (MONDO:0008965), Hirschsprung disease (MONDO:0018309), skeletal dysplasia (MONDO:0018230)

Orphanet (2): Hirschsprung disease (Orphanet:388), CHARGE syndrome (Orphanet:138)

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0001510	Growth delay
HP:0001531	Failure to thrive in infancy
HP:0001561	Polyhydramnios
HP:0001824	Weight loss
HP:0002014	Diarrhea
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002251	Aganglionic megacolon
HP:0003270	Abdominal distention
HP:0004322	Short stature
HP:0004387	Enterocolitis
HP:0005214	Intestinal obstruction
HP:0011968	Feeding difficulties
HP:0012719	Functional abnormality of the gastrointestinal tract
HP:0031369	Colon perforation
HP:0034754	Bilious emesis
HP:0100806	Sepsis
HP:6000224	Delayed passage of meconium

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004068_83	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	7.000000e-06
GCST006291_17	Spherical equivalent or myopia (age of diagnosis)	4.000000e-08
GCST006979_130	Heel bone mineral density	3.000000e-09
GCST007429_47	Lung function (FVC)	2.000000e-11
GCST007430_41	Peak expiratory flow	3.000000e-13
GCST007432_81	FEV1	2.000000e-16
GCST008163_448	Height	4.000000e-06
GCST010307_6	Urinary albumin excretion	2.000000e-08
GCST90002403_577	Red blood cell count	3.000000e-09
GCST90020025_354	Waist-to-hip ratio adjusted for BMI	3.000000e-09
GCST90020027_1315	Waist-hip index	6.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0009270	heel bone mineral density
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0004314	forced expiratory volume
EFO:0004285	albuminuria
EFO:0004305	erythrocyte count
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D058747	CHARGE Syndrome	C09.218.458.341.186.500.250; C10.597.751.418.341.186.500.250; C10.597.751.941.162.625.250; C11.270.147.500; C11.966.075.375.250; C16.131.077.299.250; C16.320.165; C23.888.592.763.393.341.186.500.500; C23.888.592.763.941.162.625.500
D006627	Hirschsprung Disease	C06.198.439; C06.405.469.158.701.439; C16.131.314.439

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
arsenite	affects binding, decreases reaction, decreases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	2
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
geldanamycin	increases expression	1
bisphenol A	decreases methylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Amiodarone	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Estradiol	decreases expression	1
Folic Acid	increases expression	1
Ketoconazole	affects expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	decreases expression	1
Testosterone	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02343562	PHASE4	UNKNOWN	Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis
NCT07186647	PHASE4	COMPLETED	Laparoscopic-Assisted Transanal Pull-Through for Hirschsprung Disease in Pediatric:Short and Intermediate Outcomes of Two Different Techniques
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT03660176	PHASE3	UNKNOWN	Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung’s Disease
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00001754	Not specified	COMPLETED	Study of Skeletal Disorders and Short Stature
NCT02762318	Not specified	TERMINATED	Identification and Characterization of Bone-related Genetic Variants in Families
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT05247645	Not specified	RECRUITING	Data Collection of Patients With Rare Bone Diseases
NCT05876416	Not specified	RECRUITING	Decoding the Genetic Landscape of Skeletal Diseases
NCT05991609	Not specified	ACTIVE_NOT_RECRUITING	Extreme Morphology and Metabolic Health
NCT06002373	Not specified	UNKNOWN	Assessment of Artificial Intelligence for Treatment Decision Recommendation of Adult Skeletal Class III Patients
NCT01985646	EARLY_PHASE1	COMPLETED	A Trial on Conservative Treatment for Infants’ Hirschsprung Disease
NCT00478712	Not specified	RECRUITING	Hirschsprung Disease Genetic Study
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT01927809	Not specified	UNKNOWN	Genetic Mosaicism in Hirschsprung’s Disease
NCT02193685	Not specified	UNKNOWN	Identification Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease
NCT02216994	Not specified	UNKNOWN	A New Scoring System Improves Diagnostic Accuracy of Intestinal Dysganglionosis –a Prospective Study
NCT02296008	Not specified	COMPLETED	3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders
NCT02776176	Not specified	UNKNOWN	Enhanced Recovery After Surgery In Hirschsprung Disease
NCT02857205	Not specified	COMPLETED	MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung’s Associated EnteroColitis
NCT03269812	Not specified	UNKNOWN	Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT04020939	Not specified	COMPLETED	The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery.
NCT04106947	Not specified	UNKNOWN	Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations
NCT04149093	Not specified	UNKNOWN	The Association Between Calretinin and the Function of Ganglion Cells in Hirschsprung Disease
NCT04150120	Not specified	COMPLETED	eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness
NCT04213976	Not specified	UNKNOWN	Ostomy in Continuity or Conventional Ileostomy: a Retrospective Multicentric Analysis
NCT04476225	Not specified	COMPLETED	Induced Pluripotent Stem Cells for Disease Research
NCT04598841	Not specified	COMPLETED	Nutrition Support for Hirschsprung Disease
NCT04622410	Not specified	RECRUITING	Registry for Hirschsprung Disease of the BELAPS
NCT04624334	Not specified	TERMINATED	Non-invasive Assessment of Colonic Motility
NCT04730128	Not specified	COMPLETED	Translation and Validation of a Disease-specific Questionnaire for Hirschsprung’s Disease in Danish Patients
NCT04837963	Not specified	COMPLETED	Does Hirschsprung Disease Increase the Risk of Febrile Urinary Tract Infection in Children
NCT04957667	Not specified	COMPLETED	Scintigraphic Defecography for Evaluation of Functional Outcome in an Adult Hirschsprung Population
NCT05038345	Not specified	TERMINATED	Hirschsprung Disease Trends in the United States: Analysis of the National Inpatient Sample
NCT05044741	Not specified	COMPLETED	Risk Factors of Perforated HSCR in Neonates
NCT05293353	Not specified	UNKNOWN	Neokare Safety and Tolerability Assessment in Neonates With GI Problems
NCT05307419	Not specified	UNKNOWN	Full Thickness vs. Rectal Suction Biopsy in the Diagnosis of Hirschsprungs Disease