DENND3

Summary

DENND3 (DENN domain containing 3, HGNC:29134) is a protein-coding gene on chromosome 8q24.3, encoding DENN domain-containing protein 3 (A2RUS2). Guanine nucleotide exchange factor (GEF) activating RAB12.

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in endosome to lysosome transport; protein catabolic process; and regulation of Rab protein signal transduction. Predicted to be located in cytosol. Predicted to be active in cytoplasmic vesicle.

Source: NCBI Gene 22898 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 237 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_001352890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29134
Approved symbol	DENND3
Name	DENN domain containing 3
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0870
Ensembl gene	ENSG00000105339
Ensembl biotype	protein_coding
OMIM	617503
Entrez	22898

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 13 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000262585, ENST00000424248, ENST00000517813, ENST00000517985, ENST00000518198, ENST00000518249, ENST00000518347, ENST00000518668, ENST00000518806, ENST00000519291, ENST00000519811, ENST00000520482, ENST00000520571, ENST00000520725, ENST00000520986, ENST00000521477, ENST00000521835, ENST00000523015, ENST00000523058, ENST00000523066, ENST00000523308, ENST00000523530, ENST00000885117

RefSeq mRNA: 4 — MANE Select: NM_001352890 NM_001352890, NM_001352891, NM_001362798, NM_014957

CCDS: CCDS87629

Canonical transcript exons

ENST00000519811 — 23 exons

Exon	Start	End
ENSE00000664861	141192526	141192663
ENSE00001627361	141176591	141176761
ENSE00001678227	141178067	141178196
ENSE00001686346	141141203	141141324
ENSE00001699016	141144148	141144259
ENSE00001715628	141155849	141155970
ENSE00001761800	141185139	141185278
ENSE00001780401	141150834	141150953
ENSE00002092532	141128589	141128809
ENSE00003460718	141166190	141166389
ENSE00003500620	141180747	141180854
ENSE00003501063	141175200	141175459
ENSE00003515786	141168004	141168525
ENSE00003565276	141136509	141136791
ENSE00003605545	141160632	141160787
ENSE00003653714	141165186	141165289
ENSE00003655973	141163333	141163429
ENSE00003656817	141138022	141138137
ENSE00003665731	141190284	141190417
ENSE00003683844	141192331	141192449
ENSE00003685117	141188986	141189146
ENSE00003790482	141151619	141151837
ENSE00003905967	141194033	141195804

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 98.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.1263 / max 1398.2321, expressed in 1645 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91285	12.5002	1415
91284	5.3836	1387
91287	0.0852	24
91286	0.0442	19
91291	0.0412	17
91290	0.0361	14
91289	0.0257	12
91288	0.0101	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	98.76	gold quality
upper lobe of left lung	UBERON:0008952	97.42	gold quality
upper lobe of lung	UBERON:0008948	96.80	gold quality
blood	UBERON:0000178	96.73	gold quality
popliteal artery	UBERON:0002250	96.10	gold quality
tibial artery	UBERON:0007610	96.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.95	gold quality
granulocyte	CL:0000094	95.56	gold quality
mucosa of stomach	UBERON:0001199	95.54	gold quality
monocyte	CL:0000576	95.37	gold quality
mononuclear cell	CL:0000842	95.25	gold quality
omental fat pad	UBERON:0010414	95.14	gold quality
peritoneum	UBERON:0002358	95.06	gold quality
spleen	UBERON:0002106	94.95	gold quality
leukocyte	CL:0000738	94.94	gold quality
left coronary artery	UBERON:0001626	94.83	gold quality
metanephros cortex	UBERON:0010533	94.76	gold quality
cartilage tissue	UBERON:0002418	94.71	gold quality
aorta	UBERON:0000947	94.25	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.12	gold quality
left uterine tube	UBERON:0001303	94.08	gold quality
right coronary artery	UBERON:0001625	94.03	gold quality
colonic epithelium	UBERON:0000397	93.92	gold quality
endocervix	UBERON:0000458	93.81	gold quality
apex of heart	UBERON:0002098	93.80	gold quality
right frontal lobe	UBERON:0002810	93.74	gold quality
coronary artery	UBERON:0001621	93.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.65	gold quality
vermiform appendix	UBERON:0001154	93.62	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

52 targeting DENND3, 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-9-5P	100.00	72.28	2361
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-18A-5P	99.29	71.05	806
HSA-MIR-18B-5P	99.29	71.05	806
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-4735-3P	99.14	69.85	777
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-4326	98.97	67.63	962

Literature-anchored findings (GeneRIF, showing 4)

• a novel signaling pathway identified whereby starvation-induced activation of ULK leads to phosphorylation of endogenous DENND3, with subsequent activation of Rab12 and initiation of membrane trafficking events required for autophagy (PMID:25925668)
• DENND3 is the exchange factor for the small GTPase Rab12 regulated through an intramolecular interaction (PMID:28249939)
• show that DENND3 binds actin through a surface of positively charged residues on the PHenn domain of Ran12 (PMID:29352104)
• DENND3 p.L708V activating variant is involved in the pathogenesis of hereditary hemochromatosis via the RAB12/TFR2 signaling pathway. (PMID:36729283)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dennd3b	ENSDARG00000013153
danio_rerio	dennd3a	ENSDARG00000078797
mus_musculus	Dennd3	ENSMUSG00000036661
rattus_norvegicus	Dennd3	ENSRNOG00000010794
drosophila_melanogaster	Crag	FBGN0025864
caenorhabditis_elegans		WBGENE00018681

Paralogs (3): DENND4C (ENSG00000137145), DENND4A (ENSG00000174485), DENND4B (ENSG00000198837)

Protein

Protein identifiers

DENN domain-containing protein 3 — A2RUS2 (reviewed: A2RUS2)

All UniProt accessions (12): A2RUS2, B3KRG7, E5RH95, E5RHH2, E5RI43, E5RIR7, E5RJ42, E9PF32, H0YAW2, H0YAY3, H0YBH5, H0YBK9

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form. Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12. Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4. Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy.

Subunit / interactions. Forms oligomers. Interacts with 6 of the 7 known isoforms of 14-3-3 proteins.

Subcellular location. Cytoplasm.

Domain organisation. Inactive DENND3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-858 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards RAB12.

Isoforms (4)

UniProt ID	Names	Canonical?
A2RUS2-1	1	yes
A2RUS2-2	2
A2RUS2-3	3
A2RUS2-4	4

RefSeq proteins (4): NP_001339819, NP_001339820, NP_001349727, NP_055772 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001194	cDENN_dom	Domain
IPR001680	WD40_rpt	Repeat
IPR005112	dDENN_dom	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR037516	Tripartite_DENN	Domain
IPR043153	DENN_C	Homologous_superfamily
IPR051696	DENN_Domain_GEFs	Family
IPR057977	TPR_DENND3	Domain

Pfam: PF00400, PF02141, PF25570

UniProt features (24 total): repeat 7, splice variant 5, domain 3, modified residue 3, region of interest 2, sequence variant 2, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A2RUS2-F1	81.23	0.42

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 (3): 472, 490, 858

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 177 (showing top): GOBP_LYSOSOMAL_TRANSPORT, MODULE_169, MODULE_45, GOBP_ENDOSOME_TO_LYSOSOME_TRANSPORT, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, BROWNE_HCMV_INFECTION_14HR_DN, RYTTCCTG_ETS2_B, MULLIGHAN_NPM1_SIGNATURE_3_DN, HAN_SATB1_TARGETS_DN, MODULE_48, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (3): endosome to lysosome transport (GO:0008333), protein catabolic process (GO:0030163), regulation of Rab protein signal transduction (GO:0032483)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (3): cytosol (GO:0005829), cytoplasmic vesicle (GO:0031410), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Rab regulation of trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
lysosomal transport	1
intercellular transport	1
vesicle-mediated transport	1
macromolecule catabolic process	1
protein metabolic process	1
Rab protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
intracellular vesicle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

758 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DENND3	NCLN	Q969V3	703
DENND3	RAB12	Q6IQ22	674
DENND3	TBATA	Q96M53	674
DENND3	SLC45A4	Q5BKX6	542
DENND3	CHRAC1	Q9NRG0	449
DENND3	TRAPPC9	Q96Q05	436
DENND3	RAB28	P51157	426
DENND3	RAB13	P51153	416
DENND3	FHAD1	B1AJZ9	408
DENND3	TMUB2	Q71RG4	402
DENND3	DENND1C	Q8IV53	401
DENND3	EFCAB10	A6NFE3	399
DENND3	OR1N2	Q8NGR9	377
DENND3	STPG2	Q8N412	373
DENND3	C3orf62	Q6ZUJ4	371

IntAct

9 interactions, top by confidence:

A	B	Type	Score
DENND3	H4C16	psi-mi:“MI:0915”(physical association)	0.400
DENND3	H3-4	psi-mi:“MI:0915”(physical association)	0.400
MAP1LC3A		psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
cof3	DENND3	psi-mi:“MI:0915”(physical association)	0.000
DENND3	flaN	psi-mi:“MI:0915”(physical association)	0.000
DENND3		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): DENND3 (Affinity Capture-MS), HIST3H3 (Proximity Label-MS), HIST1H4A (Proximity Label-MS), DENND3 (Affinity Capture-MS), DENND3 (Affinity Capture-MS), DENND3 (Affinity Capture-MS), DENND3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: A2RT67, A2RUS2

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ULK1	“up-regulates activity”	DENND3	phosphorylation
ULK2	“up-regulates activity”	DENND3	phosphorylation
DENND3	“up-regulates activity”	RAB12	“guanine nucleotide exchange factor”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	172
Likely benign	17
Benign	12

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1676301	GRCh37/hg19 8q22.1-24.3(chr8:96496503-146295711)	Pathogenic
375278	NM_001352890.3(DENND3):c.2160del (p.Lys720fs)	Likely pathogenic

SpliceAI

5138 predictions. Top by Δscore:

Variant	Effect	Δscore
8:141136789:CAG:C	donor_loss	1.0000
8:141136790:AGG:A	donor_loss	1.0000
8:141136791:GG:G	donor_loss	1.0000
8:141136792:G:GA	donor_loss	1.0000
8:141136793:T:G	donor_loss	1.0000
8:141138113:GGCCC:G	donor_gain	1.0000
8:141138134:GCAT:G	donor_gain	1.0000
8:141138137:TG:T	donor_loss	1.0000
8:141138138:G:A	donor_loss	1.0000
8:141138138:G:GG	donor_gain	1.0000
8:141144119:C:CA	acceptor_gain	1.0000
8:141151826:G:GT	donor_gain	1.0000
8:141151837:GGT:G	donor_gain	1.0000
8:141151839:T:G	donor_gain	1.0000
8:141155968:GAG:G	donor_gain	1.0000
8:141160630:AG:A	acceptor_gain	1.0000
8:141160631:GG:G	acceptor_gain	1.0000
8:141160631:GGGT:G	acceptor_gain	1.0000
8:141160786:AGG:A	donor_loss	1.0000
8:141160788:G:GG	donor_gain	1.0000
8:141160789:T:G	donor_loss	1.0000
8:141165328:G:GT	donor_gain	1.0000
8:141165345:GACC:G	donor_gain	1.0000
8:141166180:C:CA	acceptor_gain	1.0000
8:141166183:A:AG	acceptor_gain	1.0000
8:141166184:C:G	acceptor_gain	1.0000
8:141166185:CCCA:C	acceptor_loss	1.0000
8:141166186:CCA:C	acceptor_loss	1.0000
8:141166187:CA:C	acceptor_loss	1.0000
8:141166188:A:AG	acceptor_gain	1.0000

AlphaMissense

8443 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:141194183:A:C	S1183R	0.997
8:141194185:T:A	S1183R	0.997
8:141194185:T:G	S1183R	0.997
8:141185186:T:A	W918R	0.996
8:141185186:T:C	W918R	0.996
8:141185184:T:C	L917S	0.994
8:141151727:T:A	W242R	0.993
8:141151727:T:C	W242R	0.993
8:141176705:T:A	W804R	0.993
8:141176705:T:C	W804R	0.993
8:141189019:T:A	W960R	0.993
8:141189019:T:C	W960R	0.993
8:141194219:T:A	W1195R	0.993
8:141194219:T:C	W1195R	0.993
8:141175380:C:A	A739D	0.991
8:141163370:T:C	F384L	0.989
8:141163372:T:A	F384L	0.989
8:141163372:T:G	F384L	0.989
8:141175395:G:C	R744P	0.989
8:141194221:G:C	W1195C	0.989
8:141194221:G:T	W1195C	0.989
8:141151653:T:A	V217D	0.987
8:141151802:G:C	G267R	0.985
8:141190324:T:A	W1016R	0.985
8:141190324:T:C	W1016R	0.985
8:141194213:G:C	A1193P	0.985
8:141163371:T:C	F384S	0.984
8:141163385:T:C	F389L	0.984
8:141163387:T:A	F389L	0.984
8:141163387:T:G	F389L	0.984

dbSNP variants (sampled 300 via entrez): RS1000048829 (8:141173579 G>A), RS1000117929 (8:141183515 C>T), RS1000191864 (8:141159256 C>T), RS1000346453 (8:141132414 A>G), RS1000396274 (8:141127313 G>C), RS1000405183 (8:141164837 C>T), RS1000447174 (8:141126962 C>T), RS1000455083 (8:141184570 G>A), RS1000501555 (8:141148665 G>C,T), RS1000505134 (8:141184341 G>A,C), RS1000527593 (8:141160479 C>T), RS1000578660 (8:141160179 T>G), RS1000731541 (8:141128725 G>A,T), RS1000772100 (8:141165980 G>T), RS1000778959 (8:141128561 C>A)

Disease associations

OMIM: gene MIM:617503 | disease phenotypes: MIM:142623

GenCC curated gene-disease

Mondo (2): Hirschsprung disease, susceptibility to, 1 (MONDO:0007723), Hirschsprung disease (MONDO:0018309)

Orphanet (1): Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001043_2	Response to interferon beta therapy	3.000000e-08
GCST001762_254	Obesity-related traits	2.000000e-06
GCST003265_440	Post bronchodilator FEV1/FVC ratio in COPD	4.000000e-06
GCST004649_4	Isovolumetric relaxation time	5.000000e-08
GCST010002_313	Refractive error	5.000000e-10
GCST011494_42	Daytime nap	2.000000e-09
GCST90002407_523	White blood cell count	2.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003939	energy intake
EFO:0004713	FEV/FVC ratio
EFO:0008204	left ventricular diastolic function measurement
EFO:0007828	daytime rest measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects methylation, affects expression	3
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	3
bisphenol A	decreases expression, decreases methylation, affects cotreatment	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Arsenic	decreases expression, increases abundance, affects methylation, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	increases expression	2
Particulate Matter	affects methylation, increases abundance, decreases expression	2
bisphenol F	affects cotreatment, decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	increases expression	1
sulforaphane	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
deguelin	decreases expression	1
pyrimidifen	decreases expression	1
abrine	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9D4	Ubigene HEK293 DENND3 KO	Transformed cell line	Female

Clinical trials (associated diseases)

53 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)
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
NCT05450991	Not specified	RECRUITING	Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations
NCT05655845	Not specified	UNKNOWN	Risk Factors for Bowel Dysfunction at Preschool and Early Childhood Age in Children With Hirschsprung Disease
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies
NCT06197061	Not specified	UNKNOWN	Comparison of Robot-assisted With Laparoscopic-assisted Modified Soave Procedure for Classical Hirschsprung Disease
NCT06573723	Not specified	RECRUITING	Institutional Registry of Rare Diseases
NCT06590142	Not specified	RECRUITING	Hirschsprung’s Advances; Working Towards Autologous tIssue therapIes
NCT06592534	Not specified	NOT_YET_RECRUITING	Babies With Enterocolitis - A Study of Faecal Calprotectin in Hirschsprung Disease (The BEACH Study)