Hirschsprung disease, susceptibility to, 1

Summary

Hirschsprung disease, susceptibility to, 1 (MONDO:0007723) is a disease caused by RET (GenCC Strong), with 37 cohort genes and 48 clinical trials. Top therapeutic interventions include indocyanine green acid form.

At a glance

• Causal gene: RET (GenCC Strong)
• Cohort genes: 37
• ClinVar variants: 624
• Clinical trials: 48

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Hirschsprung disease, susceptibility to, 1
Mondo ID	MONDO:0007723
OMIM	142623
UMLS	C3888239
MedGen	854827
Is cancer (heuristic)	no

Also known as: aganglionic megacolon · Hirschsprung disease · Hirschsprung disease caused by mutation in RET · Hirschsprung disease, susceptibility to, 1 · Hirschsprung disease, susceptibility to, type 1 · HSCR1 · megacolon, aganglionic · RET Hirschsprung disease · susceptibility to Hirschsprung disease 1

Data availability: 624 ClinVar variants · 1 GenCC gene-disease record · 9 cell lines.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › Hirschsprung disease, susceptibility to › Hirschsprung disease, susceptibility to, 1

Related subtypes (8): Hirschsprung disease, susceptibility to, 2, Hirschsprung disease, susceptibility to, 5, Hirschsprung disease, susceptibility to, 6, Hirschsprung disease, susceptibility to, 7, Hirschsprung disease, susceptibility to, 8, Hirschsprung disease, susceptibility to, 9, Hirschsprung disease, susceptibility to, 3, Hirschsprung disease, susceptibility to, 4

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

600 retrieved; paginated sample, class counts are floors:

249 uncertain significance, 205 conflicting classifications of pathogenicity, 55 benign/likely benign, 34 likely benign, 18 likely pathogenic, 15 pathogenic, 8 pathogenic/likely pathogenic, 8 benign, 6 risk factor, 1 benign; risk factor, 1 drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
156718	NM_001301131.1(POLR2F):c.294-27388_*10734del	LOC126863146	Pathogenic	no assertion criteria provided
13905	NM_020975.6(RET):c.1852T>G (p.Cys618Gly)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13909	NM_020975.6(RET):c.1901G>A (p.Cys634Tyr)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13915	NM_020975.6(RET):c.1858T>C (p.Cys620Arg)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13916	NM_020975.6(RET):c.1859G>A (p.Cys620Tyr)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13917	NM_020975.6(RET):c.1900T>C (p.Cys634Arg)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13919	NM_020975.6(RET):c.2753T>C (p.Met918Thr)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13925	NM_020975.6(RET):c.538C>T (p.Arg180Ter)	RET	Pathogenic	criteria provided, single submitter
13928	NM_020975.6(RET):c.1859G>T (p.Cys620Phe)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13933	NM_020975.6(RET):c.1826G>A (p.Cys609Tyr)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13946	NM_020975.6(RET):c.2410G>T (p.Val804Leu)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
13951	NM_020975.6(RET):c.2671T>G (p.Ser891Ala)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
230926	NM_020975.6(RET):c.1998G>C (p.Lys666Asn)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
24929	NM_020975.6(RET):c.1947G>A (p.Ser649=)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
24931	NM_020975.6(RET):c.1996A>G (p.Lys666Glu)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
24932	NM_020975.6(RET):c.1998G>T (p.Lys666Asn)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37102	NM_020975.6(RET):c.2410G>A (p.Val804Met)	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
38601	NM_020975.6(RET):c.1852T>A (p.Cys618Ser)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
38612	NM_020975.6(RET):c.2370G>T (p.Leu790Phe)	RET	Pathogenic	criteria provided, multiple submitters, no conflicts
4531443	NM_020975.6(RET):c.754G>T (p.Glu252Ter)	RET	Pathogenic	criteria provided, single submitter
590798	NM_020975.6(RET):c.1280_1281del (p.Val427fs)	RET	Pathogenic	criteria provided, single submitter
666595	NM_020975.6(RET):c.1879+1G>A	RET	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
692052	NM_020975.6(RET):c.712G>T (p.Glu238Ter)	RET	Pathogenic	criteria provided, single submitter
375278	NM_001352890.3(DENND3):c.2160del (p.Lys720fs)	DENND3	Likely pathogenic	no assertion criteria provided
273383	NM_002181.4(IHH):c.151C>A (p.Gln51Lys)	IHH	Likely pathogenic	criteria provided, single submitter
375276	NM_020170.4(NCLN):c.496C>T (p.Gln166Ter)	NCLN	Likely pathogenic	no assertion criteria provided
375277	NM_016320.5(NUP98):c.5207A>G (p.Asn1736Ser)	NUP98	Likely pathogenic	no assertion criteria provided
156720	NC_000022.11:g.38016208G>A	POLR2F	Likely pathogenic	no assertion criteria provided
13922	NM_020975.6(RET):c.2914A>G (p.Arg972Gly)	RET	Likely pathogenic	criteria provided, single submitter
13923	NM_020975.6(RET):c.95C>T (p.Ser32Leu)	RET	Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 16 · Orphanet: 67 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
RET	Strong	Autosomal dominant	Hirschsprung disease, susceptibility to, 1	16

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RET	Orphanet:146	Differentiated thyroid carcinoma
RET	Orphanet:1848	Renal agenesis, bilateral
RET	Orphanet:247698	Multiple endocrine neoplasia type 2A
RET	Orphanet:247709	Multiple endocrine neoplasia type 2B
RET	Orphanet:276621	Sporadic pheochromocytoma/secreting paraganglioma
RET	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
RET	Orphanet:388	Hirschsprung disease
RET	Orphanet:93100	Renal agenesis, unilateral
RET	Orphanet:99361	Isolated familial medullary thyroid carcinoma
RET	Orphanet:99803	Haddad syndrome
SEMA3D	Orphanet:388	Hirschsprung disease
TGFB2	Orphanet:60030	Loeys-Dietz syndrome
TGFB2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
TSC2	Orphanet:210159	Adult hepatocellular carcinoma
TSC2	Orphanet:269001	Isolated focal cortical dysplasia type IIa
TSC2	Orphanet:269008	Isolated focal cortical dysplasia type IIb
TSC2	Orphanet:538	Lymphangioleiomyomatosis
TSC2	Orphanet:805	Tuberous sclerosis complex
TSC2	Orphanet:88924	Autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis
LRBA	Orphanet:445018	Syndromic autoimmune enteropathy due to LRBA deficiency
CREBBP	Orphanet:353277	Rubinstein-Taybi syndrome due to CREBBP mutations
CREBBP	Orphanet:353281	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion
CREBBP	Orphanet:370026	Acute myeloid leukemia with t(8;16)(p11;p13) translocation
CREBBP	Orphanet:592574	Menke-Hennekam syndrome
DYNC2H1	Orphanet:474	Jeune syndrome
DYNC2H1	Orphanet:93269	Short rib-polydactyly syndrome, Majewski type
DYNC2H1	Orphanet:93270	Short rib-polydactyly syndrome, Saldino-Noonan type
DYNC2H1	Orphanet:93271	Short rib-polydactyly syndrome, Verma-Naumoff type
DPYD	Orphanet:1675	Dihydropyrimidine dehydrogenase deficiency
DPYD	Orphanet:293948	1p21.3 microdeletion syndrome
FBN1	Orphanet:1885	Isolated ectopia lentis
FBN1	Orphanet:2084	Glaucoma-ectopia lentis-microspherophakia-stiff joints-short stature syndrome
FBN1	Orphanet:2462	Shprintzen-Goldberg syndrome
FBN1	Orphanet:2623	Geleophysic dysplasia
FBN1	Orphanet:2833	Stiff skin syndrome
FBN1	Orphanet:284963	Marfan syndrome type 1
FBN1	Orphanet:284979	Neonatal Marfan syndrome
FBN1	Orphanet:300382	Progeroid and marfanoid aspect-lipodystrophy syndrome
FBN1	Orphanet:3449	Weill-Marchesani syndrome
FBN1	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
FBN1	Orphanet:969	Acromicric dysplasia
GDNF	Orphanet:388	Hirschsprung disease
GDNF	Orphanet:661	Congenital central hypoventilation syndrome
GFRA1	Orphanet:1848	Renal agenesis, bilateral
GLI3	Orphanet:36	Acrocallosal syndrome
GLI3	Orphanet:380	Greig cephalopolysyndactyly syndrome
GLI3	Orphanet:672	Pallister-Hall syndrome
GLI3	Orphanet:93322	Isolated tibial hemimelia
GLI3	Orphanet:93334	Postaxial polydactyly type A
GLI3	Orphanet:93335	Postaxial polydactyly type B

Cohort genes → proteins

37 cohort genes, 36 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	37

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RET	HGNC:9967	ENSG00000165731	P07949	Proto-oncogene tyrosine-protein kinase receptor Ret	gencc,clinvar
SEMA3D	HGNC:10726	ENSG00000153993	O95025	Semaphorin-3D	clinvar
TGFB2	HGNC:11768	ENSG00000092969	P61812	Transforming growth factor beta-2 proprotein	clinvar
THBS4	HGNC:11788	ENSG00000113296	P35443	Thrombospondin-4	clinvar
TSC2	HGNC:12363	ENSG00000103197	P49815	Tuberin	clinvar
NAV2	HGNC:15997	ENSG00000166833	Q8IVL1	Neuron navigator 2	clinvar
PGRMC2	HGNC:16089	ENSG00000164040	O15173	Membrane-associated progesterone receptor component 2	clinvar
CCR9	HGNC:1610	ENSG00000173585	P51686	C-C chemokine receptor type 9	clinvar
IRAK3	HGNC:17020	ENSG00000090376	Q9Y616	Interleukin-1 receptor-associated kinase 3	clinvar
LRBA	HGNC:1742	ENSG00000198589	P50851	Lipopolysaccharide-responsive and beige-like anchor protein	clinvar
ZHX2	HGNC:18513	ENSG00000178764	Q9Y6X8	Zinc fingers and homeoboxes protein 2	clinvar
CNTN5	HGNC:2175	ENSG00000149972	O94779	Contactin-5	clinvar
FAT3	HGNC:23112	ENSG00000165323	Q8TDW7	Protocadherin Fat 3	clinvar
CREBBP	HGNC:2348	ENSG00000005339	Q92793	CREB-binding protein	clinvar
TBATA	HGNC:23511	ENSG00000166220	Q96M53	Protein TBATA	clinvar
NCLN	HGNC:26923	ENSG00000125912	Q969V3	BOS complex subunit NCLN	clinvar
CLUH	HGNC:29094	ENSG00000132361	O75153	Clustered mitochondria protein homolog	clinvar
DENND3	HGNC:29134	ENSG00000105339	A2RUS2	DENN domain-containing protein 3	clinvar
DYNC2H1	HGNC:2962	ENSG00000187240	Q8NCM8	Cytoplasmic dynein 2 heavy chain 1	clinvar
DPYD	HGNC:3012	ENSG00000188641	Q12882	Dihydropyrimidine dehydrogenase [NADP(+)]	clinvar
C10orf55	HGNC:31008	ENSG00000222047		chromosome 10 putative open reading frame 55	clinvar
AHNAK	HGNC:347	ENSG00000124942	Q09666	Neuroblast differentiation-associated protein AHNAK	clinvar
FBN1	HGNC:3603	ENSG00000166147	P35555	Fibrillin-1	clinvar
GDNF	HGNC:4232	ENSG00000168621	P39905	Glial cell line-derived neurotrophic factor	clinvar
GFRA1	HGNC:4243	ENSG00000151892	P56159	GDNF family receptor alpha-1	clinvar
GLI3	HGNC:4319	ENSG00000106571	P10071	Transcriptional activator GLI3	clinvar
IHH	HGNC:5956	ENSG00000163501	Q14623	Indian hedgehog protein	clinvar
KDR	HGNC:6307	ENSG00000128052	P35968	Vascular endothelial growth factor receptor 2	clinvar
NOTCH2	HGNC:7882	ENSG00000134250	Q04721	Neurogenic locus notch homolog protein 2	clinvar
NRP2	HGNC:8005	ENSG00000118257	O60462	Neuropilin-2	clinvar
NTF3	HGNC:8023	ENSG00000185652	P20783	Neurotrophin-3	clinvar
NUP98	HGNC:8068	ENSG00000110713	P52948	Nuclear pore complex protein Nup98-Nup96	clinvar
OR1F1	HGNC:8194	ENSG00000168124	O43749	Olfactory receptor 1F1	clinvar
PCDHA4	HGNC:8670	ENSG00000204967	Q9UN74	Protocadherin alpha-4	clinvar
SERPINF1	HGNC:8824	ENSG00000132386	P36955	Pigment epithelium-derived factor	clinvar
POLR2F	HGNC:9193	ENSG00000100142	P61218	DNA-directed RNA polymerases I, II, and III subunit RPABC2	clinvar
PTCH1	HGNC:9585	ENSG00000185920	Q13635	Protein patched homolog 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…
SEMA3D	Semaphorin-3D	Induces the collapse and paralysis of neuronal growth cones.
TGFB2	Transforming growth factor beta-2 proprotein	Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.
THBS4	Thrombospondin-4	Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is involved in various processes including cellular proliferation, migration, adhesion and attachment, inflammatory response to CNS injury, regulation of…
TSC2	Tuberin	Catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule…
NAV2	Neuron navigator 2	Possesses 3’ to 5’ helicase activity and exonuclease activity.
PGRMC2	Membrane-associated progesterone receptor component 2	Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan.
CCR9	C-C chemokine receptor type 9	Receptor for chemokine SCYA25/TECK.
IRAK3	Interleukin-1 receptor-associated kinase 3	Putative inactive protein kinase which regulates signaling downstream of immune receptors including IL1R and Toll-like receptors.
LRBA	Lipopolysaccharide-responsive and beige-like anchor protein	Involved in coupling signal transduction and vesicle trafficking to enable polarized secretion and/or membrane deposition of immune effector molecules.
ZHX2	Zinc fingers and homeoboxes protein 2	Acts as a transcriptional repressor.
CNTN5	Contactin-5	Contactins mediate cell surface interactions during nervous system development.
FAT3	Protocadherin Fat 3	May play a role in the interactions between neurites derived from specific subsets of neurons during development.
CREBBP	CREB-binding protein	Acetylates histones, giving a specific tag for transcriptional activation.
TBATA	Protein TBATA	May play a role in spermatid differentiation.
NCLN	BOS complex subunit NCLN	Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes.
CLUH	Clustered mitochondria protein homolog	mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria.
DENND3	DENN domain-containing protein 3	Guanine nucleotide exchange factor (GEF) activating RAB12.
DYNC2H1	Cytoplasmic dynein 2 heavy chain 1	May function as a motor for intraflagellar retrograde transport.
DPYD	Dihydropyrimidine dehydrogenase [NADP(+)]	Involved in pyrimidine base degradation.
AHNAK	Neuroblast differentiation-associated protein AHNAK	May be required for neuronal cell differentiation.
FBN1	Fibrillin-1	Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues.
GDNF	Glial cell line-derived neurotrophic factor	Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.
GFRA1	GDNF family receptor alpha-1	Coreceptor for GDNF, a neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.
GLI3	Transcriptional activator GLI3	Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development.
IHH	Indian hedgehog protein	Plays a role in embryonic morphogenesis; it is involved in the regulation of endochondral skeleton formation, and the development of retinal pigment epithelium (RPE), photoreceptors and periocular tissues.
KDR	Vascular endothelial growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFC and VEGFD.
NOTCH2	Neurogenic locus notch homolog protein 2	Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination.
NRP2	Neuropilin-2	High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF.
NTF3	Neurotrophin-3	Seems to promote the survival of visceral and proprioceptive sensory neurons.
NUP98	Nuclear pore complex protein Nup98-Nup96	Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance.
OR1F1	Olfactory receptor 1F1	Odorant receptor.
PCDHA4	Protocadherin alpha-4	Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination.
SERPINF1	Pigment epithelium-derived factor	Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells.
POLR2F	DNA-directed RNA polymerases I, II, and III subunit RPABC2	DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
PTCH1	Protein patched homolog 1	Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH).

Protein-family classification

Druggable: 9 · Difficult: 7 · Unknown: 21 · Druggable fraction: 0.24

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	3	2.2×	0.655
Scaffold/PPI	4	1.9×	0.655
Antibody/Immunoglobulin	2	1.6×	0.836
GPCR	2	1.3×	0.836
Other/Unknown	21	1.0×	0.836
Protease	1	1.0×	0.855
Transcription factor	3	0.7×	0.960
Enzyme (other)	1	0.3×	0.960

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Cadherin-like_dom
SEMA3D	Antibody/Immunoglobulin	yes		Semap_dom, Ig_sub, Ig-like_dom
TGFB2	Other/Unknown	no		TGF-b_propeptide, TGF-b_C, TGFb2
THBS4	Other/Unknown	no		EGF, EGF-like_Ca-bd_dom, Thrombospondin_3-like_rpt
TSC2	Other/Unknown	no		Rap/Ran_GAP_dom, Tuberin, ARM-like
NAV2	Other/Unknown	no		CH_dom, AAA+_ATPase, P-loop_NTPase
PGRMC2	Other/Unknown	no		Cyt_B5-like_heme/steroid-bd, Cyt_B5-like_heme/steroid_sf, MAPR/NEUFC/NENF-like
CCR9	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR9
IRAK3	Kinase	yes		Death_dom, Prot_kinase_dom, Kinase-like_dom_sf
LRBA	Scaffold/PPI	no		BEACH_dom, WD40_rpt, NBEA-like_DUF1088
ZHX2	Transcription factor	no		HD, Homeodomain-like_sf, Znf_C2H2_type
CNTN5	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
FAT3	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Laminin_G
CREBBP	Transcription factor	no	2.3.1.48	Znf_TAZ, Znf_ZZ, Bromodomain
TBATA	Other/Unknown	no		TBATA-like
NCLN	Protease	yes		Peptidase_M28, Nicalin
CLUH	Other/Unknown	no		TPR-like_helical_dom_sf, GSKIP_dom_sf, CLU_dom
DENND3	Scaffold/PPI	no		cDENN_dom, WD40_rpt, dDENN_dom
DYNC2H1	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dynein_heavy_tail
DPYD	Enzyme (other)	yes	1.3.1.2	Dihydroorotate_DH_cat, Helical_ferredxn, Aldolase_TIM
C10orf55	Other/Unknown	no
AHNAK	Scaffold/PPI	no		PDZ, PDZ_sf, Myelin_sheath_structural
FBN1	Other/Unknown	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, EGF-like_Ca-bd_dom
GDNF	Other/Unknown	no		TGF-b_C, GDNF, Cystine-knot_cytokine
GFRA1	Other/Unknown	no		GDNF_rcpt, GDNF_rcpt_A1, GDNF/GAS1
GLI3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like
IHH	Other/Unknown	no		Hedgehog_signalling_dom, Hedgehog, Hedgehog_Hint
KDR	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
NOTCH2	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
NRP2	Other/Unknown	no		FA58C, CUB_dom, MAM_dom
NTF3	Other/Unknown	no		Nerve_growth_factor-rel, Neurotrophin-3, Nerve_growth_factor_CS
NUP98	Other/Unknown	no		Nup98_auto-Pept-S59_dom, Nup98_C, Nup98_auto-Pept-S59_dom_sf
OR1F1	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
PCDHA4	Other/Unknown	no		Cadherin-like_dom, Cadherin_N, Cadherin-like_sf
SERPINF1	Other/Unknown	no		Serpin_fam, Serpin_CS, Serpin_dom
POLR2F	Other/Unknown	no		Pol_omega/Rpo6/RPB6, Rpo6/Rpb6, DNA-dir_RNA_polK_14-18kDa_CS
PTCH1	Other/Unknown	no		SSD, TM_rcpt_patched, HMGCR/SNAP/NPC1-like_SSD

Expression context

Cohort genes with no expression data: 0.

34 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	37
unknown	0

Top tissues across cohort

Tissue	Cohort genes
tendon of biceps brachii	4
dorsal root ganglion	3
calcaneal tendon	3
islet of Langerhans	3
stromal cell of endometrium	3
left testis	3
right testis	3
olfactory bulb	3
buccal mucosa cell	2
cartilage tissue	2
tendon	2
thymus	2
monocyte	2
mononuclear cell	2
bronchial epithelial cell	2
primordial germ cell in gonad	2
sural nerve	2
tibia	2
mucosa of transverse colon	2
germinal epithelium of ovary	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RET	193	broad	marker	substantia nigra pars reticulata, dorsal root ganglion, substantia nigra pars compacta
SEMA3D	183	ubiquitous	marker	buccal mucosa cell, tendon of biceps brachii, spleen
TGFB2	206	ubiquitous	marker	calcaneal tendon, tendon, cartilage tissue
THBS4	252	broad	marker	calcaneal tendon, tendon, tendon of biceps brachii
TSC2	282	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
NAV2	275	ubiquitous	marker	blood vessel layer, cartilage tissue, cauda epididymis
PGRMC2	300	ubiquitous	marker	jejunal mucosa, islet of Langerhans, stromal cell of endometrium
CCR9	106	tissue_specific	yes	thymus, duodenum, small intestine Peyer’s patch
IRAK3	238	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
LRBA	274	ubiquitous	marker	upper leg skin, bronchial epithelial cell, epithelium of bronchus
ZHX2	293	ubiquitous	marker	superficial temporal artery, dorsal motor nucleus of vagus nerve, saphenous vein
CNTN5	130	broad	marker	adrenal tissue, primordial germ cell in gonad, islet of Langerhans
FAT3	194	broad	marker	buccal mucosa cell, Brodmann (1909) area 23, middle temporal gyrus
CREBBP	297	ubiquitous	marker	sural nerve, tibia, amniotic fluid
TBATA	67	tissue_specific	marker	right testis, thymus, left testis
NCLN	208	ubiquitous	marker	mucosa of transverse colon, stromal cell of endometrium, left adrenal gland
CLUH	283	ubiquitous	marker	gingival epithelium, apex of heart, right lobe of liver
DENND3	236	ubiquitous	marker	right lung, upper lobe of left lung, upper lobe of lung
DYNC2H1	230	ubiquitous	marker	secondary oocyte, bronchial epithelial cell, right uterine tube
DPYD	274	ubiquitous	marker	germinal epithelium of ovary, monocyte, mononuclear cell
C10orf55	122		marker	sperm, left testis, right testis
AHNAK	297	ubiquitous	marker	olfactory bulb, calcaneal tendon, tendon of biceps brachii
FBN1	275	ubiquitous	marker	synovial joint, skin of hip, decidua
GDNF	149	tissue_specific	yes	hindlimb stylopod muscle, tibialis anterior, deltoid
GFRA1	231	broad	marker	endometrium epithelium, trigeminal ganglion, dorsal root ganglion
GLI3	263	ubiquitous	marker	ventricular zone, olfactory bulb, tendon of biceps brachii
IHH	94	broad	marker	mucosa of transverse colon, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
KDR	267	broad	marker	germinal epithelium of ovary, lower lobe of lung, parietal pleura
NOTCH2	294	ubiquitous	marker	pigmented layer of retina, retina, skin of hip
NRP2	238	ubiquitous	marker	sural nerve, mucosa of stomach, lower esophagus muscularis layer

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CREBBP	6,959
NOTCH2	5,266
KDR	4,960
RET	4,203
TSC2	4,135
NUP98	4,108
AHNAK	4,006
FBN1	3,640
PTCH1	3,368
GLI3	2,825

Intra-cohort edges

A	B	Sources
DENND3	NCLN	string_interaction
DENND3	TBATA	string_interaction
GDNF	GFRA1	biogrid_interaction, string_interaction
GDNF	NTF3	string_interaction
GDNF	RET	biogrid_interaction, string_interaction
GFRA1	RET	string_interaction
GLI3	IHH	string_interaction
GLI3	PTCH1	string_interaction
IHH	PTCH1	string_interaction
KDR	NRP2	string_interaction
NCLN	TBATA	string_interaction
NRP2	SEMA3D	string_interaction
NUP98	TBATA	string_interaction
PTCH1	RET	string_interaction
RET	SERPINF1	intact

Structural data

PDB: 26 · AlphaFold-only: 10 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CREBBP	Q92793	144
POLR2F	P61218	60
KDR	P35968	54
RET	P07949	34
NUP98	P52948	22
NRP2	O60462	16
PTCH1	Q13635	16
TGFB2	P61812	11
FBN1	P35555	11
IHH	Q14623	8
NTF3	P20783	5
DYNC2H1	Q8NCM8	4
GDNF	P39905	4
IRAK3	Q9Y616	3
NCLN	Q969V3	3
AHNAK	Q09666	3
SERPINF1	P36955	3
TSC2	P49815	2
ZHX2	Q9Y6X8	2
CNTN5	O94779	2
NOTCH2	Q04721	2
NAV2	Q8IVL1	1
CCR9	P51686	1
LRBA	P50851	1
GFRA1	P56159	1
GLI3	P10071	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DPYD	Q12882	96.23
OR1F1	O43749	86.00
THBS4	P35443	84.81
SEMA3D	O95025	84.10
CLUH	O75153	83.11
DENND3	A2RUS2	81.23
PGRMC2	O15173	79.83
PCDHA4	Q9UN74	74.23
TBATA	Q96M53	60.70
FAT3	Q8TDW7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 329. Enrichment computed across 37 evidence-associated genes (25 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 25 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Neuropilin interactions with VEGF and VEGFR	2	228.4×	0.005	KDR, NRP2
Formation of the ureteric bud	3	59.6×	0.005	RET, GDNF, GFRA1
GLI proteins bind promoters of Hh responsive genes to promote transcription	2	130.5×	0.008	GLI3, PTCH1
Ligand-receptor interactions	2	114.2×	0.008	IHH, PTCH1
RET signaling	3	31.1×	0.008	RET, GDNF, GFRA1
Hedgehog ‘off’ state	3	21.4×	0.019	DYNC2H1, GLI3, PTCH1
Hedgehog ‘on’ state	3	19.0×	0.024	GLI3, IHH, PTCH1
Activation of SMO	2	50.8×	0.028	IHH, PTCH1
NOTCH4 Intracellular Domain Regulates Transcription	2	45.7×	0.031	CREBBP, NOTCH2
NPAS4 regulates expression of target genes	2	39.7×	0.037	RET, CREBBP
Activation of HOX genes during differentiation	2	35.1×	0.043	CREBBP, POLR2F
Notch-HLH transcription pathway	2	32.6×	0.046	CREBBP, NOTCH2
Elastic fibre formation	2	26.9×	0.062	TGFB2, FBN1
TGF-beta receptor signaling activates SMADs	2	26.1×	0.062	TGFB2, FBN1
Molecules associated with elastic fibres	2	24.7×	0.064	TGFB2, FBN1
Cytosolic sensors of pathogen-associated DNA	2	22.8×	0.070	CREBBP, POLR2F
NTF3 activates NTRK2 (TRKB) signaling	1	228.4×	0.074	NTF3
NTF3 activates NTRK3 signaling	1	228.4×	0.074	NTF3
Viral Messenger RNA Synthesis	2	20.8×	0.074	NUP98, POLR2F
NCAM1 interactions	2	19.9×	0.074	GDNF, GFRA1
Heme signaling	2	17.2×	0.093	PGRMC2, CREBBP
Activated NTRK3 signals through PLCG1	1	152.3×	0.098	NTF3
Class B/2 (Secretin family receptors)	2	15.2×	0.104	IHH, PTCH1
RAF/MAP kinase cascade	3	7.3×	0.104	RET, GDNF, GFRA1
Inhibition of TSC complex formation by AKT (PKB)	1	91.4×	0.109	TSC2
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production	1	91.4×	0.109	CREBBP
Defective LFNG causes SCDO3	1	91.4×	0.109	NOTCH2
HHAT G278V doesn’t palmitoylate Hh-Np	1	91.4×	0.109	IHH
RUNX2 regulates chondrocyte maturation	1	91.4×	0.109	IHH
Signaling by membrane-tethered fusions of PDGFRA or PDGFRB	1	91.4×	0.109	KDR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 36 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
axon guidance	7	17.6×	6e-05	RET, SEMA3D, TGFB2, CNTN5, GLI3, NOTCH2, NRP2
embryonic limb morphogenesis	4	44.6×	5e-04	TGFB2, DYNC2H1, NOTCH2, PTCH1
glial cell-derived neurotrophic factor receptor signaling pathway	3	100.3×	6e-04	RET, GDNF, GFRA1
negative regulation of alpha-beta T cell differentiation	2	312.1×	0.002	GLI3, IHH
cell differentiation involved in kidney development	2	312.1×	0.002	GLI3, PTCH1
regulation of bone development	2	187.2×	0.004	GLI3, KDR
metanephros development	3	42.6×	0.004	FBN1, GDNF, GLI3
semaphorin-plexin signaling pathway	3	33.4×	0.007	SEMA3D, KDR, NRP2
branching involved in ureteric bud morphogenesis	3	30.5×	0.007	GDNF, GLI3, PTCH1
kidney development	4	15.6×	0.007	TGFB2, DYNC2H1, GFRA1, SERPINF1
nervous system development	6	7.7×	0.007	NAV2, GDNF, GFRA1, NOTCH2, NTF3, PCDHA4
neural crest cell migration involved in autonomic nervous system development	2	104.0×	0.007	GDNF, NRP2
neural crest cell migration	3	28.1×	0.007	RET, SEMA3D, GDNF
positive regulation of alpha-beta T cell differentiation	2	93.6×	0.008	GLI3, IHH
stem cell proliferation	3	26.0×	0.008	GLI3, KDR, PTCH1
positive regulation of extrinsic apoptotic signaling pathway in absence of ligand	2	85.1×	0.008	RET, TGFB2
embryonic digit morphogenesis	3	25.1×	0.008	CREBBP, GLI3, IHH
atrial septum morphogenesis	2	72.0×	0.011	TGFB2, NOTCH2
negative regulation of macrophage cytokine production	2	66.9×	0.012	TGFB2, IRAK3
somite development	2	62.4×	0.012	IHH, PTCH1
positive regulation of cell adhesion mediated by integrin	2	58.5×	0.012	RET, TGFB2
limb morphogenesis	2	58.5×	0.012	GLI3, PTCH1
smooth muscle tissue development	2	58.5×	0.012	IHH, PTCH1
enteric nervous system development	2	55.1×	0.012	RET, GDNF
embryonic digestive tract development	2	55.1×	0.012	TGFB2, GLI3
commissural neuron axon guidance	2	55.1×	0.012	GDNF, PTCH1
cell fate determination	2	52.0×	0.012	NOTCH2, PTCH1
pulmonary valve morphogenesis	2	52.0×	0.012	TGFB2, NOTCH2
spinal cord motor neuron differentiation	2	52.0×	0.012	DYNC2H1, PTCH1
nerve development	2	52.0×	0.012	NRP2, NTF3

Therapeutics

Drug target analysis

Approved (phase 4): 4 · Phase ≥3: 6 · Phased (≥1): 7 · Undrugged: 30

Druggability breadth: 18 of 37 evidence-associated genes (49%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RET	PONATINIB
IRAK3	FEDRATINIB
CREBBP	COLCHICINE
KDR	VANDETANIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
KDR	172	4
RET	135	4
IRAK3	35	4
CREBBP	13	4
TGFB2	1	2
CCR9	1	3
DPYD	1	3
SEMA3D	0	0
THBS4	0	0
TSC2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	KDR, RET
AFATINIB	4	RET
VEMURAFENIB	4	KDR, RET
FEDRATINIB	4	IRAK3, KDR, RET
TIVOZANIB	4	KDR, RET
LENVATINIB	4	KDR, RET
AXITINIB	4	KDR, RET
SORAFENIB	4	KDR, RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	KDR, RET
RUXOLITINIB	4	RET
INFIGRATINIB PHOSPHATE	4	KDR, RET
INFIGRATINIB	4	KDR, RET
IBRUTINIB	4	KDR, RET
PALBOCICLIB	4	RET
REGORAFENIB	4	KDR, RET
ENTRECTINIB	4	KDR, RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	IRAK3, RET
CABOZANTINIB	4	KDR, RET
BARICITINIB	4	RET
TOFACITINIB	4	KDR, RET
CAPIVASERTIB	4	RET
CERITINIB	4	KDR, RET
VANDETANIB	4	KDR, RET
NILOTINIB	4	RET
BOSUTINIB	4	RET
GILTERITINIB	4	IRAK3, RET
BRIGATINIB	4	KDR, RET
UPADACITINIB	4	KDR, RET

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
KDR	2,687	Binding:2594, Functional:64, ADMET:27, Toxicity:2
RET	1,586	Binding:1573, Functional:10, ADMET:3
CREBBP	687	Binding:644, Functional:43
IRAK3	147	Binding:147
CCR9	30	Binding:17, Functional:13
PTCH1	4	Binding:4
TGFB2	3	Binding:3
DPYD	3	Functional:2, Binding:1
NRP2	3	Binding:3
AHNAK	2	Binding:2
GFRA1	2	Binding:2
NOTCH2	2	Binding:2
TSC2	1	Binding:1
PGRMC2	1	Binding:1
LRBA	1	Binding:1
NCLN	1	Binding:1
CLUH	1	Binding:1
SERPINF1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RET	2.7.10.1	receptor protein-tyrosine kinase
CREBBP	2.3.1.48	histone acetyltransferase
DPYD	1.3.1.2	dihydropyrimidine dehydrogenase (NADP+)
KDR	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
RET	1,586
IRAK3	147
CREBBP	687
KDR	2,687

Pharmacogenomics

Cohort genes with a PharmGKB record: 37; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
DPYD	1

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
PONATINIB	4	KDR, RET
AFATINIB	4	RET
VEMURAFENIB	4	KDR, RET
FEDRATINIB	4	IRAK3, KDR, RET
TIVOZANIB	4	KDR, RET
LENVATINIB	4	KDR, RET
AXITINIB	4	KDR, RET
SORAFENIB	4	KDR, RET
DASATINIB ANHYDROUS	4	RET
ALECTINIB	4	KDR, RET
RUXOLITINIB	4	RET
INFIGRATINIB PHOSPHATE	4	KDR, RET
INFIGRATINIB	4	KDR, RET
IBRUTINIB	4	KDR, RET
PALBOCICLIB	4	RET
REGORAFENIB	4	KDR, RET
ENTRECTINIB	4	KDR, RET
TOFACITINIB CITRATE	4	RET
FOSTAMATINIB	4	IRAK3, RET
CABOZANTINIB	4	KDR, RET
BARICITINIB	4	RET
TOFACITINIB	4	KDR, RET
CAPIVASERTIB	4	RET
CERITINIB	4	KDR, RET
VANDETANIB	4	KDR, RET
NILOTINIB	4	RET
BOSUTINIB	4	RET
GILTERITINIB	4	IRAK3, RET
BRIGATINIB	4	KDR, RET
UPADACITINIB	4	KDR, RET

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	4	RET, IRAK3, CREBBP, KDR
B	Phased (≥1) drug, not yet approved	3	TGFB2, CCR9, DPYD
C	Druggable family + PDB, no drug	2	CNTN5, NCLN
D	Druggable family + AlphaFold only, no drug	2	SEMA3D, OR1F1
E	Difficult family or no structure, no drug	26	THBS4, TSC2, NAV2, PGRMC2, LRBA, ZHX2, FAT3, TBATA, CLUH, DENND3 (+16 more)

Undrugged target profiles

30 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GDNF	0	RET
GFRA1	2	RET
SEMA3D	0	—
THBS4	0	—
TSC2	1	—
NAV2	0	—
PGRMC2	1	—
LRBA	1	—
ZHX2	0	—
CNTN5	0	—
FAT3	0	—
TBATA	0	—
NCLN	1	—
CLUH	1	—
DENND3	0	—
DYNC2H1	0	—
C10orf55	0	—
AHNAK	2	—
FBN1	0	—
GLI3	0	—
IHH	0	—
NOTCH2	2	—
NRP2	3	—
NTF3	0	—
NUP98	0	—
OR1F1	0	—
PCDHA4	0	—
SERPINF1	1	—
POLR2F	0	—
PTCH1	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 48.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	43
PHASE4	2
PHASE3	1
PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	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
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
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04622410	Not specified	RECRUITING	Registry for Hirschsprung Disease of the BELAPS
NCT05450991	Not specified	RECRUITING	Long-term Qualitative and Quantitative Outcomes of Children With Hirschsprung’s Disease and Anorectal Malformations
NCT06072976	Not specified	RECRUITING	The Influence of Feeding Source on the Gut Microbiome and Time to Full Feeds in Neonates With Congenital Gastrointestinal Pathologies
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)
NCT06650683	Not specified	RECRUITING	Impact of Providing Nursing Support on Parental Stress Related to Preoperative Care of a Newborn with Hirschsprung’s Disease
NCT07156981	Not specified	NOT_YET_RECRUITING	Effects of Physiotherapy in Children With Hirschsprung’s Disease
NCT07343622	Not specified	NOT_YET_RECRUITING	Robot/Laparoscopic-Assisted Transanal Transection Duhamel Versus Modified Soave Pull-Through for TCA
NCT07468565	Not specified	NOT_YET_RECRUITING	Surgical Approach for the Treatment of Hirschsprung Disease Using the Swenson Technique (SMILES)
NCT07519915	Not specified	RECRUITING	Improvement of Understanding of Pediatric Sacral Neuromodulation: Therapeutic Strategies and Outcome Variables
NCT07526636	Not specified	NOT_YET_RECRUITING	Pattern And Outcome Of Neonatal Gastrointestinal Emergencies In Assiut University Children Hospital
NCT01515501	Not specified	COMPLETED	Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial)
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
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

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
INDOCYANINE GREEN ACID FORM	4	3