Esophageal atresia

disease

On this page

Also known as congenital atresia of esophaguscongenital atresia of oesophaguscongenital esophageal atresiacongenital imperforate oesophagusesophageal atresia (disease)imperforate oesophagus

Summary

Esophageal atresia (MONDO:0001044) is a disease with 31 cohort genes and 32 clinical trials. Top therapeutic interventions include dextrose and fish oil triglycerides.

At a glance

Cohort genes: 31
ClinVar variants: 35
Clinical trials: 32

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	esophageal atresia
Mondo ID	MONDO:0001044
MeSH	D004933
DOID	DOID:10485
NCIT	C87072
SNOMED CT	26179002
UMLS	C0014850
MedGen	4545
Is cancer (heuristic)	no

Also known as: congenital atresia of esophagus · congenital atresia of oesophagus · congenital esophageal atresia · congenital imperforate oesophagus · esophageal atresia · esophageal atresia (disease) · imperforate oesophagus

Data availability: 35 ClinVar variants · 1 HPO phenotype · 3 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › upper digestive tract disorder › esophageal disorder › esophageal atresia

Subtypes (1): Arroyo Garcia Cimadevilla syndrome

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

35 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 2 likely pathogenic, 1 likely benign, 1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
638670	Single allele	APBA2	Pathogenic	no assertion criteria provided
4818856	NM_004247.4(EFTUD2):c.995-10T>A	EFTUD2	Likely pathogenic	criteria provided, single submitter
691346	NM_017633.3(TENT5A):c.65C>G (p.Pro22Arg)	TENT5A	Likely pathogenic	no assertion criteria provided
638671	GRCh37/hg19 15q26.3(chr15:100923767-101626187)	ALDH1A3	Uncertain significance	no assertion criteria provided
691340	NM_001387011.1(AMBRA1):c.431C>T (p.Ala144Val)	AMBRA1	Uncertain significance	no assertion criteria provided
691412	NM_152296.5(ATP1A3):c.1978C>A (p.Leu660Ile)	ATP1A3	Uncertain significance	no assertion criteria provided
691414	NM_001130021.3(ATP6V0A1):c.1340G>A (p.Arg447Gln)	ATP6V0A1	Uncertain significance	no assertion criteria provided
691415	NM_207322.3(C2CD4A):c.284A>C (p.His95Pro)	C2CD4A	Uncertain significance	no assertion criteria provided
691416	NM_000719.7(CACNA1C):c.5761C>T (p.Pro1921Ser)	CACNA1C	Uncertain significance	no assertion criteria provided
691419	NM_001256.6(CDC27):c.4A>G (p.Thr2Ala)	CDC27	Uncertain significance	no assertion criteria provided
691425	NM_198390.3(CMIP):c.1478C>G (p.Thr493Ser)	CMIP	Uncertain significance	no assertion criteria provided
1702962	NM_001377229.1(DISP1):c.4054C>T (p.Pro1352Ser)	DISP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
691431	NM_001382508.1(DROSHA):c.323G>A (p.Arg108Lys)	DROSHA	Uncertain significance	no assertion criteria provided
691432	NM_001389.5(DSCAM):c.4979T>A (p.Ile1660Asn)	DSCAM	Uncertain significance	no assertion criteria provided
691344	NM_001374736.1(DST):c.11993C>G (p.Ser3998Ter)	DST	Uncertain significance	no assertion criteria provided
691349	NM_198904.4(GABRG2):c.155A>G (p.Asn52Ser)	GABRG2	Uncertain significance	no assertion criteria provided
691355	NM_001007237.3(IGSF3):c.1841G>T (p.Arg614Leu)	IGSF3	Uncertain significance	no assertion criteria provided
691357	NM_000208.4(INSR):c.3364G>A (p.Ala1122Thr)	INSR	Uncertain significance	no assertion criteria provided
691359	NM_002211.4(ITGB1):c.2252G>A (p.Trp751Ter)	ITGB1	Uncertain significance	no assertion criteria provided
691364	NM_002235.5(KCNA6):c.233A>G (p.Asp78Gly)	KCNA6	Uncertain significance	no assertion criteria provided
691447	NM_012216.4(MID2):c.1757T>C (p.Ile586Thr)	LOC101928335	Uncertain significance	no assertion criteria provided
691452	NM_017617.5(NOTCH1):c.6032T>C (p.Leu2011Pro)	LOC126860794	Uncertain significance	no assertion criteria provided
691450	NM_153006.3(NAGS):c.1378C>G (p.Leu460Val)	NAGS	Uncertain significance	no assertion criteria provided
691367	NM_001104631.2(PDE4D):c.1339T>C (p.Tyr447His)	PDE4D	Uncertain significance	criteria provided, single submitter
691369	NM_006622.4(PLK2):c.1049C>T (p.Thr350Ile)	PLK2	Uncertain significance	no assertion criteria provided
691374	NM_001034853.2(RPGR):c.780G>T (p.Glu260Asp)	RPGR	Uncertain significance	no assertion criteria provided
691381	NM_006747.4(SIPA1):c.367A>G (p.Ser123Gly)	SIPA1	Uncertain significance	no assertion criteria provided
691386	NM_001288718.2(STAT5A):c.1279G>A (p.Ala427Thr)	STAT5A	Uncertain significance	no assertion criteria provided
691387	NM_001395460.1(TENM2):c.4165C>A (p.Leu1389Met)	TENM2	Uncertain significance	no assertion criteria provided
691345	NM_017633.3(TENT5A):c.64C>G (p.Pro22Ala)	TENT5A	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 55 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RPGR	Orphanet:1872	Cone rod dystrophy
RPGR	Orphanet:244	Primary ciliary dyskinesia
RPGR	Orphanet:247522	Primary ciliary dyskinesia-retinitis pigmentosa syndrome
RPGR	Orphanet:49382	Achromatopsia
RPGR	Orphanet:791	Retinitis pigmentosa
DST	Orphanet:314381	Hereditary sensory and autonomic neuropathy type 6
DST	Orphanet:412181	Epidermolysis bullosa simplex due to BP230 deficiency
TCF4	Orphanet:171	Primary sclerosing cholangitis
TCF4	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
TCF4	Orphanet:2896	Pitt-Hopkins syndrome
TCF4	Orphanet:98974	Fuchs endothelial corneal dystrophy
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
CACNA1C	Orphanet:101016	Romano-Ward syndrome
CACNA1C	Orphanet:130	Brugada syndrome
CACNA1C	Orphanet:528084	Non-specific syndromic intellectual disability
CACNA1C	Orphanet:595098	Timothy syndrome type 1
CACNA1C	Orphanet:595105	Timothy syndrome type 2
CACNA1C	Orphanet:595109	Atypical Timothy syndrome
NAGS	Orphanet:927	Hyperammonemia due to N-acetylglutamate synthase deficiency
TENT5A	Orphanet:216812	Osteogenesis imperfecta type 3
DISP1	Orphanet:220386	Semilobar holoprosencephaly
DISP1	Orphanet:280195	Septopreoptic holoprosencephaly
DISP1	Orphanet:280200	Microform holoprosencephaly
DISP1	Orphanet:93924	Lobar holoprosencephaly
DISP1	Orphanet:93925	Alobar holoprosencephaly
DISP1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
EFTUD2	Orphanet:79113	Mandibulofacial dysostosis-microcephaly syndrome
GABRG2	Orphanet:1945	Self-limited epilepsy with centrotemporal spikes
GABRG2	Orphanet:33069	Dravet syndrome
GABRG2	Orphanet:36387	Genetic epilepsy with febrile seizure plus
GABRG2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
GABRG2	Orphanet:64280	Childhood absence epilepsy
ALDH1A3	Orphanet:35612	Nanophthalmos
ALDH1A3	Orphanet:98938	Colobomatous microphthalmia
IGSF3	Orphanet:451612	Familial congenital nasolacrimal duct obstruction
INSR	Orphanet:2297	Insulin-resistance syndrome type A
INSR	Orphanet:263458	Hyperinsulinism due to INSR deficiency
INSR	Orphanet:508	Donohue syndrome
INSR	Orphanet:769	Rabson-Mendenhall syndrome
KCNN3	Orphanet:3473	Zimmermann-Laband syndrome
ATP1A3	Orphanet:1171	Cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss syndrome
ATP1A3	Orphanet:2131	Alternating hemiplegia of childhood

Cohort genes → proteins

31 cohort genes, 31 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	31

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPGR	HGNC:10295	ENSG00000156313	Q92834	X-linked retinitis pigmentosa GTPase regulator	clinvar
SIPA1	HGNC:10885	ENSG00000213445	Q96FS4	Signal-induced proliferation-associated protein 1	clinvar
DST	HGNC:1090	ENSG00000151914	Q03001	Dystonin	clinvar
STAT5A	HGNC:11366	ENSG00000126561	P42229	Signal transducer and activator of transcription 5A	clinvar
TCF4	HGNC:11634	ENSG00000196628	P15884	Transcription factor 4	clinvar
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
CACNA1C	HGNC:1390	ENSG00000151067	Q13936	Voltage-dependent L-type calcium channel subunit alpha-1C	clinvar
WDR13	HGNC:14352	ENSG00000101940	Q9H1Z4	WD repeat-containing protein 13	clinvar
CDC27	HGNC:1728	ENSG00000004897	P30260	Cell division cycle protein 27 homolog	clinvar
DROSHA	HGNC:17904	ENSG00000113360	Q9NRR4	Ribonuclease 3	clinvar
NAGS	HGNC:17996	ENSG00000161653	Q8N159	N-acetylglutamate synthase, mitochondrial	clinvar
TENT5A	HGNC:18345	ENSG00000112773	Q96IP4	Terminal nucleotidyltransferase 5A	clinvar
PLK2	HGNC:19699	ENSG00000145632	Q9NYY3	Serine/threonine-protein kinase PLK2	clinvar
DISP1	HGNC:19711	ENSG00000154309	Q96F81	Protein dispatched homolog 1	clinvar
CMIP	HGNC:24319	ENSG00000153815	Q8IY22	C-Maf-inducing protein	clinvar
AMBRA1	HGNC:25990	ENSG00000110497	Q9C0C7	Activating molecule in BECN1-regulated autophagy protein 1	clinvar
TENM2	HGNC:29943	ENSG00000145934	Q9NT68	Teneurin-2	clinvar
DSCAM	HGNC:3039	ENSG00000171587	O60469	Cell adhesion molecule DSCAM	clinvar
EFTUD2	HGNC:30858	ENSG00000108883	Q15029	116 kDa U5 small nuclear ribonucleoprotein component	clinvar
C2CD4A	HGNC:33627	ENSG00000198535	Q8NCU7	C2 calcium-dependent domain-containing protein 4A	clinvar
GABRG2	HGNC:4087	ENSG00000113327	P18507	Gamma-aminobutyric acid receptor subunit gamma-2	clinvar
ALDH1A3	HGNC:409	ENSG00000184254	P47895	Retinaldehyde dehydrogenase 3	clinvar
APBA2	HGNC:579	ENSG00000034053	Q99767	Amyloid-beta A4 precursor protein-binding family A member 2	clinvar
IGSF3	HGNC:5950	ENSG00000143061	O75054	Immunoglobulin superfamily member 3	clinvar
INSR	HGNC:6091	ENSG00000171105	P06213	Insulin receptor	clinvar
ITGB1	HGNC:6153	ENSG00000150093	P05556	Integrin beta-1	clinvar
KCNA6	HGNC:6225	ENSG00000151079	P17658	Potassium voltage-gated channel subfamily A member 6	clinvar
KCNN3	HGNC:6292	ENSG00000143603	Q9UGI6	Small conductance calcium-activated potassium channel protein 3	clinvar
ATP1A3	HGNC:801	ENSG00000105409	P13637	Sodium/potassium-transporting ATPase subunit alpha-3	clinvar
ATP6V0A1	HGNC:865	ENSG00000033627	Q93050	V-type proton ATPase 116 kDa subunit a 1	clinvar
PDE4D	HGNC:8783	ENSG00000113448	Q08499	3’,5’-cyclic-AMP phosphodiesterase 4D	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPGR	X-linked retinitis pigmentosa GTPase regulator	Acts as a guanine-nucleotide releasing factor (GEF) for RAB8A and RAB37 by promoting the conversion of inactive RAB-GDP to the active form RAB-GTP.
SIPA1	Signal-induced proliferation-associated protein 1	GTPase activator for the nuclear Ras-related regulatory proteins Rap1 and Rap2 in vitro, converting them to the putatively inactive GDP-bound state.
DST	Dystonin	Cytoskeletal linker protein.
STAT5A	Signal transducer and activator of transcription 5A	Carries out a dual function: signal transduction and activation of transcription.
TCF4	Transcription factor 4	Transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5-motif.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
CACNA1C	Voltage-dependent L-type calcium channel subunit alpha-1C	Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.
CDC27	Cell division cycle protein 27 homolog	Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.
DROSHA	Ribonuclease 3	Ribonuclease III double-stranded (ds) RNA-specific endoribonuclease that is involved in the initial step of microRNA (miRNA) biogenesis.
NAGS	N-acetylglutamate synthase, mitochondrial	Plays a role in the regulation of ureagenesis by producing the essential cofactor N-acetylglutamate (NAG), thus modulating carbamoylphosphate synthase I (CPS1) activity.
TENT5A	Terminal nucleotidyltransferase 5A	Cytoplasmic non-canonical poly(A) RNA polymerase that catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3’-OH terminal group and participates in the cytoplasmic polyadenylation.
PLK2	Serine/threonine-protein kinase PLK2	Tumor suppressor serine/threonine-protein kinase involved in synaptic plasticity, centriole duplication and G1/S phase transition.
DISP1	Protein dispatched homolog 1	Functions in hedgehog (Hh) signaling.
CMIP	C-Maf-inducing protein	Plays a role in T-cell signaling pathway.
AMBRA1	Activating molecule in BECN1-regulated autophagy protein 1	Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy.
TENM2	Teneurin-2	Involved in neural development, regulating the establishment of proper connectivity within the nervous system.
DSCAM	Cell adhesion molecule DSCAM	Cell adhesion molecule that plays a role in neuronal self-avoidance.
EFTUD2	116 kDa U5 small nuclear ribonucleoprotein component	Required for pre-mRNA splicing as component of the spliceosome, including pre-catalytic, catalytic and post-catalytic spliceosomal complexes.
C2CD4A	C2 calcium-dependent domain-containing protein 4A	May be involved in inflammatory process.
GABRG2	Gamma-aminobutyric acid receptor subunit gamma-2	Gamma subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.
ALDH1A3	Retinaldehyde dehydrogenase 3	Catalyzes the NAD-dependent oxidation of aldehyde substrates, such as all-trans-retinal and all-trans-13,14-dihydroretinal, to their corresponding carboxylic acids, all-trans-retinoate and all-trans-13,14-dihydroretinoate, respectively.
APBA2	Amyloid-beta A4 precursor protein-binding family A member 2	Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery.
INSR	Insulin receptor	Receptor tyrosine kinase which mediates the pleiotropic actions of insulin.
ITGB1	Integrin beta-1	Integrins alpha-1/beta-1, alpha-2/beta-1, alpha-10/beta-1 and alpha-11/beta-1 are receptors for collagen.
KCNA6	Potassium voltage-gated channel subfamily A member 6	Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes.
KCNN3	Small conductance calcium-activated potassium channel protein 3	Small conductance calcium-activated potassium channel that mediates the voltage-independent transmembrane transfer of potassium across the cell membrane through a constitutive interaction with calmodulin which binds the intracellular calci…
ATP1A3	Sodium/potassium-transporting ATPase subunit alpha-3	This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane.
ATP6V0A1	V-type proton ATPase 116 kDa subunit a 1	Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that transports protons across cellular membranes.
PDE4D	3’,5’-cyclic-AMP phosphodiesterase 4D	Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.

Protein-family classification

Druggable: 12 · Difficult: 8 · Unknown: 11 · Druggable fraction: 0.39

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
Ion channel	3	10.8×	0.019
Scaffold/PPI	5	2.8×	0.109
Kinase	3	2.7×	0.233
Antibody/Immunoglobulin	2	1.9×	0.402
Enzyme (other)	4	1.6×	0.402
Transcription factor	3	0.8×	0.866
Other/Unknown	11	0.6×	0.993

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPGR	Other/Unknown	no		Reg_chr_condens, RCC1/BLIP-II, Signaling_Regulatory_Domain
SIPA1	Scaffold/PPI	no		Rap/Ran_GAP_dom, PDZ, Rap/Ran-GAP_sf
DST	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
STAT5A	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
TCF4	Transcription factor	no	7.6.2.3	bHLH_dom, HLH_DNA-bd_sf, NeuroDiff_E-box_TFs
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
CACNA1C	Ion channel	yes		VDCCAlpha1, VDCC_L_a1su, VDCC_L_a1csu
WDR13	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_dom_sf
CDC27	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt
DROSHA	Enzyme (other)	yes	3.1.26.3	RNase_III_dom, RNase_III, dsRBD_dom
NAGS	Kinase	yes	2.3.1.1	GNAT_dom, Asp/Glu/Uridylate_kinase, Vertebrate-like_GNAT_dom
TENT5A	Enzyme (other)	yes	2.7.7.19	TET5
PLK2	Kinase	yes	2.7.11.21	Prot_kinase_dom, POLO_box_dom, Ser/Thr_kinase_AS
DISP1	Other/Unknown	no		SSD, MMPL_dom, Dispatched_Hh_regulator
CMIP	Other/Unknown	no		LRR_dom_sf, CMIP, PH_CMIP
AMBRA1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
TENM2	Other/Unknown	no		EGF, EGF-like_Ca-bd_dom, YD
DSCAM	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
EFTUD2	Other/Unknown	no		EFG_V-like, T_Tr_GTP-bd_dom, EFTu-like_2
C2CD4A	Other/Unknown	no		C2_dom, C2_domain_sf, C2_Ca-dependent_4
GABRG2	Other/Unknown	no		GABRG-1/4, GABBAg2_rcpt, GABAA/Glycine_rcpt
ALDH1A3	Enzyme (other)	yes	1.2.1.5	Aldehyde_DH_dom, Ald_DH_CS_CYS, Ald_DH/histidinol_DH
APBA2	Scaffold/PPI	no		PDZ, PTB/PI_dom, PH-like_dom_sf
IGSF3	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
INSR	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
ITGB1	Other/Unknown	no		Integrin_bsu_VWA, Integrin_bsu_tail, EGF_extracell
KCNA6	Ion channel	yes		BTB/POZ_dom, T1-type_BTB, K_chnl_volt-dep_Kv
KCNN3	Ion channel	yes		CaM-bd_dom, K_chnl_dom, K_chnl_Ca-activ_SK
ATP1A3	Transcription factor	no		P_typ_ATPase, ATPase_P-typ_cation-transptr_N, P-type_ATPase_IIC
ATP6V0A1	Other/Unknown	no		V-ATPase_116kDa_su, V-type_ATPase_116kDa_su_euka
PDE4D	Enzyme (other)	yes	3.1.4.53	PDEase_catalytic_dom, PDEase, PDEase_CS

Expression context

Cohort genes with no expression data: 0.

29 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)	31
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	5
apex of heart	3
superior frontal gyrus	3
right uterine tube	2
granulocyte	2
spleen	2
medial globus pallidus	2
endothelial cell	2
pericardium	2
buccal mucosa cell	2
oocyte	2
secondary oocyte	2
ventricular zone	2
ileal mucosa	2
male germ line stem cell (sensu Vertebrata) in testis	2
middle temporal gyrus	2
palpebral conjunctiva	2
right hemisphere of cerebellum	2
visceral pleura	2
bronchial epithelial cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPGR	281	ubiquitous	marker	sperm, bronchial epithelial cell, right uterine tube
SIPA1	191	ubiquitous	marker	granulocyte, spleen, lower esophagus mucosa
DST	305	ubiquitous	marker	corpus callosum, calcaneal tendon, medial globus pallidus
STAT5A	190	ubiquitous	marker	granulocyte, monocyte, leukocyte
TCF4	292	ubiquitous	marker	endothelial cell, skin of hip, pericardium
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
CACNA1C	134	broad	marker	apex of heart, right coronary artery, muscle layer of sigmoid colon
WDR13	292	ubiquitous	marker	body of pancreas, apex of heart, right uterine tube
CDC27	293	ubiquitous	marker	secondary oocyte, buccal mucosa cell, oocyte
DROSHA	283	ubiquitous	marker	endothelial cell, ventricular zone, germinal epithelium of ovary
NAGS	160	broad	marker	ileal mucosa, right lobe of liver, jejunal mucosa
TENT5A	270	ubiquitous	marker	parotid gland, tibia, pericardium
PLK2	289	ubiquitous	marker	spleen, apex of heart, cortical plate
DISP1	221	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, right testis, left testis
CMIP	247	ubiquitous	marker	kidney epithelium, pancreatic ductal cell, ileal mucosa
AMBRA1	279	ubiquitous	marker	oocyte, secondary oocyte, cervix squamous epithelium
TENM2	207	broad	marker	left ventricle myocardium, cardiac muscle of right atrium, middle temporal gyrus
DSCAM	83	broad	marker	endometrium epithelium, cortical plate, lateral nuclear group of thalamus
EFTUD2	253	ubiquitous	marker	bone marrow cell, tibialis anterior, ventricular zone
C2CD4A	126	broad	marker	islet of Langerhans, epithelial cell of pancreas, cartilage tissue
GABRG2	174	tissue_specific	marker	middle temporal gyrus, Brodmann (1909) area 23, superior frontal gyrus
ALDH1A3	244	ubiquitous	marker	palpebral conjunctiva, pigmented layer of retina, parietal pleura
APBA2	131	ubiquitous	marker	superior frontal gyrus, right hemisphere of cerebellum, cerebellum
IGSF3	265	ubiquitous	marker	cortical plate, tongue squamous epithelium, gingival epithelium
INSR	296	ubiquitous	marker	buccal mucosa cell, palpebral conjunctiva, visceral pleura
ITGB1	303	ubiquitous	marker	visceral pleura, seminal vesicle, pleura
KCNA6	123	tissue_specific	yes	cortical plate, male germ line stem cell (sensu Vertebrata) in testis, prefrontal cortex
KCNN3	227	broad	marker	lateral globus pallidus, substantia nigra pars reticulata, medial globus pallidus
ATP1A3	129	broad	marker	superior frontal gyrus, primary visual cortex, cortical plate
ATP6V0A1	287	ubiquitous	marker	right frontal lobe, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 4.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
EFTUD2	8,471
DROSHA	6,846
TERT	5,717
ITGB1	5,325
CDC27	5,006
INSR	4,446
AMBRA1	4,380
STAT5A	4,153
ALDH1A3	4,146
ATP1A3	3,876

Intra-cohort edges

A	B	Sources
CACNA1C	CMIP	intact
DSCAM	DST	biogrid_interaction
DSCAM	WDR13	intact
INSR	TENT5A	intact

Structural data

PDB: 23 · AlphaFold-only: 8 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDE4D	Q08499	122
INSR	P06213	88
GABRG2	P18507	75
EFTUD2	Q15029	68
CACNA1C	Q13936	33
CDC27	P30260	25
TERT	O14746	23
ITGB1	P05556	22
DROSHA	Q9NRR4	12
ALDH1A3	P47895	10
PLK2	Q9NYY3	7
ATP6V0A1	Q93050	7
STAT5A	P42229	5
TCF4	P15884	5
ATP1A3	P13637	5
DISP1	Q96F81	4
RPGR	Q92834	3
DST	Q03001	2
TENT5A	Q96IP4	2
AMBRA1	Q9C0C7	2
TENM2	Q9NT68	2
NAGS	Q8N159	1
DSCAM	O60469	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
IGSF3	O75054	81.81
WDR13	Q9H1Z4	79.85
CMIP	Q8IY22	79.52
KCNA6	P17658	75.42
SIPA1	Q96FS4	72.20
KCNN3	Q9UGI6	68.54
APBA2	Q99767	59.74
C2CD4A	Q8NCU7	59.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 227. Enrichment computed across 31 evidence-associated genes (23 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 23 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NAGS variants cause NAGS deficiency	1	496.5×	0.076	NAGS
Developmental Lineage of Mammary Stem Cells	2	66.2×	0.076	ALDH1A3, ITGB1
Developmental Lineage of Mammary Gland Myoepithelial Cells	2	47.3×	0.076	ALDH1A3, ITGB1
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	2	39.7×	0.076	ALDH1A3, ITGB1
Insulin receptor recycling	2	33.1×	0.076	INSR, ATP6V0A1
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	2	31.0×	0.076	ITGB1, PDE4D
Signaling by ERBB4	2	23.6×	0.103	STAT5A, GABRG2
Localization of the PINCH-ILK-PARVIN complex to focal adhesions	1	124.1×	0.134	ITGB1
DSCAM interactions	1	99.3×	0.134	DSCAM
IRS activation	1	99.3×	0.134	INSR
MET interacts with TNS proteins	1	99.3×	0.134	ITGB1
Erythropoietin activates STAT5	1	70.9×	0.134	STAT5A
STAT5 Activation	1	70.9×	0.134	STAT5A
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	70.9×	0.134	TERT
CHL1 interactions	1	55.2×	0.134	ITGB1
Interleukin-9 signaling	1	55.2×	0.134	STAT5A
Ca2+ activated K+ channels	1	49.6×	0.134	KCNN3
FGFR1 mutant receptor activation	1	49.6×	0.134	STAT5A
Interleukin-21 signaling	1	49.6×	0.134	STAT5A
CD163 mediating an anti-inflammatory response	1	49.6×	0.134	PLK2
Signaling by KIT in disease	1	49.6×	0.134	STAT5A
FLT3 signaling in disease	1	49.6×	0.134	STAT5A
STAT5 activation downstream of FLT3 ITD mutants	1	49.6×	0.134	STAT5A
Signaling by Leptin	1	45.1×	0.134	STAT5A
Type I hemidesmosome assembly	1	45.1×	0.134	DST
Signal attenuation	1	45.1×	0.134	INSR
Signaling by Erythropoietin	1	45.1×	0.134	STAT5A
Interleukin-2 signaling	1	41.4×	0.134	STAT5A
Urea cycle	1	38.2×	0.134	NAGS
Signaling by Insulin receptor	1	38.2×	0.134	INSR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 31 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
RNA-templated transcription	1	543.6×	0.050	TERT
patched ligand maturation	1	543.6×	0.050	DISP1
nucleus accumbens development	1	543.6×	0.050	ALDH1A3
DNA strand elongation	1	543.6×	0.050	TERT
myoblast fate specification	1	543.6×	0.050	ITGB1
siRNA transcription	1	543.6×	0.050	TERT
positive regulation of transdifferentiation	1	543.6×	0.050	TERT
optic cup morphogenesis involved in camera-type eye development	1	271.8×	0.050	ALDH1A3
RNA-templated DNA biosynthetic process	1	271.8×	0.050	TERT
regulation of collagen catabolic process	1	271.8×	0.050	ITGB1
positive regulation of hair cycle	1	271.8×	0.050	TERT
positive regulation of meiotic cell cycle	1	271.8×	0.050	INSR
positive regulation of glutamate uptake involved in transmission of nerve impulse	1	271.8×	0.050	ITGB1
post-embryonic retina morphogenesis in camera-type eye	1	271.8×	0.050	DSCAM
positive regulation of mast cell differentiation	1	271.8×	0.050	STAT5A
cardiac cell fate specification	1	271.8×	0.050	ITGB1
negative regulation of relaxation of cardiac muscle	1	271.8×	0.050	PDE4D
positive regulation of free ubiquitin chain polymerization	1	271.8×	0.050	AMBRA1
regulation of female gonad development	1	271.8×	0.050	INSR
regulation of vascular permeability involved in acute inflammatory response	1	181.2×	0.050	C2CD4A
L-arginine biosynthetic process	1	181.2×	0.050	NAGS
negative regulation of mast cell apoptotic process	1	181.2×	0.050	STAT5A
cellular response to water deprivation	1	181.2×	0.050	SIPA1
development of animal secondary female sexual characteristics	1	181.2×	0.050	STAT5A
development of animal secondary male sexual characteristics	1	181.2×	0.050	STAT5A
olfactory pit development	1	181.2×	0.050	ALDH1A3
calcium ion transmembrane transport via high voltage-gated calcium channel	1	181.2×	0.050	CACNA1C
protein-DNA complex assembly	1	181.2×	0.050	TCF4
negative regulation of apoptotic process in bone marrow cell	1	181.2×	0.050	PLK2
membrane depolarization during atrial cardiac muscle cell action potential	1	181.2×	0.050	CACNA1C

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Fish Oil Triglycerides, Soybean Oil.

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 10 · Phased (≥1): 12 · Undrugged: 19

Druggability breadth: 14 of 31 evidence-associated genes (45%) 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
STAT5A	MOMELOTINIB
TERT	BERBERINE
CACNA1C	REMIFENTANIL
PLK2	FEDRATINIB
GABRG2	ENZALUTAMIDE
INSR	FEDRATINIB
KCNN3	DEQUALINIUM CHLORIDE
ATP1A3	OMEPRAZOLE
PDE4D	INAMRINONE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDE4D	269	4
CACNA1C	85	4
GABRG2	55	4
INSR	36	4
PLK2	12	4
TERT	10	4
ATP1A3	5	4
STAT5A	4	4
ITGB1	4	3
KCNN3	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	STAT5A
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
REMIFENTANIL	4	CACNA1C
BEPRIDIL	4	CACNA1C
CLOTRIMAZOLE	4	CACNA1C
PROPIVERINE	4	CACNA1C
DIBUCAINE	4	CACNA1C
IMIPRAMINE	4	CACNA1C
DULOXETINE	4	CACNA1C
QUINIDINE	4	CACNA1C
ESTRADIOL	4	CACNA1C
TOLTERODINE	4	CACNA1C
PIMOZIDE	4	CACNA1C
NIMODIPINE	4	CACNA1C, PDE4D
NICARDIPINE	4	CACNA1C
AMLODIPINE	4	CACNA1C
VARDENAFIL	4	CACNA1C, PDE4D
CLEMASTINE	4	CACNA1C
ISRADIPINE	4	CACNA1C, PDE4D
TERFENADINE	4	CACNA1C
NISOLDIPINE	4	CACNA1C, PDE4D
SOLIFENACIN	4	CACNA1C
PINAVERIUM	4	CACNA1C
SILDENAFIL	4	CACNA1C, PDE4D
NIFEDIPINE	4	CACNA1C
XANOMELINE	4	CACNA1C
DILTIAZEM	4	CACNA1C
PRENYLAMINE	4	CACNA1C
OLICERIDINE	4	CACNA1C

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 8.

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

Symbol	Assays	Type breakdown
GABRG2	1,155	Binding:940, Functional:201, ADMET:10, Toxicity:4
INSR	954	Binding:900, Functional:49, ADMET:4, Toxicity:1
PDE4D	863	Binding:805, Functional:33, ADMET:23, Toxicity:2
CACNA1C	575	Binding:319, Functional:211, Toxicity:26, ADMET:19
ITGB1	409	Binding:376, Functional:32, ADMET:1
TERT	391	Binding:389, Functional:2
PLK2	270	Binding:268, ADMET:1, Functional:1
STAT5A	199	Binding:199
ALDH1A3	55	Binding:55
KCNN3	51	Binding:51
ATP1A3	45	Binding:45
TCF4	31	Binding:31
KCNA6	29	Binding:24, Functional:3, Toxicity:1, ADMET:1
EFTUD2	8	Binding:8

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TCF4	7.6.2.3	ABC-type glutathione-S-conjugate transporter
DROSHA	3.1.26.3	ribonuclease III
NAGS	2.3.1.1	amino-acid N-acetyltransferase
TENT5A	2.7.7.19	polynucleotide adenylyltransferase
PLK2	2.7.11.21	polo kinase
ALDH1A3	1.2.1.5	aldehyde dehydrogenase [NAD(P)+]
INSR	2.7.10.1	receptor protein-tyrosine kinase
PDE4D	3.1.4.53	3’,5’-cyclic-AMP phosphodiesterase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
STAT5A	199
TERT	391
CACNA1C	575
PLK2	270
GABRG2	1,155
INSR	954
ITGB1	409
PDE4D	863

Pharmacogenomics

Cohort genes with a PharmGKB record: 31; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

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)
MOMELOTINIB	4	STAT5A
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
REMIFENTANIL	4	CACNA1C
BEPRIDIL	4	CACNA1C
CLOTRIMAZOLE	4	CACNA1C
PROPIVERINE	4	CACNA1C
DIBUCAINE	4	CACNA1C
IMIPRAMINE	4	CACNA1C
DULOXETINE	4	CACNA1C
QUINIDINE	4	CACNA1C
ESTRADIOL	4	CACNA1C
TOLTERODINE	4	CACNA1C
PIMOZIDE	4	CACNA1C
NIMODIPINE	4	CACNA1C, PDE4D
NICARDIPINE	4	CACNA1C
AMLODIPINE	4	CACNA1C
VARDENAFIL	4	CACNA1C, PDE4D
CLEMASTINE	4	CACNA1C
ISRADIPINE	4	CACNA1C, PDE4D
TERFENADINE	4	CACNA1C
NISOLDIPINE	4	CACNA1C, PDE4D
SOLIFENACIN	4	CACNA1C
PINAVERIUM	4	CACNA1C
SILDENAFIL	4	CACNA1C, PDE4D
NIFEDIPINE	4	CACNA1C
XANOMELINE	4	CACNA1C
DILTIAZEM	4	CACNA1C
PRENYLAMINE	4	CACNA1C
OLICERIDINE	4	CACNA1C

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	9	STAT5A, TERT, CACNA1C, PLK2, GABRG2, INSR, KCNN3, ATP1A3, PDE4D
B	Phased (≥1) drug, not yet approved	3	TCF4, EFTUD2, ITGB1
C	Druggable family + PDB, no drug	5	DROSHA, NAGS, TENT5A, DSCAM, ALDH1A3
D	Druggable family + AlphaFold only, no drug	2	IGSF3, KCNA6
E	Difficult family or no structure, no drug	12	RPGR, SIPA1, DST, WDR13, CDC27, DISP1, CMIP, AMBRA1, TENM2, C2CD4A (+2 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RPGR	0	—
SIPA1	0	—
DST	0	—
WDR13	0	—
CDC27	0	—
DROSHA	0	—
NAGS	0	—
TENT5A	0	—
DISP1	0	—
CMIP	0	—
AMBRA1	0	—
TENM2	0	—
DSCAM	0	—
C2CD4A	0	—
ALDH1A3	55	—
APBA2	0	—
IGSF3	0	—
KCNA6	29	—
ATP6V0A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 32.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	30
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00226044	PHASE3	COMPLETED	Rectal and Oral Omeprazole Treatment of Reflux Disease in Infants.
NCT03127345	PHASE2	WITHDRAWN	Omega 3 Fatty Acid Treatment for Pediatric Musculoskeletal Health
NCT03730454	Not specified	ACTIVE_NOT_RECRUITING	Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair
NCT04522193	Not specified	RECRUITING	Dumping Syndrome and Esophageal Atresia
NCT05995171	Not specified	RECRUITING	Long Term Outcome of Easophageal Atresia : Transmics Profiles in Adolescence
NCT06335862	Not specified	ENROLLING_BY_INVITATION	Primary Posterior Tracheopexy Prevents Tracheal Collapse
NCT06731855	Not specified	RECRUITING	An Exploratory Physiological Study of Post-operative Recovery in Surgical Neonates and Dimethylarginine:Arginine Levels
NCT06860919	Not specified	RECRUITING	Prospective Evaluation of the Results of Multidisciplinary Follow-up After a Transitional Consultation for Esophageal Atresia
NCT06975982	Not specified	RECRUITING	Symptoms, Pulmonary Function, Muscle Strength, Exercise Capacity, and Frailty in Esophageal Atresia vs. Healthy Peers
NCT07100379	Not specified	RECRUITING	Balloon Inflation Time for Esophageal Strictures (BITES): A Randomized Multi-Center Study
NCT07210736	Not specified	NOT_YET_RECRUITING	Brazilian Multicenter Study on Esophageal Atresia
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02466451	Not specified	COMPLETED	Study in Children With the Diagnosis of Congenital Diaphragmatic Hernia (CDH) and Oesophageal Atresia (EA)
NCT02525705	Not specified	COMPLETED	Dumping Syndrome After Operation of Esophageal Atresia Type III
NCT02883725	Not specified	COMPLETED	National Register of Oesophageal Atresia
NCT03023865	Not specified	UNKNOWN	Individualized Management for Long Gap Esophageal Atresia
NCT03415893	Not specified	COMPLETED	High-resolution Esophageal Manometry
NCT03455881	Not specified	UNKNOWN	Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
NCT03615495	Not specified	COMPLETED	Flourish™ Pediatric Esophageal Atresia
NCT03619408	Not specified	UNKNOWN	Management of Esophagitis Following Repair of Esophageal Atresia
NCT03666767	Not specified	COMPLETED	Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries
NCT03767673	Not specified	UNKNOWN	Cardiorespiratory Performance and Pulmonary Microbiome in Patients After Repair of Esophageal Atresia
NCT03999008	Not specified	UNKNOWN	Oral Viscous Budesonide in Anastomotic Stricture After Esophageal Atresia Repair (OVB in EA)
NCT04072419	Not specified	UNKNOWN	Application of Enhanced Recovery After Surgery for Congenital Esophageal Atresia During Perioperative Period
NCT04136795	Not specified	UNKNOWN	Evaluation of the Respiratory Impact After Conventional or Minimally Invasive Esophageal Atresia Surgery
NCT04259528	Not specified	UNKNOWN	Endoscopic Ultrasound Findings in Esophageal Atresia Following Surgical Repair
NCT04901546	Not specified	COMPLETED	Esophageal Atresia: a Natural Experiment of the Effects of Oral Inoculation on the Gut Microbiome
NCT04932746	Not specified	COMPLETED	The Effect of Dexmedetomidine on Oxygen During One Lung Ventilation in Pediatric Surgery.
NCT05129930	Not specified	COMPLETED	Fluid Overload and Pulmonary Function
NCT05527873	Not specified	COMPLETED	Respiratory Complications of Operated Esophageal Atresia in Children
NCT06073158	Not specified	COMPLETED	Molecular Signatures of Esophageal Atresia
NCT06208449	Not specified	UNKNOWN	Robotic Versus Thoracoscopy Versus Thoracotomy Repair for Congenital Esophageal Atresia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DEXTROSE	4	1
FISH OIL TRIGLYCERIDES	4	1

Cohort genes: RPGR, SIPA1, DST, STAT5A, TCF4, TERT, CACNA1C, WDR13, CDC27, DROSHA, NAGS, TENT5A, PLK2, DISP1, CMIP, AMBRA1, TENM2, DSCAM, EFTUD2, C2CD4A, GABRG2, ALDH1A3, APBA2, IGSF3, INSR, ITGB1, KCNA6, KCNN3, ATP1A3, ATP6V0A1, PDE4D
Drugs: Dextrose, Fish Oil Triglycerides