NCLN

Summary

NCLN (nicalin, HGNC:26923) is a protein-coding gene on chromosome 19p13.3, encoding BOS complex subunit NCLN (Q969V3). Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes.

Enables ribosome binding activity. Involved in several processes, including multi-pass transmembrane protein insertion into ER membrane; protein stabilization; and regulation of protein complex stability. Located in endoplasmic reticulum membrane. Part of multi-pass translocon complex.

Source: NCBI Gene 56926 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 101 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_020170

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26923
Approved symbol	NCLN
Name	nicalin
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	NICALIN, NET59
Ensembl gene	ENSG00000125912
Ensembl biotype	protein_coding
OMIM	609156
Entrez	56926

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 14 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000246117, ENST00000586904, ENST00000587740, ENST00000588428, ENST00000590671, ENST00000591062, ENST00000592235, ENST00000592737, ENST00000862159, ENST00000862160, ENST00000862161, ENST00000922663, ENST00000922664, ENST00000922665, ENST00000922666, ENST00000952693, ENST00000952694

RefSeq mRNA: 2 — MANE Select: NM_020170 NM_001321463, NM_020170

CCDS: CCDS32869

Canonical transcript exons

ENST00000246117 — 15 exons

Exon	Start	End
ENSE00000859545	3196183	3196277
ENSE00000859546	3198817	3198897
ENSE00000859547	3201523	3201626
ENSE00000859548	3203756	3203844
ENSE00000859549	3204005	3204144
ENSE00000951267	3193284	3193428
ENSE00000951268	3204573	3204751
ENSE00000951269	3205939	3206026
ENSE00000951271	3206262	3206425
ENSE00000951273	3207391	3207469
ENSE00002864069	3185930	3186214
ENSE00002922567	3207629	3209575
ENSE00003585406	3207198	3207251
ENSE00003668359	3206152	3206190
ENSE00003692163	3192470	3192660

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 96.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.1014 / max 155.0658, expressed in 1813 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173156	28.7307	1812
173157	1.0100	591
173158	0.7776	437
173155	0.5831	359

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	96.02	gold quality
stromal cell of endometrium	CL:0002255	94.55	gold quality
left adrenal gland	UBERON:0001234	93.71	gold quality
right adrenal gland	UBERON:0001233	93.58	gold quality
left adrenal gland cortex	UBERON:0035825	93.54	gold quality
right adrenal gland cortex	UBERON:0035827	93.18	gold quality
lower esophagus mucosa	UBERON:0035834	92.18	gold quality
body of pancreas	UBERON:0001150	92.13	gold quality
adrenal gland	UBERON:0002369	91.97	gold quality
right lobe of liver	UBERON:0001114	91.81	gold quality
granulocyte	CL:0000094	91.72	gold quality
transverse colon	UBERON:0001157	91.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.09	gold quality
adrenal cortex	UBERON:0001235	90.92	gold quality
cerebellar hemisphere	UBERON:0002245	90.60	gold quality
upper lobe of left lung	UBERON:0008952	90.58	gold quality
adrenal tissue	UBERON:0018303	90.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.46	gold quality
cerebellar cortex	UBERON:0002129	90.24	gold quality
apex of heart	UBERON:0002098	90.07	gold quality
body of stomach	UBERON:0001161	89.79	gold quality
upper lobe of lung	UBERON:0008948	89.45	gold quality
right lobe of thyroid gland	UBERON:0001119	89.08	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.86	gold quality
right frontal lobe	UBERON:0002810	88.59	gold quality
small intestine	UBERON:0002108	88.46	gold quality
metanephros cortex	UBERON:0010533	88.44	gold quality
spleen	UBERON:0002106	88.24	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.18	gold quality
adenohypophysis	UBERON:0002196	88.09	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.62
E-MTAB-4850	no	392.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

74 targeting NCLN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6722-3P	99.45	67.62	1919

Literature-anchored findings (GeneRIF, showing 1)

• Identification of the soluble EphA7-interacting protein Nicalin as a regulator of EphA7 expression. (PMID:32914261)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ncln	ENSDARG00000058861
mus_musculus	Ncln	ENSMUSG00000020238
rattus_norvegicus	Ncln	ENSRNOG00000004793
drosophila_melanogaster	CG4972	FBGN0032217
caenorhabditis_elegans	nra-2	WBGENE00011488

Protein

Protein identifiers

BOS complex subunit NCLN — Q969V3 (reviewed: Q969V3)

Alternative names: Nicalin, Nicastrin-like protein

All UniProt accessions (7): Q969V3, A0A0C4DGP7, K7ELZ9, K7EMW4, K7EN96, K7ENM2, K7EQ66

UniProt curated annotations — full annotation on UniProt →

Function. Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions. May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning, via its interaction with NOMO.

Subunit / interactions. Component of the back of Sec61 (BOS) complex, composed of NCLN/Nicalin, NOMO (NOMO1, NOMO2 or NOMO3) and TMEM147. The BOS complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47). The MPT complex associates with the SEC61 complex.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in pancreas and skeletal muscle and, at lower levels, in heart.

Similarity. Belongs to the nicastrin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q969V3-1	1	yes
Q969V3-2	2

RefSeq proteins (2): NP_001308392, NP_064555* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007484	Peptidase_M28	Domain
IPR016574	Nicalin	Family

Pfam: PF04389

UniProt features (14 total): sequence conflict 4, topological domain 2, glycosylation site 2, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9C7U	ELECTRON MICROSCOPY	3.65
6W6L	ELECTRON MICROSCOPY	3.84
9C7V	ELECTRON MICROSCOPY	6.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969V3-F1	85.88	0.57

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 241, 428

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, ELVIDGE_HYPOXIA_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, SHEPARD_BMYB_MORPHOLINO_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GGAMTNNNNNTCCY_UNKNOWN, GOBP_SPECIFICATION_OF_SYMMETRY, GOBP_LATERAL_MESODERM_DEVELOPMENT, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, GOBP_PROTEIN_STABILIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_MEMBRANE, GOBP_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_REGULATION_OF_PROTEIN_STABILITY

GO Biological Process (7): determination of left/right asymmetry in lateral mesoderm (GO:0003140), regulation of signal transduction (GO:0009966), regulation of protein-containing complex assembly (GO:0043254), protein stabilization (GO:0050821), regulation of protein complex stability (GO:0061635), multi-pass transmembrane protein insertion into ER membrane (GO:0160063), negative regulation of nodal signaling pathway (GO:1900108)

GO Molecular Function (2): ribosome binding (GO:0043022), protein binding (GO:0005515)

GO Cellular Component (5): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), protein-containing complex (GO:0032991), multi-pass translocon complex (GO:0160064), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
determination of left/right symmetry	1
lateral mesoderm development	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
regulation of cellular component biogenesis	1
regulation of cellular component organization	1
protein-containing complex assembly	1
regulation of protein stability	1
regulation of biological quality	1
protein insertion into ER membrane	1
negative regulation of activin receptor signaling pathway	1
nodal signaling pathway	1
regulation of nodal signaling pathway	1
ribonucleoprotein complex binding	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cellular_component	1
ER membrane insertion complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1296 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCLN	NOMO2	Q5JPE7	993
NCLN	TMEM147	Q9BVK8	991
NCLN	NOMO3	P69849	868
NCLN	NOMO1	P78421	848
NCLN	TBATA	Q96M53	743
NCLN	DENND3	A2RUS2	703
NCLN	NCSTN	Q92542	683
NCLN	XYLT1	Q86Y38	548
NCLN	SMPD4	Q9NXE4	532
NCLN	CCDC47	Q96A33	507
NCLN	STT3A	P46977	506
NCLN	TRIR	Q9BQ61	496
NCLN	CCDC158	Q5M9N0	490
NCLN	SDR39U1	Q9NRG7	490
NCLN	STT3B	Q8TCJ2	486

IntAct

92 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CKB	CKM	psi-mi:“MI:0914”(association)	0.690
NOMO2	NCLN	psi-mi:“MI:0915”(physical association)	0.670
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
NCLN	WFS1	psi-mi:“MI:0915”(physical association)	0.560
HTT	NCLN	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
DLK1	SCAMP3	psi-mi:“MI:0914”(association)	0.530
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
FBXO6	GNS	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350

BioGRID (245): NCLN (Two-hybrid), NCLN (Affinity Capture-MS), NCLN (Affinity Capture-MS), NCLN (Affinity Capture-MS), NCLN (Affinity Capture-MS), NCLN (Affinity Capture-MS), NCLN (Co-fractionation), NCLN (Co-fractionation), NCLN (Co-fractionation), RPN2 (Co-fractionation), NCLN (Proximity Label-MS), NCLN (Proximity Label-MS), NCLN (Affinity Capture-MS), NCLN (Affinity Capture-MS), NCLN (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NGV2, A2VE47, A4IG72, A7E2V1, D3Z2R5, F1PCT7, O43909, P02786, P04844, P25235, P57716, Q07891, Q0VCN6, Q28120, Q28DV7, Q2V905, Q5R9Q9, Q5RBM1, Q5RDH6, Q5XIA1, Q5ZJH2, Q5ZL00, Q62351, Q64255, Q6DDX8, Q6NZ07, Q7TMC8, Q8BXQ2, Q8C7X2, Q8CGU6, Q8K224, Q8N766, Q8N961, Q8R553, Q8VCM8, Q8VDL4, Q92542, Q969N2, Q969V3, Q99JH7

Diamond homologs: A0A8I3NGV2, A5JYX8, Q5XIA1, Q5ZJH2, Q6NZ07, Q8VCM8, Q969V3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NCLN	“form complex”	“BOS complex, NOMO1 variant”	binding
NCLN	“form complex”	“BOS complex, NOMO2 variant”	binding
NCLN	“form complex”	“BOS complex, NOMO3 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 101 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
chloride transmembrane transport	5	13.5×	8e-03
cytoplasmic translation	6	12.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	75
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
375276	NM_020170.4(NCLN):c.496C>T (p.Gln166Ter)	Likely pathogenic

SpliceAI

2418 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3192465:CACA:C	acceptor_loss	1.0000
19:3192468:A:AG	acceptor_gain	1.0000
19:3192468:A:T	acceptor_loss	1.0000
19:3192468:AG:A	acceptor_gain	1.0000
19:3192469:G:GT	acceptor_gain	1.0000
19:3192469:GG:G	acceptor_gain	1.0000
19:3192469:GGC:G	acceptor_gain	1.0000
19:3192469:GGCA:G	acceptor_gain	1.0000
19:3192469:GGCAC:G	acceptor_gain	1.0000
19:3192649:G:GT	donor_gain	1.0000
19:3192659:GG:G	donor_gain	1.0000
19:3192660:GG:G	donor_gain	1.0000
19:3192661:G:A	donor_loss	1.0000
19:3192661:G:GG	donor_gain	1.0000
19:3192662:T:A	donor_loss	1.0000
19:3193282:A:AG	acceptor_gain	1.0000
19:3193282:A:C	acceptor_loss	1.0000
19:3193283:G:GC	acceptor_gain	1.0000
19:3193283:GC:G	acceptor_gain	1.0000
19:3193283:GCA:G	acceptor_gain	1.0000
19:3193283:GCAA:G	acceptor_gain	1.0000
19:3193283:GCAAT:G	acceptor_gain	1.0000
19:3193285:A:AG	acceptor_gain	1.0000
19:3196181:A:AG	acceptor_gain	1.0000
19:3196181:AG:A	acceptor_loss	1.0000
19:3196182:G:GA	acceptor_gain	1.0000
19:3196182:GT:G	acceptor_gain	1.0000
19:3196182:GTA:G	acceptor_gain	1.0000
19:3196182:GTAC:G	acceptor_gain	1.0000
19:3196182:GTACT:G	acceptor_gain	1.0000

AlphaMissense

3647 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3201578:T:C	L251P	0.999
19:3204045:C:G	C310W	0.999
19:3204651:T:A	W370R	0.999
19:3204651:T:C	W370R	0.999
19:3196269:A:C	S203R	0.998
19:3196271:C:A	S203R	0.998
19:3196271:C:G	S203R	0.998
19:3198817:G:A	G206R	0.998
19:3198817:G:C	G206R	0.998
19:3198817:G:T	G206W	0.998
19:3201553:A:C	S243R	0.998
19:3201555:C:A	S243R	0.998
19:3201555:C:G	S243R	0.998
19:3203805:G:A	G284R	0.998
19:3203805:G:C	G284R	0.998
19:3203817:T:A	W288R	0.998
19:3203817:T:C	W288R	0.998
19:3204653:G:C	W370C	0.998
19:3204653:G:T	W370C	0.998
19:3204666:T:C	F375L	0.998
19:3204668:C:A	F375L	0.998
19:3204668:C:G	F375L	0.998
19:3186178:C:A	R50S	0.997
19:3192470:G:A	G62D	0.997
19:3193338:T:G	Y144D	0.997
19:3198818:G:A	G206E	0.997
19:3198878:A:T	D226V	0.997
19:3201550:G:T	G242W	0.997
19:3201584:G:C	R253P	0.997
19:3203764:T:C	L270P	0.997

dbSNP variants (sampled 300 via entrez): RS1000074661 (19:3187070 C>T), RS1000159681 (19:3203295 C>A,T), RS1000170373 (19:3202594 C>A,T), RS1000205794 (19:3200490 T>C), RS1000266701 (19:3202793 C>A,T), RS1000425076 (19:3190942 G>A,T), RS1000548641 (19:3188311 C>A,G), RS1000563403 (19:3184590 G>C), RS1000641097 (19:3207529 G>C), RS1000753834 (19:3207323 G>A,C), RS1000866264 (19:3192064 G>A), RS1000872289 (19:3198728 G>A,C,T), RS1000912120 (19:3195667 T>C), RS1001028682 (19:3191481 A>G,T), RS1001146217 (19:3196466 C>T)

Disease associations

OMIM: gene MIM:609156 | disease phenotypes: MIM:142623

GenCC curated gene-disease

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

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
GCST005974_21	Neutrophil count	9.000000e-12
GCST008839_38	Height	2.000000e-09
GCST009798_49	Asthma	7.000000e-10
GCST90002380_8	Basophil percentage of white cells	5.000000e-34
GCST90002389_258	Lymphocyte percentage of white cells	2.000000e-32
GCST90002398_76	Neutrophil count	2.000000e-103
GCST90002399_215	Neutrophil percentage of white cells	4.000000e-32

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067219 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.28	Kd	52.81	nM	CHEMBL5653589
7.28	ED50	52.81	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148835: Binding affinity to human NCLN incubated for 45 mins by Kinobead based pull down assay	kd	0.0528	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression	3
sodium arsenite	increases expression, affects expression, affects cotreatment, increases abundance	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	increases expression	2
Cyclosporine	increases expression	2
bisphenol F	increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651877	Binding	Binding affinity to human NCLN incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

48 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
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)
NCT06650683	Not specified	RECRUITING	Impact of Providing Nursing Support on Parental Stress Related to Preoperative Care of a Newborn with Hirschsprung’s Disease