NDC1

Summary

NDC1 (NDC1 transmembrane nucleoporin, HGNC:25525) is a protein-coding gene on chromosome 1p32.3, encoding Nucleoporin NDC1 (Q9BTX1). Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. It is a selective cancer dependency (DepMap: 62.5% of cell lines).

A structural constituent of nuclear pore. Involved in nuclear pore complex assembly and nuclear pore localization. Located in actin cytoskeleton; nuclear membrane; and plasma membrane. Part of nuclear pore.

Source: NCBI Gene 55706 — RefSeq curated summary.

At a glance

• Gene–disease (curated): triple-A syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 137 total — 1 pathogenic
• Phenotypes (HPO): 72
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 62.5% of screened cell lines
• MANE Select transcript: NM_018087

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25525
Approved symbol	NDC1
Name	NDC1 transmembrane nucleoporin
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10407, NET3
Ensembl gene	ENSG00000058804
Ensembl biotype	protein_coding
OMIM	610115
Entrez	55706

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000371429, ENST00000480952, ENST00000874541, ENST00000874542, ENST00000874543, ENST00000874544, ENST00000874545, ENST00000874546, ENST00000874547, ENST00000874548, ENST00000923526, ENST00000923527, ENST00000923528, ENST00000923529, ENST00000923530, ENST00000923531, ENST00000945039, ENST00000945040

RefSeq mRNA: 2 — MANE Select: NM_018087 NM_001168551, NM_018087

CCDS: CCDS583

Canonical transcript exons

ENST00000371429 — 18 exons

Exon	Start	End
ENSE00000438938	53796899	53797144
ENSE00000772441	53793229	53793279
ENSE00000772555	53800693	53800848
ENSE00000814875	53835500	53835620
ENSE00001262418	53796689	53796804
ENSE00001338210	53807656	53807791
ENSE00001843774	53838205	53838296
ENSE00001858669	53765478	53768033
ENSE00003474755	53809695	53809746
ENSE00003515376	53825798	53825936
ENSE00003542889	53827999	53828173
ENSE00003569837	53772329	53772489
ENSE00003571814	53806425	53806517
ENSE00003579327	53787158	53787258
ENSE00003610711	53789133	53789196
ENSE00003659021	53803928	53804009
ENSE00003674226	53832490	53832591
ENSE00003677489	53818971	53819079

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 94.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5276 / max 211.2633, expressed in 1799 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12426	21.2747	1790
12429	2.8767	1011
12425	1.1138	737
12427	1.0444	663
12428	0.2180	102

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.41	gold quality
oocyte	CL:0000023	93.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.33	gold quality
ventricular zone	UBERON:0003053	89.67	gold quality
tibia	UBERON:0000979	89.63	gold quality
gingival epithelium	UBERON:0001949	89.43	gold quality
epithelium of nasopharynx	UBERON:0001951	89.06	gold quality
esophagus squamous epithelium	UBERON:0006920	88.97	gold quality
gingiva	UBERON:0001828	88.01	gold quality
colonic mucosa	UBERON:0000317	87.77	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.47	gold quality
germinal epithelium of ovary	UBERON:0001304	86.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.58	gold quality
ganglionic eminence	UBERON:0004023	86.03	gold quality
rectum	UBERON:0001052	85.77	gold quality
pigmented layer of retina	UBERON:0001782	85.20	gold quality
parietal pleura	UBERON:0002400	85.01	gold quality
oral cavity	UBERON:0000167	85.00	gold quality
adrenal tissue	UBERON:0018303	84.91	gold quality
trabecular bone tissue	UBERON:0002483	84.86	gold quality
visceral pleura	UBERON:0002401	84.69	gold quality
mammary duct	UBERON:0001765	84.68	gold quality
skin of hip	UBERON:0001554	84.35	gold quality
endometrium	UBERON:0001295	84.16	gold quality
pleura	UBERON:0000977	83.79	gold quality
palpebral conjunctiva	UBERON:0001812	83.60	gold quality
epithelium of esophagus	UBERON:0001976	83.38	gold quality
pharyngeal mucosa	UBERON:0000355	83.14	gold quality
penis	UBERON:0000989	83.14	gold quality
mammalian vulva	UBERON:0000997	83.10	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6379	yes	1281.52
E-ANND-3	yes	5.35
E-MTAB-7249	no	198.52

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

145 targeting NDC1, 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-8485	100.00	77.57	4731
HSA-MIR-340-5P	100.00	72.50	4437
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 62.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• Human homologue NDC1/NET3 contains three FG repeats in the C-terminus, a feature of many nuclear pore proteins. (PMID:16779818)
• NDC1-mediated localization of ALADIN to nuclear pore complexes is essential for selective nuclear protein import; abrogation of the interaction between ALADIN and NDC1 may be important for the development of triple-A syndrome. (PMID:19703420)
• ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated. (PMID:19782045)
• The biological relevance of TMEM48 in NSCLC progression. (PMID:26392108)
• In mature human spermatozoa, SEPT12 and NDC1 are majorly colocalized in the centrosome regions; however, NDC1 is only slightly co-expressed with SEPT12 at the annulus of the sperm tail. (PMID:27854341)
• miR-421 can suppress TMEM48 so that leads the non-small cancer cell lines (A549) to apoptosis. (PMID:29906465)
• TMEM48 promotes cell proliferation and invasion in cervical cancer via activation of the Wnt/beta-catenin pathway. (PMID:32896205)
• NDC1 promotes hepatocellular carcinoma tumorigenesis by targeting BCAP31 to activate PI3K/AKT signaling. (PMID:38348718)
• Biallelic NDC1 variants that interfere with ALADIN binding are associated with neuropathy and triple A-like syndrome. (PMID:39003500)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ndc1	ENSDARG00000021120
mus_musculus	Ndc1	ENSMUSG00000028614
rattus_norvegicus	Ndc1	ENSRNOG00000010620
drosophila_melanogaster	Ndc1	FBGN0039125
caenorhabditis_elegans		WBGENE00007118

Protein

Protein identifiers

Nucleoporin NDC1 — Q9BTX1 (reviewed: Q9BTX1)

Alternative names: Transmembrane protein 48

All UniProt accessions (1): Q9BTX1

UniProt curated annotations — full annotation on UniProt →

Function. Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane.

Subunit / interactions. Interacts with the NUP35/NUP53. Interacts with AAAS, anchoring it to the nuclear envelope.

Subcellular location. Nucleus. Nuclear pore complex. Nucleus membrane.

Disease relevance. Neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima (NEDAPA) [MIM:621328] An autosomal recessive neurodevelopmental disorder characterized by mild developmental delay, impaired intellectual development, peripheral polyneuropathy and motor impairment, alacrima, and achalasia. Affected individuals do not have adrenal insufficiency. The disease may be caused by variants affecting the gene represented in this entry.

Miscellaneous. Depletion of NDC1 from HeLa cells interferes with the assembly of phenylalanine-glycine (FG) repeat Nups into nuclear pore complexes.

Similarity. Belongs to the NDC1 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9BTX1-1	1	yes
Q9BTX1-2	2
Q9BTX1-3	3
Q9BTX1-4	4
Q9BTX1-5	5
Q9BTX1-6	6

RefSeq proteins (2): NP_001162023, NP_060557* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019049	Nucleoporin_prot_Ndc1/Nup	Family

Pfam: PF09531

UniProt features (36 total): modified residue 8, topological domain 7, transmembrane region 6, splice variant 6, sequence variant 3, sequence conflict 3, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7R5K	ELECTRON MICROSCOPY	12
7R5J	ELECTRON MICROSCOPY	50

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTX1-F1	76.45	0.44

Functional residue map

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

Post-translational modifications (8): 406, 414, 439, 440, 445, 449, 471, 474

Function

Pathways and Gene Ontology

Reactome pathways

81 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism
R-HSA-159227	Transport of the SLBP independent Mature mRNA
R-HSA-159230	Transport of the SLBP Dependant Mature mRNA
R-HSA-159231	Transport of Mature mRNA Derived from an Intronless Transcript
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-165054	Rev-mediated nuclear export of HIV RNA
R-HSA-168271	Transport of Ribonucleoproteins into the Host Nucleus
R-HSA-168276	NS1 Mediated Effects on Host Pathways
R-HSA-168325	Viral Messenger RNA Synthesis
R-HSA-168333	NEP/NS2 Interacts with the Cellular Export Machinery
R-HSA-170822	Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-180746	Nuclear import of Rev protein
R-HSA-180910	Vpr-mediated nuclear import of PICs
R-HSA-1855170	IPs transport between nucleus and cytosol
R-HSA-1855196	IP3 and IP4 transport between cytosol and nucleus
R-HSA-1855229	IP6 and IP7 transport between cytosol and nucleus
R-HSA-191859	snRNP Assembly
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3232142	SUMOylation of ubiquitinylation proteins
R-HSA-3301854	Nuclear Pore Complex (NPC) Disassembly
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-4085377	SUMOylation of SUMOylation proteins
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4615885	SUMOylation of DNA replication proteins
R-HSA-5619107	Defective TPR may confer susceptibility towards thyroid papillary carcinoma (TPC)
R-HSA-6784531	tRNA processing in the nucleus
R-HSA-9609690	HCMV Early Events
R-HSA-9610379	HCMV Late Events
R-HSA-9615933	Postmitotic nuclear pore complex (NPC) reformation

MSigDB gene sets: 309 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, REACTOME_VIRAL_MESSENGER_RNA_SYNTHESIS, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_NUCLEAR_PORE_ORGANIZATION, GOBP_NUCLEAR_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, TCF4_Q5, REACTOME_HIV_INFECTION, GOBP_ORGANELLE_FISSION

GO Biological Process (8): nucleocytoplasmic transport (GO:0006913), nuclear pore organization (GO:0006999), homologous chromosome pairing at meiosis (GO:0007129), spermatogenesis (GO:0007283), protein transport (GO:0015031), mRNA transport (GO:0051028), nuclear pore complex assembly (GO:0051292), nuclear pore localization (GO:0051664)

GO Molecular Function (2): structural constituent of nuclear pore (GO:0017056), protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (9): nuclear envelope (GO:0005635), nuclear pore (GO:0005643), cytoplasm (GO:0005737), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), membrane (GO:0016020), nuclear membrane (GO:0031965), nuclear pore transmembrane ring (GO:0070762), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Transport of Mature mRNAs Derived from Intronless Transcripts	3
Inositol phosphate metabolism	3
Interactions of Rev with host cellular proteins	2
Influenza Infection	2
SUMO E3 ligases SUMOylate target proteins	2
Antimicrobial mechanism of IFN-stimulated genes	1
Transport of Mature Transcript to Cytoplasm	1
Late Phase of HIV Life Cycle	1
Influenza Viral RNA Transcription and Replication	1
Export of Viral Ribonucleoproteins from Nucleus	1
Glycolysis	1
Interactions of Vpr with host cellular proteins	1
Metabolism of non-coding RNA	1
Nuclear Envelope Breakdown	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nucleus organization	2
nuclear pore	2
nucleus	2
nuclear envelope	2
nuclear protein-containing complex	2
cellular anatomical structure	2
nuclear transport	1
protein-containing complex organization	1
homologous chromosome segregation	1
chromosome organization involved in meiotic cell cycle	1
developmental process involved in reproduction	1
male gamete generation	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
RNA transport	1
nuclear pore organization	1
pore complex assembly	1
protein-containing complex localization	1
localization within membrane	1
structural molecule activity	1
nucleocytoplasmic transport	1
protein binding	1
molecular adaptor activity	1
endomembrane system	1
organelle envelope	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cytoskeleton	1
organelle membrane	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NDC1	NUP35	Q8NFH5	978
NDC1	NUP93	Q8N1F7	932
NDC1	NUP62	P37198	879
NDC1	NUP210	Q8TEM1	756
NDC1	NUP155	O75694	685
NDC1	NUP205	Q92621	668
NDC1	NUP188	Q5SRE5	600
NDC1	NUP160	Q12769	569
NDC1	NUP37	Q8NFH4	567
NDC1	NUP85	Q9BW27	564
NDC1	TMEM25	Q86YD3	541
NDC1	NUP107	P57740	540
NDC1	TMEM33	P57088	526
NDC1	AAAS	Q9NRG9	521
NDC1	NUP153	P49790	507
NDC1	NUP88	Q99567	507

IntAct

128 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
OSBPL8	CSNK2A2	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
LRRTM1	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TSPAN5	SC5D	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
ABHD14A	TMEM259	psi-mi:“MI:0914”(association)	0.530
B4GAT1	ADCY6	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
Ndc1	NDC1	psi-mi:“MI:0915”(physical association)	0.400
SEPTIN12	NDC1	psi-mi:“MI:0915”(physical association)	0.370
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
	ATP6	psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (297): NDC1 (Affinity Capture-MS), NDC1 (Affinity Capture-MS), NDC1 (Affinity Capture-MS), NDC1 (Affinity Capture-MS), NDC1 (Affinity Capture-MS), NDC1 (Affinity Capture-MS), NDC1 (Affinity Capture-MS), NDC1 (Affinity Capture-MS), NDC1 (Affinity Capture-MS), NDC1 (Synthetic Lethality), NDC1 (Affinity Capture-MS), NDC1 (Proximity Label-MS), NDC1 (Proximity Label-MS), NDC1 (Proximity Label-MS), NDC1 (Proximity Label-MS)

ESM2 similar proteins: A2RT67, A2RV80, E1C3P4, O94967, P48553, P51593, Q0VEJ0, Q3UVG3, Q3ZT31, Q4R8N2, Q5FVM6, Q5KSL6, Q5R903, Q5R989, Q5RAQ5, Q5RBY5, Q5RCP7, Q5TKA1, Q5ZKN3, Q641K1, Q658Y4, Q6AXN4, Q6IC98, Q70Z35, Q7TMY8, Q7Z699, Q7Z6Z7, Q80TA6, Q8BHY8, Q8C561, Q8C735, Q8CB19, Q8CB44, Q8CGF6, Q8N3S3, Q8TAP6, Q8VCB1, Q8VDD9, Q8WWQ0, Q91W96

Diamond homologs: Q5RBY5, Q6AX31, Q6AXN4, Q7SZC5, Q8VCB1, Q9BTX1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NDC1	“form complex”	NPC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 162 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
NEP/NS2 Interacts with the Cellular Export Machinery	5	17.3×	2e-03
Nuclear import of Rev protein	5	16.8×	2e-03
Rev-mediated nuclear export of HIV RNA	5	15.9×	2e-03
tRNA processing in the nucleus	5	9.8×	6e-03
Transport of Mature mRNA derived from an Intron-Containing Transcript	6	9.1×	4e-03
G alpha (i) signalling events	11	4.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	8	12.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	93
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4082136	NM_018087.5(NDC1):c.892-21G>A	Pathogenic

SpliceAI

2602 predictions. Top by Δscore:

Variant	Effect	Δscore
1:53768029:CAGCA:C	acceptor_gain	1.0000
1:53768032:CA:C	acceptor_gain	1.0000
1:53768034:C:CC	acceptor_gain	1.0000
1:53772322:AACTT:A	donor_loss	1.0000
1:53772323:ACTTA:A	donor_loss	1.0000
1:53772324:CTTAC:C	donor_loss	1.0000
1:53772325:TTA:T	donor_loss	1.0000
1:53772326:TAC:T	donor_loss	1.0000
1:53772327:A:AC	donor_gain	1.0000
1:53772327:ACT:A	donor_loss	1.0000
1:53772328:C:CT	donor_gain	1.0000
1:53772328:CT:C	donor_gain	1.0000
1:53772328:CTT:C	donor_gain	1.0000
1:53772486:CTGC:C	acceptor_gain	1.0000
1:53772488:GCCT:G	acceptor_loss	1.0000
1:53772490:CT:C	acceptor_loss	1.0000
1:53772496:C:CT	acceptor_gain	1.0000
1:53772497:A:T	acceptor_gain	1.0000
1:53787152:TCTTA:T	donor_loss	1.0000
1:53787153:CTTA:C	donor_loss	1.0000
1:53787154:TTA:T	donor_loss	1.0000
1:53787155:TACCT:T	donor_loss	1.0000
1:53787156:A:AG	donor_loss	1.0000
1:53787157:C:G	donor_loss	1.0000
1:53787157:CCT:C	donor_gain	1.0000
1:53787254:CAGAC:C	acceptor_gain	1.0000
1:53787259:C:T	acceptor_gain	1.0000
1:53787261:C:CT	acceptor_gain	1.0000
1:53787262:A:T	acceptor_gain	1.0000
1:53789197:C:CC	acceptor_gain	1.0000

AlphaMissense

4395 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:53800831:A:G	W362R	0.999
1:53800831:A:T	W362R	0.999
1:53772359:C:G	R644P	0.998
1:53772369:C:G	A641P	0.998
1:53772377:A:G	L638P	0.998
1:53787207:A:T	V584D	0.998
1:53787223:C:G	D579H	0.998
1:53789133:C:G	G567R	0.998
1:53803990:A:G	L335P	0.998
1:53767998:A:G	L666P	0.997
1:53772343:A:C	F649L	0.997
1:53772343:A:T	F649L	0.997
1:53772345:A:G	F649L	0.997
1:53787165:A:G	L598P	0.997
1:53787183:A:G	L592P	0.997
1:53787213:C:T	G582E	0.997
1:53787222:T:G	D579A	0.997
1:53787255:A:G	L568P	0.997
1:53772356:A:C	I645R	0.996
1:53772356:A:T	I645K	0.996
1:53787195:A:G	L588P	0.996
1:53787222:T:A	D579V	0.996
1:53800829:C:A	W362C	0.996
1:53800829:C:G	W362C	0.996
1:53803935:G:C	S353R	0.996
1:53803935:G:T	S353R	0.996
1:53803937:T:G	S353R	0.996
1:53803956:T:A	R346S	0.996
1:53803956:T:G	R346S	0.996
1:53787235:A:G	S575P	0.995

dbSNP variants (sampled 300 via entrez): RS1000155418 (1:53787366 AG>A), RS1000196524 (1:53833080 A>C), RS1000222528 (1:53785357 G>A,T), RS1000296310 (1:53785710 C>T), RS1000301827 (1:53827324 A>G), RS1000306529 (1:53797281 T>C,G), RS1000336690 (1:53814977 A>C), RS1000378722 (1:53839141 T>C), RS1000385881 (1:53816974 C>A), RS1000423455 (1:53827626 A>G), RS1000429306 (1:53799201 G>A), RS1000455782 (1:53792016 C>A), RS1000529073 (1:53831816 T>C), RS1000566476 (1:53798844 C>T), RS1000598406 (1:53792103 T>C)

Disease associations

OMIM: gene MIM:610115 | disease phenotypes: MIM:621328, MIM:121300

GenCC curated gene-disease

Disease	Classification	Inheritance
triple-A syndrome	Strong	Autosomal recessive
polyneuropathy	Limited	Autosomal recessive

Mondo (6): neurodevelopmental disorder with achalasia, polyneuropathy, and alacrima (MONDO:0979875), hereditary coproporphyria (MONDO:0007369), retinal disorder (MONDO:0005283), cleft palate (MONDO:0016064), polyneuropathy (MONDO:0001824), triple-A syndrome (MONDO:0009279)

Orphanet (2): Hereditary coproporphyria (Orphanet:79273), Cleft palate (Orphanet:2014)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000384	Preauricular skin tag
HP:0000460	Narrow nose
HP:0000494	Downslanted palpebral fissures
HP:0000522	Alacrima
HP:0000618	Blindness
HP:0000718	Aggressive behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0000962	Hyperkeratosis
HP:0001182	Tapered finger
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001271	Polyneuropathy
HP:0001288	Gait disturbance
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001611	Hypernasal speech
HP:0001761	Pes cavus
HP:0002015	Dysphagia
HP:0002028	Chronic diarrhea
HP:0002359	Frequent falls
HP:0002460	Distal muscle weakness

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003813_5	Response to antidepressants and depression	2.000000e-06

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D002972	Cleft Palate	C05.500.460.185; C05.660.207.540.460.185; C07.320.440.185; C07.465.525.185; C07.650.500.460.185; C07.650.525.185; C16.131.621.207.540.460.185; C16.131.850.500.460.185; C16.131.850.525.185
D046349	Coproporphyria, Hereditary	C06.552.830.074; C16.320.850.742.074; C17.800.827.742.074; C18.452.811.400.074
D011115	Polyneuropathies	C10.668.829.800
D012164	Retinal Diseases	C11.768
C536008	Achalasia Addisonianism Alacrimia syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067254 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects cotreatment	4
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
sodium arsenite	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Acetaminophen	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
incobotulinumtoxinA	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	increases methylation, decreases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	decreases expression	1
Caffeine	affects phosphorylation	1
Copper	affects binding, decreases 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
CHEMBL5651879	Binding	Binding affinity to human NDC1 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

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1YB	Abcam HeLa NDC1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00162968	PHASE4	COMPLETED	Escitalopram as a Treatment for Pain in Polyneuropathy
NCT00832572	PHASE4	TERMINATED	Study of Ranexa in Patients With Coronary Artery Disease and Painful Polyneuropathy
NCT01047488	PHASE4	UNKNOWN	Imipramine and Pregabalin Combination in Painful Polyneuropathy
NCT01076478	PHASE4	COMPLETED	Asian Study on Cilostazol Effectivity in Neuropathies of Diabetes Mellitus Type 2-A Pilot Study in the Philippines
NCT01302275	PHASE4	COMPLETED	Oxcarbazepine for the Treatment of Chronic Peripheral Neuropathic Pain
NCT02033057	PHASE4	UNKNOWN	Muscular Electrostimulation of the Sedated and Mechanically Ventilated Critically Ill Patient. Analysis of the Effect on Acquired Muscular Weakness and Its Clinical Consequences.
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
NCT02422056	PHASE4	COMPLETED	Acid Tranexamic Effectiveness in Reducing the Intraoperative Bleeding in Palatoplasty
NCT02915042	PHASE4	WITHDRAWN	Dexmedetomidine vs Placebo for Pediatric Cleft Palate Repair
NCT02953145	PHASE4	WITHDRAWN	The Use of Fibrin Sealant to Reduce Post Operative Pain in Cleft Palate Surgery
NCT03632044	PHASE4	ACTIVE_NOT_RECRUITING	Evaluation of Trigeminal Nerve Blockade
NCT06962306	PHASE4	RECRUITING	Optimizing Perioperative Analgesia to Lower Pain Following Cleft Palate Surgery
NCT00259974	PHASE3	COMPLETED	RIMAG Study: Trial of Rituximab Versus Placebo in Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy
NCT01263132	PHASE3	COMPLETED	Neuropathic Pain Management
NCT01450163	PHASE3	COMPLETED	Evaluate The Efficacy and Safety Of Pregabalin In Prevention, Reduction of Oxaliplatin-Induced Painful Neuropathy
NCT06563895	PHASE3	RECRUITING	Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant
NCT06672237	PHASE3	RECRUITING	A Phase 3 Study of NTLA-2001 in ATTRv-PN
NCT07116473	PHASE3	NOT_YET_RECRUITING	To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)
NCT03338816	PHASE3	COMPLETED	ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP)
NCT00098319	PHASE3	COMPLETED	Oral Cleft Prevention Trial in Brazil
NCT00397917	PHASE3	COMPLETED	Oral Cleft Prevention Program
NCT04928352	PHASE3	RECRUITING	Nebulized Bupivacaine Analgesia for Cleft Palate Repair
NCT04928391	PHASE3	COMPLETED	A Single Bolus of Dexmedetomidine Versus Normal Saline in Postoperative Agitation
NCT00050245	PHASE2	COMPLETED	Rituximab to Treat Neuropathy With Anti-MAG Antibodies
NCT00082316	PHASE2	COMPLETED	Tolerability of Three Local Anesthetic Formulations in Conjunction With NGX-4010 for the Treatment of Neuropathic Pain
NCT00089557	PHASE2	TERMINATED	An Open-Label Extension Study of NGX-4010 for the Treatment of Neuropathic Pain
NCT00231673	PHASE2	COMPLETED	A Study To Evaluate The Effect Of Topiramate On Clinical And Electrophysiological Parameters In Subjects With Diabetic Peripheral Polyneuropathy
NCT00723918	PHASE2	WITHDRAWN	Combination of an Investigational Cannabinoid and Methadone for HIV-associated Neuropathy
NCT01088256	PHASE2	TERMINATED	Efficacy of Etoricoxib on Peripheral Hyperalgesia
NCT02922413	PHASE2	TERMINATED	Panhematin for Prevention of Acute Attacks of Porphyria
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
NCT00004639	PHASE2	COMPLETED	Cleft Palate Surgery and Speech Development
NCT00760006	PHASE2	COMPLETED	Preventing Complications in Cleft Palate Repair With Antibiotics
NCT01760330	PHASE2	WITHDRAWN	IV Acetaminophen in Children Undergoing Palatoplasty
NCT02350803	PHASE2	COMPLETED	Does Use of Rigid Fixation After Removing Distraction Osteogenesis Device Reduce the Relapse?
NCT03412474	PHASE2	COMPLETED	Suprazygomatic Block in Cleft Palate Surgery in Children
NCT00614562	PHASE1	COMPLETED	Neurally Adjusted Ventilatory Assist (NAVA) in Patients With Critical Illness Associated Polyneuropathy / or Polymyopathy (CIP/M)
NCT01867645	PHASE1	TERMINATED	The Impact of IVIG Treatment on Critical Illness Polyneuropathy and/or Myopathy in Patients With MOF and SIRS/Sepsis
NCT05023889	EARLY_PHASE1	COMPLETED	Spectrum of Peripheral and Autonomic Neuropathies in Patients With aTTRwt Amyloidosis and Response to Patisiran Therapy