NECTIN3

Summary

NECTIN3 (nectin cell adhesion molecule 3, HGNC:17664) is a protein-coding gene on chromosome 3q13.13, encoding Nectin-3 (Q9NQS3). Cell adhesion molecule that promotes cell-cell adhesion through heterophilic trans-interactions with nectins-like or other nectins, such as trans-interaction with NECTIN2 at Sertoli-spermatid junctions.

This gene encodes a member of the nectin family of proteins, which function as adhesion molecules at adherens junctions. This family member interacts with other nectin-like proteins and with afadin, a filamentous actin-binding protein involved in the regulation of directional motility, cell proliferation and survival. This gene plays a role in ocular development involving the ciliary body. Mutations in this gene are believed to result in congenital ocular defects. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 25945 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 37 total
• MANE Select transcript: NM_015480

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17664
Approved symbol	NECTIN3
Name	nectin cell adhesion molecule 3
Location	3q13.13
Locus type	gene with protein product
Status	Approved
Aliases	nectin-3, PPR3, PVRR3, DKFZP566B0846, CDw113, CD113
Ensembl gene	ENSG00000177707
Ensembl biotype	protein_coding
OMIM	607147
Entrez	25945

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 10 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000319792, ENST00000461477, ENST00000470618, ENST00000478327, ENST00000481766, ENST00000485303, ENST00000485506, ENST00000486596, ENST00000488016, ENST00000491525, ENST00000493615, ENST00000911298, ENST00000911299

RefSeq mRNA: 3 — MANE Select: NM_015480 NM_001243286, NM_001243288, NM_015480

CCDS: CCDS2957, CCDS58842, CCDS58843

Canonical transcript exons

ENST00000485303 — 6 exons

Exon	Start	End
ENSE00001240523	111118656	111118952
ENSE00001656135	111126184	111126335
ENSE00001847483	111071816	111072177
ENSE00001901574	111133635	111137560
ENSE00002019335	111122121	111122238
ENSE00003469533	111112030	111112371

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 94.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.0976 / max 267.6819, expressed in 1465 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37856	10.6475	1427
37857	0.8517	429
37853	0.5309	316
37852	0.4218	229
37854	0.2292	81
37858	0.2057	100
37855	0.1849	43
37859	0.0258	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	94.19	gold quality
sperm	CL:0000019	92.67	gold quality
calcaneal tendon	UBERON:0003701	92.36	gold quality
islet of Langerhans	UBERON:0000006	91.28	gold quality
male germ cell	CL:0000015	90.76	gold quality
placenta	UBERON:0001987	90.11	gold quality
left testis	UBERON:0004533	89.78	gold quality
rectum	UBERON:0001052	89.77	gold quality
right testis	UBERON:0004534	89.54	gold quality
testis	UBERON:0000473	89.27	gold quality
jejunal mucosa	UBERON:0000399	88.81	gold quality
duodenum	UBERON:0002114	88.27	gold quality
cortical plate	UBERON:0005343	87.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.99	gold quality
adrenal tissue	UBERON:0018303	86.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.65	gold quality
colonic epithelium	UBERON:0000397	85.41	gold quality
secondary oocyte	CL:0000655	84.69	gold quality
colonic mucosa	UBERON:0000317	83.79	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.31	gold quality
ventricular zone	UBERON:0003053	82.63	gold quality
stomach	UBERON:0000945	80.97	gold quality
thyroid gland	UBERON:0002046	80.81	gold quality
liver	UBERON:0002107	80.65	gold quality
left lobe of thyroid gland	UBERON:0001120	80.56	gold quality
right lobe of thyroid gland	UBERON:0001119	80.46	gold quality
mucosa of transverse colon	UBERON:0004991	80.38	gold quality
smooth muscle tissue	UBERON:0001135	80.27	gold quality
oocyte	CL:0000023	80.21	gold quality
right lobe of liver	UBERON:0001114	79.92	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	18.51
E-ENAD-27	yes	11.11
E-GEOD-83139	yes	10.06
E-ANND-3	yes	6.30
E-ENAD-21	no	31.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1

miRNA regulators (miRDB)

197 targeting NECTIN3, 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-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
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-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-493-5P	99.96	72.47	2382

Literature-anchored findings (GeneRIF, showing 9)

• Data suggest that expression of nectin-3 is up-regulated in eutopic endometrium of patients with endometriosis as compared with control subjects and up-regulated in all endometriotic lesions investigated compared with eutopic endometrium. (PMID:22926846)
• Nectin-3 trans-interacts with Nectin-2 to promote lymphocyte and monocyte extravasation. (PMID:24116228)
• Nectin-3 is associated with the formation of cell junctions and be a putative suppressor molecule to the invasion of breast cancer cells. (PMID:24386110)
• Expression of nectin-3 in pancreatic cancer can be a prognostic factor. (PMID:25690753)
• PVRL3 is a physiologically relevant binding partner that can serve as a target for the prevention of TcdB-induced cytotoxicity in C. difficile infection. (PMID:26038560)
• Data suggest that 3 independent regions of TcdB (Clostridium difficile toxin B; 1372-1493, 1493-1848, 1851-2366) contribute to binding and entry of TcdB into mammalian cells; residues 1372-1493 are sufficient for interaction with PVRL3. (PMID:26602083)
• Nectin-3 mutation in men with severe teratospermia (PMID:28689229)
• Nectin-3 expression was associated with ovarian cancer, and a greater expression level of nectin-3 was related to poor overall survival. (PMID:30469078)
• Loss of nectin-3 expression as a marker of tumor aggressiveness in pancreatic neuroendocrine tumor. (PMID:31855317)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nectin3b	ENSDARG00000006604
danio_rerio		ENSDARG00000103638
mus_musculus	Nectin3	ENSMUSG00000022656
rattus_norvegicus	Nectin3	ENSRNOG00000002176
drosophila_melanogaster	Fas3	FBGN0000636

Paralogs (14): PVR (ENSG00000073008), CD200 (ENSG00000091972), CADM4 (ENSG00000105767), CRTAM (ENSG00000109943), NECTIN1 (ENSG00000110400), NECTIN2 (ENSG00000130202), NECTIN4 (ENSG00000143217), CD226 (ENSG00000150637), CADM3 (ENSG00000162706), SMAGP (ENSG00000170545), CADM2 (ENSG00000175161), TIGIT (ENSG00000181847), CADM1 (ENSG00000182985), NCR3 (ENSG00000204475)

Protein

Protein identifiers

Nectin-3 — Q9NQS3 (reviewed: Q9NQS3)

Alternative names: CDw113, Nectin cell adhesion molecule 3, Poliovirus receptor-related protein 3

All UniProt accessions (6): Q9NQS3, C9IZE6, C9J795, C9JMW3, H7C4L0, H7C5G5

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion molecule that promotes cell-cell adhesion through heterophilic trans-interactions with nectins-like or other nectins, such as trans-interaction with NECTIN2 at Sertoli-spermatid junctions. Trans-interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1. Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation. Involved in axon guidance by promoting contacts between the commissural axons and the floor plate cells. Also involved in the formation of cell-cell junctions, including adherens junctions and synapses. Promotes formation of checkerboard-like cellular pattern of hair cells and supporting cells in the auditory epithelium via heterophilic interaction with NECTIN1: NECTIN1 is present in the membrane of hair cells and associates with NECTIN3 on supporting cells, thereby mediating heterotypic adhesion between these two cell types. Plays a role in the morphology of the ciliary body.

Subunit / interactions. Cis- and trans-homodimer. Can form trans-heterodimers with NECTIN1, NECTIN2, PVR, IGSF4B/Necl-1 and with IGSF4. Interaction between NECTIN1 and NECTIN3 on the pre- and postsynaptic sites, respectively, initiates the formation of puncta adherentia junctions between axons and dendrites. Interacts (via Cytoplasmic domain) with AFDN, providing a connection with the actin cytoskeleton. Binds with low affinity to TIGIT. (Microbial infection) Interacts with C.difficile toxin TcdB, suggesting that it may contribute to TcdB toxin entry into cells. It was however shown that NECTIN3/PVRL3 does not act as a major receptor for TcdB.

Subcellular location. Cell membrane. Postsynaptic cell membrane. Cell junction. Adherens junction.

Tissue specificity. Predominantly expressed in testis and placenta as well as in many cell lines, including epithelial cell lines.

Similarity. Belongs to the nectin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NQS3-1	1	yes
Q9NQS3-2	2
Q9NQS3-3	3

RefSeq proteins (3): NP_001230215, NP_001230217, NP_056295* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR033319	Nectin-3_IgV_dom	Domain
IPR033320	IgC1_2_Nectin-3-4-like	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051427	Nectin/Nectin-like	Family

Pfam: PF07686, PF08205

UniProt features (28 total): glycosylation site 6, sequence conflict 6, splice variant 4, disulfide bond 3, domain 3, topological domain 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4FOM	X-RAY DIFFRACTION	3.93

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQS3-F1	72.95	0.50

Functional residue map

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

Disulfide bonds (3): 78–148, 193–246, 291–338

Glycosylation sites (6): 125, 186, 222, 331, 73, 83

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-418990	Adherens junctions interactions
R-HSA-420597	Nectin/Necl trans heterodimerization
R-HSA-1500931	Cell-Cell communication
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization

MSigDB gene sets: 268 (showing top): GOBP_HETEROPHILIC_CELL_CELL_ADHESION, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_SYNAPSE_ASSEMBLY, NKX25_02, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_CELL_CELL_ADHESION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_EAR_DEVELOPMENT, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN

GO Biological Process (12): lens morphogenesis in camera-type eye (GO:0002089), homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), fertilization (GO:0009566), symbiont entry into host cell (GO:0046718), retina morphogenesis in camera-type eye (GO:0060042), establishment of protein localization to plasma membrane (GO:0061951), cochlea morphogenesis (GO:0090103), regulation of postsynapse assembly (GO:0150052), protein localization to cell junction (GO:1902414), cell adhesion (GO:0007155), cell-cell adhesion (GO:0098609)

GO Molecular Function (5): identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), cell adhesion molecule binding (GO:0050839), cell adhesion mediator activity (GO:0098631), protein binding (GO:0005515)

GO Cellular Component (13): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), adherens junction (GO:0005912), axon (GO:0030424), dendrite (GO:0030425), apical junction complex (GO:0043296), cell-cell contact zone (GO:0044291), hippocampal mossy fiber to CA3 synapse (GO:0098686), postsynaptic density membrane (GO:0098839), membrane (GO:0016020), synapse (GO:0045202), postsynaptic membrane (GO:0045211), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cell-cell junction organization	1
Adherens junctions interactions	1
Cell junction organization	1
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell junction	3
anatomical structure morphogenesis	2
camera-type eye morphogenesis	2
cell-cell adhesion	2
cell adhesion	2
protein binding	2
neuron projection	2
cell junction	2
lens development in camera-type eye	1
sexual reproduction	1
reproductive process	1
viral life cycle	1
symbiont entry into host	1
retina development in camera-type eye	1
establishment of protein localization to membrane	1
inner ear morphogenesis	1
embryonic morphogenesis	1
cochlea development	1
regulation of synapse assembly	1
postsynapse assembly	1
regulation of postsynapse organization	1
intracellular protein localization	1
cellular process	1
identical protein binding	1
protein dimerization activity	1
cell adhesion molecule binding	1
binding	1
membrane	1
cell periphery	1
anchoring junction	1
dendritic tree	1
thorny excrescence	1
neuron to neuron synapse	1
hippocampal mossy fiber expansion	1
postsynaptic density	1
postsynaptic membrane	1
postsynaptic specialization membrane	1
cellular anatomical structure	1
synaptic membrane	1
postsynapse	1

Protein interactions and networks

STRING

950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NECTIN3	AFDN	P55196	994
NECTIN3	TIGIT	Q495A1	994
NECTIN3	NECTIN2	Q92692	953
NECTIN3	NECTIN1	Q15223	869
NECTIN3	PVR	P15151	774
NECTIN3	SHROOM3	Q8TF72	711
NECTIN3	PALS2	Q9NZW5	703
NECTIN3	ACKR4	Q9NPB9	684
NECTIN3	PVRIG	Q6DKI7	670
NECTIN3	CDH17	Q12864	667
NECTIN3	CSPG4	Q6UVK1	626
NECTIN3	MPP3	Q13368	625
NECTIN3	CD96	P40200	614
NECTIN3	CD226	Q15762	610
NECTIN3	JAM3	Q9BX67	608

IntAct

202 interactions, top by confidence:

A	B	Type	Score
NECTIN3	NECTIN1	psi-mi:“MI:0915”(physical association)	0.840
NECTIN1	NECTIN3	psi-mi:“MI:0915”(physical association)	0.840
NECTIN1	NECTIN3	psi-mi:“MI:0407”(direct interaction)	0.840
NECTIN2	NECTIN3	psi-mi:“MI:0915”(physical association)	0.790
NECTIN2	NECTIN3	psi-mi:“MI:0407”(direct interaction)	0.790
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NOTCH2NLA	NECTIN3	psi-mi:“MI:0915”(physical association)	0.670
NECTIN3	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
AFDN	NECTIN3	psi-mi:“MI:0915”(physical association)	0.650
NECTIN3	TIGIT	psi-mi:“MI:0915”(physical association)	0.610
PVR	NECTIN3	psi-mi:“MI:0915”(physical association)	0.610
NECTIN3	PVR	psi-mi:“MI:0407”(direct interaction)	0.610
NECTIN3	TIGIT	psi-mi:“MI:0407”(direct interaction)	0.610
NECTIN3	PICK1	psi-mi:“MI:0407”(direct interaction)	0.590
NECTIN3	RGS20	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	NECTIN3	psi-mi:“MI:0915”(physical association)	0.560
NECTIN3	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	NECTIN3	psi-mi:“MI:0915”(physical association)	0.560
NECTIN3		psi-mi:“MI:0915”(physical association)	0.560

BioGRID (134): PVRL3 (Two-hybrid), KRTAP4-2 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), PVRL3 (Affinity Capture-MS), PVRL1 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), SDF2 (Affinity Capture-MS), ASPH (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), COL14A1 (Affinity Capture-MS), MAK (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IGV4, A0A8M2B818, A0JM41, A2VD98, B0CLX4, B6ZK77, D3YX43, F1LW30, O00241, O18906, O54901, O88775, O95256, P00545, P04218, P0C673, P10522, P13369, P17948, P21995, P27931, P35916, P35917, P35969, P37301, P42071, P42703, P53767, Q08DK1, Q15762, Q58EG3, Q5DX21, Q5FWR8, Q5R412, Q5U2P2, Q5VJ70, Q6GMZ9, Q6PCB8, Q6X936, Q7TSN7

Diamond homologs: A0A8M2B818, B0JYH6, B4KPU0, P06731, P15151, P20273, P31997, P32506, P32507, Q15223, Q5FWR8, Q92692, Q9GL76, Q9JKF6, Q9JLB9, Q9N1E4, Q9N1E5, Q9N1E6, Q9NQS3, P41217, Q5ZPR3, Q7TPB4, Q8VE98, P28685, Q58EG3, Q5E9Z9, Q00889, Q8R007, Q96NY8, B3NS99, B4MR28, B4P5Q9, B4QC63, E1C8P7, O00533, P85171, Q0PMG2, Q4VA61, Q66KX2, Q6AWJ9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 146 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
Ras activation upon Ca2+ influx through NMDA receptor	7	42.5×	6e-08
Assembly and cell surface presentation of NMDA receptors	7	18.9×	1e-05
Neurexins and neuroligins	9	18.9×	2e-07
Protein-protein interactions at synapses	6	16.9×	8e-05
RHOQ GTPase cycle	6	11.6×	6e-04
RAF/MAP kinase cascade	7	4.5×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	9	41.2×	5e-10
protein localization to synapse	6	36.2×	3e-06
receptor clustering	7	34.4×	4e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	23.4×	3e-05
establishment of protein localization	5	17.0×	9e-04
establishment of cell polarity	5	15.1×	1e-03
bicellular tight junction assembly	5	13.0×	2e-03
Ras protein signal transduction	6	9.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	8
Benign	16

Top pathogenic / likely-pathogenic (0)

SpliceAI

954 predictions. Top by Δscore:

Variant	Effect	Δscore
3:111071905:G:GT	donor_gain	1.0000
3:111118654:A:AG	acceptor_gain	1.0000
3:111118654:AGTT:A	acceptor_gain	1.0000
3:111118655:G:GG	acceptor_gain	1.0000
3:111118655:GTT:G	acceptor_gain	1.0000
3:111118655:GTTG:G	acceptor_gain	1.0000
3:111118951:GT:G	donor_gain	1.0000
3:111122115:TTATA:T	acceptor_loss	1.0000
3:111122117:ATAG:A	acceptor_loss	1.0000
3:111122119:AGA:A	acceptor_loss	1.0000
3:111122120:GAT:G	acceptor_gain	1.0000
3:111122234:AGCAG:A	donor_loss	1.0000
3:111122235:GCAG:G	donor_gain	1.0000
3:111122236:CAGGT:C	donor_loss	1.0000
3:111122237:AGGTA:A	donor_loss	1.0000
3:111122238:GG:G	donor_loss	1.0000
3:111122240:T:A	donor_loss	1.0000
3:111126333:CAGGT:C	donor_loss	1.0000
3:111126335:GGTA:G	donor_loss	1.0000
3:111126336:G:GG	donor_gain	1.0000
3:111133621:ACT:A	acceptor_gain	1.0000
3:111133623:T:A	acceptor_gain	1.0000
3:111071902:C:G	donor_gain	0.9900
3:111112225:G:T	donor_gain	0.9900
3:111118651:AACAG:A	acceptor_loss	0.9900
3:111118652:ACAGT:A	acceptor_loss	0.9900
3:111118653:CAGTT:C	acceptor_loss	0.9900
3:111118654:A:AC	acceptor_loss	0.9900
3:111118655:GT:G	acceptor_gain	0.9900
3:111118655:GTTGA:G	acceptor_gain	0.9900

AlphaMissense

3565 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:111112140:T:A	W91R	1.000
3:111112140:T:C	W91R	1.000
3:111112142:G:C	W91C	1.000
3:111112142:G:T	W91C	1.000
3:111112311:T:A	C148S	1.000
3:111112312:G:C	C148S	1.000
3:111118730:T:A	C193S	1.000
3:111118730:T:C	C193R	1.000
3:111118731:G:A	C193Y	1.000
3:111118731:G:C	C193S	1.000
3:111118732:C:G	C193W	1.000
3:111118769:T:A	W206R	1.000
3:111118769:T:C	W206R	1.000
3:111118771:G:C	W206C	1.000
3:111118771:G:T	W206C	1.000
3:111118889:T:C	C246R	1.000
3:111122127:C:A	P269H	1.000
3:111122187:T:C	L289P	1.000
3:111122192:T:A	C291S	1.000
3:111122192:T:C	C291R	1.000
3:111122193:G:C	C291S	1.000
3:111122231:T:A	W304R	1.000
3:111122231:T:C	W304R	1.000
3:111122233:G:C	W304C	1.000
3:111122233:G:T	W304C	1.000
3:111126272:T:G	Y336D	1.000
3:111126278:T:A	C338S	1.000
3:111126279:G:C	C338S	1.000
3:111126292:T:A	N342K	1.000
3:111126292:T:G	N342K	1.000

dbSNP variants (sampled 300 via entrez): RS1000001747 (3:111114520 G>A,C), RS1000081016 (3:111096754 T>A,C), RS1000082548 (3:111137180 C>T), RS1000101676 (3:111157182 C>G), RS1000141057 (3:111072766 G>A,T), RS1000149126 (3:111102321 T>C), RS1000167571 (3:111119919 T>C), RS1000175912 (3:111079160 T>C), RS1000190830 (3:111144239 T>G), RS1000203369 (3:111102106 A>G), RS1000257660 (3:111163317 A>G), RS1000281041 (3:111150031 T>G), RS1000283150 (3:111119728 A>C,G), RS1000288593 (3:111084950 G>A,T), RS1000332291 (3:111150294 A>G)

Disease associations

OMIM: gene MIM:607147 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002759_1	Motion sickness	4.000000e-44
GCST003447_3	Neuroticism	4.000000e-08
GCST006951_40	Feeling hurt	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006928	motion sickness
EFO:0007660	neuroticism measurement
EFO:0009599	feeling emotionally hurt measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	4
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects methylation	3
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Vorinostat	increases expression	1
Leflunomide	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Niclosamide	decreases expression	1
Ouabain	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8LC	Abcam HCT 116 NECTIN3 KO	Cancer cell line	Male
CVCL_B9NI	Abcam A-549 NECTIN3 KO	Cancer cell line	Male
CVCL_D2GN	Abcam MCF-7 NECTIN3 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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