NID1

Summary

NID1 (nidogen 1, HGNC:7821) is a protein-coding gene on chromosome 1q42.3, encoding Nidogen-1 (P14543). Sulfated glycoprotein widely distributed in basement membranes and tightly associated with laminin.

This gene encodes a member of the nidogen family of basement membrane glycoproteins. The protein interacts with several other components of basement membranes, and may play a role in cell interactions with the extracellular matrix.

Source: NCBI Gene 4811 — RefSeq curated summary.

At a glance

• Gene–disease (curated): central nervous system malformation (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 304 total — 2 likely-pathogenic
• MANE Select transcript: NM_002508

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7821
Approved symbol	NID1
Name	nidogen 1
Location	1q42.3
Locus type	gene with protein product
Status	Approved
Aliases	entactin
Ensembl gene	ENSG00000116962
Ensembl biotype	protein_coding
OMIM	131390
Entrez	4811

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000264187, ENST00000366595, ENST00000856585, ENST00000856586, ENST00000856587, ENST00000856588, ENST00000856589, ENST00000856590, ENST00000924973, ENST00000924974, ENST00000955835, ENST00000955836, ENST00000955837

RefSeq mRNA: 1 — MANE Select: NM_002508 NM_002508

CCDS: CCDS1608

Canonical transcript exons

ENST00000264187 — 20 exons

Exon	Start	End
ENSE00000793456	235978995	235979107
ENSE00000793457	235979822	235979945
ENSE00000793458	235980496	235980653
ENSE00000793459	235981611	235981782
ENSE00000793460	235985379	235985505
ENSE00000793461	235990886	235991058
ENSE00000793462	235993645	235993872
ENSE00000793463	236011921	236012043
ENSE00000793464	236013411	236013560
ENSE00000793465	236017148	236017273
ENSE00000793466	236024070	236024213
ENSE00000793467	236025896	236026141
ENSE00001022658	236032401	236032652
ENSE00001022659	236029550	236029750
ENSE00001022661	236038104	236038253
ENSE00001022662	236045457	236045683
ENSE00001022663	236048690	236048989
ENSE00001022668	236041910	236042292
ENSE00001442138	235975830	235977988
ENSE00001935339	236064855	236065090

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.0827 / max 1416.8736, expressed in 1357 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18215	24.3005	1236
18217	11.3254	1271
18216	2.7593	903
18218	1.5153	819
18219	0.1822	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.16	gold quality
mucosa of stomach	UBERON:0001199	98.25	gold quality
lower lobe of lung	UBERON:0008949	98.08	gold quality
left uterine tube	UBERON:0001303	97.78	gold quality
right lung	UBERON:0002167	97.22	gold quality
pericardium	UBERON:0002407	96.96	gold quality
pylorus	UBERON:0001166	96.83	gold quality
endocervix	UBERON:0000458	96.75	gold quality
placenta	UBERON:0001987	96.72	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.70	gold quality
saphenous vein	UBERON:0007318	96.69	gold quality
cardia of stomach	UBERON:0001162	96.66	gold quality
urethra	UBERON:0000057	96.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.32	gold quality
lower esophagus	UBERON:0013473	96.27	gold quality
adipose tissue	UBERON:0001013	96.09	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.99	gold quality
peritoneum	UBERON:0002358	95.95	gold quality
omental fat pad	UBERON:0010414	95.95	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.90	gold quality
smooth muscle tissue	UBERON:0001135	95.77	gold quality
myometrium	UBERON:0001296	95.75	gold quality
gall bladder	UBERON:0002110	95.72	gold quality
right ovary	UBERON:0002118	95.71	gold quality
endometrium	UBERON:0001295	95.67	gold quality
superficial temporal artery	UBERON:0001614	95.52	gold quality
connective tissue	UBERON:0002384	95.39	gold quality
cauda epididymis	UBERON:0004360	95.36	gold quality
left ovary	UBERON:0002119	95.33	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	856.09
E-MTAB-6678	yes	704.88
E-GEOD-83139	yes	343.97
E-GEOD-81608	yes	167.44
E-MTAB-10287	yes	114.45
E-CURD-46	yes	23.19
E-MTAB-9543	yes	19.52
E-MTAB-8410	yes	17.05
E-CURD-112	yes	12.70
E-MTAB-5061	yes	12.27
E-GEOD-81547	yes	11.02
E-HCAD-11	yes	9.58
E-GEOD-84465	yes	9.30
E-HCAD-35	yes	8.57
E-ENAD-27	yes	6.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

148 targeting NID1, 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-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227

Literature-anchored findings (GeneRIF, showing 25)

• found to be ubiquitous component of basement membrane zones underneath developing epithelia of most of the major organ systems; may participate in cell biological functions during human development (PMID:12005023)
• nidogen-2 is equivalent to nidogen-1 in skin-organotypic coculture, and both can promote the development of a functional basement membrane zone (PMID:17008882)
• CpG islands of both NID1 and NID2 genes are aberrantly methylated in human cancer samples and cancer cell lines. (PMID:17328794)
• NID1 gene is a biologically plausible locus for nevogenesis and melanoma development (PMID:21478494)
• Cleavage of nidogen-1 by cathepsin S impairs its binding to basement membrane partners (PMID:22952693)
• results demonstrate that mutation in either NID1 or LAMC1 disrupts the interaction NID1-LAMC1 complex; findings implicate the extracellular matrix in the pathogenesis of Dandy-Walker spectrum disorders (PMID:23674478)
• The cleavage of nidogen-1 and -2 is partially inhibited in human tumor samples. (PMID:23681936)
• NID1 was confirmed as a target gene of MiR-192/215 in Hirschsprung’s disease patients. (PMID:25857602)
• Increase of NID1 protein expression is associated with endometrial cancer invasion. (PMID:25924802)
• Differential protein expression of collagen IV, laminin alpha2, and nidogen-1 indicated basal lamina remodeling develops in ischemic failing versus nonfailing human hearts. (PMID:26756417)
• nidogen-1 degraded by CatS can be quantified in serum by the NIC assay. The current data strongly suggest that cathepsin-S degradation of nidogen-1 is strongly associated with NSCLC, which needs validation in larger clinical cohorts. (PMID:28282545)
• Results demonstrated that NID1 was a mesenchymal associated gene and its high expression was significantly correlated with shorter overall survival of ovarian cancer patients. The study presents evidence that NID1 promotes the migration, invasion and chemoresistance of ovarian cancer cells via EMT and its molecular mechanism involves the activation of ERK/MAPK signaling. (PMID:28416770)
• Nidogen 1 (NID1) was confirmed to promote lung metastasis of breast cancer and melanoma. (PMID:28827399)
• Findings imply that the surrounding stromal cells of basal cell carcinoma (BCC), but not squamous cell carcinoma (SCC) or actinic keratosis (AK), excessively produce nidogen 1 (NID1), which may be involved in preventing BCC cells from destroying the basement membrane (BM) and invading the dermis. (PMID:30276677)
• This case report provides further evidence that variants in NID1 may be clinically relevant for the development of a phenotype that is consistent with ADDWOC, and extends the phenotype of NID1-associated ADDWOC to include arachnoid cysts. (PMID:30773799)
• Nidogen-1 Contributes to the Interaction Network Involved in Pro-B Cell Retention in the Peri-sinusoidal Hematopoietic Stem Cell Niche. (PMID:30893599)
• With the demonstration of the anti-migratory effect of endothelial cell-derived nidogen-1 on SK-BR-3 breast cancer cells study adds nidogen-1 to the regulators of endothelial control over cancer cell migration. (PMID:30947697)
• Results showed that NID1 level in oral cavity squamous cell carcinoma (OSCC) tissues was increased compared with adjacent noncancerous epithelium. Importantly, the elevated NID1 level was correlated with the advanced stages of OSCC, as well as the poor survival of OSCC patients. (PMID:31315917)
• Increased NID1 Expression among Breast Cancer Lung Metastatic Women; A Comparative Analysis between Naive and Treated Cases. (PMID:32116201)
• MicroRNA-1298-3p inhibits proliferation and invasion of glioma cells by downregulating Nidogen-1. (PMID:32355035)
• Nidogen-1 expression is associated with overall survival and temozolomide sensitivity in low-grade glioma patients. (PMID:33735110)
• Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2. (PMID:33890711)
• Obesity impairs skeletal muscle repair through NID-1 mediated extracellular matrix remodeling by mesenchymal progenitors. (PMID:35963565)
• Human Cytomegalovirus Utilizes Multiple Viral Proteins to Regulate the Basement Membrane Protein Nidogen 1. (PMID:36218358)
• Nidogen-1 could play a role in diabetic kidney disease development in type 2 diabetes: a genome-wide association meta-analysis. (PMID:36271454)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nid1a	ENSDARG00000068710
danio_rerio	nid1b	ENSDARG00000103129
mus_musculus	Nid1	ENSMUSG00000005397
rattus_norvegicus	Nid1	ENSRNOG00000002461

Paralogs (14): LRP6 (ENSG00000070018), LRP2 (ENSG00000081479), NID2 (ENSG00000087303), LRP1 (ENSG00000123384), LDLR (ENSG00000130164), LRP3 (ENSG00000130881), LRP4 (ENSG00000134569), EGF (ENSG00000138798), LRP12 (ENSG00000147650), VLDLR (ENSG00000147852), LRP8 (ENSG00000157193), LRP5 (ENSG00000162337), LRP1B (ENSG00000168702), LRP10 (ENSG00000197324)

Protein

Protein identifiers

Nidogen-1 — P14543 (reviewed: P14543)

Alternative names: Entactin

All UniProt accessions (1): P14543

UniProt curated annotations — full annotation on UniProt →

Function. Sulfated glycoprotein widely distributed in basement membranes and tightly associated with laminin. Also binds to collagen IV and perlecan. It probably has a role in cell-extracellular matrix interactions.

Subunit / interactions. Interacts with FBLN1. Interacts with LGALS3BP. Interacts with PLXDC1. Interacts with SVEP1.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Post-translational modifications. N- and O-glycosylated.

Isoforms (2)

UniProt ID	Names	Canonical?
P14543-1	1	yes
P14543-2	2

RefSeq proteins (1): NP_002499* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000033	LDLR_classB_rpt	Repeat
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000716	Thyroglobulin_1	Domain
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR003886	NIDO_dom	Domain
IPR006605	G2_nidogen/fibulin_G2F	Domain
IPR009017	GFP	Homologous_superfamily
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR024731	NELL2-like_EGF	Domain
IPR026823	cEGF	Domain
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR050778

Pfam: PF00058, PF00086, PF06119, PF07474, PF07645, PF12662, PF12947, PF14670

UniProt features (60 total): disulfide bond 22, sequence variant 13, domain 9, repeat 4, sequence conflict 4, modified residue 2, glycosylation site 2, signal peptide 1, chain 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14543-F1	78.50	0.36

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 (2): 289, 296

Disulfide bonds (22): 390–403, 397–412, 411–618, 414–425, 672–685, 679–695, 697–708, 714–727, 721–736, 738–750, 762–777, 769–787, 789–800, 806–817, 811–826, 828–839, 849–878, 889–896, 898–919, 1212–1223 …

Glycosylation sites (2): 922, 935

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-3000157	Laminin interactions

MSigDB gene sets: 285 (showing top): WALLACE_PROSTATE_CANCER_RACE_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, LUCAS_HNF4A_TARGETS_UP, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM3, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_CDC25_UP, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, BLALOCK_ALZHEIMERS_DISEASE_UP

GO Biological Process (10): cell-matrix adhesion (GO:0007160), positive regulation of cell-substrate adhesion (GO:0010811), glomerular basement membrane development (GO:0032836), positive regulation of cell adhesion (GO:0045785), positive regulation of muscle cell differentiation (GO:0051149), basement membrane organization (GO:0071711), regulation of basement membrane organization (GO:0110011), positive regulation of integrin-mediated signaling pathway (GO:2001046), cell adhesion (GO:0007155), extracellular matrix organization (GO:0030198)

GO Molecular Function (7): extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), collagen binding (GO:0005518), laminin binding (GO:0043236), laminin-1 binding (GO:0043237), proteoglycan binding (GO:0043394), extracellular matrix binding (GO:0050840)

GO Cellular Component (6): extracellular region (GO:0005576), basement membrane (GO:0005604), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), protein complex involved in cell-matrix adhesion (GO:0098637), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-substrate adhesion	2
extracellular matrix organization	2
extracellular matrix	2
protein binding	2
cellular anatomical structure	2
regulation of cell-substrate adhesion	1
positive regulation of cell adhesion	1
glomerulus development	1
anatomical structure development	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
muscle cell differentiation	1
positive regulation of cell differentiation	1
regulation of muscle cell differentiation	1
basement membrane organization	1
regulation of extracellular matrix organization	1
integrin-mediated signaling pathway	1
positive regulation of signal transduction	1
regulation of integrin-mediated signaling pathway	1
cellular process	1
extracellular structure organization	1
external encapsulating structure organization	1
structural molecule activity	1
metal ion binding	1
protein-containing complex binding	1
extracellular matrix binding	1
laminin binding	1
carbohydrate derivative binding	1
binding	1
external encapsulating structure	1
extracellular vesicle	1
protein complex involved in cell adhesion	1

Protein interactions and networks

STRING

1612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NID1	HSPG2	P98160	999
NID1	FN1	P02751	997
NID1	VTN	P01141	992
NID1	CD44	P16070	991
NID1	AGRN	O00468	979
NID1	NCR2	O95944	953
NID1	LAMC1	P11047	894
NID1	ELN	P15502	857
NID1	ZAN	Q9Y493	844
NID1	FBLN2	P98095	819
NID1	DAG1	Q14118	785
NID1	LAMA2	P24043	782
NID1	COL4A2	P08572	765
NID1	SPARC	P09486	764
NID1	BGN	P13247	744

IntAct

46 interactions, top by confidence:

A	B	Type	Score
ARRDC1	WWP2	psi-mi:“MI:0914”(association)	0.850
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
	NID1	psi-mi:“MI:0915”(physical association)	0.370
SKIL	NID1	psi-mi:“MI:0915”(physical association)	0.370
NID1		psi-mi:“MI:0915”(physical association)	0.370
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
KSR1		psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ATXN1		psi-mi:“MI:0914”(association)	0.350
CSAG2	CAMK2D	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
ANGPT4	POTEF	psi-mi:“MI:0914”(association)	0.350
FBLN2	ZNF316	psi-mi:“MI:0914”(association)	0.350
TAFAZZIN	MANBA	psi-mi:“MI:0914”(association)	0.350
NID2	AGRN	psi-mi:“MI:0914”(association)	0.350
LGALS9	PODXL	psi-mi:“MI:0914”(association)	0.350
LAMC3	TGFB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): NID1 (Affinity Capture-MS), NID1 (Affinity Capture-MS), NID1 (Affinity Capture-MS), NID1 (Affinity Capture-MS), NID1 (Affinity Capture-MS), NID1 (Affinity Capture-MS), NID1 (Affinity Capture-MS), NID1 (Reconstituted Complex), NID1 (Reconstituted Complex), NID1 (Reconstituted Complex), NID1 (Reconstituted Complex), NID1 (Reconstituted Complex), NID1 (Affinity Capture-MS), NID1 (Affinity Capture-MS), S (Reconstituted Complex)

ESM2 similar proteins: A0A8M9PFP2, A1X150, A2A863, A4IH88, B0S5G3, B2RXS4, F1LW30, F1R520, G5ED46, L7VG99, O08721, O08722, O08747, O60486, O73878, O94985, O95185, P10493, P14543, P16144, P35590, P54761, P55292, Q06806, Q0VCN6, Q14393, Q5FWR8, Q5R9Q9, Q61592, Q63772, Q64632, Q6DDG2, Q6Q0N0, Q6UXZ4, Q6ZN44, Q761X5, Q7T2Z5, Q8IZJ1, Q8K1S2, Q8K1S3

Diamond homologs: A0A6I8RMG7, A2AJ76, B3EWY9, B5DFC9, O35568, O77469, O88322, P10493, P14543, P41413, P48960, P98095, Q04592, Q09165, Q14112, Q19267, Q2KIT5, Q2Q421, Q2Q426, Q4G063, Q4V7F2, Q4V7M2, Q5EA46, Q5RBP1, Q5XH36, Q60438, Q6UXH1, Q6UXI9, Q7SXF6, Q7ZXL5, Q86XX4, Q8BPB5, Q8K4G1, Q8R4U0, Q8R4Y4, Q91XD7, Q96HD1, Q96RW7, Q9CYA0, Q9JJS0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	NID1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	190
Likely benign	17
Benign	70

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
183319	NM_002508.3(NID1):c.3385+1G>A	Likely pathogenic
418386	NM_002508.3(NID1):c.2T>A (p.Met1Lys)	Likely pathogenic

SpliceAI

3619 predictions. Top by Δscore:

Variant	Effect	Δscore
1:235978990:GTTA:G	donor_loss	1.0000
1:235978991:TTAC:T	donor_loss	1.0000
1:235978992:TACCT:T	donor_loss	1.0000
1:235978994:C:CT	donor_loss	1.0000
1:235979108:C:CC	acceptor_gain	1.0000
1:235979119:C:CT	acceptor_gain	1.0000
1:235979120:A:T	acceptor_gain	1.0000
1:235979816:ACGT:A	donor_loss	1.0000
1:235979819:TA:T	donor_loss	1.0000
1:235979820:A:AC	donor_gain	1.0000
1:235979821:C:A	donor_loss	1.0000
1:235979821:C:CC	donor_gain	1.0000
1:235980531:T:C	donor_gain	1.0000
1:235980564:T:TA	donor_gain	1.0000
1:235980649:GGTTC:G	acceptor_gain	1.0000
1:235980650:GTTC:G	acceptor_gain	1.0000
1:235980650:GTTCC:G	acceptor_gain	1.0000
1:235980651:TTC:T	acceptor_gain	1.0000
1:235980651:TTCCT:T	acceptor_gain	1.0000
1:235980652:TC:T	acceptor_gain	1.0000
1:235980652:TCC:T	acceptor_gain	1.0000
1:235980653:CC:C	acceptor_gain	1.0000
1:235980653:CCT:C	acceptor_gain	1.0000
1:235980654:C:CC	acceptor_gain	1.0000
1:235980654:C:T	acceptor_gain	1.0000
1:235981609:AC:A	donor_gain	1.0000
1:235981610:CC:C	donor_gain	1.0000
1:235981610:CCCT:C	donor_gain	1.0000
1:235981617:A:AC	donor_gain	1.0000
1:235981618:C:CC	donor_gain	1.0000

AlphaMissense

8149 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:236032565:A:G	L458P	0.998
1:235980632:C:A	W1083C	0.997
1:235980632:C:G	W1083C	0.997
1:236025931:C:G	R650P	0.997
1:236032452:A:G	W496R	0.997
1:236032452:A:T	W496R	0.997
1:236032523:G:T	A472D	0.997
1:236038115:C:G	C425S	0.997
1:236038116:A:G	C425R	0.997
1:236038116:A:T	C425S	0.997
1:235980643:A:G	W1080R	0.996
1:235980643:A:T	W1080R	0.996
1:235981729:A:G	W1037R	0.996
1:235981729:A:T	W1037R	0.996
1:236032524:C:G	A472P	0.996
1:236032563:G:C	H459D	0.996
1:236032631:C:T	G436D	0.996
1:235980634:A:G	W1083R	0.995
1:235980634:A:T	W1083R	0.995
1:236026115:A:C	Y589D	0.995
1:236029735:C:G	R518P	0.995
1:236032450:C:A	W496C	0.995
1:236032450:C:G	W496C	0.995
1:236032516:G:C	S474R	0.995
1:236032516:G:T	S474R	0.995
1:236032518:T:G	S474R	0.995
1:236048746:A:G	W157R	0.995
1:236048746:A:T	W157R	0.995
1:235977943:C:G	C1223S	0.994
1:235977944:A:T	C1223S	0.994

dbSNP variants (sampled 300 via entrez): RS1000005655 (1:235999484 C>A), RS1000135538 (1:236018479 G>A), RS1000152787 (1:236032344 G>A,T), RS1000169064 (1:235986741 C>A,T), RS1000202924 (1:236032555 G>A), RS1000241377 (1:236017472 G>C), RS1000283240 (1:235987035 C>G), RS1000284397 (1:236028599 A>C), RS1000286760 (1:236020879 G>A), RS1000392587 (1:236059467 T>G), RS1000423803 (1:236021177 C>T), RS1000435108 (1:235981108 T>C), RS1000437060 (1:236044588 C>A), RS1000452969 (1:236038738 T>A), RS1000459116 (1:236004378 C>T)

Disease associations

OMIM: gene MIM:131390 | disease phenotypes: MIM:614756

GenCC curated gene-disease

Disease	Classification	Inheritance
central nervous system malformation	Strong	Autosomal dominant

Mondo (4): hydrocephalus (MONDO:0001150), focal epilepsy (MONDO:0005384), cerebellar dysfunction with variable cognitive and behavioral abnormalities (MONDO:0013886), central nervous system malformation (MONDO:0020022)

Orphanet (1): Non-progressive cerebellar ataxia with intellectual disability (Orphanet:314647)

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001034_1	Cutaneous nevi	7.000000e-08
GCST002829_24	Urate levels in overweight individuals	9.000000e-06
GCST008256_5	Diverticulitis	3.000000e-06
GCST010293_8	Response to levetiracetam in genetic generalized epilepsy	6.000000e-06
GCST010396_308	Gut microbiota (bacterial taxa, hurdle binary method)	6.000000e-06
GCST90002395_510	Mean platelet volume	1.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0000625	nevus
EFO:0004531	urate measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004828	Epilepsies, Partial	C10.228.140.490.360
D006849	Hydrocephalus	C10.228.140.602
D009421	Nervous System Malformations	C10.500; C16.131.666

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, affects expression, decreases methylation	5
Valproic Acid	affects cotreatment, increases expression, affects expression	5
bisphenol A	affects expression, affects cotreatment, decreases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects cotreatment, increases expression, decreases expression, increases abundance	2
Arsenic	affects expression, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	increases expression, increases methylation	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
lead acetate	affects cotreatment, increases expression	1
salinomycin	decreases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
hydroquinone	decreases expression	1
nivalenol	decreases expression	1
4-nonylphenol	affects cotreatment, decreases expression	1
pentanal	increases expression	1
4-tert-octylphenol	affects cotreatment, decreases expression	1
entinostat	increases expression	1
monomethylarsonous acid	increases 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
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_RY70	HEK293 rLN10_hNid1	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01323764	PHASE4	COMPLETED	ShuntCheck Versus Radionuclide in Evaluating Shunt Function in Symptomatic NPH Patients
NCT01685450	PHASE4	UNKNOWN	NIMIP: Non Invasive Measurement of the Intracranial Pressure
NCT03513757	PHASE4	COMPLETED	Dexmedetomidine and Propofol for Pediatric MRI Sedation
NCT07547826	PHASE4	NOT_YET_RECRUITING	Efficacy and Cost-Effectiveness of Topical Vancomycin Powder in Preventing Pediatric Ventriculoperitoneal Shunt Infections Across Different Etiologies
NCT00438451	PHASE4	COMPLETED	Study on the Treatment of Elderly Patients With Older and Newer Antiepileptic Drugs
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00855738	PHASE4	COMPLETED	A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice
NCT00955357	PHASE4	COMPLETED	Trial to Assess Lacosamide as the First add-on Anti-epileptic Drug Treatment in Patients With Partial-onset Seizures
NCT01190098	PHASE4	COMPLETED	Randomized Controlled Trial to Assess Effects of Lacosamide on Sleep and Wake in Adults With Focal Epilepsy
NCT01235403	PHASE4	COMPLETED	Trial to Assess Optimized Dosage of Lacosamide as add-on Therapy in Patients With Partial Onset Seizure
NCT02208492	PHASE4	COMPLETED	The Effects on Cognitive Function of Levetiracetam (Keppra®) Compared to Carbamazepine (Tegretol®, Carmazepine®) as Monotherapy for Children With Partial Seizure; A Multicentric Randomized Controlled Study
NCT03607851	PHASE4	COMPLETED	Efficacy and Safety of Rapid Titration Protocols of Lacosamide
NCT05748236	PHASE4	UNKNOWN	The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy
NCT07193277	PHASE4	RECRUITING	Butylphthalide for Cognitive Impairment in Elderly Patients With Focal Epilepsy
NCT00196196	PHASE3	COMPLETED	A Precision and Accuracy Study of the Codman Valve Position Verification (VPV) System.
NCT00286104	PHASE3	COMPLETED	Impact of Ventricular Catheter Used With Antimicrobial Agents on Patients With a Ventricular Catheter
NCT01936272	PHASE3	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Shunt vs ETV/CPC for PIH in Ugandan Infants
NCT02425761	PHASE3	UNKNOWN	The CSF Shunt Entry Site Trial
NCT02512809	PHASE3	TERMINATED	Isoflurane-induced Neuroinflammation in Children With Hydrocephalus
NCT04177914	PHASE3	RECRUITING	HCRN Endoscopic Versus Shunt Treatment of Hydrocephalus in Infants
NCT00391534	PHASE3	TERMINATED	EXTENT: EXtended Tolerability and Efficacy of a Novel Formulation of Oxcarbazepine in a Trial in Partial Epilepsy
NCT00522275	PHASE3	COMPLETED	Determine Safety and Efficacy of Long-term Oral Lacosamide in Patients With Partial Seizures
NCT00655486	PHASE3	COMPLETED	Study to Assess the Long-term Safety of Oral Lacosamide in Subjects With Partial-onset Seizures
NCT00655551	PHASE3	COMPLETED	Safety of Intravenous Lacosamide Dose Followed by Twice Daily Oral Lacosamide in Subjects With Partial-onset Seizures
NCT00908349	PHASE3	COMPLETED	Safety and Tolerability of OXC XR as Adjunctive Therapy in Subjects With Refractory Partial Epilepsy
NCT00957047	PHASE3	COMPLETED	Efficacy and Safety Study of BIA 2-093 in Combination With Other Anti-Epileptic Drugs to Treat Partial Epilepsy
NCT00957372	PHASE3	COMPLETED	Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Epilepsy
NCT00957684	PHASE3	COMPLETED	Efficacy and Safety of Eslicarbazepine Acetate as Adjunctive Therapy for Refractory Partial Seizures
NCT00988429	PHASE3	COMPLETED	Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures
NCT02076698	PHASE3	COMPLETED	Deep Brain Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy
NCT02535091	PHASE3	COMPLETED	Safety and Pharmacokinetic Study of YKP3089 as Adjunctive Therapy in Subjects With Partial Onset Seizures
NCT05067634	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study of Cenobamate in Pediatric Subjects 2-17 Years of Age With Partial-onset (Focal) Seizures
NCT05718817	PHASE3	ENROLLING_BY_INVITATION	An Open-label Study of XEN1101 in Epilepsy
NCT07505004	PHASE3	RECRUITING	Double-blind, Randomized Clinical Trial Evaluating the Efficacy and Safety of Vormatrigine in Adults With Focal Seizures
NCT07563881	PHASE3	RECRUITING	Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures FOCUS-1
NCT07594119	PHASE3	NOT_YET_RECRUITING	Study Evaluating the Efficacy and Safety of RAP-219 in Adult Participants With Focal Seizures
NCT07594158	PHASE3	RECRUITING	A Study to Evaluate the Safety, Efficacy, and PK of ONO-2017 in Japanese Patients With POS 2 to 17 Year Olds
NCT00652470	PHASE2	COMPLETED	A Study Comparing Two Treatments for Infants With Hydrocephalus
NCT00465517	PHASE2	COMPLETED	A Randomized, Controlled Trial of Ganaxolone in Adult Uncontrolled Partial-Onset Seizures
NCT00552305	PHASE2	COMPLETED	To Determine Tolerability and Efficacy of Long-term Oral Lacosamide in Patients With Partial Seizures