NAV2

Summary

NAV2 (neuron navigator 2, HGNC:15997) is a protein-coding gene on chromosome 11p15.1, encoding Neuron navigator 2 (Q8IVL1). Possesses 3’ to 5’ helicase activity and exonuclease activity.

This gene encodes a member of the neuron navigator gene family, which may play a role in cellular growth and migration. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 89797 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 27
• Clinical variants (ClinVar): 422 total
• MANE Select transcript: NM_145117

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15997
Approved symbol	NAV2
Name	neuron navigator 2
Location	11p15.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10633, FLJ11030, HELAD1, KIAA1419, POMFIL2, RAINB1, FLJ23707
Ensembl gene	ENSG00000166833
Ensembl biotype	protein_coding
OMIM	607026
Entrez	89797

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000349880, ENST00000360655, ENST00000396085, ENST00000396087, ENST00000525025, ENST00000525322, ENST00000526675, ENST00000528008, ENST00000528923, ENST00000530408, ENST00000533746, ENST00000533917, ENST00000534229, ENST00000534299, ENST00000650578

RefSeq mRNA: 5 — MANE Select: NM_145117 NM_001111018, NM_001111019, NM_001244963, NM_145117, NM_182964

CCDS: CCDS44552, CCDS53612, CCDS58126, CCDS7850, CCDS7851

Canonical transcript exons

ENST00000349880 — 38 exons

Exon	Start	End
ENSE00001107068	20092206	20092368
ENSE00001107072	20062307	20062359
ENSE00001107074	20077552	20077635
ENSE00001107076	20105531	20105727
ENSE00001107078	20068324	20068398
ENSE00001107080	20077993	20078104
ENSE00001107082	20093099	20093199
ENSE00001149268	20055769	20055957
ENSE00001149275	20054080	20054240
ENSE00001149282	20051289	20051333
ENSE00001149290	20049836	20049901
ENSE00001149296	20048728	20049195
ENSE00001149301	20044968	20045670
ENSE00001149322	19984125	19984247
ENSE00001149329	19948691	19949080
ENSE00001149336	19946401	19946509
ENSE00001149343	19939661	19939773
ENSE00001149353	19933176	19934277
ENSE00001149361	19892434	19892594
ENSE00001206236	20103255	20103409
ENSE00001216265	20068186	20068209
ENSE00001308061	20095672	20095767
ENSE00001329669	20090865	20091018
ENSE00001331342	20103653	20103724
ENSE00001331345	20100937	20101172
ENSE00001331350	20083007	20083179
ENSE00001523878	20097577	20097745
ENSE00002716718	20080064	20080209
ENSE00003512943	19832484	19832601
ENSE00003534521	20107664	20107782
ENSE00003543361	19842871	19842923
ENSE00003564367	20043981	20044272
ENSE00003594583	20035959	20036097
ENSE00003600365	19868925	19868997
ENSE00003603006	20114592	20114795
ENSE00003694733	19879869	19880127
ENSE00003846126	19712837	19713962
ENSE00003849829	20118133	20121601

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8918 / max 319.6796, expressed in 1541 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113382	15.5608	1342
113403	2.7036	562
113368	1.6470	485
113381	1.4519	658
113383	1.3695	672
113404	0.9267	310
113405	0.7435	273
113386	0.6245	245
113406	0.4759	195
113385	0.4149	182

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	97.72	gold quality
cartilage tissue	UBERON:0002418	96.13	gold quality
cauda epididymis	UBERON:0004360	95.47	gold quality
corpus epididymis	UBERON:0004359	94.81	gold quality
visceral pleura	UBERON:0002401	94.70	gold quality
medial globus pallidus	UBERON:0002477	94.65	gold quality
bronchial epithelial cell	CL:0002328	94.57	gold quality
caput epididymis	UBERON:0004358	94.47	gold quality
oocyte	CL:0000023	94.13	gold quality
globus pallidus	UBERON:0001875	94.05	gold quality
medulla oblongata	UBERON:0001896	93.81	gold quality
epithelium of mammary gland	UBERON:0003244	93.81	gold quality
mammary duct	UBERON:0001765	93.63	gold quality
saphenous vein	UBERON:0007318	93.55	gold quality
epithelium of bronchus	UBERON:0002031	93.29	gold quality
renal medulla	UBERON:0000362	93.13	gold quality
sural nerve	UBERON:0015488	93.10	gold quality
thoracic aorta	UBERON:0001515	93.09	gold quality
ascending aorta	UBERON:0001496	93.05	gold quality
bronchus	UBERON:0002185	92.94	gold quality
descending thoracic aorta	UBERON:0002345	92.78	gold quality
superior vestibular nucleus	UBERON:0007227	92.67	gold quality
seminal vesicle	UBERON:0000998	92.21	gold quality
corpus callosum	UBERON:0002336	91.87	gold quality
cortical plate	UBERON:0005343	91.69	gold quality
secondary oocyte	CL:0000655	91.65	gold quality
inferior olivary complex	UBERON:0002127	91.59	gold quality
parotid gland	UBERON:0001831	91.48	gold quality
tibia	UBERON:0000979	91.43	gold quality
ventral tegmental area	UBERON:0002691	91.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-119	yes	2156.31
E-GEOD-131882	yes	2125.30
E-HCAD-35	yes	53.96
E-ANND-3	yes	9.28
E-MTAB-7381	no	331.15

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZMYND8

miRNA regulators (miRDB)

215 targeting NAV2, 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-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-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-103A-3P	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 9)

• regulated by all-trans retinoic acid in neuroblastoma cells (PMID:11904404)
• a novel gene, termed HELAD1 (helicase, APC down-regulated 1) plays important role in colorectal carcinogenesis (HELAD1) (PMID:12214280)
• interaction between NAV2 and 14-3-3epsilon (PMID:24161943)
• NAV2 and CCND2 are novel candidate prognostic markers in uterine leiomyosarcoma and uterine low-grade endometrial stromal sarcoma, respectively. (PMID:28643014)
• The present study is the first study providing evidence of several genetic variants within the NAV2 gene influencing the risk and age at onset of Alzheimer’s disease. (PMID:28778446)
• Study found that melanoma tissues showed an upregulated expression of NAV2 which correlated with poor prognosis of cutaneous melanoma. NAV2-mediated invasion of melanoma cells was driven by enhanced epithelial-mesenchymal transition, which was resulted from SNAI2 upregulation via the GSK-3beta/beta-catenin pathway. (PMID:30997569)
• DNA hypermethylation is associated with invasive phenotype of malignant melanoma. (PMID:31602702)
• NAV2 positively modulates inflammatory response of fibroblast-like synoviocytes through activating Wnt/beta-catenin signaling pathway in rheumatoid arthritis. (PMID:33931978)
• Identification of novel genes including NAV2 associated with isolated tall stature. (PMID:38152138)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nav2b	ENSDARG00000001879
danio_rerio	nav2a	ENSDARG00000073688
mus_musculus	Nav2	ENSMUSG00000052512
rattus_norvegicus	Nav2	ENSRNOG00000014530
caenorhabditis_elegans		WBGENE00006788

Paralogs (2): NAV3 (ENSG00000067798), NAV1 (ENSG00000134369)

Protein

Protein identifiers

Neuron navigator 2 — Q8IVL1 (reviewed: Q8IVL1)

Alternative names: Helicase APC down-regulated 1, Pore membrane and/or filament-interacting-like protein 2, Retinoic acid inducible in neuroblastoma 1, Steerin-2, Unc-53 homolog 2

All UniProt accessions (4): Q8IVL1, A0A3B3ISY2, E9PLU3, E9PNV5

UniProt curated annotations — full annotation on UniProt →

Function. Possesses 3’ to 5’ helicase activity and exonuclease activity. Involved in cytoskeleton organization. Required for neurite outgrowth in response to stimulation by all-trans retinoic acid (atRA). Involved in neuronal development, specifically in the development of different sensory organs. Important for brain and cerebellar development. Involved in the differentiation, migration and axonal extension of granule cells in the developing cerebellum. Involved in the development of the glossopharyngeal cranial nerve IX and the vagus cranial nerve X, possibly by influencing neuronal cell elongation or survival; influencing the efficiency of the baroreceptor reflex response to changes in blood pressure.

Subcellular location. Nucleus. Cytoplasm. Cytoskeleton. Cell projection. Axon. Perikaryon.

Tissue specificity. Broadly expressed at low levels. Highly expressed in the brain, kidney and liver. Also expressed in the thyroid, mammary gland, spinal cord, heart, placenta and lung. Abundantly expressed in colon cancers.

Domain organisation. Possesses a cytoskeleton interacting domain (CSID) essential and sufficient to localize to microtubules.

Induction. By all-trans retinoic acid (atRA). Up-regulated in colorectal carcinomas.

Similarity. Belongs to the Nav/unc-53 family.

Isoforms (13)

UniProt ID	Names	Canonical?
Q8IVL1-1	1	yes
Q8IVL1-2	2, RAINB1d
Q8IVL1-3	3, HELAD1L
Q8IVL1-4	4, HELAD1S
Q8IVL1-5	5
Q8IVL1-6	6
Q8IVL1-7	7
Q8IVL1-8	8
Q8IVL1-9	9
Q8IVL1-10	10
Q8IVL1-11	11
Q8IVL1-12	12
Q8IVL1-13	13

RefSeq proteins (5): NP_001104488, NP_001104489, NP_001231892, NP_660093, NP_892009 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR003593	AAA+_ATPase	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036872	CH_dom_sf	Homologous_superfamily
IPR039041	Nav/unc-53	Family
IPR057126	NAV1-like_ubiquitin-like	Domain
IPR057568	CortBP2_NAV1-like_AAA_lid	Domain

Pfam: PF00307, PF23092, PF25408

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (96 total): compositionally biased region 30, region of interest 15, splice variant 15, sequence conflict 13, sequence variant 6, helix 6, modified residue 4, coiled-coil region 3, chain 1, domain 1, binding site 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2YRN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVL1-F1	46.79	0.10

Functional residue map

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

Ligand- & substrate-binding residues (1): 2157–2164

Post-translational modifications (4): 1480, 1484, 1488, 1977

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 304 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, BOYAULT_LIVER_CANCER_SUBCLASS_G56_DN, GOBP_NEUROGENESIS, CTATGCA_MIR153, AAAYRNCTG_UNKNOWN, TTGGGAG_MIR150, CTAGGAA_MIR384, AGTCTTA_MIR499, MARTINEZ_RB1_TARGETS_UP, TCF4_Q5, GOBP_CEREBELLAR_CORTEX_DEVELOPMENT

GO Biological Process (10): regulation of systemic arterial blood pressure by baroreceptor feedback (GO:0003025), nervous system development (GO:0007399), sensory perception of sound (GO:0007605), sensory perception of smell (GO:0007608), locomotory behavior (GO:0007626), optic nerve development (GO:0021554), glossopharyngeal nerve development (GO:0021563), vagus nerve development (GO:0021564), cerebellar cortex development (GO:0021695), neurogenesis (GO:0022008)

GO Molecular Function (8): ATP binding (GO:0005524), heparin binding (GO:0008201), ATP hydrolysis activity (GO:0016887), 3’-5’ DNA helicase activity (GO:0043138), nucleotide binding (GO:0000166), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): interstitial matrix (GO:0005614), nucleoplasm (GO:0005654), nucleus (GO:0005634), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cranial nerve development	3
ATP-dependent activity	2
nervous system process involved in regulation of systemic arterial blood pressure	1
system development	1
sensory perception of mechanical stimulus	1
sensory perception of chemical stimulus	1
behavior	1
preganglionic parasympathetic fiber development	1
cerebellum development	1
anatomical structure development	1
nervous system development	1
cell differentiation	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
ribonucleoside triphosphate phosphatase activity	1
DNA helicase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
binding	1
catalytic activity	1
extracellular matrix	1
nuclear lumen	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
external encapsulating structure	1

Protein interactions and networks

STRING

1498 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAV2	CNN1	P51911	692
NAV2	TCF7L1	Q9HCS4	674
NAV2	ABI1	Q8IZP0	551
NAV2	CAPN6	Q9Y6Q1	506
NAV2	GAS2	O43903	404
NAV2	MGAT5B	Q3V5L5	404
NAV2	ARHGAP22	Q7Z5H3	400
NAV2	SYNDIG1	Q9H7V2	397
NAV2	NALCN	Q8IZF0	389
NAV2	SCN7A	Q01118	387
NAV2	TMEM132A	Q24JP5	385
NAV2	AMDHD1	Q96NU7	364
NAV2	BAHCC1	Q9P281	351
NAV2	IQCC	Q4KMZ1	328
NAV2	VTI1A	Q96AJ9	321

IntAct

52 interactions, top by confidence:

A	B	Type	Score
ING5	NAV2	psi-mi:“MI:0915”(physical association)	0.740
NAV2	ING5	psi-mi:“MI:0915”(physical association)	0.740
PIAS2	NAV2	psi-mi:“MI:0915”(physical association)	0.670
NAV2	PIAS2	psi-mi:“MI:0915”(physical association)	0.670
CFAP58	NAV2	psi-mi:“MI:0915”(physical association)	0.560
NAV2	ADAT2	psi-mi:“MI:0915”(physical association)	0.560
NAV2	RBM15B	psi-mi:“MI:0915”(physical association)	0.560
RBM15B	NAV2	psi-mi:“MI:0915”(physical association)	0.560
RBM15	NAV2	psi-mi:“MI:0915”(physical association)	0.560
NAV2	MORF4L1	psi-mi:“MI:0915”(physical association)	0.560
ING4	NAV2	psi-mi:“MI:0915”(physical association)	0.560
NAV2	CFAP58	psi-mi:“MI:0915”(physical association)	0.560
NAV2	RBM15	psi-mi:“MI:0915”(physical association)	0.560
NAV2	ING4	psi-mi:“MI:0915”(physical association)	0.560
MORF4L1	NAV2	psi-mi:“MI:0915”(physical association)	0.560
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530

BioGRID (49): NAV2 (Two-hybrid), NAV2 (Two-hybrid), NAV2 (Two-hybrid), NAV2 (Two-hybrid), NAV2 (Two-hybrid), NAV2 (Two-hybrid), ADAT2 (Two-hybrid), CFAP58 (Two-hybrid), NAV2 (Two-hybrid), NAV2 (Two-hybrid), NAV2 (Two-hybrid), NAV2 (Proximity Label-MS), NAV2 (Two-hybrid), NAV2 (Two-hybrid), NAV2 (Two-hybrid)

ESM2 similar proteins: A0A0R4IZ84, A0A1L8H8C0, A0A1L8HFX9, A2RUV4, F1LP90, F5HSE3, O43310, O60237, O75167, O88453, P41110, P61406, Q12830, Q1LVF3, Q2HJG4, Q2PFD7, Q3TLH4, Q5RAK6, Q5ZMS6, Q66HC1, Q6A0A2, Q6NRP6, Q6NZL0, Q6P1U3, Q6PKG0, Q75N33, Q7TN02, Q7TPM1, Q7YZA2, Q7Z6E9, Q80TN7, Q80XI3, Q86UR5, Q86US8, Q8IVL0, Q8IVL1, Q8K0V4, Q8N4C8, Q90YL3, Q90YY5

Diamond homologs: A0M8S4, A0M8T5, A1X157, B9EJA2, Q00PJ1, Q07DV1, Q07DW4, Q07DX4, Q07DY4, Q07DZ5, Q07E15, Q07E28, Q07E41, Q09YG9, Q09YI1, Q09YJ3, Q09YK4, Q09YM8, Q108T9, Q2IBA2, Q2IBB2, Q2IBD4, Q2IBE6, Q2IBF7, Q2IBF8, Q2QL82, Q2QLA2, Q2QLB3, Q2QLF8, Q2QLG9, Q5RDH2, Q6P6L0, Q8IVL1, Q8WZ74, Q99LJ0, Q9P2B4, A5D7D1, D3ZBP4, D3ZHA0, D3ZHV2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ZMYND8	“up-regulates quantity by expression”	NAV2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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
Activation of BAD and translocation to mitochondria	7	231.7×	4e-14
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	204.4×	6e-14
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	204.4×	6e-14
Activation of BH3-only proteins	7	151.1×	5e-13
RHO GTPases activate PKNs	7	96.5×	1e-11
Intrinsic Pathway for Apoptosis	7	89.1×	2e-11
FOXO-mediated transcription	5	73.0×	7e-08
Apoptosis	9	65.7×	2e-13

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	68.7×	8e-08
intracellular protein localization	7	22.9×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	326
Likely benign	26
Benign	25

Top pathogenic / likely-pathogenic (0)

SpliceAI

2344 predictions. Top by Δscore:

Variant	Effect	Δscore
11:19832479:TACA:T	acceptor_loss	1.0000
11:19832481:C:G	acceptor_gain	1.0000
11:19832482:A:AG	acceptor_gain	1.0000
11:19832482:A:G	acceptor_loss	1.0000
11:19832483:G:GC	acceptor_gain	1.0000
11:19832483:GAT:G	acceptor_gain	1.0000
11:19832600:GG:G	donor_gain	1.0000
11:19832601:GG:G	donor_gain	1.0000
11:19832602:G:GG	donor_gain	1.0000
11:19842867:TCAGC:T	acceptor_loss	1.0000
11:19842868:CAGCA:C	acceptor_loss	1.0000
11:19842869:A:AG	acceptor_gain	1.0000
11:19842870:G:GG	acceptor_gain	1.0000
11:19842870:GC:G	acceptor_gain	1.0000
11:19842870:GCA:G	acceptor_gain	1.0000
11:19842870:GCAA:G	acceptor_gain	1.0000
11:19842870:GCAAA:G	acceptor_gain	1.0000
11:19842920:AATG:A	donor_gain	1.0000
11:19842921:ATG:A	donor_gain	1.0000
11:19842922:TG:T	donor_gain	1.0000
11:19842923:GG:G	donor_gain	1.0000
11:19842923:GGTA:G	donor_loss	1.0000
11:19842924:G:GG	donor_gain	1.0000
11:19842924:G:T	donor_loss	1.0000
11:19713961:AGG:A	donor_loss	0.9900
11:19713962:GG:G	donor_loss	0.9900
11:19713963:GTGA:G	donor_loss	0.9900
11:19813280:GCAT:G	donor_gain	0.9900
11:19832479:TACAG:T	acceptor_gain	0.9900
11:19832480:A:AG	acceptor_gain	0.9900

AlphaMissense

15949 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:19832496:T:A	W94R	1.000
11:19832496:T:C	W94R	1.000
11:19832498:G:C	W94C	1.000
11:19832498:G:T	W94C	1.000
11:19832512:T:C	L99P	1.000
11:19832548:T:C	L111P	1.000
11:19868943:T:C	C153R	1.000
11:19868956:T:C	L157P	1.000
11:19879905:T:C	L183P	1.000
11:19879917:T:C	L187P	1.000
11:19933644:C:A	A490D	1.000
11:19946445:G:C	A754P	1.000
11:19946452:T:C	L756P	1.000
11:19946455:G:C	R757P	1.000
11:19946464:T:C	L760S	1.000
11:20035960:T:A	W947R	1.000
11:20035960:T:C	W947R	1.000
11:20068334:T:C	L1696P	1.000
11:20068346:T:C	L1700P	1.000
11:20068388:T:C	L1714P	1.000
11:20077552:G:C	A1718P	1.000
11:20077559:T:C	L1720P	1.000
11:20077567:G:C	A1723P	1.000
11:20077583:T:C	L1728P	1.000
11:20077604:T:C	L1735P	1.000
11:20077613:T:C	L1738P	1.000
11:20078003:T:C	L1749P	1.000
11:20078033:T:C	L1759P	1.000
11:20078053:G:C	A1766P	1.000
11:20078066:T:A	I1770N	1.000

dbSNP variants (sampled 300 via entrez): RS1000004774 (11:19963417 C>A,T), RS1000005922 (11:19428723 T>C), RS1000006959 (11:19938934 A>C), RS1000012375 (11:19816853 C>T), RS1000018887 (11:19813994 C>A,T), RS1000020175 (11:19980750 T>G), RS1000027858 (11:19643286 A>G), RS1000028791 (11:19605400 T>G), RS1000031738 (11:19528727 C>T), RS1000043930 (11:19887455 G>A), RS1000044872 (11:19937857 G>A), RS1000050486 (11:19380615 T>C), RS1000050798 (11:19976737 C>G,T), RS1000056258 (11:19540033 G>A,T), RS1000065594 (11:19565234 C>T)

Disease associations

OMIM: gene MIM:607026 | disease phenotypes: MIM:142623

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (2): Hirschsprung disease, susceptibility to, 1 (MONDO:0007723), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Hirschsprung disease (Orphanet:388)

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST001762_74	Obesity-related traits	7.000000e-06
GCST002730_1	Hepatitis	1.000000e-09
GCST002754_2	Response to inhaled glucocorticoid treatment in asthma (change in FEV1)	6.000000e-11
GCST003560_10	Coronary artery aneurysm in Kawasaki disease	3.000000e-06
GCST003996_13	Monobrow	2.000000e-11
GCST006061_146	Atrial fibrillation	9.000000e-17
GCST006061_167	Atrial fibrillation	2.000000e-14
GCST006133_2	Bone mineral density x blood lead interaction in current smokers (2df test)	5.000000e-06
GCST006269_736	General cognitive ability	1.000000e-08
GCST006414_5	Atrial fibrillation	2.000000e-20
GCST006609_1	Response to TNF inhibitor in rheumatoid arthritis (change in tender 28-joint count)	4.000000e-08
GCST006976_131	Macular thickness	2.000000e-08
GCST007045_35	PR interval	2.000000e-09
GCST008151_62	Waist circumference	9.000000e-06
GCST008160_21	Waist circumference	9.000000e-06
GCST008502_12	Low susceptibility to hepatitis C infection	5.000000e-06
GCST008810_87	Smoking initiation (ever regular vs never regular)	1.000000e-08
GCST009028_14	Adverse response to drug	3.000000e-07
GCST009277_3	Subjective response to placebo treatment in childhood asthma (change in cough/wheeze)	7.000000e-06
GCST010321_128	PR interval	5.000000e-12
GCST010703_293	Brain morphology (MOSTest)	1.000000e-14
GCST010796_4527	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4528	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4529	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4530	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST012008_11	Lateral thalamic nuclei volume	2.000000e-11
GCST012488_33	L1-L4 bone mineral density x serum urate levels interaction	5.000000e-07

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0005921	FEV change measurement
EFO:0007906	synophrys measurement
EFO:0004337	intelligence
EFO:0004653	response to TNF antagonist
EFO:0005413	joint damage measurement
EFO:0004462	PR interval
EFO:0010101	decreased susceptibility to hepatitis C infection
EFO:0005670	smoking initiation
EFO:0009658	adverse effect
EFO:0008344	response to placebo
EFO:0010068	respiratory symptom change measurement
EFO:0004346	neuroimaging measurement
EFO:0004327	electrocardiography
EFO:0006935	thalamus volume
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2254237	NAV2		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	5
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, affects expression	5
Valproic Acid	decreases methylation, affects cotreatment, increases expression, affects expression	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Estradiol	decreases expression, affects expression, increases expression, increases reaction, affects cotreatment	4
Tretinoin	decreases reaction, increases expression	4
Arsenic	increases expression, affects methylation, affects cotreatment, decreases expression, increases abundance	3
Cyclosporine	increases expression	3
bisphenol A	affects cotreatment, decreases expression, decreases methylation	2
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Vehicle Emissions	decreases methylation, decreases expression, increases abundance	2
Cisplatin	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Quercetin	decreases expression, increases phosphorylation	2
Silicon Dioxide	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects methylation, increases methylation	2
Asbestos, Crocidolite	decreases expression, increases expression	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
glycidyl methacrylate	increases expression	1
trichostatin A	increases expression	1
N,N-diethyl 4-phenylenediamine	affects response to substance	1
dodecyldimethylamine oxide	increases expression	1
beta-lapachone	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
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
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT04904081	PHASE3	UNKNOWN	Feasibility of Use of Indocyanine Green in Pediatric Colorectal Surgery
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00630838	PHASE2	COMPLETED	Probiotic Prophylaxis of Hirschprung’s Disease Associated Enterocolitis (HAEC)
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase