NAV3

Summary

NAV3 (neuron navigator 3, HGNC:15998) is a protein-coding gene on chromosome 12q21.2, encoding Neuron navigator 3 (Q8IVL0). Is involved in microtubule cytoskeleton organization and plays a role in cell migration.

This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain characteristic for ATPases associated with a variety of cellular activities. This gene is similar to unc-53, a Caenorhabditis elegans gene involved in axon guidance. Multiple alternatively spliced transcript variants for this gene have been described but only one has had its full-length nature determined.

Source: NCBI Gene 89795 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 24
• Clinical variants (ClinVar): 357 total — 7 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 66
• MANE Select transcript: NM_001024383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15998
Approved symbol	NAV3
Name	neuron navigator 3
Location	12q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0938, POMFIL1
Ensembl gene	ENSG00000067798
Ensembl biotype	protein_coding
OMIM	611629
Entrez	89795

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000397909, ENST00000536525, ENST00000547725, ENST00000547884, ENST00000548948, ENST00000549369, ENST00000549464, ENST00000550042, ENST00000550503, ENST00000550673, ENST00000550788, ENST00000551162, ENST00000551277, ENST00000552300, ENST00000552895, ENST00000644176

RefSeq mRNA: 2 — MANE Select: NM_001024383 NM_001024383, NM_014903

CCDS: CCDS41815, CCDS66432

Canonical transcript exons

ENST00000397909 — 40 exons

Exon	Start	End
ENSE00000910575	78127167	78127208
ENSE00000910591	78200473	78200591
ENSE00000910592	78204935	78205138
ENSE00001221680	78116772	78116904
ENSE00001221842	78121940	78122428
ENSE00001221859	78118027	78118297
ENSE00001299535	78177620	78177685
ENSE00001596286	77994803	77994871
ENSE00001602637	78189984	78190219
ENSE00001613542	78140282	78140334
ENSE00001626146	78006419	78007445
ENSE00001628691	78188609	78188777
ENSE00001641301	78146369	78146392
ENSE00001661213	78198605	78198676
ENSE00001667942	78050764	78051147
ENSE00001675567	78176439	78176459
ENSE00001681900	78021747	78021862
ENSE00001702911	78197247	78197401
ENSE00001712027	78058996	78059115
ENSE00001714784	78148842	78148919
ENSE00001718321	78179529	78179682
ENSE00001724281	78159203	78159286
ENSE00001724339	78175306	78175427
ENSE00001733949	77966229	77966301
ENSE00001737377	78137177	78137365
ENSE00001740961	78049993	78050101
ENSE00001749023	78168755	78168866
ENSE00001783225	78177141	78177313
ENSE00001788895	78119237	78119945
ENSE00001799284	78128706	78128866
ENSE00002357417	78210398	78213010
ENSE00002692660	78199335	78199531
ENSE00003461604	77968519	77968702
ENSE00003471205	77998337	77998476
ENSE00003507890	78188248	78188343
ENSE00003609960	78180871	78181045
ENSE00003614441	78185601	78185698
ENSE00003671755	77940319	77940436
ENSE00003677187	77941081	77941133
ENSE00003848762	77830894	77831704

Expression profiles

Bgee: expression breadth ubiquitous, 232 present calls, max score 96.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.9157 / max 350.2229, expressed in 1357 samples.

FANTOM5 promoters (35 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126964	3.7985	627
126986	2.6839	648
126985	2.0890	611
126987	1.3962	516
126982	0.4794	261
126963	0.4434	201
206811	0.4217	211
126965	0.3692	203
126977	0.3018	81
127001	0.2764	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	96.92	gold quality
cortical plate	UBERON:0005343	96.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.57	gold quality
orbitofrontal cortex	UBERON:0004167	95.43	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.31	gold quality
pigmented layer of retina	UBERON:0001782	95.30	gold quality
corpus callosum	UBERON:0002336	95.28	gold quality
CA1 field of hippocampus	UBERON:0003881	94.76	gold quality
decidua	UBERON:0002450	94.44	gold quality
entorhinal cortex	UBERON:0002728	93.56	gold quality
sural nerve	UBERON:0015488	92.72	gold quality
superior frontal gyrus	UBERON:0002661	92.47	gold quality
postcentral gyrus	UBERON:0002581	92.31	gold quality
cerebellar vermis	UBERON:0004720	92.11	gold quality
frontal pole	UBERON:0002795	92.06	gold quality
parietal lobe	UBERON:0001872	91.77	gold quality
Brodmann (1909) area 10	UBERON:0013541	91.71	gold quality
endothelial cell	CL:0000115	90.79	gold quality
secondary oocyte	CL:0000655	90.58	gold quality
paraflocculus	UBERON:0005351	90.09	gold quality
adrenal tissue	UBERON:0018303	89.33	gold quality
occipital lobe	UBERON:0002021	89.21	gold quality
inferior olivary complex	UBERON:0002127	89.06	gold quality
primary visual cortex	UBERON:0002436	89.00	gold quality
oocyte	CL:0000023	88.55	gold quality
subthalamic nucleus	UBERON:0001906	88.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.93	gold quality
prefrontal cortex	UBERON:0000451	87.22	gold quality
frontal cortex	UBERON:0001870	86.95	gold quality
middle frontal gyrus	UBERON:0002702	86.95	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6075	yes	3283.21
E-MTAB-7052	yes	919.79
E-HCAD-35	yes	68.84
E-ANND-3	yes	10.37
E-MTAB-7249	no	536.08
E-CURD-11	no	480.06
E-GEOD-75140	no	405.51

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

246 targeting NAV3, 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-3163	100.00	77.23	8605
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-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-34C-5P	99.97	70.45	1577

Literature-anchored findings (GeneRIF, showing 11)

• Allelic NAV3 aberrations (LOH or deletion by FISH were identified in 44% of the subcutaneous panniculitis-like T-cell lymphoma samples. (PMID:18337827)
• An imbalanced fluorescence in situ hybridization pattern between NAV3 and pericentromeric control probes was seen in three patients in accordance with CGH array data. No NAV3 specific breakpoint or partial deletion was detected. (PMID:18509363)
• NAV3 gene would not be frequently deleted in cutaneous type leukemia/lymphoma including those with mycosis fungoides-like manifestations (PMID:19626031)
• characterized copy number changes of NAV3 in 24 basal cell cancers, eight squamous cell cancers and eight non-malignant inflammatory skin lesions (PMID:21995814)
• NAV3 has a role in linking tissue inflammation to cancer development in the colon. (PMID:22173670)
• Data indicate that neuron navigator 3 (NAV3) may be a potential new prognostic biomarker and a potential therapeutic target. (PMID:23097141)
• The authers propose that NAV3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells. (PMID:25678558)
• Together, our findings suggest an important role for miR-21 in the progression of HCC, which negatively regulated Navigator-3 in the migration of HCC. (PMID:26210448)
• Tumour Suppressor Neuron Navigator 3 and Matrix Metalloproteinase 14 are Co-expressed in Most Melanomas but Downregulated in Thick Tumours. (PMID:36883877)
• Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly. (PMID:38977784)
• Mutated neuron navigator 3 as a candidate gene for a rare neurodevelopmental disorder. (PMID:39038237)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nav3	ENSDARG00000005476
mus_musculus	Nav3	ENSMUSG00000020181
rattus_norvegicus	Nav3	ENSRNOG00000052157
caenorhabditis_elegans		WBGENE00006788

Paralogs (2): NAV1 (ENSG00000134369), NAV2 (ENSG00000166833)

Protein

Protein identifiers

Neuron navigator 3 — Q8IVL0 (reviewed: Q8IVL0)

Alternative names: Pore membrane and/or filament-interacting-like protein 1, Steerin-3, Unc-53 homolog 3

All UniProt accessions (7): Q8IVL0, A0A1B0GTC4, A0A2R8YFX5, F8VZV4, H0YHA8, H0YHX7, H0YI14

UniProt curated annotations — full annotation on UniProt →

Function. Is involved in microtubule cytoskeleton organization and plays a role in cell migration.

Subunit / interactions. Interacts with the microtubules.

Subcellular location. Nucleus outer membrane. Cytoplasm. Cytoskeleton.

Tissue specificity. Present in activated T-cells but not in resting T-cells (at protein level). Highly expressed in brain. Expressed at low levels in heart and placenta. Down-regulated in primary neuroblastoma.

Disease relevance. Neurodevelopmental disorder with poor or absent speech, dysmorphic facies, and behavioral abnormalities (NEDSFB) [MIM:621182] An autosomal recessive disorder characterized by global developmental delay, mild to severe intellectual disability, facial dysmorphism, and behavioral abnormalities including aggression, hyperactivity, and autism. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration disrupting NAV3 has been found in patients with Sezary syndrome. Translocation t(12;18)(q21;q21.2).

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IVL0-1	1	yes
Q8IVL0-2	2
Q8IVL0-3	3

RefSeq proteins (2): NP_001019554, NP_055718 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	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: PF00004, PF00307, PF23092, PF25408

UniProt features (58 total): compositionally biased region 30, sequence variant 9, region of interest 8, coiled-coil region 3, modified residue 2, splice variant 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVL0-F1	48.21	0.11

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): 1459, 1463

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 311 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GGTGTGT_MIR329, HNF3ALPHA_Q6, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, TTTGTAG_MIR520D, BOYAULT_LIVER_CANCER_SUBCLASS_G2, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, TAL1ALPHAE47_01

GO Biological Process (7): microtubule cytoskeleton organization (GO:0000226), negative regulation of microtubule depolymerization (GO:0007026), nervous system development (GO:0007399), neurogenesis (GO:0022008), negative regulation of cell migration (GO:0030336), positive regulation of microtubule polymerization (GO:0031116), negative regulation of interleukin-2 production (GO:0032703)

GO Molecular Function (4): ATP binding (GO:0005524), microtubule binding (GO:0008017), ATP hydrolysis activity (GO:0016887), protein binding (GO:0005515)

GO Cellular Component (5): nuclear outer membrane (GO:0005640), microtubule (GO:0005874), nucleus (GO:0005634), membrane (GO:0016020), microtubule end (GO:1990752)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoskeleton organization	1
microtubule-based process	1
microtubule depolymerization	1
negative regulation of microtubule polymerization or depolymerization	1
regulation of microtubule depolymerization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
system development	1
nervous system development	1
cell differentiation	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1
negative regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
binding	1
nuclear membrane	1
organelle outer membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
intracellular membrane-bounded organelle	1
microtubule	1

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAV3	CNN1	P51911	698
NAV3	MEF2C	Q06413	611
NAV3	CSMD3	Q7Z407	518
NAV3	ZFHX4	Q86UP3	474
NAV3	XIRP2	A4UGR9	470
NAV3	SYT1	P21579	457
NAV3	PTPRQ	Q9UMZ3	456
NAV3	ZNF536	O15090	448
NAV3	SPTA1	P02549	446
NAV3	CSRNP2	Q9H175	435
NAV3	FAT3	Q8TDW7	426
NAV3	ZBTB39	O15060	423
NAV3	RNF43	Q68DV7	423
NAV3	MRPL11	Q9Y3B7	410
NAV3	DDR2	Q16832	410

IntAct

11 interactions, top by confidence:

A	B	Type	Score
NAV3	SERF2	psi-mi:“MI:0915”(physical association)	0.400
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
	ARID1A	psi-mi:“MI:0914”(association)	0.350
MYC		psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
NAV3	CUX2	psi-mi:“MI:0914”(association)	0.350
ING5	CCDC85C	psi-mi:“MI:0914”(association)	0.350
NAV3	APC	psi-mi:“MI:0915”(physical association)	0.000
LCOR	NAV3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): NAV3 (Synthetic Lethality), NAV3 (Protein-RNA), NAV3 (Proximity Label-MS), NAV3 (Proximity Label-MS), NAV3 (Affinity Capture-MS), NAV3 (Affinity Capture-MS), NAV3 (Affinity Capture-MS), KDM3A (Affinity Capture-MS), CUX2 (Affinity Capture-MS), VPS9D1 (Affinity Capture-MS), PDX1 (Affinity Capture-MS), NAV2 (Affinity Capture-MS), PITRM1 (Affinity Capture-MS), TUBA3C (Affinity Capture-MS), RNF41 (Affinity Capture-MS)

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: A5D7D1, D3ZBP4, D3ZHA0, D3ZHV2, D3ZVM4, E7FAM5, F6QEU4, G3V7L1, L7UZ85, M9MRD1, O13728, O15020, O43707, O75369, O76329, O88990, O97592, P05094, P05095, P11277, P11530, P11531, P11532, P11533, P12814, P15508, P18091, P20111, P21333, P30427, P35609, P46939, P57780, Q00963, Q01082, Q03001, Q08043, Q0III9, Q14315, Q15149

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	294
Likely benign	8
Benign	8

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
3391919	GRCh37/hg19 12q21.2-21.31(chr12:77722340-80774552)x1	Pathogenic
3896729	NM_001024383.2(NAV3):c.2604_2605del (p.Val870fs)	Pathogenic
3896730	NAV3, ARG2261CYS	Pathogenic
3896731	NAV3, TRP332TER	Pathogenic
3896732	NAV3, SER1326ASN	Pathogenic
3896734	NM_001024383.2(NAV3):c.6325C>T (p.Gln2109Ter)	Pathogenic
4845377	NM_001024383.2(NAV3):c.2906del (p.Pro969fs)	Pathogenic
3387755	NM_001024383.2(NAV3):c.6577C>T (p.Arg2193Ter)	Likely pathogenic
4819922	NM_001024383.2(NAV3):c.5692+1G>A	Likely pathogenic

SpliceAI

112 predictions. Top by Δscore:

Variant	Effect	Δscore
12:77556704:A:C	donor_gain	0.7100
12:77556709:A:C	donor_gain	0.7100
12:77556771:ATCAC:A	donor_loss	0.7100
12:77556772:TCACC:T	donor_loss	0.7100
12:77556773:CAC:C	donor_loss	0.7100
12:77556774:ACCT:A	donor_loss	0.7100
12:77556775:CCTGG:C	donor_loss	0.7100
12:77556776:C:G	donor_loss	0.7000
12:77556740:A:C	donor_gain	0.6200
12:77556739:CAT:C	donor_gain	0.6100
12:77556707:A:AC	donor_gain	0.5900
12:77556708:C:CC	donor_gain	0.5900
12:77556738:A:AC	donor_gain	0.5800
12:77556739:C:CC	donor_gain	0.5800
12:77556777:T:A	donor_loss	0.5500
12:77556741:T:TA	donor_gain	0.5400
12:77556711:A:AC	donor_gain	0.4800
12:77556760:A:C	donor_gain	0.4800
12:77555857:C:CC	acceptor_gain	0.4600
12:77556785:G:T	donor_gain	0.4600
12:77556736:A:T	donor_gain	0.4500
12:77556712:A:C	donor_gain	0.4400
12:77556759:A:AC	donor_gain	0.4400
12:77556151:CATG:C	acceptor_gain	0.4300
12:77556553:C:CT	donor_gain	0.4100
12:77556554:T:TT	donor_gain	0.4100
12:77556782:TGTG:T	donor_gain	0.4100
12:77555829:CA:C	acceptor_gain	0.3800
12:77555831:C:CC	acceptor_gain	0.3700
12:77556154:G:C	acceptor_gain	0.3600

AlphaMissense

15609 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:77940331:T:A	W86R	1.000
12:77940331:T:C	W86R	1.000
12:77940333:G:C	W86C	1.000
12:77940333:G:T	W86C	1.000
12:77940347:T:C	L91P	1.000
12:77940425:T:A	I117N	1.000
12:77966260:T:C	L149P	1.000
12:77968555:T:C	L175P	1.000
12:77968560:T:C	F177L	1.000
12:77968562:C:A	F177L	1.000
12:77968562:C:G	F177L	1.000
12:78050026:T:A	V686D	1.000
12:78050037:G:C	A690P	1.000
12:78050044:T:C	L692S	1.000
12:78050056:T:C	L696S	1.000
12:78148855:T:C	L1574P	1.000
12:78148867:T:C	L1578P	1.000
12:78148897:T:C	L1588P	1.000
12:78148909:T:C	L1592P	1.000
12:78159210:T:C	L1598P	1.000
12:78159221:T:C	F1602L	1.000
12:78159222:T:C	F1602S	1.000
12:78159223:T:A	F1602L	1.000
12:78159223:T:G	F1602L	1.000
12:78159255:T:C	L1613S	1.000
12:78159264:T:C	L1616P	1.000
12:78168765:T:C	L1627P	1.000
12:78168774:T:C	L1630P	1.000
12:78168795:T:C	L1637P	1.000
12:78177154:T:C	F1713S	1.000

dbSNP variants (sampled 300 via entrez): RS1000004974 (12:77584355 T>C), RS1000011581 (12:77592421 C>T), RS1000013285 (12:77712568 C>G,T), RS1000017086 (12:77830782 G>T), RS1000017608 (12:78024026 A>G), RS1000018862 (12:78104192 A>C), RS1000021142 (12:78199029 G>A), RS1000024920 (12:78045692 C>A), RS1000046647 (12:77888628 G>C), RS1000051116 (12:77675752 G>A), RS1000052655 (12:77848997 C>T), RS1000055509 (12:77942049 T>G), RS1000059113 (12:77876710 C>A), RS1000064372 (12:78020797 G>A), RS1000071137 (12:77752237 G>A,T)

Disease associations

OMIM: gene MIM:611629 | disease phenotypes: MIM:621182

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	Autosomal recessive
neurodevelopmental disorder	Strong	Autosomal recessive

Mondo (8): trigonocephaly (MONDO:0000156), sleep apnea syndrome (MONDO:0005296), hearing loss disorder (MONDO:0005365), cardiac rhythm disease (MONDO:0007263), obesity disorder (MONDO:0011122), neurodevelopmental disorder with poor or absent speech, dysmorphic facies, and behavioral abnormalities (MONDO:0976285), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), NON RARE IN EUROPE: Non rare obesity (Orphanet:521399)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000154	Wide mouth
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000448	Prominent nose
HP:0000486	Strabismus
HP:0000540	Hypermetropia
HP:0000568	Microphthalmia
HP:0000574	Thick eyebrow
HP:0000577	Exotropia
HP:0000582	Upslanted palpebral fissure
HP:0000637	Long palpebral fissure
HP:0000639	Nystagmus
HP:0000718	Aggressive behavior
HP:0000739	Anxiety
HP:0000744	Low frustration tolerance
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0000817	Reduced eye contact
HP:0000957	Cafe-au-lait spot
HP:0001000	Abnormality of skin pigmentation
HP:0001250	Seizure
HP:0001252	Hypotonia

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000747_4	Self-rated health	5.000000e-06
GCST003098_37	Diabetic kidney disease	1.000000e-06
GCST003806_4	Response to bupropion and depression	1.000000e-06
GCST004607_50	Plateletcrit	2.000000e-09
GCST005173_39	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	2.000000e-06
GCST006030_8	Chloride levels	2.000000e-09
GCST006032_7	Sodium levels	7.000000e-10
GCST006288_16	Heel bone mineral density	5.000000e-08
GCST006288_200	Heel bone mineral density	8.000000e-08
GCST006464_17	Endometrial cancer	3.000000e-07
GCST006465_26	Endometrial cancer (endometrioid histology)	1.000000e-06
GCST006979_1069	Heel bone mineral density	3.000000e-19
GCST007385_6	Plasma free amino acid levels	3.000000e-08
GCST007576_197	Chronotype	6.000000e-09
GCST008839_551	Height	9.000000e-09
GCST009462_71	Optic disc size	5.000000e-11
GCST009640_44	Urinary albumin-to-creatinine ratio	4.000000e-08
GCST010703_22	Brain morphology (MOSTest)	2.000000e-09
GCST010724_21	HOMA-B (corrected for HOMA-IR)	3.000000e-08
GCST011382_5	Systemic mastocytosis	1.000000e-08
GCST011503_2	Gastroesophageal reflux disease	3.000000e-08
GCST012311_24	Schizophrenia x sex interaction	4.000000e-06
GCST90002400_722	Plateletcrit	9.000000e-14
GCST90002402_140	Platelet count	5.000000e-13

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004778	self rated health
EFO:0007985	platelet crit
EFO:0004723	coronary artery calcification
EFO:0009282	sodium measurement
EFO:0009270	heel bone mineral density
EFO:0005134	amino acid measurement
EFO:0009770	leucine measurement
EFO:0008328	chronotype measurement
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004346	neuroimaging measurement
EFO:0004469	HOMA-B
EFO:0008343	sex interaction measurement
EFO:0004309	platelet count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D065886	Neurodevelopmental Disorders	F03.625
D012891	Sleep Apnea Syndromes	C08.618.085.852; C10.886.425.800.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression, decreases expression	4
sodium arsenite	increases abundance, increases expression, affects expression, affects cotreatment	4
Valproic Acid	affects cotreatment, increases expression	4
(+)-JQ1 compound	affects cotreatment, decreases expression	3
Cadmium Chloride	increases expression	3
nickel sulfate	increases expression	2
bisphenol S	increases expression, decreases methylation	2
Arsenic Trioxide	decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation	2
Calcitriol	decreases expression, increases expression, affects cotreatment	2
Doxorubicin	decreases expression, increases expression	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Folic Acid	affects cotreatment, decreases expression	2
Formaldehyde	decreases expression	2
Lipopolysaccharides	affects cotreatment, affects expression, increases expression, affects reaction, affects response to substance	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Particulate Matter	increases expression	2
FR900359	affects phosphorylation	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
lead acetate	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
cupric chloride	increases expression	1

Clinical trials (associated diseases)

504 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,
NCT00127348	PHASE4	COMPLETED	Effect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients With Sleep Apnea and no Daytime Sleepiness
NCT00299910	PHASE4	UNKNOWN	Inflammatory Response to Anti Inflammatory Therapy in Children With Sleep Disordered Breathing
NCT00424658	PHASE4	COMPLETED	Sleep Apnea. Concordance Between Non-reference and Reference Centres
NCT00487929	PHASE4	COMPLETED	Oxidative Stress and Cardiovascular Morbidity in Sleep Apnea-Hypopnea Syndrome (SAHS)
NCT00517777	PHASE4	UNKNOWN	Continuous Positive Airway Pressure in Sleep Apnea Syndrome: Effects on Metabolic Syndrome and Cardiac Damage
NCT00547937	PHASE4	COMPLETED	Sleep Apnea and Oxidative Stress and Nitric Oxide
NCT00701428	PHASE4	COMPLETED	Losartan in Hypertensive Men and Women With Sleep Apnea Before and on Continuous Positive Airway Pressure (CPAP) Treatment
NCT00765713	PHASE4	COMPLETED	Sleep Apnea-hypopnea Syndrome (SAHS) and Ventricular Arrhythmias
NCT00804349	PHASE4	COMPLETED	Treatment of Sleep Disordered Breathing In Acute Decompensated Heart Failure Patients
NCT01164631	PHASE4	COMPLETED	Pharyngeal Size in Patients With Obstructive Tonsils Under Orthodontic Treatment
NCT01505959	PHASE4	UNKNOWN	Blood Pressure Reduction Induced by CPAP in Sleep Apnea Patients at High Cardiovascular Risk : OPTISAS 2 Study
NCT01796769	PHASE4	UNKNOWN	Multidisciplinary and Coordinated Follow-up Based on a Telemonitoring Web Platform for Improving CPAP Compliance in Low Cardiovascular Risk Sleep Apnea Patients : OPTISAS 1 Study
NCT01801150	PHASE4	COMPLETED	CPAP in Diabetes Type 2 Patients With Sleep Apnea
NCT01807897	PHASE4	COMPLETED	Oxygen Versus PAP for Sleep Apnea in Heart Failure
NCT01861145	PHASE4	WITHDRAWN	Intranasal Steroids for the Treatment of Nocturnal Enuresis With Associated Obstructive Sleep Apnea
NCT02045173	PHASE4	COMPLETED	Automate Detection of Sleep Apnea by ApneascanTM
NCT02058823	PHASE4	TERMINATED	Intermittent Hypoxia 2: Cardiovascular and Metabolism
NCT02295202	PHASE4	COMPLETED	Impact of Obstructive Sleep Apnea Treatment in Patients With Metabolic Syndrome
NCT02296840	PHASE4	TERMINATED	Post-operative Pain Control After Pediatric Adenotonsillectomy
NCT02398032	PHASE4	COMPLETED	CPAP in SAHS Patients With Hypertension
NCT02426424	PHASE4	WITHDRAWN	Effect Of Early C-PAP Treatment For Sleep Apnea On Rehabilitation Of Stroke Patients
NCT02566226	PHASE4	COMPLETED	Impact of Intrathecal Morphine on Sleep Apnea Syndrome
NCT02630121	PHASE4	RECRUITING	Effect of Oxymetazoline Hydrochloride in Combination With Fluticasone Propionate on the Apnea Hypopnea Index (AHI) in Subject With Persistent Nasal Congestion and Mild Obstructive Sleep Apnea
NCT02643979	PHASE4	TERMINATED	Ketamine and Propofol Combination Versus Propofol for Upper Gastrointestinal Endoscopy
NCT02703220	PHASE4	RECRUITING	Sleep Apnea in Elderly
NCT02717780	PHASE4	COMPLETED	Short Life Agents in Balanced Anesthesia on Obstructive Sleep Apnea Syndrome
NCT02816762	PHASE4	COMPLETED	CPAP Effect on Albuminuria in Patients With Diabetic Nephropathy and Obstructive Sleep Apnea
NCT02874313	PHASE4	COMPLETED	CPAP Effect on the Progression of Diabetic Retinopathy in Patients With Sleep Apnea
NCT02916160	PHASE4	COMPLETED	Sacubitril-valsartan and Heart Failure Patients : the ENTRESTO-SAS Study
NCT02922894	PHASE4	RECRUITING	Treatment of Sleep Apnea in Patients With Cervical Spinal Cord Injury
NCT03011294	PHASE4	COMPLETED	Cardiovascular Impact, Quality e Quantity of Sleep in Bed Partners of Patients With Obstructive Sleep Apnea
NCT03335904	PHASE4	COMPLETED	AT1R Blockade and Periodic Breathing During Sleep in Hypoxia
NCT03454217	PHASE4	COMPLETED	Impact of Tramadol and Oxycodone on Sleep Apnea
NCT03890939	PHASE4	UNKNOWN	Effect of Servo-Ventilation on CO2 Regulation and Heart Rate Variability
NCT04118387	PHASE4	RECRUITING	Central Sleep Apnea : Physiologic Mechanisms to Inform Treatment
NCT04161339	PHASE4	UNKNOWN	Anti-Inflammatory Drug and Endothelial Function
NCT04162743	PHASE4	COMPLETED	The Effect of Trazodone on the Severity of Obstructive Sleep Apnea in Insomnic Stroke Patients With Depression
NCT04452383	PHASE4	UNKNOWN	f Adding Ketamine to Propofol For Drug-induced Sleep Endoscopy in Adult Patients With Obstructive Sleep Apnea