NTF4

Summary

NTF4 (neurotrophin 4, HGNC:8024) is a protein-coding gene on chromosome 19q13.33, encoding Neurotrophin-4 (P34130). Target-derived survival factor for peripheral sensory sympathetic neurons.

This gene is a member of a family of neurotrophic factors, neurotrophins, that control survival and differentiation of mammalian neurons. The expression of this gene is ubiquitous and less influenced by environmental signals. While knock-outs of other neurotrophins including nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 prove lethal during early postnatal development, NTF5-deficient mice only show minor cellular deficits and develop normally to adulthood.

Source: NCBI Gene 4909 — RefSeq curated summary.

At a glance

• Gene–disease (curated): glaucoma 1, open angle, O (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 49 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_006179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8024
Approved symbol	NTF4
Name	neurotrophin 4
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	NT-4/5, GLC1O
Ensembl gene	ENSG00000225950
Ensembl biotype	protein_coding
OMIM	162662
Entrez	4909

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000593537, ENST00000594938, ENST00000595857, ENST00000696088, ENST00000696089, ENST00000696090, ENST00000696091, ENST00000907827, ENST00000939689

RefSeq mRNA: 2 — MANE Select: NM_006179 NM_001395489, NM_006179

CCDS: CCDS12754

Canonical transcript exons

ENST00000593537 — 2 exons

Exon	Start	End
ENSE00003224235	49061128	49062009
ENSE00003965967	49063739	49064818

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 96.14.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2525 / max 35.3114, expressed in 125 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181985	0.2525	125

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.14	silver quality
skeletal muscle tissue	UBERON:0001134	83.46	gold quality
skin of abdomen	UBERON:0001416	83.31	gold quality
zone of skin	UBERON:0000014	81.88	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.06	gold quality
skin of leg	UBERON:0001511	80.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.52	gold quality
prostate gland	UBERON:0002367	80.13	gold quality
esophagus mucosa	UBERON:0002469	79.79	gold quality
lower esophagus mucosa	UBERON:0035834	79.52	gold quality
gastrocnemius	UBERON:0001388	79.08	gold quality
muscle of leg	UBERON:0001383	78.20	gold quality
minor salivary gland	UBERON:0001830	76.79	gold quality
saliva-secreting gland	UBERON:0001044	76.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.69	gold quality
right uterine tube	UBERON:0001302	76.58	gold quality
placenta	UBERON:0001987	73.02	gold quality
vagina	UBERON:0000996	72.56	gold quality
right lung	UBERON:0002167	71.64	gold quality
upper lobe of left lung	UBERON:0008952	68.38	gold quality
muscle tissue	UBERON:0002385	67.88	gold quality
stromal cell of endometrium	CL:0002255	65.66	gold quality
lung	UBERON:0002048	64.43	gold quality
urinary bladder	UBERON:0001255	63.66	gold quality
left uterine tube	UBERON:0001303	63.49	gold quality
tonsil	UBERON:0002372	62.64	gold quality
fallopian tube	UBERON:0003889	61.21	gold quality
thoracic mammary gland	UBERON:0005200	60.26	gold quality
thyroid gland	UBERON:0002046	59.53	gold quality
left lobe of thyroid gland	UBERON:0001120	59.35	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF6, SP1

miRNA regulators (miRDB)

15 targeting NTF4, 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-4267	99.96	66.53	2368
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-3670	97.88	64.39	763
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-5586-5P	96.29	68.02	685
HSA-MIR-7848-3P	95.69	65.00	363

Literature-anchored findings (GeneRIF, showing 28)

• The gene expression of this protein was studied in the developing human tooth. (PMID:12397373)
• Data suggest that activation of bronchial eosinophils by neurotrophins (nerve growth factor, brain-derived neurotrophic factor, neurotrophins-3 and -4) might play a role in the regulation of eosinophilic inflammation in allergic asthma. (PMID:12900521)
• A mechanism to understand the defect associated with variant BDNF and provide a framework two ligands for BDNF and NT-4. (PMID:15987945)
• Re-expression of the p75NTR appears to partially reverse de-differentiation of prostate cancer cells by up-regulating the expression of CRABPI for localized sequestration of retinoids. (PMID:16316409)
• Results revealed the expression of NT-4/5 mainly in oocytes and, in a minority of samples, also in the granulosa cells (GCs). (PMID:16648150)
• These novel data demonstrate that neurotrophins influence ASM Ca(2+) and force regulation and suggest a potential role for neurotrophins in airway diseases (PMID:16648236)
• NT-3, NT-4, and nerve growth factor (NGF) induce cell migration in melanoma, with a stronger effect on metastatic cell lines. (PMID:18305571)
• Neurotrophin 4/5 plays a role in the proliferation and differentiation of periodontal ligament cells. (PMID:18980528)
• Data show that the levels of NT-4/5 levels are significantly higher in bipolar disorder patients than in controlsNT-4/5. immunocontent alterations in bipolar disorder. (PMID:19081579)
• NTF4 mutations impair neurotrophin-4 signaling in patients with primary open-angle glaucoma and lead to decreased activation of TrkB (PMID:19765683)
• Expression of human NTF4 was unchanged during gestation in the developping ovary. (PMID:20175187)
• No evidence of association of heterozygous NTF4 mutations in patients with primary open-angle glaucoma. (PMID:20215012)
• In vitro follicular assembly is significantly increased in fetal ovaries cultured with NT-4. (PMID:20447632)
• present data indicate a lack of involvement of variations in NTF4, VAV2, and VAV3 with glaucoma pathogenesis in an Indian population. (PMID:20463313)
• Identification of a single mutation in our study suggests that NTF4 mutations are a rare cause of primary open-angle glaucoma (0.6%, 95%CI 0.02%-3.16%) in Chinese people. (PMID:20806036)
• Suggest that a dysregulated TrkB/NT4/5 axis may contribute to several of the pathological lesions associated with pulmonary fibrosis, including type 2 alveolar cell hyperplasia and the proliferation of fibroblasts. (PMID:21330466)
• neurotrophin 4 contributes to breast cancer cell survival and can serve as prospective target to inhibit tumor growth (PMID:21350004)
• NT-4/5 expression is associated with atrophy of the brain-parenchymal fraction measured by magnetic resonance imaging methods in patients with relapsing-remitting multiple sclerosis. (PMID:22036954)
• Studies indicate neurotrophin family comprises nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4 , and Zn(2+) and Cu(2+) interactions with them and modulate their activities through conformational changes. (PMID:22192858)
• The NTF4 variants p.Gly157Ala and p.Ala182Val have been shown to be functional mutations, occurring in 2 of a total of 720 Chinese primary open-angle glaucoma patients. (PMID:22815630)
• Patients with mastocytosis featured elevated serum levels of NGF, NT-3, and NT-4. TrkA, TrkB, and TrkC expression was also elevated. (PMID:23869086)
• Elevated intra-amniotic levels of docosahexaenoic acid and arachidonic acid in the mid-trimester are correlated with increased NT4 concentrations. (PMID:24607879)
• No differences in plasma BDNF, NGF, NT3, NT4 and GDNF were found between autism spectrum disorders and control. (PMID:25275256)
• Meta-analysis found the levels of both NT-3 and NT-4/5 were significantly increased in bipolar disorder patients. Through subgroup analysis, this increase persisted only in patients in depressed state, but not in manic or euthymic state. In addition, we found the differences in NT-3 and NT-4/5 were significantly associated with the duration of illness, but not by the mean age or female proportion. (PMID:27214525)
• Upregulated NTF4 in colorectal cancer promotes tumor development via regulating autophagy. (PMID:32236587)
• NTF4 stimulates the progression of gastric cancer via regulating FOXL1. (PMID:34076998)
• The Impact of Physical Exercise on the Circulating Levels of BDNF and NT 4/5: A Review. (PMID:34445512)
• Single-cell transcriptome and cell-specific network analysis reveal the reparative effect of neurotrophin-4 in preantral follicles grown in vitro. (PMID:34481496)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ntf5	ENSMUSG00000074121
rattus_norvegicus	Ntf4	ENSRNOG00000020783

Paralogs (3): NGF (ENSG00000134259), BDNF (ENSG00000176697), NTF3 (ENSG00000185652)

Protein

Protein identifiers

Neurotrophin-4 — P34130 (reviewed: P34130)

Alternative names: Neurotrophin-5, Neutrophic factor 4

All UniProt accessions (2): M0R0X2, P34130

UniProt curated annotations — full annotation on UniProt →

Function. Target-derived survival factor for peripheral sensory sympathetic neurons. May promote ameloblast differentiation and subsequent reduction in proliferation of ameloblasts.

Subcellular location. Secreted.

Tissue specificity. Highest levels in prostate, lower levels in thymus, placenta, and skeletal muscle. Expressed in embryonic and adult tissues.

Disease relevance. Glaucoma 1, open angle, O (GLC1O) [MIM:613100] A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the NGF-beta family.

RefSeq proteins (2): NP_001382418, NP_006170* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002072	Nerve_growth_factor-rel	Domain
IPR019846	Nerve_growth_factor_CS	Conserved_site
IPR020408	Nerve_growth_factor-like	Family
IPR020432	Neurotrophin-4	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00243

UniProt features (36 total): sequence variant 14, strand 12, disulfide bond 3, turn 2, signal peptide 1, propeptide 1, chain 1, helix 1, glycosylation site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1HCF	X-RAY DIFFRACTION	2.7
1B8M	X-RAY DIFFRACTION	2.75
1B98	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P34130-F1	78.69	0.48

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): 97–170, 141–199, 158–201

Glycosylation sites (1): 76

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9026357	NTF4 activates NTRK2 (TRKB) signaling
R-HSA-9026519	Activated NTRK2 signals through RAS
R-HSA-9026527	Activated NTRK2 signals through PLCG1
R-HSA-9028335	Activated NTRK2 signals through PI3K
R-HSA-9028731	Activated NTRK2 signals through FRS2 and FRS3

MSigDB gene sets: 149 (showing top): PID_SHP2_PATHWAY, GOBP_MEMORY, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, KEGG_MAPK_SIGNALING_PATHWAY, GOBP_ADULT_BEHAVIOR, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_ADULT_LOCOMOTORY_BEHAVIOR, GGGTGGRR_PAX4_03, CAGCTG_AP4_Q5, SP1_Q2_01, GOBP_CELL_CELL_SIGNALING

GO Biological Process (17): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), ganglion mother cell fate determination (GO:0007402), long-term memory (GO:0007616), sensory organ boundary specification (GO:0008052), adult locomotory behavior (GO:0008344), epidermis development (GO:0008544), nerve development (GO:0021675), ameloblast differentiation (GO:0036305), nerve growth factor signaling pathway (GO:0038180), mechanoreceptor differentiation (GO:0042490), negative regulation of neuron apoptotic process (GO:0043524), neuron projection morphogenesis (GO:0048812), modulation of chemical synaptic transmission (GO:0050804), innervation (GO:0060384), taste bud development (GO:0061193), signal transduction (GO:0007165), negative regulation of programmed cell death (GO:0043069)

GO Molecular Function (4): nerve growth factor receptor binding (GO:0005163), growth factor activity (GO:0008083), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), synaptic vesicle (GO:0008021), axon (GO:0030424), dendrite (GO:0030425)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by NTRK2 (TRKB)	5
Intracellular signaling by second messengers	1
PI3K/AKT Signaling in Cancer	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sensory organ development	2
neuron projection	2
enzyme-linked receptor protein signaling pathway	1
cell fate determination	1
memory	1
formation of animal organ boundary	1
locomotory behavior	1
adult behavior	1
tissue development	1
nervous system development	1
anatomical structure development	1
columnar/cuboidal epithelial cell differentiation	1
neurotrophin signaling pathway	1
cellular response to nerve growth factor stimulus	1
neuron differentiation	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
nerve development	1
multicellular organismal process	1
tongue development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
programmed cell death	1
regulation of programmed cell death	1
negative regulation of cellular process	1
death receptor binding	1
neurotrophin receptor binding	1
receptor ligand activity	1
protein binding	1
binding	1
cellular anatomical structure	1
exocytic vesicle	1

Protein interactions and networks

STRING

942 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NTF4	NTRK2	Q16620	999
NTF4	NTRK3	Q16288	999
NTF4	NTRK1	P04629	999
NTF4	NGFR	P08138	998
NTF4	NGF	P01138	922
NTF4	GDNF	P39905	897
NTF4	SORT1	Q99523	883
NTF4	WDR36	Q8NI36	758
NTF4	CNTF	P26441	721
NTF4	ASB10	Q8WXI3	720
NTF4	NTSR1	P30989	708
NTF4	MYOC	Q99972	702
NTF4	LRP6	O75581	666
NTF4	GFRA2	O00451	651
NTF4	GFRA1	P56159	649

IntAct

23 interactions, top by confidence:

A	B	Type	Score
BDNF	NTF4	psi-mi:“MI:2364”(proximity)	0.720
BDNF	NTF4	psi-mi:“MI:0915”(physical association)	0.720
BDNF	NTF4	psi-mi:“MI:0407”(direct interaction)	0.720
NTF4	BDNF	psi-mi:“MI:2364”(proximity)	0.720
NTF4	ADAMTSL4	psi-mi:“MI:0915”(physical association)	0.560
NTF4	TRIM68	psi-mi:“MI:0915”(physical association)	0.560
CRX	NTF4	psi-mi:“MI:0915”(physical association)	0.560
GLRX3	NTF4	psi-mi:“MI:0915”(physical association)	0.560
NTF4	NTF4	psi-mi:“MI:0407”(direct interaction)	0.440
NTF4	NTRK2	psi-mi:“MI:2364”(proximity)	0.410
NTF4	CLIC1	psi-mi:“MI:0915”(physical association)	0.370
NTF4	FADD	psi-mi:“MI:0914”(association)	0.350
NTF4	CRX	psi-mi:“MI:0915”(physical association)	0.000
NTF4	GLRX3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): ADAMTSL4 (Two-hybrid), TRIM68 (Affinity Capture-MS), NTF4 (Co-localization), NTF4 (Co-localization), TRIM68 (Affinity Capture-MS), NTF4 (FRET), BDNF (Affinity Capture-Luminescence), BDNF (FRET), NTF4 (Affinity Capture-Luminescence), NTRK2 (FRET), NTF4 (FRET), NTF4 (Two-hybrid), NTF4 (Two-hybrid), NTF4 (Reconstituted Complex), NTF4 (Affinity Capture-RNA)

ESM2 similar proteins: A2BDP1, A4IFM1, A5A8Y8, A5D7T4, A8MVW0, F1SAM7, O18753, O60542, O70183, O75949, O88200, O88201, P03971, P03972, P04087, P04088, P07994, P09529, P17491, P25429, P34130, P34131, P42917, P43031, P51693, P55101, P55108, P97463, Q02193, Q03157, Q04999, Q08AU9, Q08DX6, Q0EAB7, Q3SAT7, Q4G0M1, Q5T4W7, Q6AYE8, Q76KP1, Q7YRB4

Diamond homologs: A6MFL5, A6MFL6, A6MFL7, F8RKW5, O18752, O18753, O18755, O70183, O97759, P01138, P01139, P05200, P13600, P14082, P18280, P19093, P20181, P20675, P20783, P21237, P21617, P23363, P23560, P24727, P25427, P25428, P25429, P25432, P25433, P25435, P34128, P34130, P34131, Q02193, Q06225, Q06AV0, Q08DT3, Q0EAB7, Q1HN31, Q1HN32

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NTF4	up-regulates	NTRK2	binding
NTF4	up-regulates	NTRK1	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	39
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
208763	NM_006179.5(NTF4):c.521A>G (p.Gln174Arg)	Likely pathogenic

SpliceAI

349 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49061561:G:C	donor_gain	0.9400
19:49061555:T:TA	donor_gain	0.9300
19:49061642:TCC:T	donor_gain	0.8700
19:49061699:A:AC	donor_gain	0.8600
19:49061700:C:CC	donor_gain	0.8600
19:49061566:ATCAG:A	donor_gain	0.8400
19:49061595:A:AC	donor_gain	0.8300
19:49061596:C:CC	donor_gain	0.8300
19:49061569:AG:A	donor_gain	0.7600
19:49061091:A:C	acceptor_gain	0.7400
19:49061096:T:TC	acceptor_gain	0.7000
19:49061380:CCGG:C	acceptor_gain	0.7000
19:49061381:CGGC:C	acceptor_gain	0.7000
19:49061570:G:GA	donor_gain	0.7000
19:49061384:C:CC	acceptor_gain	0.6900
19:49061534:C:CT	donor_gain	0.6800
19:49061643:C:CT	donor_gain	0.6800
19:49061081:C:CC	acceptor_gain	0.6700
19:49061560:AG:A	donor_gain	0.6700
19:49061698:G:T	donor_gain	0.6700
19:49061093:G:C	acceptor_gain	0.6600
19:49061640:CCT:C	donor_gain	0.6600
19:49061641:CTC:C	donor_gain	0.6600
19:49061381:CGG:C	acceptor_gain	0.6500
19:49061089:T:TC	acceptor_gain	0.6400
19:49061540:G:A	donor_gain	0.6400
19:49061642:T:TA	donor_gain	0.6400
19:49061089:T:C	acceptor_gain	0.6300
19:49061095:A:C	acceptor_gain	0.6300
19:49061644:C:CT	donor_gain	0.6300

AlphaMissense

1313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49061396:C:T	C201Y	1.000
19:49061420:A:G	I193T	1.000
19:49061422:C:A	W192C	1.000
19:49061422:C:G	W192C	1.000
19:49061428:C:A	W190C	1.000
19:49061428:C:G	W190C	1.000
19:49061430:A:G	W190R	1.000
19:49061430:A:T	W190R	1.000
19:49061489:C:G	C170S	1.000
19:49061490:A:T	C170S	1.000
19:49061500:C:A	W166C	1.000
19:49061500:C:G	W166C	1.000
19:49061591:A:C	F136C	1.000
19:49061689:C:A	W103C	1.000
19:49061689:C:G	W103C	1.000
19:49061691:A:G	W103R	1.000
19:49061691:A:T	W103R	1.000
19:49061390:A:T	L203H	0.999
19:49061395:G:C	C201W	0.999
19:49061396:C:A	C201F	0.999
19:49061396:C:G	C201S	0.999
19:49061397:A:G	C201R	0.999
19:49061397:A:T	C201S	0.999
19:49061402:C:T	C199Y	0.999
19:49061414:A:T	I195N	0.999
19:49061420:A:C	I193S	0.999
19:49061420:A:T	I193N	0.999
19:49061424:A:G	W192R	0.999
19:49061424:A:T	W192R	0.999
19:49061576:C:G	C141S	0.999

dbSNP variants (sampled 300 via entrez): RS1000344385 (19:49064112 C>T), RS1000373517 (19:49058545 C>G), RS1000476557 (19:49058905 A>G), RS1000716225 (19:49065535 C>T), RS1000820047 (19:49057873 G>C,T), RS1001047979 (19:49062862 CAGGCTCAG>C), RS1001375139 (19:49060817 C>A), RS1001486129 (19:49065092 GGGGCGGCGCC>G), RS1001820073 (19:49066131 C>T), RS1002617388 (19:49060041 A>C,T), RS1003059705 (19:49060309 A>G), RS1003212973 (19:49063840 C>A,T), RS1004394151 (19:49061726 C>A,T), RS1004630905 (19:49057928 T>C,G), RS1004704480 (19:49059063 G>C,T)

Disease associations

OMIM: gene MIM:162662 | disease phenotypes: MIM:300919, MIM:613100

GenCC curated gene-disease

Disease	Classification	Inheritance
glaucoma 1, open angle, O	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
glaucoma 1, open angle, O	Disputed	AD

Mondo (2): intellectual disability, X-linked 99 (MONDO:0010487), glaucoma 1, open angle, O (MONDO:0013134)

Orphanet (1): X-linked non-syndromic intellectual disability (Orphanet:777)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0012108	Open angle glaucoma

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003501_8	Asparaginase-induced acute pancreatitis in acute lymphoblastic leukemia (onset time)	7.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001507	asparaginase-induced acute pancreatitis

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567753	Glaucoma 1, Open Angle, O (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	2
entinostat	increases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bisphenol F	decreases methylation	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	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	affects cotreatment, increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Coal	increases abundance, increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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