CNTF

Summary

CNTF (ciliary neurotrophic factor, HGNC:2169) is a protein-coding gene on chromosome 11q12.1, encoding Ciliary neurotrophic factor (P26441). CNTF is a survival factor for various neuronal cell types.

The protein encoded by this gene is a polypeptide hormone whose actions appear to be restricted to the nervous system where it promotes neurotransmitter synthesis and neurite outgrowth in certain neuronal populations. The protein is a potent survival factor for neurons and oligodendrocytes and may be relevant in reducing tissue destruction during inflammatory attacks. A mutation in this gene, which results in aberrant splicing, leads to ciliary neurotrophic factor deficiency, but this phenotype is not causally related to neurologic disease. A read-through transcript variant composed of the upstream ZFP91 gene and CNTF sequence has been identified, but it is thought to be non-coding. Read-through transcription of ZFP91 and CNTF has also been observed in mouse.

Source: NCBI Gene 1270 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_000614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2169
Approved symbol	CNTF
Name	ciliary neurotrophic factor
Location	11q12.1
Locus type	gene with protein product
Status	Approved
Aliases	HCNTF
Ensembl gene	ENSG00000242689
Ensembl biotype	protein_coding
OMIM	118945
Entrez	1270

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000361987

RefSeq mRNA: 1 — MANE Select: NM_000614 NM_000614

CCDS: CCDS31554

Canonical transcript exons

ENST00000361987 — 2 exons

Exon	Start	End
ENSE00002441176	58624034	58625733
ENSE00002500168	58622665	58622866

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 97.49.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3602 / max 110.9323, expressed in 64 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114358	0.2731	51
114359	0.0871	27

Top tissues by expression

132 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	97.49	gold quality
tibial nerve	UBERON:0001323	95.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.26	gold quality
sural nerve	UBERON:0015488	78.99	gold quality
gastrocnemius	UBERON:0001388	74.46	gold quality
muscle of leg	UBERON:0001383	73.25	gold quality
substantia nigra	UBERON:0002038	73.15	gold quality
monocyte	CL:0000576	70.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	70.32	gold quality
leukocyte	CL:0000738	69.99	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	69.90	gold quality
bone marrow	UBERON:0002371	69.64	gold quality
islet of Langerhans	UBERON:0000006	68.50	gold quality
skeletal muscle tissue	UBERON:0001134	68.14	gold quality
granulocyte	CL:0000094	68.05	gold quality
right uterine tube	UBERON:0001302	67.23	gold quality
fallopian tube	UBERON:0003889	67.20	gold quality
muscle tissue	UBERON:0002385	64.02	gold quality
bone marrow cell	CL:0002092	63.45	silver quality
corpus callosum	UBERON:0002336	62.21	gold quality
Ammon’s horn	UBERON:0001954	62.12	gold quality
temporal lobe	UBERON:0001871	61.13	gold quality
amygdala	UBERON:0001876	61.12	gold quality
duodenum	UBERON:0002114	61.04	gold quality
hypothalamus	UBERON:0001898	60.79	gold quality
primary visual cortex	UBERON:0002436	60.61	gold quality
left uterine tube	UBERON:0001303	60.54	gold quality
mucosa of stomach	UBERON:0001199	60.50	gold quality
rectum	UBERON:0001052	60.26	gold quality
right lobe of liver	UBERON:0001114	60.00	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, ELK3, NFIC, NFKB, PAX3, POU1F1, POU2F1, POU3F1, POU5F1, SATB2, SOX10, STAT1

miRNA regulators (miRDB)

58 targeting CNTF, 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-3120-5P	100.00	65.56	965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-29A-5P	99.08	68.59	1813

Literature-anchored findings (GeneRIF, showing 40)

• Expanded is required for proliferation arrest and apoptosis in developing imaginal discs. Our genetic and biochemical data place Merlin and Expanded upstream of Hippo and identify a pathway through which they act as tumour-suppressor genes. (PMID:16341207)
• The tumor suppressor expanded (ex)controls proliferation by regulating the abundance, localization, and turnover of cell-surface receptors. (PMID:16581517)
• The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling. (PMID:17258190)
• Expanded and fat regulate growth and differentiation in the Drosophila eye through multiple signaling pathways. (PMID:17359963)
• Data show that expanded genes are dispensable in germline cells for their proliferation control and it appears that expanded acts from the somatic support cells surrounding the germline to restrict spermatogonial amplification. (PMID:18095349)
• new model whereby Expanded functions downstream of Warts, in concert with 14-3-3 proteins to sequester Yorkie in the cytoplasm, inhibiting growth activity of the Hippo pathway (PMID:19289086)
• Mer and Ex signal through the Hippo pathway in Drosophila. (PMID:19531584)
• Kibra functions together with Mer and Ex in a protein complex localized to the apical domain of epithelial cells, and this protein complex regulates the Hippo kinase cascade via direct binding to Hpo and Sav. (PMID:20159598)
• The Ex-regulatory domain of Crb maps to the juxtamembrane FERM-binding motif (JM), a cytoskeletal interaction domain distinct from the PDZ-binding motif (PBM) through which Crb binds polarity factors. (PMID:20362445)
• results show that Zyxin is a functional antagonist of Expanded in growth control (PMID:25728696)
• Merlin and Kibra activate Hippo signaling in parallel to Expanded at a spatially distinct cellular domain, the medial apical cortex. (PMID:28292426)
• study suggests that a complex pattern of ex transcription results from integration of a uniform SWH signal with multiple other inputs, rather than from a pattern of SWH signaling. (PMID:30063727)
• Here, the authors show that the Casein Kinase 1 (CKI) family is required for Expanded phosphorylation. CKI expression promotes Expanded phosphorylation and interaction with Slimb/beta-TrCP. (PMID:31567070)
• Merlin and expanded integrate cell signaling that regulates cyst stem cell proliferation in the Drosophila testis niche. (PMID:34044021)
• Expanded directly binds conserved regions of Fat to restrain growth via the Hippo pathway. (PMID:37071483)
• A null mutation in this protein was evaluated for a relationship to disease susceptibility and disease severity in patients with multiple sclerosis. (PMID:11857064)
• Association of a null mutation in the CNTF gene with early onset of multiple sclerosis. (PMID:11890844)
• Early onset of severe familial amyotrophic lateral sclerosis with a SOD-1 mutation: potential impact of CNTF as a candidate modifier gene. (PMID:11951178)
• CTNF binds to the IL-6 receptor and has a role in neuroprotection (PMID:12643274)
• no evidence found to suggest that ciliary neurotrophic factor is involved in the pathogenesis of pelvic endometriosis (PMID:12890930)
• Constitutive expression of cytokines in brain induces changes in gene expression characteristic of chronic inflammation leading to either temporal weight reduction (CNTF) or severe cachexia (leukemia inhibitory factor). (PMID:14715713)
• Results do not support an effect of the CNTF null allele on body composition, contrary to previous findings. (PMID:14747836)
• findings support the hypothesis that CNTF and leptin engage distinct CNS sites and CNTF possesses inflammatory properties distinct from leptin (PMID:15047605)
• In spite of axokine gene expression in retinal pigment epithelium, no photoreceptor rescue in retinal degeneration mice. (PMID:15180291)
• myogenic lineage-committed human myoblasts can dedifferentiate at a clonal level; CNTF is a novel regulator of skeletal myoblast dedifferentiation via p44/p42 MAPK pathway (PMID:15843428)
• CNTF negatively regulates phototransduction, which reduces the photoresponsiveness of rods, resulting in lower electroretinogram amplitudes following light stimulus. (PMID:17192435)
• Possible neuroprotective role of CNTF in the optic nerve head. (PMID:17563726)
• We conclude that absence of CNTF does not increase susceptibility for neurodegenerative disorders and confirm that it does not affect onset and course of familial and sporadic ALS. (PMID:17651970)
• Continuous expression of striatal CNTF at the dose mediated by the expression cassette used in this study was detrimental to transgenic mice with Huntington’s disease. (PMID:18293418)
• The relative treatment benefit of iloperidone compared with placebo in patients with schizophrenia is enhanced in patients homozygous G/G for the rs1800169 polymorphism of CNTF. (PMID:18303965)
• In vivo and in vitro experiments implicate CNTF as an endogenous regulatory component of dopamine D2-receptor-dependent neurogenesis in the subventricular zone and the dentate gyrus of the hippocampus. (Review) (PMID:18524890)
• CNTF-mediated signaling is a molecular switch for neuronal versus glial differentiation of retinal stem cells/progenitors. (PMID:18669911)
• Ciliary neurotrophic factor, cardiotrophin-like cytokine, and neuropoietin share a conserved binding site on the ciliary neurotrophic factor receptor alpha chain (PMID:18728012)
• PTP-1B constitutes a key divergent element between leptin/insulin and CNTF signaling pathways at the neuronal level. (PMID:19008309)
• Certain SNP patterns in VDR and CNTF genes showed better improvement of parameters associated with the effects of low-resistance training using exercise machines as analyzed by comparison between SNP patterns and factor analysis. (PMID:19082510)
• The results of this study provided further evidence that the production of ciliary neurotrophic factor by Schwann cells is markedly reduced in Charcot-Marie-Tooth type 1A neuropathy. (PMID:19525893)
• Fusion of HIV-1 TAT to CNTF may have modified the CNTF capacity to induce intracellular signaling in hypothalamic neurons. (PMID:19573019)
• The CNTF 1357 G –> A polymorphism explains only a small portion of the variability in the muscle strength response to training in women. (PMID:19628720)
• Studies indicate that leptin, CNTF, LIF and IL-6 present similar three-dimensional fold structure, interact with related class-I receptors and activate similar intracellular pathways. (PMID:19751193)
• In women the CNTF polymorphism (odds ratio (OR) = 2.15, 95%CI: 1.27-3.64, p = 0.004) are associated with weight gain. (PMID:19833146)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	m17	ENSDARG00000035435
mus_musculus	Cntf	ENSMUSG00000079415
rattus_norvegicus	Cntf	ENSRNOG00000012460

Protein

Protein identifiers

Ciliary neurotrophic factor — P26441 (reviewed: P26441)

All UniProt accessions (1): P26441

UniProt curated annotations — full annotation on UniProt →

Function. CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Tissue specificity. Nervous system.

Similarity. Belongs to the CNTF family.

RefSeq proteins (1): NP_000605* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000151	Ciliary_neurotrophic_fac_CNTF	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily

Pfam: PF01110

UniProt features (11 total): helix 4, sequence variant 2, turn 2, strand 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1CNT	X-RAY DIFFRACTION	2.4
8D74	ELECTRON MICROSCOPY	3.03

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26441-F1	85.84	0.67

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6788467	IL-6-type cytokine receptor ligand interactions

MSigDB gene sets: 188 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOMF_GROWTH_FACTOR_ACTIVITY, TGACCTY_ERR1_Q2, GOBP_RESPONSE_TO_AXON_INJURY, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT

GO Biological Process (18): signal transduction (GO:0007165), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), negative regulation of neuron apoptotic process (GO:0043524), negative regulation of photoreceptor cell differentiation (GO:0046533), regulation of retinal cell programmed cell death (GO:0046668), astrocyte activation (GO:0048143), muscle organ morphogenesis (GO:0048644), neuron development (GO:0048666), positive regulation of axon regeneration (GO:0048680), retinal rod cell differentiation (GO:0060221), ciliary neurotrophic factor-mediated signaling pathway (GO:0070120), cell surface receptor signaling pathway via STAT (GO:0097696), nervous system development (GO:0007399), cell differentiation (GO:0030154), regulation of programmed cell death (GO:0043067)

GO Molecular Function (6): cytokine activity (GO:0005125), ciliary neurotrophic factor receptor binding (GO:0005127), interleukin-6 receptor binding (GO:0005138), growth factor activity (GO:0008083), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), axon (GO:0030424), neuronal cell body (GO:0043025), glial cell projection (GO:0097386)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interleukin-6 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	2
receptor ligand activity	2
cytokine receptor binding	2
binding	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
cell surface receptor signaling pathway via STAT	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
tyrosine phosphorylation of STAT protein	1
regulation of tyrosine phosphorylation of STAT protein	1
positive regulation of peptidyl-tyrosine phosphorylation	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
negative regulation of neuron differentiation	1
photoreceptor cell differentiation	1
regulation of photoreceptor cell differentiation	1
negative regulation of multicellular organismal process	1
regulation of programmed cell death	1
retinal cell programmed cell death	1
regulation of developmental process	1
astrocyte development	1
glial cell activation	1
muscle organ development	1
animal organ morphogenesis	1
neuron differentiation	1
cell development	1
axon regeneration	1
positive regulation of response to external stimulus	1
regulation of axon regeneration	1
positive regulation of neuron projection regeneration	1
positive regulation of response to wounding	1

Protein interactions and networks

STRING

1362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNTF	CNTFR	P26992	999
CNTF	LIFR	P42702	997
CNTF	LIF	P15018	946
CNTF	IL11	P20809	927
CNTF	BDNF	P23560	916
CNTF	GDNF	P39905	913
CNTF	FGF2	P09038	894
CNTF	IL6ST	P40189	894
CNTF	IL6	P05231	888
CNTF	OSM	P13725	887
CNTF	IL6R	P08887	884
CNTF	IL27RA	Q6UWB1	880
CNTF	CLCF1	Q9UBD9	879
CNTF	CTF1	Q16619	874
CNTF	NGF	P01138	836

IntAct

67 interactions, top by confidence:

A	B	Type	Score
CNTFR	CNTF	psi-mi:“MI:0407”(direct interaction)	0.810
CNTF	CNTFR	psi-mi:“MI:0915”(physical association)	0.810
LIFR	CNTF	psi-mi:“MI:0407”(direct interaction)	0.810
CNTF	CNTFR	psi-mi:“MI:0407”(direct interaction)	0.810
IL6ST	CNTF	psi-mi:“MI:0407”(direct interaction)	0.780
SORT1	CNTF	psi-mi:“MI:0407”(direct interaction)	0.570
SORT1	CNTF	psi-mi:“MI:0915”(physical association)	0.570
SORT1	CNTF	psi-mi:“MI:0403”(colocalization)	0.570
CNTF	TRIP6	psi-mi:“MI:0915”(physical association)	0.560
KRT40	CNTF	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	CNTF	psi-mi:“MI:0915”(physical association)	0.560
CNTF	KRT40	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (30): TRIP6 (Two-hybrid), KRT40 (Two-hybrid), CNTF (Affinity Capture-MS), CORO7 (Affinity Capture-MS), CHM (Affinity Capture-MS), RBM12 (Affinity Capture-MS), FEM1B (Affinity Capture-MS), STK16 (Affinity Capture-MS), CNTF (Affinity Capture-MS), CNTF (Affinity Capture-MS), CNTF (Affinity Capture-MS), EIF3E (Affinity Capture-MS), CNTF (Affinity Capture-MS), CNTF (Reconstituted Complex), CNTF (Affinity Capture-Western)

ESM2 similar proteins: A0S0B0, A3FBE9, B6CKP4, O73848, P01241, P01244, P05231, P06880, P08505, P08998, P09321, P09586, P09611, P0DML2, P0DML3, P11228, P14188, P16038, P19795, P20294, P20607, P22077, P26441, P37886, P41683, P43431, P46650, P51494, P51642, P58343, P58756, P58757, P79341, Q07370, Q0GGL7, Q14406, Q25BC2, Q28819, Q2XNF5, Q5I6E3

Diamond homologs: O02732, P14188, P20294, P26441, P51642, Q02011

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CNTF	up-regulates	CRLF1	binding
TEAD	“up-regulates quantity by expression”	CNTF	“transcriptional regulation”
CNTF	up-regulates	IL6ST	binding
CNTF	up-regulates	CNTFR	binding
CNTF	up-regulates	LIFR	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

362 predictions. Top by Δscore:

Variant	Effect	Δscore
11:58622827:G:GT	donor_gain	0.9900
11:58622862:CCTAT:C	donor_gain	0.9900
11:58622863:CTAT:C	donor_gain	0.9900
11:58622864:TAT:T	donor_gain	0.9900
11:58622864:TATG:T	donor_loss	0.9900
11:58622865:AT:A	donor_gain	0.9900
11:58622865:ATG:A	donor_loss	0.9900
11:58622866:TG:T	donor_loss	0.9900
11:58622867:G:GA	donor_loss	0.9900
11:58622867:G:GG	donor_gain	0.9900
11:58622868:T:G	donor_loss	0.9900
11:58624022:A:AG	acceptor_gain	0.9900
11:58624027:C:A	acceptor_gain	0.9900
11:58624028:G:A	acceptor_gain	0.9900
11:58624023:T:G	acceptor_gain	0.9800
11:58624019:T:TA	acceptor_gain	0.9700
11:58624032:A:AG	acceptor_gain	0.9700
11:58624033:G:GG	acceptor_gain	0.9700
11:58624031:CA:C	acceptor_loss	0.9500
11:58624019:T:A	acceptor_loss	0.9300
11:58624033:GGT:G	acceptor_gain	0.9200
11:58624032:A:AC	acceptor_loss	0.9100
11:58622733:T:TA	acceptor_gain	0.8600
11:58622872:T:G	donor_gain	0.8600
11:58624180:GGC:G	acceptor_gain	0.8100
11:58622869:AA:A	donor_loss	0.8000
11:58622697:A:AG	acceptor_gain	0.7900
11:58622698:G:GG	acceptor_gain	0.7900
11:58622732:CTGGG:C	acceptor_gain	0.7900
11:58622733:TGGG:T	acceptor_gain	0.7800

AlphaMissense

1317 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:58624421:T:A	W168R	0.985
11:58624421:T:C	W168R	0.985
11:58624423:G:C	W168C	0.978
11:58624423:G:T	W168C	0.978
11:58624413:T:C	L165P	0.970
11:58624433:T:C	S172P	0.968
11:58624446:T:C	L176P	0.965
11:58624432:G:C	R171S	0.964
11:58624432:G:T	R171S	0.964
11:58624149:T:C	L77P	0.962
11:58622844:T:C	L31P	0.961
11:58624157:T:G	Y80D	0.961
11:58624188:T:C	L90P	0.960
11:58624413:T:A	L165H	0.959
11:58624434:C:T	S172F	0.958
11:58624134:G:C	R72P	0.957
11:58624147:C:A	N76K	0.957
11:58624147:C:G	N76K	0.957
11:58624391:G:C	G158R	0.956
11:58624442:G:C	D175H	0.952
11:58624137:T:C	L73P	0.949
11:58624179:T:C	L87S	0.948
11:58624404:T:C	L162P	0.947
11:58624443:A:C	D175A	0.947
11:58624443:A:G	D175G	0.946
11:58624431:G:T	R171M	0.944
11:58624161:G:C	R81P	0.943
11:58624434:C:A	S172Y	0.943
11:58624422:G:C	W168S	0.942
11:58624443:A:T	D175V	0.942

dbSNP variants (sampled 300 via entrez): RS1000069415 (11:58622037 G>A), RS1000789397 (11:58622934 G>A), RS1001391032 (11:58622187 T>C), RS1001799970 (11:58620896 C>T), RS1001825397 (11:58623038 C>G), RS1002401284 (11:58622464 A>G,T), RS1002650173 (11:58626109 C>G,T), RS1002676750 (11:58625869 A>G), RS1002793234 (11:58625533 AC>A), RS1002845731 (11:58625231 C>T), RS1004303574 (11:58625423 C>G,T), RS1004352013 (11:58622076 G>A), RS1004966543 (11:58623664 G>A), RS1005161010 (11:58625739 A>G), RS1005911075 (11:58624453 C>T)

Disease associations

OMIM: gene MIM:118945 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001725_9	Inflammatory bowel disease	7.000000e-10
GCST004133_47	Ulcerative colitis	9.000000e-06
GCST007094_73	Diastolic blood pressure	3.000000e-06
GCST007096_85	Pulse pressure	1.000000e-12
GCST007099_73	Systolic blood pressure	1.000000e-13
GCST007930_36	Medication use (agents acting on the renin-angiotensin system)	2.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0009931	Agents acting on the renin-angiotensin system use measurement

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
rs1800169	CNTF, ZFP91-CNTF		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases activity, decreases reaction, increases phosphorylation, decreases expression, affects localization	3
Acetylcysteine	decreases expression, decreases reaction, increases phosphorylation	2
Hydrogen Peroxide	affects localization, decreases reaction, increases activity, increases phosphorylation, decreases activity	2
Mercuric Chloride	decreases reaction, increases phosphorylation, decreases activity	2
Rotenone	decreases activity, decreases reaction, increases activity, increases phosphorylation, increases reaction	2
testosterone undecanoate	increases expression	1
trichostatin A	affects expression	1
oxophenylarsine	affects activity, affects phosphorylation, decreases reaction	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases reaction, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Ascorbic Acid	decreases reaction, increases phosphorylation	1
Vehicle Emissions	affects methylation, increases expression	1
Cadmium	affects localization, decreases reaction, increases phosphorylation	1
Cisplatin	affects reaction, affects expression	1
Dimethyl Sulfoxide	affects expression	1
Folic Acid	affects expression, affects reaction	1
Glutathione	decreases reaction, increases phosphorylation	1
Thioctic Acid	decreases reaction, increases phosphorylation, decreases activity	1
Methylmercury Compounds	increases reaction, increases phosphorylation	1
Nitrofurantoin	increases activity, increases phosphorylation, increases reaction, decreases reaction	1
Nitrous Oxide	decreases reaction, increases activity, increases phosphorylation, decreases activity	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	affects cotreatment, increases expression	1
2,6-Dichloroindophenol	increases phosphorylation, decreases reaction	1
1-Methyl-4-phenylpyridinium	decreases response to substance, increases expression	1
Zinc Sulfate	decreases reaction, increases phosphorylation	1
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine	affects activity, affects phosphorylation, decreases reaction	1

Cellosaurus cell lines

7 cell lines: 3 cancer cell line, 3 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7MP	Ubigene A-549 CNTF KO	Cancer cell line	Male
CVCL_D8J5	Ubigene HCT 116 CNTF KO	Cancer cell line	Male
CVCL_D9C5	Ubigene HEK293 CNTF KO	Transformed cell line	Female
CVCL_E0AH	Ubigene HeLa CNTF KO	Cancer cell line	Female
CVCL_IQ60	ARPE-19/CNTF	Spontaneously immortalized cell line	Male
CVCL_IQ63	ARPE-19/CNTF-10	Spontaneously immortalized cell line	Male
CVCL_IQ64	ARPE-19/CNTF-6A	Spontaneously immortalized cell line	Male

Clinical trials (associated diseases)

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