CNTFR

Summary

CNTFR (ciliary neurotrophic factor receptor, HGNC:2170) is a protein-coding gene on chromosome 9p13.3, encoding Ciliary neurotrophic factor receptor subunit alpha (P26992). Binds to CNTF.

This gene encodes a member of the type 1 cytokine receptor family. The encoded protein is the ligand-specific component of a tripartite receptor for ciliary neurotrophic factor, which plays a critical role in neuronal cell survival, differentiation and gene expression. Binding of ciliary neurotrophic factor to the encoded protein recruits the transmembrane components of the receptor, gp130 and leukemia inhibitory factor receptor, facilitating signal transduction. Single nucleotide polymorphisms in this gene may be associated with variations in muscle strength, as well as early onset of eating disorders. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 1271 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_147164

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2170
Approved symbol	CNTFR
Name	ciliary neurotrophic factor receptor
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000122756
Ensembl biotype	protein_coding
OMIM	118946
Entrez	1271

Gene structure

Transcript identifiers

Ensembl transcripts: 55 — 55 protein_coding

ENST00000351266, ENST00000378980, ENST00000417345, ENST00000610543, ENST00000868690, ENST00000868691, ENST00000868692, ENST00000868693, ENST00000868694, ENST00000868695, ENST00000868696, ENST00000868697, ENST00000868698, ENST00000868699, ENST00000868700, ENST00000868701, ENST00000868702, ENST00000868703, ENST00000868704, ENST00000868705, ENST00000868706, ENST00000868707, ENST00000868708, ENST00000868709, ENST00000868710, ENST00000868711, ENST00000868712, ENST00000868713, ENST00000868714, ENST00000868715, ENST00000868716, ENST00000923809, ENST00000923810, ENST00000923811, ENST00000923812, ENST00000923813, ENST00000923814, ENST00000950013, ENST00000950014, ENST00000950015, ENST00000950016, ENST00000950017, ENST00000950018, ENST00000950019, ENST00000950020, ENST00000950021, ENST00000950022, ENST00000950023, ENST00000950024, ENST00000950025, ENST00000950026, ENST00000950027, ENST00000950028, ENST00000950029, ENST00000950030

RefSeq mRNA: 3 — MANE Select: NM_147164 NM_001207011, NM_001842, NM_147164

CCDS: CCDS6558

Canonical transcript exons

ENST00000378980 — 10 exons

Exon	Start	End
ENSE00000832916	34552161	34552329
ENSE00000832917	34552674	34552854
ENSE00000832919	34557526	34557692
ENSE00000832920	34557867	34557984
ENSE00000928113	34564599	34564832
ENSE00001221746	34581095	34581205
ENSE00001479479	34589555	34589724
ENSE00003759799	34568897	34568981
ENSE00003784906	34556255	34556418
ENSE00003845565	34551433	34552071

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 98.99.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8078 / max 94.3717, expressed in 431 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100521	2.0131	380
100522	0.4463	234
100523	0.2208	114
100520	0.1275	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.99	gold quality
ganglionic eminence	UBERON:0004023	97.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.56	gold quality
cortical plate	UBERON:0005343	95.51	gold quality
cerebellar hemisphere	UBERON:0002245	94.94	gold quality
cerebellar cortex	UBERON:0002129	94.76	gold quality
gastrocnemius	UBERON:0001388	94.52	gold quality
right frontal lobe	UBERON:0002810	93.83	gold quality
caudate nucleus	UBERON:0001873	93.49	gold quality
muscle of leg	UBERON:0001383	93.01	gold quality
omental fat pad	UBERON:0010414	92.82	gold quality
peritoneum	UBERON:0002358	92.74	gold quality
nucleus accumbens	UBERON:0001882	92.70	gold quality
putamen	UBERON:0001874	92.58	gold quality
amygdala	UBERON:0001876	92.35	gold quality
cerebellum	UBERON:0002037	91.75	gold quality
cingulate cortex	UBERON:0003027	91.28	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.23	gold quality
anterior cingulate cortex	UBERON:0009835	91.17	gold quality
right atrium auricular region	UBERON:0006631	91.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.41	gold quality
cardiac atrium	UBERON:0002081	89.12	gold quality
embryo	UBERON:0000922	88.58	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.47	gold quality
prefrontal cortex	UBERON:0000451	88.01	gold quality
hypothalamus	UBERON:0001898	87.42	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	86.68	gold quality
muscle organ	UBERON:0001630	86.49	gold quality
ectocervix	UBERON:0012249	86.03	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.73
E-GEOD-84465	yes	11.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR4A1

miRNA regulators (miRDB)

92 targeting CNTFR, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3121-3P	99.82	71.96	3630

Literature-anchored findings (GeneRIF, showing 16)

• interactions of CNTFR with LIFR and gp130 in vitro (PMID:12707266)
• C174T polymorphism in exon 9 of CNTFR is significantly associated with fat-free mass in men and women, with concomitant differences in muscular strength. (PMID:12807897)
• Structural and docking interaction studies showed that the R197L substitution destabilized the contact site between CLC and CNTFRalpha. (PMID:16782820)
• In liver CNTFRalpha serves as a key modulator in regulating PI3K and AMP-activated protein kinase dynamically under CNTF stimulation, resulting in the increase of glucose uptake and translocation of glucose transporter 4. (PMID:18307269)
• These results indicate that humanin protects neurons by binding to a complex or complexes involving CNTFR/WSX-1/gp130. (PMID:19386761)
• Data show that variants in CNTFR were significantly associated with a lower age at onset of the eating disorders. (PMID:20219210)
• expression of neurotrophin receptors Pan-Trk, p75 neurotrophin receptor (p75(NTR) and ciliary neurotrophic factor receptor-alpha in ulveal melanoma does not show a role in growth. (PMID:22343487)
• Data indicate that CNTFRalpha plays a role in the formation or maintenance of tumor-initiating cells in gliomas, is a marker that correlates with histological grade, may underlie treatment resistance in some cases, and is a potential therapeutic target. (PMID:23061382)
• gene expression and surface expression in NK92 cells of ciliary neurotrophic factor alpha (CNTFR-alpha) and glycoprotein (gp)130 in natural killer (NK) cells, in the context of malaria, were investigated. (PMID:23398366)
• The family-based study showed no association between the CNTFR rs7036351, NET rs3785143 polymorphisms, and attention-deficit hyperactivity disorder. (PMID:24565995)
• R28E mutation in CNTF abrogatesIL-6 receptor-dependent but retains CNTF receptor-dependent signaling via glycoprotein 130/ LIFR. (PMID:24802752)
• This study demonstrated that hypomethylation leading to CNTFRalpha up-regulation, together with autocrine expression of CNTF, was involved in glioma growth regulation. (PMID:28765641)
• miR-146a could promote the proliferation, migration, and invasion and inhibit the apoptosis of AL Jurkat and HL-60 cells by downregulating CNTFR and activating the JAK2/STAT3 pathway. (PMID:31538427)
• we nominate blockade of CLCF1-CNTFR signaling as a novel therapeutic opportunity for lung adenocarcinoma and potentially for other tumor types in which CLCF1 is present in the tumor microenvironment. (PMID:31700175)
• Ciliary Neurotrophic Factor Receptor rs41274853 Polymorphism Is Associated With Weightlifting Performance in Japanese Weightlifters. (PMID:33105352)
• Ciliary neurotrophic factor (CNTF) and its receptor (CNTFRalpha) signal through MAPK/ERK pathway in human prostate tissues: a morphological and biomolecular study. (PMID:33131268)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cntfr	ENSDARG00000028661
mus_musculus	Cntfr	ENSMUSG00000028444
rattus_norvegicus	Cntfr	ENSRNOG00000047307

Paralogs (23): CRLF1 (ENSG00000006016), IL12RB2 (ENSG00000081985), IL5RA (ENSG00000091181), IL12RB1 (ENSG00000096996), IL27RA (ENSG00000104998), EBI3 (ENSG00000105246), GHR (ENSG00000112964), PRLR (ENSG00000113494), LIFR (ENSG00000113594), LEPR (ENSG00000116678), CSF3R (ENSG00000119535), IL13RA2 (ENSG00000123496), IL13RA1 (ENSG00000131724), IL6ST (ENSG00000134352), IL11RA (ENSG00000137070), OSMR (ENSG00000145623), IL2RG (ENSG00000147168), IL6R (ENSG00000160712), IL23R (ENSG00000162594), IL31RA (ENSG00000164509), IL3RA (ENSG00000185291), CSF2RA (ENSG00000198223), CRLF2 (ENSG00000205755)

Protein

Protein identifiers

Ciliary neurotrophic factor receptor subunit alpha — P26992 (reviewed: P26992)

All UniProt accessions (3): A0A0A0N0N2, P26992, Q5T8H6

UniProt curated annotations — full annotation on UniProt →

Function. Binds to CNTF. The alpha subunit provides the receptor specificity. Receptor for heterodimeric neurotropic cytokine composed of CLCF1/CLC and CRLF1/CLF-1. Acts as a receptor for the neuroprotective peptide humanin as part of a complex with IL6ST/GP130 and IL27RA/WSX1.

Subunit / interactions. Forms a heterotrimer with LIFR and IL6ST. Interacts with heterodimeric neurotropic cytokine composed of CLCF1/CLC and CRLF1/CLF-1. Either alone or in complex with the heterodimer CLCF1-CRLF1 interacts with SORL1; this interaction may promote internalization and lysosomal degradation. Component of a receptor complex composed of IL6ST/GP130, IL27RA/WSX1 and CNTFR which interacts with the neuroprotective peptide humanin.

Subcellular location. Cell membrane.

Tissue specificity. Nervous system and skeletal muscle.

Domain organisation. The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.

Similarity. Belongs to the type I cytokine receptor family. Type 3 subfamily.

RefSeq proteins (3): NP_001193940, NP_001833, NP_671693* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003530	Hematopoietin_rcpt_L_F3_CS	Conserved_site
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003961	FN3_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050379	Type-I_Cytokine_Rcpt	Family

Pfam: PF00041

UniProt features (42 total): strand 24, glycosylation site 4, domain 3, helix 2, signal peptide 1, chain 1, disulfide bond 1, propeptide 1, turn 1, region of interest 1, short sequence motif 1, compositionally biased region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8D7E	ELECTRON MICROSCOPY	2.93
8D74	ELECTRON MICROSCOPY	3.03
8D7H	ELECTRON MICROSCOPY	3.4
8D7R	ELECTRON MICROSCOPY	3.9
1UC6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P26992-F1	84.12	0.72

Antibody-complex structures (SAbDab): 1 — 8D7E

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 (1): 342

Disulfide bonds (1): 46–89

Glycosylation sites (4): 60, 70, 142, 190

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 174 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, PAX4_01, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, RORA1_01, SP3_Q3, MODULE_64, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_SUCKLING_BEHAVIOR, GOCC_CELL_SURFACE, TGACCTY_ERR1_Q2, CATTTCA_MIR203, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (13): suckling behavior (GO:0001967), brainstem development (GO:0003360), signal transduction (GO:0007165), nervous system development (GO:0007399), sex differentiation (GO:0007548), positive regulation of cell population proliferation (GO:0008284), negative regulation of neuron apoptotic process (GO:0043524), skeletal muscle organ development (GO:0060538), ciliary neurotrophic factor-mediated signaling pathway (GO:0070120), motor neuron apoptotic process (GO:0097049), negative regulation of motor neuron apoptotic process (GO:2000672), cytokine-mediated signaling pathway (GO:0019221), interleukin-11-mediated signaling pathway (GO:0038154)

GO Molecular Function (7): ciliary neurotrophic factor receptor activity (GO:0004897), interleukin-11 receptor activity (GO:0004921), signaling receptor binding (GO:0005102), cytokine binding (GO:0019955), interleukin-11 binding (GO:0019970), cytokine receptor activity (GO:0004896), protein binding (GO:0005515)

GO Cellular Component (8): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), apical plasma membrane (GO:0016324), extrinsic component of membrane (GO:0019898), ciliary neurotrophic factor receptor complex (GO:0070110), CNTFR-CLCF1 complex (GO:0097059), membrane (GO:0016020), side of membrane (GO:0098552)

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
cytokine-mediated signaling pathway	3
membrane	3
cellular anatomical structure	3
neuron apoptotic process	2
cytokine receptor activity	2
protein binding	2
cytokine binding	2
feeding behavior	1
anatomical structure development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
system development	1
developmental process involved in reproduction	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
muscle organ development	1
negative regulation of neuron apoptotic process	1
motor neuron apoptotic process	1
regulation of motor neuron apoptotic process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
ciliary neurotrophic factor binding	1
ciliary neurotrophic factor-mediated signaling pathway	1
interleukin-11 binding	1
interleukin-11-mediated signaling pathway	1
growth factor binding	1
transmembrane signaling receptor activity	1
immune receptor activity	1
binding	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
apical part of cell	1

Protein interactions and networks

STRING

1084 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNTFR	CNTF	P26441	999
CNTFR	LIFR	P42702	996
CNTFR	IL27RA	Q6UWB1	995
CNTFR	CTF1	Q16619	943
CNTFR	IL6ST	P40189	906
CNTFR	CLCF1	Q9UBD9	881
CNTFR	LIF	P15018	832
CNTFR	IL11	P20809	829
CNTFR	IL11RA	Q14626	810
CNTFR	BDNF	P23560	801
CNTFR	OSMR	Q99650	746
CNTFR	IL6	P05231	741
CNTFR	NFX1	Q12986	711
CNTFR	IL6R	P08887	693
CNTFR	STAT3	P40763	689

IntAct

48 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
CNTF	CNTFR	psi-mi:“MI:0407”(direct interaction)	0.810
CLCF1	CRLF1	psi-mi:“MI:0915”(physical association)	0.770
CNTFR	SORL1	psi-mi:“MI:0403”(colocalization)	0.670
CNTFR	SORL1	psi-mi:“MI:0407”(direct interaction)	0.670
CNTFR	SORL1	psi-mi:“MI:0915”(physical association)	0.670
SORL1	CNTFR	psi-mi:“MI:0915”(physical association)	0.670
CRLF1	CNTFR	psi-mi:“MI:0407”(direct interaction)	0.610
CRLF1	CNTFR	psi-mi:“MI:0915”(physical association)	0.610
CLCF1	CNTFR	psi-mi:“MI:0407”(direct interaction)	0.570
CLCF1	CNTFR	psi-mi:“MI:0915”(physical association)	0.490
CNTFR	CRLF1	psi-mi:“MI:0915”(physical association)	0.460

BioGRID (19): APPBP2 (Two-hybrid), PLSCR1 (Two-hybrid), KRTAP4-12 (Two-hybrid), RPS6KA4 (Negative Genetic), STMN1 (Positive Genetic), CNTFR (Positive Genetic), NPR2 (Positive Genetic), CNTFR (Reconstituted Complex), CNTFR (Reconstituted Complex), LIFR (Affinity Capture-Western), IL6ST (Affinity Capture-Western), CNTFR (Affinity Capture-MS), CLCF1 (Affinity Capture-Western), CLCF1 (Co-purification), CNTF (Reconstituted Complex)

ESM2 similar proteins: A5D8T8, O35217, O75078, O75882, O75900, O88272, O88507, O88676, O95633, P08887, P0C7M8, P0C7M9, P26992, P78539, Q00961, Q01098, Q08406, Q0ZCA7, Q14957, Q1LZB9, Q2TBM7, Q4V7F2, Q5EA46, Q5VV63, Q63769, Q642A6, Q6A051, Q6IA17, Q6P1D5, Q6PCB0, Q6UXF7, Q71DR4, Q7TNS7, Q7TSQ1, Q8NCF0, Q8R2Z5, Q8R366, Q91XD7, Q96FT7, Q96HD1

Diamond homologs: O18796, O88507, P08887, P22272, P22273, P26992, P51641, Q08406, Q71DR4, O35228, P70225, Q14213, Q14626, Q5RF19, Q64385, Q99MF4, O02744, P29460, P43432, P46282, P46658, P48095, P68220, P68221, Q28234, Q28268, Q28938, Q2PE76, Q61729, Q62959, Q865Y3, Q866G3, Q8CJE6, Q91ZK7, Q9MYL0, Q9XSQ5, D3YYU8

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CNTFR	up-regulates	STAT1
CNTFR	up-regulates	STAT3
CNTF	up-regulates	CNTFR	binding
CLCF1	up-regulates	CNTFR	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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
FCGR3A-mediated phagocytosis	5	58.5×	4e-06

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of neuron apoptotic process	5	26.4×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1885 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34552072:C:CC	acceptor_gain	1.0000
9:34552157:CTAC:C	donor_loss	1.0000
9:34552158:TACC:T	donor_loss	1.0000
9:34552159:A:AC	donor_gain	1.0000
9:34552160:C:CC	donor_gain	1.0000
9:34552328:CT:C	acceptor_gain	1.0000
9:34552330:C:CC	acceptor_gain	1.0000
9:34552688:T:TA	donor_gain	1.0000
9:34552867:C:CT	acceptor_gain	1.0000
9:34556253:A:AC	donor_gain	1.0000
9:34556254:C:CC	donor_gain	1.0000
9:34556254:CATG:C	donor_gain	1.0000
9:34558263:A:C	donor_gain	1.0000
9:34558268:T:C	donor_gain	1.0000
9:34568895:AC:A	donor_gain	1.0000
9:34568896:CC:C	donor_gain	1.0000
9:34552068:GGCT:G	acceptor_gain	0.9900
9:34552070:CT:C	acceptor_gain	0.9900
9:34552325:GGTCT:G	acceptor_gain	0.9900
9:34552326:GTCT:G	acceptor_gain	0.9900
9:34552328:CTCTG:C	acceptor_loss	0.9900
9:34552329:TC:T	acceptor_loss	0.9900
9:34552668:GCTCA:G	donor_loss	0.9900
9:34552669:CTCAC:C	donor_loss	0.9900
9:34552670:TCA:T	donor_loss	0.9900
9:34552671:CACCC:C	donor_loss	0.9900
9:34552672:A:AC	donor_gain	0.9900
9:34552673:C:A	donor_loss	0.9900
9:34552673:C:CC	donor_gain	0.9900
9:34552856:T:C	acceptor_loss	0.9900

AlphaMissense

2410 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34552741:G:C	S294R	1.000
9:34552741:G:T	S294R	1.000
9:34552742:C:A	S294I	1.000
9:34552743:T:G	S294R	1.000
9:34552744:C:A	W293C	1.000
9:34552744:C:G	W293C	1.000
9:34552745:C:G	W293S	1.000
9:34552746:A:G	W293R	1.000
9:34552746:A:T	W293R	1.000
9:34552750:A:C	S291R	1.000
9:34552750:A:T	S291R	1.000
9:34552751:C:A	S291I	1.000
9:34552752:T:G	S291R	1.000
9:34552753:C:A	W290C	1.000
9:34552753:C:G	W290C	1.000
9:34552755:A:G	W290R	1.000
9:34552755:A:T	W290R	1.000
9:34552760:C:A	G288V	1.000
9:34552760:C:T	G288E	1.000
9:34552761:C:A	G288W	1.000
9:34552761:C:G	G288R	1.000
9:34552761:C:T	G288R	1.000
9:34552779:C:G	A282P	1.000
9:34552782:C:G	A281P	1.000
9:34552787:T:G	Q279P	1.000
9:34552790:A:T	I278N	1.000
9:34552814:G:T	A270D	1.000
9:34552817:T:A	D269V	1.000
9:34552818:C:G	D269H	1.000
9:34552823:A:C	I267S	1.000

dbSNP variants (sampled 300 via entrez): RS1000191382 (9:34553719 C>T), RS1000245228 (9:34592451 C>T), RS1000294345 (9:34579451 CAG>C), RS1000337098 (9:34565981 C>A,G,T), RS1000605310 (9:34569960 C>G), RS1000663865 (9:34571244 C>G), RS1000727368 (9:34591447 G>A), RS1000730234 (9:34564384 G>C,T), RS1000740288 (9:34559807 C>T), RS1000799603 (9:34570410 C>T), RS1000954881 (9:34570183 G>A,T), RS1000972317 (9:34586517 A>T), RS1001003346 (9:34586699 A>C,G), RS1001040766 (9:34574848 C>T), RS1001092734 (9:34574670 G>A,C,T)

Disease associations

OMIM: gene MIM:118946 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_1318	Blood protein levels	3.000000e-18
GCST006585_351	Blood protein levels	8.000000e-15
GCST010059_1	Physiological traits	8.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — IL-6 receptor family

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
bisphenol A	increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects expression, affects response to substance	1
ethyl-p-hydroxybenzoate	decreases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects expression	1
Cytarabine	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Formaldehyde	decreases expression	1
Methapyrilene	increases methylation	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	decreases response to substance, increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_3607	TF-1.CN5a.1	Cancer cell line	Male
CVCL_D9C6	Ubigene HEK293 CNTFR KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer