RNF6

Summary

RNF6 (ring finger protein 6, HGNC:10069) is a protein-coding gene on chromosome 13q12.13, encoding E3 ubiquitin-protein ligase RNF6 (Q9Y252). E3 ubiquitin-protein ligase mediating ‘Lys-48’-linked polyubiquitination of LIMK1 and its subsequent targeting to the proteasome for degradation.

The protein encoded by this gene contains a RING-H2 finger motif. Deletions and mutations in this gene were detected in esophageal squamous cell carcinoma (ESCC), suggesting that this protein may be a potential tumor suppressor. Studies of the mouse counterpart suggested a role of this protein in the transcription regulation that controls germinal differentiation. Multiple alternatively spliced transcript variants encoding the same protein are observed.

Source: NCBI Gene 6049 — RefSeq curated summary.

At a glance

• Gene–disease (curated): esophageal cancer (No Known Disease Relationship, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 104 total — 3 pathogenic
• Phenotypes (HPO): 9
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_005977

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10069
Approved symbol	RNF6
Name	ring finger protein 6
Location	13q12.13
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp686P0776
Ensembl gene	ENSG00000127870
Ensembl biotype	protein_coding
OMIM	604242
Entrez	6049

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000346166, ENST00000381570, ENST00000381588, ENST00000468480, ENST00000474280, ENST00000476347, ENST00000498039, ENST00000902197, ENST00000902198, ENST00000902199, ENST00000902200, ENST00000902201, ENST00000902202, ENST00000902203, ENST00000902204, ENST00000902205, ENST00000902206, ENST00000911857, ENST00000911858, ENST00000911859, ENST00000945715, ENST00000945716, ENST00000945717, ENST00000945718, ENST00000945719, ENST00000945720, ENST00000945721

RefSeq mRNA: 4 — MANE Select: NM_005977 NM_005977, NM_183043, NM_183044, NM_183045

CCDS: CCDS9316

Canonical transcript exons

ENST00000381588 — 5 exons

Exon	Start	End
ENSE00001384350	26221248	26221330
ENSE00001912048	26212775	26215592
ENSE00001939145	26222003	26222314
ENSE00003484159	26218511	26218606
ENSE00003592813	26219457	26219667

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2419 / max 358.8404, expressed in 1802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136474	13.7305	1786
136473	7.5115	1677

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	97.36	gold quality
epithelium of nasopharynx	UBERON:0001951	96.71	gold quality
choroid plexus epithelium	UBERON:0003911	96.64	gold quality
biceps brachii	UBERON:0001507	96.17	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.87	gold quality
skin of hip	UBERON:0001554	95.79	gold quality
islet of Langerhans	UBERON:0000006	95.67	gold quality
adrenal tissue	UBERON:0018303	95.63	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.57	gold quality
colonic mucosa	UBERON:0000317	95.47	gold quality
upper leg skin	UBERON:0004262	95.35	gold quality
oral cavity	UBERON:0000167	95.30	gold quality
jejunal mucosa	UBERON:0000399	95.04	gold quality
postcentral gyrus	UBERON:0002581	95.01	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.96	gold quality
lateral nuclear group of thalamus	UBERON:0002736	94.80	gold quality
epithelium of bronchus	UBERON:0002031	94.69	gold quality
endothelial cell	CL:0000115	94.26	gold quality
caput epididymis	UBERON:0004358	94.26	gold quality
palpebral conjunctiva	UBERON:0001812	94.18	gold quality
bronchus	UBERON:0002185	94.17	gold quality
superior frontal gyrus	UBERON:0002661	93.86	gold quality
corpus epididymis	UBERON:0004359	93.83	gold quality
trabecular bone tissue	UBERON:0002483	93.80	gold quality
Brodmann (1909) area 23	UBERON:0013554	93.76	gold quality
entorhinal cortex	UBERON:0002728	93.72	gold quality
pigmented layer of retina	UBERON:0001782	93.63	gold quality
parietal lobe	UBERON:0001872	93.58	gold quality
parietal pleura	UBERON:0002400	93.55	gold quality
heart right ventricle	UBERON:0002080	93.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	14.38
E-ANND-3	yes	5.12

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PBX1, PKNOX1

miRNA regulators (miRDB)

137 targeting RNF6, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-219A-5P	99.91	73.36	735

Literature-anchored findings (GeneRIF, showing 19)

• Functional anaylysis of the mouse homolog (PMID:11971979)
• Rnf6 controls cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics (PMID:16204183)
• Results describe thet cloning and identification of a novel RNF6 transcriptional splice variant, Spg2, in human development. (PMID:18368307)
• This study thus suggests that RNF6 overexpression in leukemia is under the direction of PBX1 and that the PBX1/RNF6 axis can be developed as a novel therapeutic target of leukemia. (PMID:26971355)
• High RNF6 expression is associated with breast cancer. (PMID:28223545)
• Data suggest that targeting the ring finger 6 protein (RNF6)/protein-tyrosine phosphatase SHP-1 (SHP-1)/signal transducer and activator of transcription 3 (STAT3) axis provides a potential therapeutic option for RNF6-amplified tumors. (PMID:29288235)
• RNF6-mediated ubiquitination and degradation of TLE3 activates the Wnt/beta-catenin pathway in colorectal carcinogenesis (PMID:29374067)
• the oncogenic effect of RNF6 in hepatocellular carcinoma is partially dependent on FoxA1 degradation. (PMID:30496760)
• downregulation of miR-26a-5p plays essential roles in breast cancer by mediating RNF6/ERalpha/Bcl-xL axis. (PMID:31063232)
• RNF6 promotes myeloma cell proliferation and survival by inducing glucocorticoid receptor polyubiquitination. (PMID:31645658)
• RNF6 serves as a diagnostic hallmark of non-alcoholic fatty liver disease with hepatocellular carcinoma: a clinical research. (PMID:33215420)
• Gene commander in the trash heap: Transcriptional regulation and ubiquitination modification mediated by RNF6 in carcinogenesis. (PMID:33485842)
• Knockdown of RNF6 inhibits HeLa cervical cancer cell growth via suppression of MAPK/ERK signaling. (PMID:34081837)
• RNF6 promotes colorectal cancer invasion and migration via the Wnt/beta-catenin pathway by inhibiting GSK3beta activity. (PMID:34352441)
• RING-finger protein 6 promotes colorectal tumorigenesis by transcriptionally activating SF3B2. (PMID:34611311)
• Ring finger protein 6 enhances chemo-resistance by transcriptionally activating proliferating cell nuclear antigen expression and attenuating DNA damage in lung adenocarcinoma. (PMID:35278611)
• RING-Finger Protein 6 promotes Drug Resistance in Retinoblastoma via JAK2/STAT3 Signaling Pathway. (PMID:35369571)
• E3 ubiquitin ligase RNF6 promotes antiviral immune responses through enhancing the expression of interferon stimulated genes in myeloid cells. (PMID:35973638)
• Non-adherent culture method affects the proliferation and apoptosis of mesenchymal stem cells through inhibiting LINC00707 to promote RNF6-mediated QKI ubiquitination. (PMID:38072302)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf6	ENSDARG00000077955
mus_musculus	Rnf6	ENSMUSG00000029634
rattus_norvegicus	Rnf6	ENSRNOG00000000968

Paralogs (3): RLIM (ENSG00000131263), RNF38 (ENSG00000137075), RNF44 (ENSG00000146083)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF6 — Q9Y252 (reviewed: Q9Y252)

All UniProt accessions (2): Q9Y252, A0A024RDP2

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase mediating ‘Lys-48’-linked polyubiquitination of LIMK1 and its subsequent targeting to the proteasome for degradation. Negatively regulates axonal outgrowth through regulation of the LIMK1 turnover. Mediates ‘Lys-6’ and ‘Lys-27’-linked polyubiquitination of AR/androgen receptor thereby modulating its transcriptional activity. May also bind DNA and function as a transcriptional regulator. Mediates polyubiquitination of QKI in macrophages, leading to its degradation.

Subcellular location. Nucleus. Cytoplasm. Cell projection. Axon. PML body.

Tissue specificity. Weakly expressed in peripheral blood, spleen, prostate, testis and ovary. According to a report, it is preferentially expressed in testis and ovary and hardly detected in other tissues.

Disease relevance. Esophageal cancer (ESCR) [MIM:133239] A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. The disease may be caused by variants affecting the gene represented in this entry.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the RNF12 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y252-1	1	yes
Q9Y252-2	2
Q9Y252-3	3

RefSeq proteins (4): NP_005968, NP_898864, NP_898865, NP_898866 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR051834	RING_finger_E3_ligase	Family
IPR058896	RNF6/12_N	Domain

Pfam: PF13639, PF25914

UniProt features (29 total): compositionally biased region 9, sequence variant 8, region of interest 6, splice variant 4, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y252-F1	49.92	0.06

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-983168	Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-983169	Class I MHC mediated antigen processing & presentation

MSigDB gene sets: 314 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, MORF_MBD4, TSENG_IRS1_TARGETS_UP, GOBP_NEURON_PROJECTION_EXTENSION, MORF_RAB5A, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_CELLULAR_RESPONSE_TO_LIPID, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS

GO Biological Process (10): regulation of DNA-templated transcription (GO:0006355), ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), negative regulation of axon extension (GO:0030517), protein K27-linked ubiquitination (GO:0044314), positive regulation of DNA-templated transcription (GO:0045893), axon extension (GO:0048675), regulation of androgen receptor signaling pathway (GO:0060765), protein K48-linked ubiquitination (GO:0070936), protein K6-linked ubiquitination (GO:0085020)

GO Molecular Function (8): DNA binding (GO:0003677), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), nuclear androgen receptor binding (GO:0050681), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), PML body (GO:0016605), axon (GO:0030424), nuclear membrane (GO:0031965), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Class I MHC mediated antigen processing & presentation	1
Immune System	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein polyubiquitination	3
DNA-templated transcription	2
cellular anatomical structure	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
negative regulation of cell growth	1
regulation of axon extension	1
negative regulation of developmental growth	1
axon extension	1
negative regulation of axonogenesis	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
axonogenesis	1
neuron projection extension	1
androgen receptor signaling pathway	1
regulation of intracellular steroid hormone receptor signaling pathway	1
nucleic acid binding	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
nuclear receptor binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
nuclear body	1
neuron projection	1
nucleus	1
nuclear envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1073 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF6	ATP8A2	Q9NTI2	853
RNF6	DLEC1	Q9Y238	752
RNF6	S100A14	Q9HCY8	683
RNF6	LZTS1	Q9Y250	670
RNF6	ADH1B	P00325	565
RNF6	WWOX	Q9NZC7	532
RNF6	RNF14	Q9UBS8	517
RNF6	SIAH2	O43255	512
RNF6	ALDH2	P05091	496
RNF6	TLE3	Q04726	479
RNF6	NKX6-3	A6NJ46	476
RNF6	B7Z1P2	B7Z1P2	442
RNF6	SLC52A3	Q9NQ40	435
RNF6	STUB1	Q9UNE7	433
RNF6	TRIM9	Q9C026	432

IntAct

15 interactions, top by confidence:

A	B	Type	Score
AR	KLK3	psi-mi:“MI:0914”(association)	0.600
AR	KLK3	psi-mi:“MI:0915”(physical association)	0.600
RNF6	AR	psi-mi:“MI:0915”(physical association)	0.580
RNF6	AR	psi-mi:“MI:0403”(colocalization)	0.580
RNF6	ALOX5	psi-mi:“MI:0914”(association)	0.530
RNF14	AR	psi-mi:“MI:0914”(association)	0.500
RNF6	UBE2H	psi-mi:“MI:0915”(physical association)	0.370
RNF6		psi-mi:“MI:0914”(association)	0.350
BRCA1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (99): RNF6 (Affinity Capture-Western), AR (Biochemical Activity), UBE2D1 (Reconstituted Complex), ALOX5 (Affinity Capture-MS), VASN (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), LRRFIP2 (Affinity Capture-MS), GNA11 (Affinity Capture-MS), TJP3 (Affinity Capture-MS), GNAI3 (Affinity Capture-MS), CTNNB1 (Affinity Capture-MS), CD59 (Affinity Capture-MS), NT5E (Affinity Capture-MS), ABLIM1 (Affinity Capture-MS)

ESM2 similar proteins: A2AH22, E7FAG6, O22197, O42967, P0CH30, P14349, P22470, P28990, P32828, P34256, P34675, P84445, P87237, Q07G42, Q0II22, Q21127, Q48B61, Q4ZMD6, Q5R9W2, Q5XI50, Q641J8, Q6AVN2, Q6DIP3, Q6IRP0, Q7T037, Q7T0Q3, Q87039, Q8LPN7, Q8RK09, Q8RK12, Q8RP04, Q8RSY1, Q8SV35, Q91YL2, Q94AK4, Q9BV68, Q9C0C7, Q9C1X4, Q9DBU5, Q9FMM4

Diamond homologs: A5WWA0, E9QAU8, G3X9R7, O22197, O22755, O43567, O54965, O64763, P0C034, P0CH30, P0DPR2, Q06003, Q07G42, Q08D68, Q0II22, Q0VD51, Q10R93, Q14B02, Q29RU0, Q2TA44, Q3U2C5, Q4KLR8, Q4R6Y5, Q5NCP0, Q5RCV8, Q5RF74, Q5SPX3, Q5SSZ7, Q5XF85, Q641J8, Q66HG0, Q68DV7, Q69U49, Q6AY01, Q6DIP3, Q6IRP0, Q6NML0, Q6NQG7, Q6NRX0, Q6Y290

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF6	ubiquitination
RNF6	“down-regulates quantity by destabilization”	LIMK1	polyubiquitination

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — COADREAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	87
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
5700	NM_005977.4(RNF6):c.305G>A (p.Arg102Lys)	Pathogenic
5701	NM_005977.4(RNF6):c.724G>A (p.Ala242Thr)	Pathogenic
5702	NM_005977.4(RNF6):c.731G>A (p.Gly244Asp)	Pathogenic

SpliceAI

789 predictions. Top by Δscore:

Variant	Effect	Δscore
13:26215593:C:CC	acceptor_gain	1.0000
13:26218510:CCT:C	donor_gain	1.0000
13:26218604:CTC:C	acceptor_gain	1.0000
13:26218607:C:CC	acceptor_gain	1.0000
13:26218607:CTA:C	acceptor_loss	1.0000
13:26218608:T:C	acceptor_loss	1.0000
13:26219455:A:AC	donor_gain	1.0000
13:26219456:C:CC	donor_gain	1.0000
13:26219664:CTTT:C	acceptor_gain	1.0000
13:26219665:TTT:T	acceptor_gain	1.0000
13:26219666:TT:T	acceptor_gain	1.0000
13:26219668:C:CC	acceptor_gain	1.0000
13:26221251:ATTTT:A	donor_gain	1.0000
13:26215591:GT:G	acceptor_gain	0.9900
13:26215591:GTCT:G	acceptor_loss	0.9900
13:26215592:TC:T	acceptor_loss	0.9900
13:26215593:CT:C	acceptor_loss	0.9900
13:26215594:T:G	acceptor_loss	0.9900
13:26218433:A:AC	donor_gain	0.9900
13:26218434:C:CC	donor_gain	0.9900
13:26218434:CTATA:C	donor_gain	0.9900
13:26218435:TA:T	donor_gain	0.9900
13:26218505:TAGTA:T	donor_loss	0.9900
13:26218507:GTA:G	donor_loss	0.9900
13:26218508:TA:T	donor_loss	0.9900
13:26218509:A:AT	donor_loss	0.9900
13:26218510:C:CT	donor_loss	0.9900
13:26218512:T:TA	donor_gain	0.9900
13:26218602:TTCTC:T	acceptor_gain	0.9900
13:26218605:TC:T	acceptor_gain	0.9900

AlphaMissense

4480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:26213877:A:G	C669R	1.000
13:26213896:C:A	W662C	1.000
13:26213896:C:G	W662C	1.000
13:26213898:A:G	W662R	1.000
13:26213898:A:T	W662R	1.000
13:26213908:A:C	C658W	1.000
13:26213920:A:C	F654L	1.000
13:26213920:A:T	F654L	1.000
13:26213922:A:G	F654L	1.000
13:26213868:A:G	C672R	0.999
13:26213875:A:C	C669W	0.999
13:26213876:C:T	C669Y	0.999
13:26213894:A:G	L663P	0.999
13:26213909:C:A	C658F	0.999
13:26213909:C:G	C658S	0.999
13:26213909:C:T	C658Y	0.999
13:26213910:A:G	C658R	0.999
13:26213910:A:T	C658S	0.999
13:26213934:A:G	C650R	0.999
13:26213939:A:G	L648S	0.999
13:26213977:A:C	C635W	0.999
13:26213979:A:G	C635R	0.999
13:26213986:A:C	C632W	0.999
13:26213987:C:T	C632Y	0.999
13:26213988:A:G	C632R	0.999
13:26213866:A:C	C672W	0.998
13:26213867:C:G	C672S	0.998
13:26213867:C:T	C672Y	0.998
13:26213868:A:T	C672S	0.998
13:26213873:G:T	P670Q	0.998

dbSNP variants (sampled 300 via entrez): RS1000012585 (13:26147209 A>G,T), RS1000052605 (13:26185519 G>A), RS1000101876 (13:26190457 T>A,C), RS1000124330 (13:26164164 A>C), RS1000149322 (13:26146889 C>A,G,T), RS1000253831 (13:26168935 C>A), RS1000277251 (13:26169408 C>G), RS1000284939 (13:26169176 G>A,C,T), RS1000298664 (13:26210694 C>G), RS1000305723 (13:26190871 A>G), RS1000315500 (13:26141191 C>A), RS1000359302 (13:26174342 T>C), RS1000388341 (13:26198593 G>C), RS1000406299 (13:26220375 G>A), RS1000429755 (13:26205377 G>A)

Disease associations

OMIM: gene MIM:604242 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
esophageal cancer	No Known Disease Relationship	Unknown

Mondo (1): esophageal cancer (MONDO:0007576)

Orphanet (0):

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0001442	Typified by somatic mosaicism
HP:0001608	Abnormality of the voice
HP:0001864	Clinodactyly of the 5th toe
HP:0002017	Nausea and vomiting
HP:0002716	Lymphadenopathy
HP:0008872	Feeding difficulties in infancy
HP:0011459	Esophageal carcinoma
HP:0012735	Cough
HP:0100749	Chest pain

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002352_26	Type 2 diabetes	2.000000e-07
GCST002826_5	Urate levels (BMI interaction)	3.000000e-06
GCST002940_4	Sporadic pituitary adenoma	2.000000e-08
GCST004894_118	Type 2 diabetes	1.000000e-09
GCST004894_14	Type 2 diabetes	2.000000e-06
GCST007847_2	Type 2 diabetes	1.000000e-15
GCST009379_355	Type 2 diabetes	2.000000e-10
GCST010118_91	Type 2 diabetes	3.000000e-22

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, increases abundance	2
Silicon Dioxide	increases expression	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
aflatoxin B2	increases methylation	1
epigallocatechin gallate	increases expression, affects cotreatment	1
pentanal	decreases expression	1
avobenzone	increases expression	1
K 7174	increases expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1
Folic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00333099	PHASE4	COMPLETED	INEC Study: Immuno-modulating Enteral Nutrition in Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00754468	PHASE4	COMPLETED	Study of CryoSpray Ablation(TM)to Determine Treatment Effect, Depth of Injury, and Side Effects in the Esophagus.
NCT00790140	PHASE4	UNKNOWN	Trial of Enteral Nutrition Enriched With Eicosapentaenoic Acid (EPA) in Upper Gastrointestinal Cancer Surgery
NCT00911092	PHASE4	COMPLETED	Predictive Proteomic Factors of the Response to Concomitant Radiochemotherapy in Esophageal Cancer
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01416077	PHASE4	COMPLETED	Decreasing Postoperative Complications by Goal-Directed Fluid Therapy During Esophageal Resection
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT02042313	PHASE4	UNKNOWN	Postoperative Pain Management After Minimally Invasive Esophagectomy
NCT02320734	PHASE4	COMPLETED	Deep Neuromuscular Relaxation in Patients for Thoraco-laparoscopic Esophagectomy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03413436	PHASE4	COMPLETED	Lobaplation or Cisplatin in Adjuvant Chemotherapy for Esophageal Carcinoma
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT06437288	PHASE4	ENROLLING_BY_INVITATION	Hematoporphyrin Photodynamic Therapy for Esophageal Cancer
NCT07124351	PHASE4	RECRUITING	Intraoperative Imaging of Gastrointestinal Malignancies Using Pafolacianine (CYTALUX™)
NCT00002631	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Cancer of the Esophagus
NCT00002883	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Cancer of the Esophagus
NCT00002884	PHASE3	UNKNOWN	Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Esophagus
NCT00002897	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage II or Stage III Cancer of the Esophagus
NCT00003118	PHASE3	COMPLETED	Surgery With or Without Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Esophagus
NCT00020787	PHASE3	COMPLETED	Vaccine Therapy Plus Chemotherapy in Treating Patients With Metastatic or Locally Recurrent Stomach Cancer or Esophageal Cancer
NCT00041262	PHASE3	UNKNOWN	Combination Chemotherapy in Treating Patients With Esophageal Cancer
NCT00047112	PHASE3	COMPLETED	Surgery With or Without Radiation Therapy and Chemotherapy in Treating Patients With Esophageal Cancer
NCT00052910	PHASE3	COMPLETED	Chemotherapy and Radiation Therapy After Surgery in Treating Patients With Stomach or Esophageal Cancer
NCT00165061	PHASE3	COMPLETED	Multi-Center Prospective Randomized Trial Comparing Standard Esophagectomy Against Chemo-Radiotherapy for Treatment of Squamous Esophageal Cancer - Early Results From the Chinese University Research Group for Esophageal Cancer (CURE)
NCT00193817	PHASE3	UNKNOWN	Three Field Radical Esophagectomy Versus Two Field Esophagectomy - a Prospective Trial
NCT00193882	PHASE3	COMPLETED	Advanced Oesophageal Cancer Study to Compare Quality of Life and Palliation of Dysphagia.
NCT00270166	PHASE3	COMPLETED	The Effect of Epoetin Alfa on the Anemia of Patients With Selected Cancers Receiving Chemotherapy
NCT00357682	PHASE3	COMPLETED	A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett’s Metaplasia
NCT00359645	PHASE3	COMPLETED	Randomized Trial to Assess the Impact of a Screening Program on Upper Aerodigestive Tract Cancer Mortality in a High Risk Population
NCT00387348	PHASE3	TERMINATED	Escitalopram in Treating Depression in Patients With Advanced Lung or Gastrointestinal Cancer
NCT00416858	PHASE3	COMPLETED	Radiation Therapy and Combination Chemotherapy With or Without Surgery in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed By Surgery
NCT00525200	PHASE3	COMPLETED	p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer
NCT00655876	PHASE3	COMPLETED	Paclitaxel, Cisplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Locally Advanced Esophageal Cancer
NCT00665197	PHASE3	COMPLETED	Palliative Radiotherapy and Brachytherapy for Oesophageal Cancer Dysphagia
NCT00686114	PHASE3	UNKNOWN	Concurrent Chemoradiotherapy Containing Paclitaxel&Cisplatin With/Without Tarceva in Locally Advanced Esophageal Cancer