RNF126

Summary

RNF126 (ring finger protein 126, HGNC:21151) is a protein-coding gene on chromosome 19p13.3, encoding E3 ubiquitin-protein ligase RNF126 (Q9BV68). E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins.

The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions.

Source: NCBI Gene 55658 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 88 total
• Druggable target: yes
• MANE Select transcript: NM_194460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21151
Approved symbol	RNF126
Name	ring finger protein 126
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20552
Ensembl gene	ENSG00000070423
Ensembl biotype	protein_coding
OMIM	615177
Entrez	55658

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 12 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000292363, ENST00000586749, ENST00000589762, ENST00000590885, ENST00000591394, ENST00000592626, ENST00000605891, ENST00000868233, ENST00000868234, ENST00000868235, ENST00000868236, ENST00000868237, ENST00000868238, ENST00000921284, ENST00000921285, ENST00000958433, ENST00000958434

RefSeq mRNA: 2 — MANE Select: NM_194460 NM_001366018, NM_194460

CCDS: CCDS12039

Canonical transcript exons

ENST00000292363 — 9 exons

Exon	Start	End
ENSE00000655248	651611	651855
ENSE00002943886	647526	648277
ENSE00003511857	652233	652296
ENSE00003541846	648372	648487
ENSE00003563556	652826	652884
ENSE00003642790	650234	650296
ENSE00003646879	648882	648975
ENSE00003702081	663047	663214
ENSE00003728733	649679	649748

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 96.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.2104 / max 471.2949, expressed in 1812 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177912	26.1259	1808
177913	1.5567	790
177914	0.7668	404
177911	0.7609	500

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.05	gold quality
lower esophagus mucosa	UBERON:0035834	95.24	gold quality
skin of abdomen	UBERON:0001416	95.20	gold quality
skin of leg	UBERON:0001511	95.19	gold quality
left testis	UBERON:0004533	94.91	gold quality
right testis	UBERON:0004534	94.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.48	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.69	gold quality
mucosa of transverse colon	UBERON:0004991	93.65	gold quality
gastrocnemius	UBERON:0001388	93.37	gold quality
esophagus mucosa	UBERON:0002469	93.34	gold quality
right lobe of liver	UBERON:0001114	93.15	gold quality
zone of skin	UBERON:0000014	92.92	gold quality
testis	UBERON:0000473	92.70	gold quality
transverse colon	UBERON:0001157	92.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.46	gold quality
muscle of leg	UBERON:0001383	92.14	gold quality
spleen	UBERON:0002106	92.09	gold quality
esophagus	UBERON:0001043	91.98	gold quality
body of stomach	UBERON:0001161	91.67	gold quality
right frontal lobe	UBERON:0002810	91.54	gold quality
ectocervix	UBERON:0012249	91.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.18	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.10	gold quality
lower esophagus	UBERON:0013473	91.00	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.00	gold quality
adenohypophysis	UBERON:0002196	90.98	gold quality
metanephros cortex	UBERON:0010533	90.96	gold quality
apex of heart	UBERON:0002098	90.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.94

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 23)

• These findings suggest that RNF126 promotes cancer cell proliferation by targeting p21 for ubiquitin-mediated degradation (PMID:23026136)
• identify a unique cofactor, RING finger protein 126 (RNF126), verify its interaction by traditional techniques, and show that it has functional consequences as RNF126 is able to ubiquitylate activation-induced cytidine deaminase (PMID:23277564)
• RNF126 and Rabring7 play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. (PMID:23418353)
• The ubiquitin ligase RNF126 has a role in the retrograde sorting of the CI-MPR. (PMID:24275455)
• RNF126 is recruited to the N-terminal Ubl domain of Bag6 and preferentially ubiquitinates juxtahydrophobic lysine residues on Bag6-associated clients. (PMID:24981174)
• this results suggest a novel role of RNF126 in promoting Homologous recombination-mediated repair through positive regulation on BRCA1 expression by direct interaction with E2F1. (PMID:26234677)
• Studies present the solution structure of the RNF126_NZF (N-terminal zinc finger domain) as well as the structure of RNF126_NZF/BAG6_UBL complex and characterize the interaction of RNF126 with the UBL domains from both BAG6 and UBL4A from the BAG6 sortase complex. (PMID:27193484)
• These data suggested that RNF126 might be related to the progression of tongue cancer through regulating AKT signaling pathway. (PMID:27227488)
• RNF126 is a novel regulator of NHEJ that promotes completion of DNA repair by ubiquitylating Ku80 and releasing Ku70/80 from damaged DNA. (PMID:27895153)
• RNF126 depletion results in frataxin accumulation in cells derived from FRDA patients. (PMID:28228265)
• CHEK1 inhibition targets breast cancer cells expressing higher levels of RNF126 by enhancing replication stress. (PMID:29326282)
• RNF126 negatively regulates RNF168 function in DNA damage response and its appropriate cellular expression levels are essential for homologous recombination-mediated DNA double-strand break repair. (PMID:30529286)
• We conclude that the RNF126/BAG6 complex contributes to G0S2 degradation and that interventions to prevent G0S2 degradation may offer a therapeutic strategy for managing ischemic diseases. (PMID:31371451)
• RNF126 expression was significantly associated with tumor depth and presence of venous invasion. (PMID:32132033)
• Roles of RNF126 and BCA2 E3 ubiquitin ligases in DNA damage repair signaling and targeted cancer therapy. (PMID:32147403)
• High Expression of RING Finger Protein 126 Predicts Unfavorable Prognosis of Epithelial Ovarian Cancer. (PMID:32254065)
• RNF126-Mediated Reubiquitination Is Required for Proteasomal Degradation of p97-Extracted Membrane Proteins. (PMID:32645369)
• E3 ubiquitin ligase RNF126 affects bladder cancer progression through regulation of PTEN stability. (PMID:33664240)
• CHFR-mediated degradation of RNF126 confers sensitivity to PARP inhibitors in triple-negative breast cancer cells. (PMID:34388456)
• Overexpression of RNF126 is associated with poor prognosis and contributes to the progression of lung adenocarcinoma. (PMID:34533052)
• RNF126 contributes to stem cell-like properties and metastasis in hepatocellular carcinoma through ubiquitination and degradation of LKB1. (PMID:36068398)
• Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors. (PMID:36539893)
• RNF126-Mediated MRE11 Ubiquitination Activates the DNA Damage Response and Confers Resistance of Triple-Negative Breast Cancer to Radiotherapy. (PMID:36563124)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf126	ENSDARG00000104076
mus_musculus	Rnf126	ENSMUSG00000035890
rattus_norvegicus	Rnf126	ENSRNOG00000009028

Paralogs (2): RNF181 (ENSG00000168894), RNF115 (ENSG00000265491)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF126 — Q9BV68 (reviewed: Q9BV68)

Alternative names: RING finger protein 126

All UniProt accessions (3): Q9BV68, K7EIY6, U3KQF4

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins. Depending on the associated E2 ligase, mediates ‘Lys-27’-, ‘Lys-29’-, ‘Lys-48’- and/or ‘Lys-63’-linked polyubiquitination of substrates. Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome. May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor. May play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating their ubiquitination. By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation. May monoubiquitinate AICDA. Acts as a regulator of DNA repair by mediating ‘Lys-27’- and ‘Lys-29’-linked polyubiquitination of MRE11, thereby promoting the exonuclease activity of MRE11.

Subunit / interactions. Interacts with CCDC50, EGFR, FLT3 and SCAMP3. Interacts with BAG6 (via ubiquitin-like domain); required for BAG6-dependent ubiquitination of proteins mislocalized to the cytosol. Interacts with CDKN1A. Interacts with AICDA.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in liver and testis.

Post-translational modifications. Ubiquitinated. May undergo autoubiquitination.

Domain organisation. The C4-type zinc finger is required for interaction with BAG6.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (2): NP_001352947, NP_919442* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR039525	RNF126-like_zinc-ribbon	Domain

Pfam: PF13639, PF14369

UniProt features (30 total): region of interest 5, compositionally biased region 4, binding site 4, mutagenesis site 4, strand 3, turn 3, modified residue 2, zinc finger region 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2N9O	SOLUTION NMR
2N9P	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV68-F1	61.83	0.01

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 13; 16; 29; 32

Post-translational modifications (2): 2, 5

Mutagenesis-validated functional residues (4):

Position	Phenotype
14	impaired interaction with bag6.
36	impaired interaction with bag6.
38–39	impaired interaction with bag6.
229–232	loss of e3 ligase activity.

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: 174 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, REACTOME_ANTIGEN_PROCESSING_UBIQUITINATION_PROTEASOME_DEGRADATION, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, MORF_HDAC2, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, PUJANA_CHEK2_PCC_NETWORK

GO Biological Process (17): ubiquitin-dependent protein catabolic process (GO:0006511), protein monoubiquitination (GO:0006513), protein ubiquitination (GO:0016567), protein K29-linked ubiquitination (GO:0035519), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), regulation of cell population proliferation (GO:0042127), retrograde transport, endosome to Golgi (GO:0042147), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), protein K27-linked ubiquitination (GO:0044314), protein K63-linked ubiquitination (GO:0070534), protein K48-linked ubiquitination (GO:0070936), cytoplasm protein quality control by the ubiquitin-proteasome system (GO:0071629), positive regulation of double-strand break repair via homologous recombination (GO:1905168), protein polyubiquitination (GO:0000209), double-strand break repair via homologous recombination (GO:0000724), DNA strand resection involved in replication fork processing (GO:0110025)

GO Molecular Function (6): epidermal growth factor receptor binding (GO:0005154), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

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	4
protein ubiquitination	3
cellular anatomical structure	3
ubiquitin-dependent protein catabolic process	2
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
cell population proliferation	1
regulation of cellular process	1
intercellular transport	1
endosomal transport	1
cytosolic transport	1
proteasomal protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
cellular response to misfolded protein	1
cytoplasm protein quality control	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
recombinational repair	1
double-strand break repair	1
DNA metabolic process	1
replication fork processing	1
5’-3’ DNA exonuclease activity	1
growth factor receptor binding	1
transition metal ion 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
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF126	BAG6	P46379	683
RNF126	SGTA	O43765	664
RNF126	GET4	Q7L5D6	640
RNF126	GET3	O43681	619
RNF126	UBL4A	P11441	612
RNF126	RNF138	Q8WVD3	601
RNF126	LTN1	O94822	563
RNF126	E2F1	Q01094	560
RNF126	RNF168	Q8IYW5	537
RNF126	NEDD4L	Q96PU5	521
RNF126	RNF151	Q2KHN1	502
RNF126	SPPL3	Q8TCT6	493
RNF126	ZNF70	Q9UC06	474
RNF126	FXN	Q16595	465
RNF126	RNF169	Q8NCN4	454

IntAct

75 interactions, top by confidence:

A	B	Type	Score
BAG6	RNF126	psi-mi:“MI:0915”(physical association)	0.890
RNF126	BAG6	psi-mi:“MI:0915”(physical association)	0.890
UBE2D1	RNF126	psi-mi:“MI:0915”(physical association)	0.820
RNF126	UBE2D1	psi-mi:“MI:0915”(physical association)	0.820
GET4	GET3	psi-mi:“MI:0914”(association)	0.800
UBE2D3	RNF126	psi-mi:“MI:0915”(physical association)	0.710
BAG6	RNF126	psi-mi:“MI:0915”(physical association)	0.670
UBE2D4	RNF126	psi-mi:“MI:0915”(physical association)	0.620
TSPYL6	NME4	psi-mi:“MI:0914”(association)	0.530
CASTOR3P	SNX2	psi-mi:“MI:0914”(association)	0.530
BCAT1	ARNT	psi-mi:“MI:0914”(association)	0.530
BBS1	RAB8A	psi-mi:“MI:0914”(association)	0.510
RNF126	UBE2D2	psi-mi:“MI:0915”(physical association)	0.490
RNF126	TSG101	psi-mi:“MI:0915”(physical association)	0.370
TRIM23	RNF126	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (265): RNF126 (Two-hybrid), RNF126 (Two-hybrid), RNF126 (Biochemical Activity), UBB (Affinity Capture-MS), BAG6 (Affinity Capture-MS), GET4 (Affinity Capture-MS), FAM63A (Affinity Capture-MS), TAX1BP1 (Affinity Capture-MS), LRWD1 (Affinity Capture-MS), ABCB6 (Affinity Capture-MS), CRYM (Affinity Capture-MS), ASNA1 (Affinity Capture-MS), SKP2 (Affinity Capture-MS), SLC25A16 (Affinity Capture-MS), PJA1 (Affinity Capture-MS)

ESM2 similar proteins: A0A482PJF5, A0A482PJY4, A0A482PUS2, A8WWR3, B3M1F2, B3P4M4, B4GZ07, B4HJA7, B4JSL2, B4KCG1, B4M686, B4N8G7, B4PVI7, B4QVV3, E7FAG6, O13826, O22197, O92503, P13810, P23801, P24647, P32511, P32512, P32828, P38239, P38428, P43528, P90859, Q29B72, Q48B61, Q4ZMD6, Q6FS98, Q7T0Q3, Q8B9B2, Q8QME4, Q8RK09, Q8RK12, Q8RSY1, Q8VYC8, Q8XAN6

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

4 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF126	ubiquitination
RNF126	“down-regulates quantity by destabilization”	CDKN1A	polyubiquitination
RNF126	“down-regulates quantity by destabilization”	EGFR	polyubiquitination
RNF126	“down-regulates quantity by destabilization”	FXN	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
TICAM1, RIP1-mediated IKK complex recruitment	5	53.7×	7e-06
IKK complex recruitment mediated by RIP1	5	44.3×	1e-05
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	7	24.6×	6e-06
SPOP-mediated proteasomal degradation of PD-L1(CD274)	5	20.4×	2e-04
Defective CFTR causes cystic fibrosis	5	19.6×	2e-04
Degradation of CRY and PER proteins	5	19.6×	2e-04
AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	5	17.3×	4e-04
FCERI mediated NF-kB activation	6	16.8×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein autoubiquitination	6	21.6×	6e-05
ERAD pathway	6	16.7×	2e-04
protein K48-linked ubiquitination	6	15.6×	2e-04
ubiquitin-dependent protein catabolic process	11	12.6×	6e-07
protein polyubiquitination	7	12.4×	2e-04
proteasome-mediated ubiquitin-dependent protein catabolic process	12	9.6×	1e-06
protein ubiquitination	11	7.0×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2030 predictions. Top by Δscore:

Variant	Effect	Δscore
19:648274:CGTG:C	acceptor_gain	1.0000
19:648276:TG:T	acceptor_gain	1.0000
19:648278:C:CC	acceptor_gain	1.0000
19:648279:T:C	acceptor_gain	1.0000
19:648280:T:C	acceptor_gain	1.0000
19:648280:T:TC	acceptor_gain	1.0000
19:648282:G:C	acceptor_gain	1.0000
19:648282:G:GC	acceptor_gain	1.0000
19:648289:C:CT	acceptor_gain	1.0000
19:648290:A:T	acceptor_gain	1.0000
19:648295:C:CT	acceptor_gain	1.0000
19:648367:CTCA:C	donor_loss	1.0000
19:648368:TCA:T	donor_loss	1.0000
19:648369:CA:C	donor_loss	1.0000
19:648370:A:AC	donor_gain	1.0000
19:648371:C:CA	donor_gain	1.0000
19:648371:CCT:C	donor_gain	1.0000
19:648371:CCTG:C	donor_gain	1.0000
19:648489:T:G	acceptor_loss	1.0000
19:648884:A:AC	donor_gain	1.0000
19:648885:C:CC	donor_gain	1.0000
19:648885:CGTG:C	donor_gain	1.0000
19:649673:CTGTA:C	donor_loss	1.0000
19:649674:TGTAC:T	donor_loss	1.0000
19:649675:GTAC:G	donor_loss	1.0000
19:649676:TAC:T	donor_loss	1.0000
19:649677:ACCT:A	donor_loss	1.0000
19:649744:CTCCC:C	acceptor_gain	1.0000
19:649745:TCCC:T	acceptor_gain	1.0000
19:649746:CCC:C	acceptor_gain	1.0000

AlphaMissense

2018 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:648257:G:C	C269W	1.000
19:648258:C:G	C269S	1.000
19:648258:C:T	C269Y	1.000
19:648259:A:G	C269R	1.000
19:648259:A:T	C269S	1.000
19:648264:G:T	P267H	1.000
19:648266:G:C	C266W	1.000
19:648267:C:G	C266S	1.000
19:648267:C:T	C266Y	1.000
19:648268:A:G	C266R	1.000
19:648268:A:T	C266S	1.000
19:648379:A:G	L260P	1.000
19:648381:C:A	W259C	1.000
19:648381:C:G	W259C	1.000
19:648383:A:G	W259R	1.000
19:648383:A:T	W259R	1.000
19:648394:C:T	C255Y	1.000
19:648395:A:G	C255R	1.000
19:648405:G:C	F251L	1.000
19:648405:G:T	F251L	1.000
19:648406:A:G	F251S	1.000
19:648407:A:G	F251L	1.000
19:648413:G:C	H249D	1.000
19:648418:C:T	C247Y	1.000
19:648419:A:G	C247R	1.000
19:648424:A:G	L245P	1.000
19:648462:G:C	C232W	1.000
19:648463:C:G	C232S	1.000
19:648463:C:T	C232Y	1.000
19:648464:A:G	C232R	1.000

dbSNP variants (sampled 300 via entrez): RS1000043025 (19:656524 C>T), RS1000069905 (19:659765 C>A), RS1000443627 (19:661219 G>A,C), RS1000472787 (19:653068 A>C), RS1000481732 (19:663355 CG>C,CGG), RS1000623891 (19:664640 G>C,T), RS1000649645 (19:659358 G>A,C), RS1000807562 (19:647981 C>G,T), RS1000859844 (19:648065 C>T), RS1000931676 (19:659460 G>A), RS1001104172 (19:650945 TCTTA>T), RS1001261974 (19:654106 C>G,T), RS1001439386 (19:649887 G>A,C), RS1001620508 (19:661568 C>A), RS1001641012 (19:655769 C>T)

Disease associations

OMIM: gene MIM:615177 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007269_171	Pulse pressure	7.000000e-10
GCST007846_3	Arterial stiffness	1.000000e-07
GCST008403_28	Arterial stiffness index	8.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004517	arterial stiffness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL6066843 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195604 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195605 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195606 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
cobaltous chloride	increases expression	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
acetochlor	increases abundance, affects methylation	1
monomethylarsonous acid	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Estradiol	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Herbicides	affects methylation, increases abundance	1
Ivermectin	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
1-Butanol	affects cotreatment, increases abundance, increases expression	1

ChEMBL screening assays

59 unique, capped per target: 59 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5580352	Binding	PROTAC activity at RNF126/STING in human THP-1 cells assessed as induction of STING degradation upto 30 uM incubated for 24 hrs by Western blot analysis	Development of STING degrader with double covalent ligands. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2JK	HAP1 RNF126 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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