RNF115

Summary

RNF115 (ring finger protein 115, HGNC:18154) is a protein-coding gene on chromosome 1q21.1, encoding E3 ubiquitin-protein ligase RNF115 (Q9Y4L5). E3 ubiquitin-protein ligase that catalyzes the ‘Lys-48’- and/or ‘Lys-63’-linked polyubiquitination of various substrates and thereby plays a role in a number of signaling pathways including autophagy, innate immunity, cell proliferation and cell death.

Enables ubiquitin protein ligase activity. Involved in negative regulation of signal transduction; protein ubiquitination; and ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Is active in endoplasmic reticulum.

Source: NCBI Gene 27246 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_014455

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18154
Approved symbol	RNF115
Name	ring finger protein 115
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	BCA2, Rabring7, CL469780
Ensembl gene	ENSG00000265491
Ensembl biotype	protein_coding
OMIM	619535
Entrez	27246

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000539368, ENST00000582693, ENST00000891105, ENST00000891106

RefSeq mRNA: 1 — MANE Select: NM_014455 NM_014455

CCDS: CCDS72863

Canonical transcript exons

ENST00000582693 — 9 exons

Exon	Start	End
ENSE00002686783	145788908	145788966
ENSE00002693766	145750407	145750500
ENSE00002694107	145823772	145824095
ENSE00002699095	145752978	145753049
ENSE00002702006	145747995	145748110
ENSE00002717112	145751438	145751510
ENSE00002717241	145784539	145784596
ENSE00002728992	145771711	145771919
ENSE00003739724	145738868	145746997

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.6871 / max 430.8507, expressed in 1823 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14133	18.5830	1806
14135	15.0503	1801
14134	7.4483	1770
14136	0.3531	161
14137	0.2254	103
14138	0.0271	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gluteal muscle	UBERON:0002000	98.74	gold quality
heart right ventricle	UBERON:0002080	97.71	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.41	gold quality
triceps brachii	UBERON:0001509	97.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.08	gold quality
biceps brachii	UBERON:0001507	96.61	gold quality
paraflocculus	UBERON:0005351	96.49	gold quality
cauda epididymis	UBERON:0004360	96.23	gold quality
endometrium epithelium	UBERON:0004811	95.04	gold quality
myocardium	UBERON:0002349	94.74	gold quality
vastus lateralis	UBERON:0001379	94.66	gold quality
quadriceps femoris	UBERON:0001377	94.38	gold quality
left ventricle myocardium	UBERON:0006566	94.24	gold quality
skeletal muscle tissue	UBERON:0001134	94.22	gold quality
diaphragm	UBERON:0001103	94.02	gold quality
deltoid	UBERON:0001476	93.59	gold quality
muscle tissue	UBERON:0002385	93.36	gold quality
trabecular bone tissue	UBERON:0002483	93.36	gold quality
nipple	UBERON:0002030	93.30	gold quality
tendon of biceps brachii	UBERON:0008188	93.17	gold quality
vena cava	UBERON:0004087	92.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.90	gold quality
body of tongue	UBERON:0011876	92.84	gold quality
frontal pole	UBERON:0002795	92.60	gold quality
saphenous vein	UBERON:0007318	92.38	gold quality
muscle organ	UBERON:0001630	92.16	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.49	gold quality
tibialis anterior	UBERON:0001385	91.45	gold quality
tendon	UBERON:0000043	91.35	gold quality
middle frontal gyrus	UBERON:0002702	91.30	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.76
E-MTAB-4850	no	229.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1

miRNA regulators (miRDB)

65 targeting RNF115, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
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-4500	99.99	72.72	2367
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-106A-3P	99.53	67.58	995

Literature-anchored findings (GeneRIF, showing 19)

• The autoubiquitination activity of BCA2 indicates that it is a novel RING-type E3 ligase. (PMID:16288031)
• BCA2 E3 ligase is coregulated with estrogen receptor and plays a role in the regulation of epidermal growth factor receptor (EGF-R) trafficking (PMID:16925951)
• These results suggest that Rabring7 is involved in the endocytic trafficking of EGFR through its E3 ligase activity. (PMID:17462600)
• BCA2 accelerates the internalization and degradation of viral particles following their tethering to the cell surface and is a co-factor or enhancer for the tetherin-dependent restriction of HIV-1 release from infected cells. (PMID:20019814)
• Rabring7 stimulates c-Myc degradation via mono-ubiquitination of MM-1 (PMID:22844532)
• BCA2 is therefore a newly identified transcriptional target of estrogen receptor. (PMID:22850893)
• High BCA2 expression is associated with renal oncocytoma. (PMID:23242606)
• RNF126 and Rabring7 play a role in the ubiquitin-dependent sorting and downregulation of membrane receptors. (PMID:23418353)
• BCA2, a potential oncogenic E3 ubiquitin ligase, promotes breast cancer cell proliferation partially through targeting p21 for ubiquitination and proteasomal degradation. (PMID:24027428)
• BCA2 is an endogenous inhibitor of AMPK activation in breast cancer cells and BCA2 inhibition increases the efficacy of metformin. (PMID:24403860)
• BCA2 functions as an antiviral factor that targets HIV-1 Gag for degradation, impairing virus assembly and release. (PMID:24852021)
• Results from a study on gene expression variability markers in early-stage human embryos shows that RNF115 is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• Specifically, BCA2 serves as an E3 SUMO ligase in the SUMOylation of IkappaBalpha, which in turn enhances the sequestration of NF-kappaB components in the cytoplasm. Since HIV-1 utilizes NF-kappaB to promote proviral transcription, the BCA2-mediated inhibition of NF-kappaB significantly decreases the transcriptional activity of HIV-1. (PMID:28122985)
• these findings indicate that USP9X is a stabilizer of RNF115 protein and that the USP9X-RNF115 signaling axis is implicated in the breast cancer malignant phenotype. (PMID:30689267)
• Roles of RNF126 and BCA2 E3 ubiquitin ligases in DNA damage repair signaling and targeted cancer therapy. (PMID:32147403)
• RNF115-mediated ubiquitination of p53 regulates lung adenocarcinoma proliferation. (PMID:32553631)
• RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA. (PMID:33139700)
• RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma. (PMID:38376606)
• E3 ubiquitin ligase BCA2 promotes breast cancer stemness by up-regulation of SOX9 by LPS. (PMID:38725852)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf115a	ENSDARG00000062450
danio_rerio	rnf115b	ENSDARG00000062900
mus_musculus	Rnf115	ENSMUSG00000028098
rattus_norvegicus	Rnf115	ENSRNOG00000000098

Paralogs (2): RNF126 (ENSG00000070423), RNF181 (ENSG00000168894)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF115 — Q9Y4L5 (reviewed: Q9Y4L5)

Alternative names: RING finger protein 115, RING-type E3 ubiquitin transferase RNF115, Rab7-interacting RING finger protein, Zinc finger protein 364

All UniProt accessions (1): Q9Y4L5

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that catalyzes the ‘Lys-48’- and/or ‘Lys-63’-linked polyubiquitination of various substrates and thereby plays a role in a number of signaling pathways including autophagy, innate immunity, cell proliferation and cell death. Plays a role in the endosomal trafficking and degradation of membrane receptors including EGFR, FLT3, MET and CXCR4 through their polyubiquitination. Participates together with BST2 in antiviral immunity by facilitating the internalization of HIV-1 virions into intracellular vesicles leading to their lysosomal degradation. Also possesses an antiviral activity independently of BST2 by promoting retroviral GAG proteins ubiquitination, redistribution to endo-lysosomal compartments and, ultimately, lysosomal degradation. Catalyzes distinct types of ubiquitination on MAVS and STING1 at different phases of viral infection to promote innate antiviral response. Mediates the ‘Lys-48’-linked ubiquitination of MAVS leading to its proteasomal degradation and ubiquitinates STING1 via ‘Lys-63’-linked polyubiquitination, critical for its oligomerization and the subsequent recruitment of TBK1. Plays a positive role in the autophagosome-lysosome fusion by interacting with STX17 and enhancing its stability without affecting ‘Lys-48’- or ‘Lys-63’-linked polyubiquitination levels, which in turn promotes autophagosome maturation. Negatively regulates TLR-induced expression of proinflammatory cytokines by catalyzing ‘Lys-11’-linked ubiquitination of RAB1A and RAB13 to inhibit post-ER trafficking of TLRs to the Golgi by RAB1A and subsequently from the Golgi apparatus to the cell surface by RAB13.

Subunit / interactions. Interacts with RAB7A. Interacts with EGFR and FLT3. Interacts with BST2. Interacts with STX17. Interacts with YWHAE.

Subcellular location. Cytoplasm. Nucleus. Endoplasmic reticulum. Golgi apparatus.

Tissue specificity. Expressed at extremely low levels in normal breast, prostate, lung, colon. Higher levels of expression are detected in heart, skeletal muscle, testis as well as in breast and prostate cancer cells.

Post-translational modifications. Phosphorylated by AKT1, allowing association with the 14-3-3 chaperones that facilitates associating with TLRs. RING-type zinc finger-dependent and E2-dependent autoubiquitination. Deubiquitinated by USP9X; antogonizing its autoubiquitination and subsequent proteasomal degradation.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (1): NP_055270* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR051834	RING_finger_E3_ligase	Family

Pfam: PF13639

UniProt features (20 total): mutagenesis site 8, modified residue 3, region of interest 2, compositionally biased region 2, initiator methionine 1, chain 1, sequence variant 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4L5-F1	60.08	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.

Post-translational modifications (3): 2, 132, 133

Mutagenesis-validated functional residues (8):

Position	Phenotype
26	loss of autoubiquitination; when associated with r-32.
32	loss of autoubiquitination; when associated with r-26.
132	about 50% loss of phosphorylation; when associated with a-133.
133	about 50% loss of phosphorylation; when associated with a-132.
228	loss of autoubiquitination.
228	loss of e3 ligase activity. maintains the ability to restrict viral particle production; when associated with a-232.
231	loss of autoubiquitination.
231	loss of e3 ligase activity. maintains the ability to restrict viral particle production; when associated with a-228.

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: 191 (showing top): MORF_MBD4, 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, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_NEGATIVE_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_TOLL_LIKE_RECEPTOR_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (13): protein ubiquitination (GO:0016567), negative regulation of toll-like receptor signaling pathway (GO:0034122), negative regulation of epidermal growth factor receptor signaling pathway (GO:0042059), ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway (GO:0043162), protein autoubiquitination (GO:0051865), protein K63-linked ubiquitination (GO:0070534), protein K48-linked ubiquitination (GO:0070936), protein K11-linked ubiquitination (GO:0070979), protein polyubiquitination (GO:0000209), endoplasmic reticulum to Golgi vesicle-mediated transport (GO:0006888), Golgi to plasma membrane transport (GO:0006893), positive regulation of toll-like receptor signaling pathway (GO:0034123), toll-like receptor 4 signaling pathway (GO:0034142)

GO Molecular Function (6): ubiquitin-protein transferase activity (GO:0004842), 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 (5): nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), 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
cytoplasm	4
protein polyubiquitination	3
intracellular membrane-bounded organelle	3
toll-like receptor signaling pathway	2
regulation of toll-like receptor signaling pathway	2
protein ubiquitination	2
cellular anatomical structure	2
endomembrane system	2
protein modification by small protein conjugation	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
epidermal growth factor receptor signaling pathway	1
regulation of epidermal growth factor receptor signaling pathway	1
negative regulation of ERBB signaling pathway	1
ubiquitin-dependent protein catabolic process	1
protein catabolic process in the vacuole	1
multivesicular body sorting pathway	1
intercellular transport	1
intracellular transport	1
Golgi vesicle transport	1
post-Golgi vesicle-mediated transport	1
vesicle-mediated transport to the plasma membrane	1
positive regulation of pattern recognition receptor signaling pathway	1
cell surface toll-like receptor signaling pathway	1
ubiquitin-like protein transferase activity	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 anatomical structure	1

Protein interactions and networks

STRING

1236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF115	BST2	Q10589	633
RNF115	A0A087WY85	A0A087WY85	537
RNF115	RILP	Q96NA2	501
RNF115	POLR3C	Q9BUI4	501
RNF115	CUL2	Q13617	477
RNF115	RAB7A	P51149	473
RNF115	RNF4	P78317	452
RNF115	PIAS3	Q9Y6X2	416
RNF115	UBXN6	Q9BZV1	408
RNF115	AKIP1	Q9NQ31	400
RNF115	NUDT17	P0C025	399
RNF115	ZNF784	Q8NCA9	393
RNF115	BIRC7	Q96CA5	391
RNF115	UBXN1	Q04323	378
RNF115	MICOS10	Q5TGZ0	346

IntAct

107 interactions, top by confidence:

A	B	Type	Score
MDM2	TP53	psi-mi:“MI:0915”(physical association)	1.000
RNF115	UBE2D1	psi-mi:“MI:0915”(physical association)	0.830
UBE2D4	RNF115	psi-mi:“MI:0915”(physical association)	0.830
UBE2D1	RNF115	psi-mi:“MI:0915”(physical association)	0.830
RNF115	UBE2D4	psi-mi:“MI:0915”(physical association)	0.830
RNF115	UBE2D3	psi-mi:“MI:0915”(physical association)	0.780
UBE2D3	RNF115	psi-mi:“MI:0915”(physical association)	0.780
DAZAP2	RNF115	psi-mi:“MI:0915”(physical association)	0.740
RNF115	DAZAP2	psi-mi:“MI:0915”(physical association)	0.740
RNF115	UBE2D2	psi-mi:“MI:0915”(physical association)	0.670
UBE2E3	RNF115	psi-mi:“MI:0915”(physical association)	0.670
UBE2D2	RNF115	psi-mi:“MI:0915”(physical association)	0.670
RNF115	MDM4	psi-mi:“MI:0915”(physical association)	0.560
MDM4	RNF115	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (202): RNF115 (Two-hybrid), RNF115 (Two-hybrid), RNF115 (Two-hybrid), RNF115 (Two-hybrid), UBE2D4 (Two-hybrid), UBE2D2 (Reconstituted Complex), YWHAB (Affinity Capture-Western), RNF115 (Affinity Capture-MS), RNF115 (Affinity Capture-MS), RNF115 (Affinity Capture-MS), DAZAP2 (Two-hybrid), RNF115 (Co-purification), RNF115 (Affinity Capture-MS), TAX1BP1 (Affinity Capture-MS), RNF115 (Affinity Capture-MS)

ESM2 similar proteins: A0A482PJY4, A2AH22, A3KPW9, A4IH17, A5D9M6, A7X5R6, A8Y4B2, B3P4M4, B4HJA7, B4KCG1, B4N8G7, B4PVI7, B4QVV3, E7FAG6, O22197, O74757, P0CH30, P32628, P32828, P38428, P46379, Q09463, Q0II22, Q20798, Q3KPV4, Q68FU0, Q6DIP3, Q6FS98, Q6IRP0, Q6MG49, Q6P135, Q6PA26, Q6PC78, Q7T0Q3, Q8LPN7, Q91W67, Q91YL2, Q94AK4, Q96S82, Q9BV68

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

3 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF115	ubiquitination
RNF115	“down-regulates quantity by destabilization”	EGFR	polyubiquitination
RNF115	“down-regulates quantity by destabilization”	MYC	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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	58.9×	2e-06
IKK complex recruitment mediated by RIP1	5	48.7×	4e-06
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	6	43.3×	6e-07
Regulation of TNFR1 signaling	8	35.1×	1e-08
Negative regulators of DDX58/IFIH1 signaling	5	32.0×	2e-05
Ovarian tumor domain proteases	5	27.3×	4e-05
Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha	6	23.2×	1e-05
E3 ubiquitin ligases ubiquitinate target proteins	6	22.8×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein K11-linked ubiquitination	5	31.1×	5e-05
protein monoubiquitination	5	27.3×	9e-05
protein K48-linked ubiquitination	8	21.4×	7e-07
protein polyubiquitination	9	16.5×	7e-07
negative regulation of canonical NF-kappaB signal transduction	6	16.4×	1e-04
ERAD pathway	5	14.4×	2e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	15	12.4×	4e-10
ubiquitin-dependent protein catabolic process	10	11.8×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2396 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145746861:C:G	donor_gain	1.0000
1:145747990:GAGTA:G	donor_loss	1.0000
1:145747991:TGAG:T	donor_loss	1.0000
1:145747992:G:GG	donor_gain	1.0000
1:145747992:G:T	donor_loss	1.0000
1:145750403:T:A	donor_loss	1.0000
1:145750404:G:GG	donor_gain	1.0000
1:145750404:GTAG:G	donor_loss	1.0000
1:145750407:TTGG:T	donor_loss	1.0000
1:145750408:G:GG	donor_gain	1.0000
1:145750408:GTTG:G	donor_loss	1.0000
1:145750409:AGTTG:A	donor_loss	1.0000
1:145750499:G:GA	acceptor_gain	1.0000
1:145750499:G:GT	acceptor_loss	1.0000
1:145750499:GC:G	acceptor_gain	1.0000
1:145750499:GCTTT:G	acceptor_gain	1.0000
1:145750500:A:AG	acceptor_gain	1.0000
1:145750503:T:A	acceptor_gain	1.0000
1:145752974:T:A	donor_loss	1.0000
1:145752975:G:GG	donor_gain	1.0000
1:145753048:G:GG	acceptor_gain	1.0000
1:145753048:GA:G	acceptor_gain	1.0000
1:145753049:A:AG	acceptor_gain	1.0000
1:145771707:T:A	donor_loss	1.0000
1:145771708:G:GG	donor_gain	1.0000
1:145771708:GT:G	donor_loss	1.0000
1:145771709:GG:G	donor_gain	1.0000
1:145771710:GG:G	donor_gain	1.0000
1:145771711:AGGG:A	donor_loss	1.0000
1:145771713:GAAGG:G	donor_gain	1.0000

AlphaMissense

2016 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145746975:C:A	R269M	1.000
1:145746975:C:G	R269T	1.000
1:145746977:A:C	C268W	1.000
1:145746978:C:A	C268F	1.000
1:145746978:C:G	C268S	1.000
1:145746978:C:T	C268Y	1.000
1:145746979:A:G	C268R	1.000
1:145746979:A:T	C268S	1.000
1:145746984:G:T	P266H	1.000
1:145746986:A:C	C265W	1.000
1:145746987:C:A	C265F	1.000
1:145746987:C:G	C265S	1.000
1:145746987:C:T	C265Y	1.000
1:145746988:A:C	C265G	1.000
1:145746988:A:G	C265R	1.000
1:145746988:A:T	C265S	1.000
1:145746997:G:C	H262D	1.000
1:145748002:A:G	L259P	1.000
1:145748002:A:T	L259Q	1.000
1:145748004:C:A	W258C	1.000
1:145748004:C:G	W258C	1.000
1:145748006:A:G	W258R	1.000
1:145748006:A:T	W258R	1.000
1:145748014:A:T	I255N	1.000
1:145748016:A:C	C254W	1.000
1:145748017:C:A	C254F	1.000
1:145748017:C:G	C254S	1.000
1:145748017:C:T	C254Y	1.000
1:145748018:A:G	C254R	1.000
1:145748018:A:T	C254S	1.000

dbSNP variants (sampled 300 via entrez): RS1000066364 (1:145771388 A>G), RS1000073992 (1:145823949 T>C,G), RS1000128423 (1:145764728 G>A), RS1000157536 (1:145748508 C>T), RS1000205868 (1:145765497 T>C), RS1000241789 (1:145779011 A>G), RS1000296665 (1:145785156 A>G), RS1000481257 (1:145764864 G>A), RS1000538267 (1:145790298 G>A,C,T), RS1000551937 (1:145746599 T>C,G), RS1000613012 (1:145783621 A>C), RS1000626117 (1:145791910 C>A), RS1000665274 (1:145783310 G>A), RS1000675855 (1:145740653 T>C), RS1000992617 (1:145802380 A>G)

Disease associations

OMIM: gene MIM:619535 | 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
GCST004950_28	Breast cancer	8.000000e-09
GCST004988_203	Breast cancer	6.000000e-10
GCST007236_63	Breast cancer	2.000000e-07
GCST010241_297	Apolipoprotein A1 levels	1.000000e-08
GCST010242_202	HDL cholesterol levels	6.000000e-09
GCST90002401_359	Platelet distribution width	4.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	increases expression	1
bisphenol F	decreases expression, affects cotreatment	1
cobaltous chloride	increases expression	1
2-aminophenol	affects response to substance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
K 7174	increases expression	1
abrine	increases expression	1
eprenetapopt	affects expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Gasoline	decreases expression, increases abundance, affects cotreatment	1
Indomethacin	affects cotreatment, decreases expression	1
Ketoconazole	increases expression	1
Methyl Methanesulfonate	increases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, affects cotreatment, decreases expression	1
Testosterone	increases expression	1
Tretinoin	affects expression	1

Clinical trials (associated diseases)

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