RNF145

Summary

RNF145 (ring finger protein 145, HGNC:20853) is a protein-coding gene on chromosome 5q33.3, encoding RING finger protein 145 (Q96MT1). E3 ubiquitin ligase that catalyzes the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate.

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ERAD pathway and proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endomembrane system.

Source: NCBI Gene 153830 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_001199383

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20853
Approved symbol	RNF145
Name	ring finger protein 145
Location	5q33.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31951
Ensembl gene	ENSG00000145860
Ensembl biotype	protein_coding
OMIM	620640
Entrez	153830

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000274542, ENST00000424310, ENST00000518062, ENST00000518284, ENST00000518802, ENST00000519865, ENST00000519985, ENST00000520548, ENST00000520638, ENST00000521266, ENST00000521606

RefSeq mRNA: 5 — MANE Select: NM_001199383 NM_001199380, NM_001199381, NM_001199382, NM_001199383, NM_144726

CCDS: CCDS4344, CCDS56390, CCDS56391, CCDS56392, CCDS56393

Canonical transcript exons

ENST00000424310 — 11 exons

Exon	Start	End
ENSE00001232073	159157409	159159035
ENSE00001724051	159209231	159209553
ENSE00003476264	159181960	159182051
ENSE00003500182	159194716	159194824
ENSE00003501545	159161266	159161622
ENSE00003528258	159203434	159203656
ENSE00003547255	159173983	159174158
ENSE00003580669	159162932	159163079
ENSE00003585848	159176632	159176867
ENSE00003609228	159169679	159169819
ENSE00003623043	159168873	159169055

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.4189 / max 163.6229, expressed in 1742 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64604	8.2455	1727
64603	0.9974	590
203776	0.1760	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nasal cavity epithelium	UBERON:0005384	99.58	gold quality
lower lobe of lung	UBERON:0008949	98.99	gold quality
nasal cavity mucosa	UBERON:0001826	98.31	gold quality
trachea	UBERON:0003126	98.08	gold quality
ileal mucosa	UBERON:0000331	98.03	gold quality
palpebral conjunctiva	UBERON:0001812	98.01	gold quality
secondary oocyte	CL:0000655	98.00	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.88	gold quality
visceral pleura	UBERON:0002401	97.87	gold quality
upper arm skin	UBERON:0004263	97.71	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.58	gold quality
cartilage tissue	UBERON:0002418	97.55	gold quality
upper lobe of lung	UBERON:0008948	97.54	gold quality
lung	UBERON:0002048	97.53	gold quality
left ventricle myocardium	UBERON:0006566	97.53	gold quality
cortical plate	UBERON:0005343	97.51	gold quality
upper lobe of left lung	UBERON:0008952	97.44	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.42	gold quality
eye	UBERON:0000970	97.41	gold quality
seminal vesicle	UBERON:0000998	97.34	gold quality
colonic mucosa	UBERON:0000317	97.28	gold quality
decidua	UBERON:0002450	97.27	gold quality
esophagus squamous epithelium	UBERON:0006920	97.21	gold quality
bronchus	UBERON:0002185	97.16	gold quality
bronchial epithelial cell	CL:0002328	97.14	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.05	gold quality
right lung	UBERON:0002167	96.90	gold quality
skin of hip	UBERON:0001554	96.88	gold quality
penis	UBERON:0000989	96.68	gold quality
ganglionic eminence	UBERON:0004023	96.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	23.80
E-GEOD-130148	yes	8.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

114 targeting RNF145, 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-188-3P	100.00	68.76	1240
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-589-3P	99.91	69.62	2088

Literature-anchored findings (GeneRIF, showing 2)

• Genetic variation of RNF145 gene and blood lipid levels in Xinjiang population, China. (PMID:33727652)
• CircZDBF2 up-regulates RNF145 by ceRNA model and recruits CEBPB to accelerate oral squamous cell carcinoma progression via NFkappaB signaling pathway. (PMID:35365168)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf145a	ENSDARG00000002609
danio_rerio	rnf145b	ENSDARG00000032373
mus_musculus	Rnf145	ENSMUSG00000019189
rattus_norvegicus	Rnf145	ENSRNOG00000004602
drosophila_melanogaster	sip3	FBGN0039875
caenorhabditis_elegans		WBGENE00004768

Paralogs (4): AMFR (ENSG00000159461), SYVN1 (ENSG00000162298), RNF139 (ENSG00000170881), DZIP3 (ENSG00000198919)

Protein

Protein identifiers

RING finger protein 145 — Q96MT1 (reviewed: Q96MT1)

All UniProt accessions (1): Q96MT1

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase that catalyzes the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. In response to bacterial infection, negatively regulates the phagocyte oxidative burst by controlling the turnover of the NADPH oxidase complex subunits. Promotes monoubiquitination of CYBA and ‘Lys-48’-linked polyubiquitination and degradation of CYBB NADPH oxidase catalytic subunits, both essential for the generation of antimicrobial reactive oxygen species. Involved in the maintenance of cholesterol homeostasis. In response to high sterol concentrations ubiquitinates HMGCR, a rate-limiting enzyme in cholesterol biosynthesis, and targets it for degradation. The interaction with INSIG1 is required for this function. In addition, triggers ubiquitination of SCAP, likely inhibiting its transport to the Golgi apparatus and the subsequent processing/maturation of SREBPF2, ultimately down-regulating cholesterol biosynthesis.

Subunit / interactions. Interacts (via YLYF motif) with INSIG1 and INSIG2.

Subcellular location. Endoplasmic reticulum membrane.

Isoforms (5)

UniProt ID	Names	Canonical?
Q96MT1-1	1	yes
Q96MT1-2	2
Q96MT1-3	3
Q96MT1-4	4
Q96MT1-5	5

RefSeq proteins (5): NP_001186309, NP_001186310, NP_001186311, NP_001186312, NP_653327 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR011016	Znf_RING-CH	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR025754	TRC8_N_dom	Domain
IPR047823	RNF145_RING-H2	Domain
IPR050731	HRD1_E3_ubiq-ligases	Family

Pfam: PF13639, PF13705

UniProt features (28 total): transmembrane region 14, splice variant 4, sequence conflict 4, chain 1, zinc finger region 1, region of interest 1, short sequence motif 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MT1-F1	78.73	0.30

Functional residue map

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

Catalytic / active sites (1): 537

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 244 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, RNGTGGGC_UNKNOWN, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_YELLOW_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GGCNKCCATNK_UNKNOWN, TGTGTGA_MIR377, RYTAAWNNNTGAY_UNKNOWN, ACATTCC_MIR1_MIR206, CORRE_MULTIPLE_MYELOMA_UP, LIAO_METASTASIS, TGANTCA_AP1_C

GO Biological Process (2): ERAD pathway (GO:0036503), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), endomembrane system (GO:0012505), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteasomal protein catabolic process	2
cellular anatomical structure	2
response to endoplasmic reticulum stress	1
response to chemical	1
ubiquitin-dependent protein catabolic process	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
cation binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vacuole	1
plasma membrane	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

992 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF145	MARCHF6	O60337	691
RNF145	INSIG2	Q9Y5U4	639
RNF145	INSIG1	O15503	632
RNF145	UBIAD1	Q9Y5Z9	530
RNF145	AK3	Q9UIJ7	520
RNF145	UBLCP1	Q8WVY7	513
RNF145	PALMD	Q9NP74	509
RNF145	HMGCR	P04035	474
RNF145	RNFT1	Q5M7Z0	465
RNF145	NPEPL1	Q8NDH3	465
RNF145	RNF170	Q96K19	450
RNF145	CLINT1	Q14677	447
RNF145	SCAP	Q12770	442
RNF145	RNF185	Q96GF1	441
RNF145	TMEM129	A0AVI4	431

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RNF145		psi-mi:“MI:0915”(physical association)	0.550
	DENND11	psi-mi:“MI:0914”(association)	0.350
RNF145	SPTB	psi-mi:“MI:0914”(association)	0.350
LILRB4	ATP2B1	psi-mi:“MI:0914”(association)	0.350
SLC2A7	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC35F1	C15orf61	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): RNF145 (Synthetic Lethality), RNF145 (Co-localization), UBC (Biochemical Activity), RNF145 (Affinity Capture-Western), RNF145 (Affinity Capture-Western), RNF145 (Synthetic Lethality), RNF145 (PCA), RNF145 (Affinity Capture-MS), RNF145 (Affinity Capture-RNA), SETD2 (Affinity Capture-MS), SUPT6H (Affinity Capture-MS), NES (Affinity Capture-MS), SPTB (Affinity Capture-MS), NOL10 (Affinity Capture-MS), PRKAR2B (Affinity Capture-MS)

ESM2 similar proteins: A2BD92, A4FV45, A5D7N3, A7S641, B0BN86, D3Z2R5, F1Q930, O76024, O95870, P17152, P97587, Q0IJ20, Q17QW2, Q1JPD2, Q1JPG0, Q2HJ63, Q3B8H3, Q4QQM5, Q5BK13, Q5BLE2, Q5RAS8, Q5RJQ8, Q5SWK7, Q5SYH2, Q5ZLD4, Q66H44, Q6DC66, Q6DF19, Q6GR21, Q6MG55, Q6NRI4, Q6NUQ4, Q6NWH5, Q6ZQE4, Q7L4E1, Q7SZC5, Q7ZW11, Q7ZWF4, Q7ZYA0, Q810L4

Diamond homologs: A8Y4B2, F1MM41, F4I2Y3, F7EP40, O22255, O22283, O94400, P30631, Q07G42, Q08CN9, Q20798, Q28GL3, Q2KHN1, Q2TBT8, Q4R6Y5, Q5M7Z0, Q5RBT7, Q5SWK7, Q5XHH7, Q5Z880, Q641J8, Q66KG7, Q6NPT7, Q6NRL6, Q6NTV1, Q6P4U6, Q7T037, Q7TMV1, Q7ZW78, Q7ZWF4, Q803I8, Q86TM6, Q8LGA5, Q8ND25, Q8RXD3, Q8RXX9, Q8WWF5, Q91V17, Q95SP2, Q96MT1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF145	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1833 predictions. Top by Δscore:

Variant	Effect	Δscore
5:159161587:C:CT	acceptor_gain	1.0000
5:159161620:AACCT:A	acceptor_loss	1.0000
5:159161621:ACCTG:A	acceptor_loss	1.0000
5:159161623:CTG:C	acceptor_loss	1.0000
5:159168871:A:AC	donor_gain	1.0000
5:159168872:C:CC	donor_gain	1.0000
5:159168872:CTTGT:C	donor_gain	1.0000
5:159169673:ACTTA:A	donor_loss	1.0000
5:159169674:CTTAC:C	donor_loss	1.0000
5:159169675:TTA:T	donor_loss	1.0000
5:159169676:TA:T	donor_loss	1.0000
5:159169677:A:AC	donor_gain	1.0000
5:159169678:C:CC	donor_gain	1.0000
5:159169678:C:CT	donor_loss	1.0000
5:159169815:CAATA:C	acceptor_gain	1.0000
5:159169818:TA:T	acceptor_gain	1.0000
5:159169820:C:CC	acceptor_gain	1.0000
5:159176708:T:TA	donor_gain	1.0000
5:159181955:CTT:C	donor_loss	1.0000
5:159181956:TTAC:T	donor_loss	1.0000
5:159181958:A:AC	donor_gain	1.0000
5:159181959:C:CA	donor_gain	1.0000
5:159181959:CCT:C	donor_gain	1.0000
5:159182047:AGTCC:A	acceptor_gain	1.0000
5:159182048:GTCC:G	acceptor_gain	1.0000
5:159182049:TCC:T	acceptor_gain	1.0000
5:159182050:CC:C	acceptor_gain	1.0000
5:159182050:CCC:C	acceptor_gain	1.0000
5:159182051:CC:C	acceptor_gain	1.0000
5:159182051:CCTA:C	acceptor_loss	1.0000

AlphaMissense

4344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:159158951:A:G	C571R	1.000
5:159158968:A:G	L565P	1.000
5:159158970:C:A	W564C	1.000
5:159158970:C:G	W564C	1.000
5:159158972:A:G	W564R	1.000
5:159158972:A:T	W564R	1.000
5:159158980:A:G	L561P	1.000
5:159158980:A:T	L561H	1.000
5:159158982:A:C	C560W	1.000
5:159158983:C:G	C560S	1.000
5:159158983:C:T	C560Y	1.000
5:159158984:A:G	C560R	1.000
5:159158984:A:T	C560S	1.000
5:159159000:A:C	H554Q	1.000
5:159159000:A:T	H554Q	1.000
5:159161272:A:C	C540W	1.000
5:159161273:C:A	C540F	1.000
5:159161273:C:G	C540S	1.000
5:159161273:C:T	C540Y	1.000
5:159161274:A:G	C540R	1.000
5:159161274:A:T	C540S	1.000
5:159161276:A:T	I539N	1.000
5:159161281:A:C	C537W	1.000
5:159161282:C:A	C537F	1.000
5:159161282:C:G	C537S	1.000
5:159161282:C:T	C537Y	1.000
5:159161283:A:G	C537R	1.000
5:159161283:A:T	C537S	1.000
5:159161379:C:G	G505R	1.000
5:159161379:C:T	G505R	1.000

dbSNP variants (sampled 300 via entrez): RS1000048061 (5:159189902 G>A), RS1000066113 (5:159176346 G>C), RS1000067933 (5:159195683 T>A), RS1000120060 (5:159196041 A>C), RS1000127447 (5:159202896 A>G), RS1000207224 (5:159178586 T>C), RS1000243826 (5:159211021 G>A), RS1000275114 (5:159171950 G>C), RS1000295834 (5:159190303 G>C), RS1000307647 (5:159171735 C>T), RS1000334249 (5:159163331 T>C), RS1000336985 (5:159184788 T>A), RS1000369344 (5:159183408 C>A), RS1000513138 (5:159199467 A>G), RS1000657791 (5:159173069 A>G)

Disease associations

OMIM: gene MIM:620640 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001335_15	Mean platelet volume	4.000000e-08
GCST003129_3	Primary biliary cholangitis	1.000000e-10
GCST003270_7	Psoriatic arthritis	1.000000e-24
GCST004599_38	Mean platelet volume	6.000000e-58
GCST004603_10	Platelet count	4.000000e-11
GCST008479_33	Psoriasis	6.000000e-11
GCST010241_225	Apolipoprotein A1 levels	2.000000e-09
GCST010242_384	HDL cholesterol levels	4.000000e-10
GCST90002395_468	Mean platelet volume	2.000000e-135
GCST90002401_28	Platelet distribution width	6.000000e-25
GCST90002402_713	Platelet count	1.000000e-24

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
manganese chloride	decreases expression, increases abundance, increases expression, affects cotreatment	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Indomethacin	decreases expression, affects cotreatment, increases expression	2
Manganese	decreases expression, increases abundance, increases expression, affects cotreatment	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Cadmium Chloride	increases expression, decreases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
cupric chloride	decreases expression	1
beta-methylcholine	affects expression	1
K 7174	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Calcitriol	increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Endosulfan	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1

Clinical trials (associated diseases)

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