RNF175

Summary

RNF175 (ring finger protein 175, HGNC:27735) is a protein-coding gene on chromosome 4q31.3, encoding RING finger protein 175 (Q8N4F7).

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ERAD pathway. Predicted to be located in membrane. Predicted to be active in Golgi membrane and endoplasmic reticulum membrane.

Source: NCBI Gene 285533 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 50 total
• MANE Select transcript: NM_173662

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27735
Approved symbol	RNF175
Name	ring finger protein 175
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34190
Ensembl gene	ENSG00000145428
Ensembl biotype	protein_coding
Entrez	285533

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000347063, ENST00000503694, ENST00000506358, ENST00000506505, ENST00000507512, ENST00000508248, ENST00000508967, ENST00000509321, ENST00000513656, ENST00000897861, ENST00000897862, ENST00000897863, ENST00000955649

RefSeq mRNA: 1 — MANE Select: NM_173662 NM_173662

CCDS: CCDS47149

Canonical transcript exons

ENST00000347063 — 9 exons

Exon	Start	End
ENSE00001359759	153759797	153760024
ENSE00002076958	153710160	153710489
ENSE00002431507	153712475	153712576
ENSE00003471216	153715529	153715662
ENSE00003532367	153751438	153751475
ENSE00003571351	153748645	153748786
ENSE00003584091	153728207	153728361
ENSE00003631595	153723351	153723458
ENSE00003785371	153720184	153720304

Expression profiles

Bgee: expression breadth ubiquitous, 192 present calls, max score 95.36.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3460 / max 83.0958, expressed in 496 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54436	1.8754	474
54437	0.4060	187
54435	0.0646	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	95.36	gold quality
endothelial cell	CL:0000115	93.98	gold quality
pons	UBERON:0000988	93.34	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.10	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.94	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.22	gold quality
prefrontal cortex	UBERON:0000451	90.21	gold quality
right frontal lobe	UBERON:0002810	89.62	gold quality
frontal cortex	UBERON:0001870	89.59	gold quality
anterior cingulate cortex	UBERON:0009835	89.58	gold quality
neocortex	UBERON:0001950	89.36	gold quality
nucleus accumbens	UBERON:0001882	89.01	gold quality
cerebral cortex	UBERON:0000956	88.38	gold quality
hypothalamus	UBERON:0001898	87.83	gold quality
cortical plate	UBERON:0005343	87.50	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.33	gold quality
superior frontal gyrus	UBERON:0002661	87.23	gold quality
forebrain	UBERON:0001890	86.64	gold quality
cerebellar vermis	UBERON:0004720	86.52	gold quality
caudate nucleus	UBERON:0001873	86.44	gold quality
occipital lobe	UBERON:0002021	86.36	gold quality
ventricular zone	UBERON:0003053	86.36	gold quality
primary visual cortex	UBERON:0002436	86.32	gold quality
brain	UBERON:0000955	86.16	gold quality
cerebellar hemisphere	UBERON:0002245	85.97	gold quality
cerebellar cortex	UBERON:0002129	85.96	gold quality
superior vestibular nucleus	UBERON:0007227	85.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.74	gold quality
monocyte	CL:0000576	85.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.52

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting RNF175, 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-4282	99.99	75.36	6408
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-4717-3P	99.06	66.34	1072
HSA-MIR-876-5P	97.99	68.49	1345
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-4776-5P	97.14	66.63	405
HSA-MIR-769-3P	97.06	64.83	464
HSA-MIR-3167	96.81	67.09	1236
HSA-MIR-4781-3P	95.78	65.66	572

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf175	ENSDARG00000037647
drosophila_melanogaster	CG15814	FBGN0030873
caenorhabditis_elegans		WBGENE00007626

Paralogs (1): RNF121 (ENSG00000137522)

Protein

Protein identifiers

RING finger protein 175 — Q8N4F7 (reviewed: Q8N4F7)

All UniProt accessions (5): Q8N4F7, D6RAJ1, D6RB06, D6RB46, D6RID2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N4F7-1	1	yes
Q8N4F7-2	2

RefSeq proteins (1): NP_775933* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR018957	Znf_C3HC4_RING-type	Domain
IPR040176	RNF121/RNF175	Family

Pfam: PF00097

UniProt features (15 total): transmembrane region 5, splice variant 4, sequence variant 4, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4F7-F1	83.78	0.48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, HATADA_METHYLATED_IN_LUNG_CANCER_DN, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_ERAD_PATHWAY, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_PROTEOLYSIS, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY

GO Biological Process (1): ERAD pathway (GO:0036503)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

300 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF175	RNF150	Q9ULK6	512
RNF175	RNF186	Q9NXI6	504
RNF175	RNF182	Q8N6D2	503
RNF175	ZNRF4	Q8WWF5	499
RNF175	DBF4B	Q8NFT6	494
RNF175	RNF183	Q96D59	490
RNF175	RNF151	Q2KHN1	489
RNF175	WSCD1	Q658N2	479
RNF175	THAP9	Q9H5L6	459
RNF175	CCDC77	Q9BR77	449
RNF175	TMC5	Q6UXY8	435
RNF175	EXD3	Q8N9H8	434
RNF175	TBC1D14	Q9P2M4	414
RNF175	CPO	Q8IVL8	401
RNF175	TRERF1	Q96PN7	398

IntAct

9 interactions, top by confidence:

A	B	Type	Score
KRTAP10-7	RNF175	psi-mi:“MI:0915”(physical association)	0.560
RNF175		psi-mi:“MI:0915”(physical association)	0.560
	RNF175	psi-mi:“MI:0915”(physical association)	0.560
RNF175	HSBP1	psi-mi:“MI:0915”(physical association)	0.400
RNF175	MAPRE2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (7): KRTAP10-7 (Two-hybrid), KRTAP10-3 (Two-hybrid), RNF175 (PCA), HSBP1 (Affinity Capture-MS), MAPRE2 (Affinity Capture-MS), RNF175 (Reconstituted Complex), RNF175 (Affinity Capture-RNA)

ESM2 similar proteins: A0PK00, A1L2R7, A3KNK1, A4FUY9, A6QPF8, A7MBC7, A8DZH4, D3ZWZ9, O14524, O95427, P86044, Q01685, Q0ZHH6, Q15629, Q1LY80, Q28CV2, Q3TA38, Q3ZBX1, Q4R8A8, Q5BJF2, Q5EAX9, Q5FWV6, Q5HZE5, Q5PQQ4, Q5R7Z3, Q5RDB4, Q5U4X7, Q5XI41, Q63ZG0, Q6AXF6, Q6DD88, Q6DE21, Q6DED0, Q6DHU1, Q6GQE1, Q6Q3F5, Q6R8G5, Q6R8G7, Q7ZX75, Q86X19

Diamond homologs: O94400, Q09251, Q6DD32, Q6P360, Q8N4F7, Q8R1Z9, Q9H920, Q0V9R0, Q5R476, Q5XHH7, Q66J97, Q6NRL6, Q6NRV8, Q6ZNA4, Q86TM6, Q90ZT7, Q99ML9, Q9DBY1, Q0II22

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF175	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1770 predictions. Top by Δscore:

Variant	Effect	Δscore
4:153715663:C:CC	acceptor_gain	1.0000
4:153720177:CACTT:C	donor_loss	1.0000
4:153720178:ACTT:A	donor_loss	1.0000
4:153720179:CTTA:C	donor_loss	1.0000
4:153720180:TTA:T	donor_loss	1.0000
4:153720181:TA:T	donor_loss	1.0000
4:153720182:A:AC	donor_gain	1.0000
4:153720182:A:AT	donor_loss	1.0000
4:153720182:AC:A	donor_gain	1.0000
4:153720182:ACC:A	donor_gain	1.0000
4:153720182:ACCC:A	donor_gain	1.0000
4:153720183:C:CC	donor_gain	1.0000
4:153720183:C:CT	donor_loss	1.0000
4:153720183:CC:C	donor_gain	1.0000
4:153720183:CCC:C	donor_gain	1.0000
4:153720183:CCCC:C	donor_gain	1.0000
4:153720183:CCCCT:C	donor_gain	1.0000
4:153720303:TT:T	acceptor_gain	1.0000
4:153720305:C:CC	acceptor_gain	1.0000
4:153720308:T:TC	acceptor_gain	1.0000
4:153723345:ACTT:A	donor_loss	1.0000
4:153723346:CT:C	donor_loss	1.0000
4:153723347:TT:T	donor_loss	1.0000
4:153723348:TAC:T	donor_loss	1.0000
4:153723349:A:AC	donor_gain	1.0000
4:153723349:ACT:A	donor_loss	1.0000
4:153723350:C:CG	donor_gain	1.0000
4:153723350:CT:C	donor_gain	1.0000
4:153723350:CTT:C	donor_gain	1.0000
4:153748643:A:AC	donor_gain	1.0000

AlphaMissense

2156 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:153728340:A:G	W90R	0.996
4:153728340:A:T	W90R	0.996
4:153710428:A:G	W310R	0.995
4:153710428:A:T	W310R	0.995
4:153728283:A:G	W109R	0.993
4:153728283:A:T	W109R	0.993
4:153723419:G:C	S147R	0.991
4:153723419:G:T	S147R	0.991
4:153723421:T:G	S147R	0.991
4:153712551:A:G	W264R	0.990
4:153712551:A:T	W264R	0.990
4:153723400:C:G	G154R	0.990
4:153723399:C:T	G154D	0.987
4:153720242:C:T	G191E	0.985
4:153723440:A:C	F140L	0.984
4:153723440:A:T	F140L	0.984
4:153723442:A:G	F140L	0.984
4:153728330:G:C	P93R	0.984
4:153728330:G:T	P93H	0.981
4:153712535:T:A	K269I	0.979
4:153712549:C:A	W264C	0.979
4:153712549:C:G	W264C	0.979
4:153712573:A:C	F256L	0.978
4:153712573:A:T	F256L	0.978
4:153712575:A:G	F256L	0.978
4:153720243:C:G	G191R	0.978
4:153720243:C:T	G191R	0.978
4:153723445:A:G	W139R	0.978
4:153723445:A:T	W139R	0.978
4:153720249:A:C	Y189D	0.977

dbSNP variants (sampled 300 via entrez): RS10000608 (4:153716933 C>G,T), RS1000086817 (4:153726481 T>C), RS1000137409 (4:153752081 A>G), RS1000269083 (4:153723712 T>A,G), RS1000318908 (4:153737684 C>G), RS1000358668 (4:153711872 T>C), RS1000425830 (4:153712384 C>A,G), RS1000496118 (4:153756522 A>C,T), RS1000604584 (4:153753660 C>A,T), RS10006303 (4:153724071 G>A,C), RS1000720744 (4:153723374 C>T), RS1000802780 (4:153743250 C>G,T), RS1000846429 (4:153740715 C>T), RS10009539 (4:153725217 C>A,T), RS10009844 (4:153760424 C>A,G,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002675_2	Response to statins (LDL cholesterol change)	1.000000e-06
GCST003941_10	Acute graft versus host disease in bone marrow transplantation (recipient effect)	1.000000e-07
GCST010701_3	Cortical surface area (MOSTest)	1.000000e-08
GCST010702_5	Subcortical volume (MOSTest)	3.000000e-08
GCST010703_140	Brain morphology (MOSTest)	4.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004599	acute graft vs. host disease
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Panobinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
triphenyl phosphate	affects expression	1
butyraldehyde	increases expression	1
cupric chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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