RNFT1

Summary

RNFT1 (ring finger protein, transmembrane 1, HGNC:30206) is a protein-coding gene on chromosome 17q23.1, encoding E3 ubiquitin-protein ligase RNFT1 (Q5M7Z0). E3 ubiquitin-protein ligase that acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation.

Enables ubiquitin binding activity and ubiquitin protein ligase activity. Involved in positive regulation of ERAD pathway and protein autoubiquitination. Located in endoplasmic reticulum.

Source: NCBI Gene 51136 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_016125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30206
Approved symbol	RNFT1
Name	ring finger protein, transmembrane 1
Location	17q23.1
Locus type	gene with protein product
Status	Approved
Aliases	PTD016
Ensembl gene	ENSG00000189050
Ensembl biotype	protein_coding
OMIM	615172
Entrez	51136

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000305783, ENST00000466544, ENST00000477207, ENST00000482446, ENST00000484257, ENST00000486103, ENST00000493737, ENST00000586083, ENST00000589113, ENST00000893032, ENST00000893033, ENST00000893034, ENST00000932028, ENST00000941633

RefSeq mRNA: 1 — MANE Select: NM_016125 NM_016125

CCDS: CCDS11622

Canonical transcript exons

ENST00000305783 — 9 exons

Exon	Start	End
ENSE00001823295	59952240	59953111
ENSE00001900269	59964608	59964740
ENSE00003501927	59957224	59957382
ENSE00003503275	59954045	59954146
ENSE00003529129	59958291	59958444
ENSE00003559742	59960068	59960168
ENSE00003587151	59956488	59956553
ENSE00003640997	59962827	59963284
ENSE00003660281	59962540	59962616

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 95.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3203 / max 200.2817, expressed in 1776 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167353	15.9747	1774
167352	0.3286	173
167354	0.0171	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adult organism	UBERON:0007023	95.68	gold quality
monocyte	CL:0000576	95.22	gold quality
right testis	UBERON:0004534	94.87	gold quality
left testis	UBERON:0004533	94.65	gold quality
leukocyte	CL:0000738	94.56	gold quality
testis	UBERON:0000473	94.01	gold quality
sperm	CL:0000019	92.99	gold quality
oocyte	CL:0000023	92.65	gold quality
rectum	UBERON:0001052	91.77	gold quality
jejunal mucosa	UBERON:0000399	91.73	gold quality
body of pancreas	UBERON:0001150	91.10	gold quality
vermiform appendix	UBERON:0001154	90.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.56	gold quality
bronchial epithelial cell	CL:0002328	89.71	gold quality
granulocyte	CL:0000094	89.25	gold quality
secondary oocyte	CL:0000655	88.92	gold quality
adrenal tissue	UBERON:0018303	88.58	gold quality
right lobe of liver	UBERON:0001114	88.39	gold quality
bronchus	UBERON:0002185	88.33	gold quality
pancreas	UBERON:0001264	88.17	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.13	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.90	gold quality
right adrenal gland cortex	UBERON:0035827	87.81	gold quality
colonic mucosa	UBERON:0000317	87.58	gold quality
right adrenal gland	UBERON:0001233	87.57	gold quality
left adrenal gland	UBERON:0001234	87.55	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.41	gold quality
stromal cell of endometrium	CL:0002255	87.33	gold quality
corpus epididymis	UBERON:0004359	87.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

67 targeting RNFT1, 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-3163	100.00	77.23	8605
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-200A-5P	99.76	69.10	949

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnft1	ENSDARG00000015917
mus_musculus	Rnft1	ENSMUSG00000020521
rattus_norvegicus	Rnft1	ENSRNOG00000003805
drosophila_melanogaster	CG13605	FBGN0039150
caenorhabditis_elegans		WBGENE00022502

Paralogs (1): RNFT2 (ENSG00000135119)

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNFT1 — Q5M7Z0 (reviewed: Q5M7Z0)

Alternative names: Protein PTD016, RING finger and transmembrane domain-containing protein 1

All UniProt accessions (4): E9PI44, H0YEZ8, K7EJ18, Q5M7Z0

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed at highest levels in testis, lower levels in heart, liver, lung, and kidney. Not detected in brain, ovary, and uterus. Down-regulated in testis from patients with maturation arrest (MA) or Sertoli cell-only syndrome (SCOS). Ubiquitously expressed with high expression in testis.

Induction. Up-regulated by endoplasmic reticulum (ER) stress triggered by thapsigargin or tunicamycin.

Pathway. Protein modification; protein ubiquitination.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5M7Z0-1	1	yes
Q5M7Z0-2	2
Q5M7Z0-3	3

RefSeq proteins (1): NP_057209* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR044235	RNFT1/2	Family

Pfam: PF13639

UniProt features (19 total): transmembrane region 6, splice variant 4, compositionally biased region 2, mutagenesis site 2, region of interest 2, chain 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5M7Z0-F1	72.71	0.32

Functional residue map

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

Mutagenesis-validated functional residues (2):

Position	Phenotype
375	decreased ubiquitin ligase activity; when associated with s-378.
378	decreased ubiquitin ligase activity; when associated with s-375.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 155 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GGGTGGRR_PAX4_03, WANG_LMO4_TARGETS_DN, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_PROTEIN_AUTOUBIQUITINATION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN

GO Biological Process (3): protein autoubiquitination (GO:0051865), positive regulation of ERAD pathway (GO:1904294), protein ubiquitination (GO:0016567)

GO Molecular Function (5): zinc ion binding (GO:0008270), ubiquitin binding (GO:0043130), ubiquitin protein ligase activity (GO:0061630), transferase activity (GO:0016740), metal ion binding (GO:0046872)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein ubiquitination	1
ERAD pathway	1
positive regulation of proteasomal protein catabolic process	1
regulation of ERAD pathway	1
positive regulation of response to endoplasmic reticulum stress	1
protein modification by small protein conjugation	1
transition metal ion binding	1
ubiquitin-like protein binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
cation binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

270 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNFT1	CGRRF1	Q99675	584
RNFT1	RNF223	E7ERA6	580
RNFT1	CHCT1	Q86WR6	508
RNFT1	RNF170	Q96K19	504
RNFT1	RNF183	Q96D59	478
RNFT1	TMEM129	A0AVI4	472
RNFT1	RNF103	O00237	469
RNFT1	TRIM59	Q8IWR1	467
RNFT1	RNF145	Q96MT1	465
RNFT1	PDCD10	Q9BUL8	465
RNFT1	RNF130	Q86XS8	458
RNFT1	RNF121	Q9H920	433
RNFT1	RNF144A	P50876	430
RNFT1	RNF148	Q8N7C7	424
RNFT1	PTRH2	Q9Y3E5	423

IntAct

19 interactions, top by confidence:

A	B	Type	Score
REEP5	SCAMP1	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530
REEP5	PLSCR1	psi-mi:“MI:0914”(association)	0.530
RNFT1	GAPDHS	psi-mi:“MI:0915”(physical association)	0.400
UBE2U	RNFT1	psi-mi:“MI:0915”(physical association)	0.370
UBE2D2	RNFT1	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
IL17RB	RHOBTB3	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
PCDH10	TMEM223	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
TMEM63C	GPR89A	psi-mi:“MI:0914”(association)	0.350
MS4A15	ABCD4	psi-mi:“MI:0914”(association)	0.350
IL17RB	ATP1A3	psi-mi:“MI:0914”(association)	0.350
REEP5	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A2	LGALS8	psi-mi:“MI:0914”(association)	0.350
SLC30A8	UPK3BL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (42): RNFT1 (Affinity Capture-RNA), RNFT1 (Synthetic Growth Defect), RNFT1 (Affinity Capture-MS), RNFT1 (Affinity Capture-MS), RNFT1 (Biochemical Activity), UBE2D3 (Reconstituted Complex), RNFT1 (PCA), RNFT1 (Proximity Label-MS), RNFT1 (Affinity Capture-MS), RNFT1 (Affinity Capture-MS), RNFT1 (Affinity Capture-MS), ABHD13 (Affinity Capture-MS), CYB5R3 (Affinity Capture-MS), GEMIN4 (Affinity Capture-MS), CBR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A571BF63, A0JMQ9, A0JN69, A1L1R5, E7EZI4, O41933, P0C7U3, P33279, P40145, P97490, Q0IH10, Q0VD59, Q11122, Q1L8G6, Q1LVZ2, Q28EX7, Q28GL3, Q28IK8, Q32L65, Q3UF64, Q4R8E0, Q5I0I2, Q5M7Z0, Q5PQ35, Q5RAG4, Q5T0T0, Q5XH39, Q5XIE5, Q68FA7, Q6NRX0, Q6NTV1, Q6NZ21, Q6NZQ8, Q6ZPS6, Q6ZUJ8, Q803Q4, Q86UD3, Q8BGN6, Q8BPQ7, Q8BRX9

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”	RNFT1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1540 predictions. Top by Δscore:

Variant	Effect	Δscore
17:59956486:A:AC	donor_gain	1.0000
17:59956487:C:CC	donor_gain	1.0000
17:59956554:C:CC	acceptor_gain	1.0000
17:59957222:A:AC	donor_gain	1.0000
17:59957223:C:CC	donor_gain	1.0000
17:59958644:C:A	donor_gain	1.0000
17:59954145:CT:C	acceptor_gain	0.9900
17:59956479:AGTAC:A	donor_loss	0.9900
17:59956480:GTAC:G	donor_loss	0.9900
17:59956481:TACTT:T	donor_loss	0.9900
17:59956482:AC:A	donor_loss	0.9900
17:59956483:C:T	donor_loss	0.9900
17:59956484:T:TG	donor_loss	0.9900
17:59956485:TACT:T	donor_loss	0.9900
17:59956486:A:C	donor_loss	0.9900
17:59956487:C:T	donor_loss	0.9900
17:59956487:CT:C	donor_gain	0.9900
17:59956487:CTG:C	donor_gain	0.9900
17:59956487:CTGG:C	donor_gain	0.9900
17:59956487:CTGGT:C	donor_gain	0.9900
17:59956552:AGCTG:A	acceptor_loss	0.9900
17:59956553:GCT:G	acceptor_loss	0.9900
17:59956554:C:G	acceptor_loss	0.9900
17:59956555:T:C	acceptor_loss	0.9900
17:59957277:CG:C	donor_gain	0.9900
17:59957381:CC:C	acceptor_gain	0.9900
17:59957382:CC:C	acceptor_gain	0.9900
17:59958440:TTAAG:T	acceptor_gain	0.9900
17:59958441:TAAG:T	acceptor_gain	0.9900
17:59958445:C:CC	acceptor_gain	0.9900

AlphaMissense

2849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:59957316:A:G	W305R	0.991
17:59957316:A:T	W305R	0.991
17:59953103:A:C	F394L	0.990
17:59953103:A:T	F394L	0.990
17:59953105:A:G	F394L	0.990
17:59954050:A:G	C390R	0.990
17:59958339:T:A	K266N	0.990
17:59958339:T:G	K266N	0.990
17:59953050:C:G	C412S	0.989
17:59953051:A:G	C412R	0.989
17:59953051:A:T	C412S	0.989
17:59953060:A:G	C409R	0.988
17:59953109:A:C	H392Q	0.988
17:59953109:A:T	H392Q	0.988
17:59953047:C:A	R413I	0.987
17:59954095:A:G	C375R	0.987
17:59954048:A:C	C390W	0.986
17:59958340:T:A	K266I	0.985
17:59953049:G:C	C412W	0.984
17:59954049:C:T	C390Y	0.984
17:59953050:C:T	C412Y	0.982
17:59954093:A:C	C375W	0.982
17:59962595:A:G	L179P	0.981
17:59953102:A:G	C395R	0.980
17:59953047:C:G	R413T	0.979
17:59953101:C:T	C395Y	0.979
17:59954094:C:G	C375S	0.979
17:59954095:A:T	C375S	0.979
17:59953050:C:A	C412F	0.978
17:59954049:C:G	C390S	0.978

dbSNP variants (sampled 300 via entrez): RS1000522282 (17:59957023 C>G,T), RS1000553592 (17:59960488 G>A,T), RS1000834952 (17:59966268 C>T), RS1000888696 (17:59965980 C>T), RS1001327092 (17:59959227 C>G), RS1001535501 (17:59955422 C>A), RS1001640144 (17:59955991 C>T), RS1001898939 (17:59964684 G>A,T), RS1001923390 (17:59957411 C>A,G), RS1002245266 (17:59964757 C>T), RS1002589056 (17:59954331 T>A), RS1002644588 (17:59954702 C>G), RS1003231191 (17:59961401 T>C), RS1004356480 (17:59964770 A>G,T), RS1004636594 (17:59966603 T>G)

Disease associations

OMIM: gene MIM:615172 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_939	Obesity-related traits	3.000000e-06
GCST004132_90	Crohn’s disease	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite 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
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	7
mercuric bromide	increases expression, affects cotreatment	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases expression	1
Calcitriol	increases expression	1
Carbamazepine	affects expression	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Gold	decreases expression	1
Hydrogen Peroxide	increases expression	1
Manganese	increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Oxygen	decreases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	increases methylation	1

Clinical trials (associated diseases)

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