RNF103

Summary

RNF103 (ring finger protein 103, HGNC:12859) is a protein-coding gene on chromosome 2p11.2, encoding E3 ubiquitin-protein ligase RNF103 (O00237). Acts as an E2-dependent E3 ubiquitin-protein ligase, probably involved in the ER-associated protein degradation pathway.

The protein encoded by this gene contains a RING-H2 finger, a motif known to be involved in protein-protein and protein-DNA interactions. This gene is highly expressed in normal cerebellum, but not in the cerebral cortex. The expression of the rat counterpart in the frontal cortex and hippocampus was shown to be induced by elctroconvulsive treatment (ECT) as well as chronic antidepressant treatment, suggesting that this gene may be a molecular target for ECT and antidepressants. The protein is a ubiquitin ligase that functions in the endoplasmic reticulum-associated degradation pathway. Alternative splicing of this gene results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream CHMP3 (charged multivesicular body protein 3) gene.

Source: NCBI Gene 7844 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_005667

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12859
Approved symbol	RNF103
Name	ring finger protein 103
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	hkf-1, KF1
Ensembl gene	ENSG00000239305
Ensembl biotype	protein_coding
OMIM	602507
Entrez	7844

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000237455, ENST00000463333, ENST00000465629, ENST00000472030, ENST00000472680, ENST00000477307, ENST00000886122, ENST00000886123, ENST00000949491, ENST00000949492

RefSeq mRNA: 3 — MANE Select: NM_005667 NM_001198951, NM_001198952, NM_005667

CCDS: CCDS33237

Canonical transcript exons

ENST00000237455 — 4 exons

Exon	Start	End
ENSE00000799947	86622661	86623865
ENSE00001826083	86603398	86605418
ENSE00003509303	86612159	86612274
ENSE00003519000	86620330	86620469

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.8588 / max 399.3637, expressed in 1798 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29554	16.3487	1790
29553	2.0026	1210
29552	0.5075	265

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	97.83	gold quality
amniotic fluid	UBERON:0000173	97.02	gold quality
corpus epididymis	UBERON:0004359	95.92	gold quality
jejunal mucosa	UBERON:0000399	95.79	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.74	gold quality
ileal mucosa	UBERON:0000331	95.56	gold quality
germinal epithelium of ovary	UBERON:0001304	95.36	gold quality
trigeminal ganglion	UBERON:0001675	95.14	gold quality
corpus callosum	UBERON:0002336	95.05	gold quality
paraflocculus	UBERON:0005351	95.01	gold quality
cartilage tissue	UBERON:0002418	94.96	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.82	gold quality
cauda epididymis	UBERON:0004360	94.75	gold quality
esophagus squamous epithelium	UBERON:0006920	94.74	gold quality
colonic mucosa	UBERON:0000317	94.70	gold quality
medial globus pallidus	UBERON:0002477	94.68	gold quality
duodenum	UBERON:0002114	94.60	gold quality
calcaneal tendon	UBERON:0003701	94.60	gold quality
globus pallidus	UBERON:0001875	94.46	gold quality
pancreatic ductal cell	CL:0002079	94.42	silver quality
tongue squamous epithelium	UBERON:0006919	94.31	gold quality
parietal pleura	UBERON:0002400	94.23	gold quality
vena cava	UBERON:0004087	94.22	silver quality
dorsal root ganglion	UBERON:0000044	94.21	gold quality
epithelial cell of pancreas	CL:0000083	93.92	gold quality
seminal vesicle	UBERON:0000998	93.89	gold quality
cerebellum	UBERON:0002037	93.89	gold quality
epithelium of esophagus	UBERON:0001976	93.88	gold quality
parotid gland	UBERON:0001831	93.85	gold quality
jejunum	UBERON:0002115	93.76	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-89	no	276.20
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting RNF103, 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-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-543	99.52	69.03	2595

Literature-anchored findings (GeneRIF, showing 2)

• Analysis reveals that the main determinants of selectivity between ubiquitin ligases RNF103 and E2 ubiquitin-conjugating enzymes resides on ring domains, rather than on the E2s. (PMID:18615712)
• Kf-1 is an ER ubiquitin ligase involved in the endoplasmic reticulum-associated degradation pathway. (PMID:18675248)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf103	ENSDARG00000100850
mus_musculus	Rnf103	ENSMUSG00000052656
rattus_norvegicus	Rnf103	ENSRNOG00000007272

Protein

Protein identifiers

E3 ubiquitin-protein ligase RNF103 — O00237 (reviewed: O00237)

Alternative names: KF-1, RING finger protein 103, RING-type E3 ubiquitin transferase RNF103, Zinc finger protein 103 homolog

All UniProt accessions (1): O00237

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an E2-dependent E3 ubiquitin-protein ligase, probably involved in the ER-associated protein degradation pathway.

Subunit / interactions. Interacts with DERL1 and VCP.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in the normal cerebellum but not in the cerebral cortex.

Pathway. Protein modification; protein ubiquitination.

RefSeq proteins (2): NP_001185880, NP_005658* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR042494	RNF103	Family

Pfam: PF13639

UniProt features (13 total): transmembrane region 4, sequence conflict 4, chain 1, zinc finger region 1, region of interest 1, compositionally biased region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00237-F1	73.72	0.12

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 (1):

Position	Phenotype
621	loss of e2-dependent ubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-901032	ER Quality Control Compartment (ERQC)
R-HSA-392499	Metabolism of proteins
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-532668	N-glycan trimming in the ER and Calnexin/Calreticulin cycle
R-HSA-597592	Post-translational protein modification
R-HSA-901042	Calnexin/calreticulin cycle

MSigDB gene sets: 216 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, DORSAM_HOXA9_TARGETS_UP, MODULE_255, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_317, TACAATC_MIR508, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, COUP_01, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5

GO Biological Process (4): central nervous system development (GO:0007417), protein ubiquitination (GO:0016567), ERAD pathway (GO:0036503), endoplasmic reticulum mannose trimming (GO:1904380)

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 (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum quality control compartment (GO:0044322), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Calnexin/calreticulin cycle	1
Post-translational protein modification	1
Asparagine N-linked glycosylation	1
Metabolism of proteins	1
N-glycan trimming in the ER and Calnexin/Calreticulin cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nervous system development	1
system development	1
protein modification by small protein conjugation	1
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
protein alpha-1,2-demannosylation	1
endoplasmic reticulum quality control compartment	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
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
endoplasmic reticulum	1

Protein interactions and networks

STRING

694 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF103	RAPSN	Q13702	785
RNF103	ZPR1	O75312	719
RNF103	RNF170	Q96K19	603
RNF103	RNF139	Q8WU17	585
RNF103	ZNRF4	Q8WWF5	538
RNF103	UBE2N	P61088	533
RNF103	AMFR	P26442	485
RNF103	RNF5	Q99942	482
RNF103	MARCHF6	O60337	477
RNF103	RNFT1	Q5M7Z0	469
RNF103	C11orf71	Q6IPW1	453
RNF103	RWDD2A	Q9UIY3	436
RNF103	TMEM129	A0AVI4	429
RNF103	DENND11	A4D1U4	423
RNF103	SYVN1	Q86TM6	422

IntAct

11 interactions, top by confidence:

A	B	Type	Score
UBE2D1	RNF103	psi-mi:“MI:0915”(physical association)	0.370
RNF103	UBE2D2	psi-mi:“MI:0915”(physical association)	0.370
RNF103	UBE2D3	psi-mi:“MI:0915”(physical association)	0.370
UBE2D4	RNF103	psi-mi:“MI:0915”(physical association)	0.370
RNF103	UBE2H	psi-mi:“MI:0915”(physical association)	0.370
UBE2N	RNF103	psi-mi:“MI:0915”(physical association)	0.370
RNF103	UBE2W	psi-mi:“MI:0915”(physical association)	0.370
UBE2Z	RNF103	psi-mi:“MI:0915”(physical association)	0.370
DISC1	RNF103	psi-mi:“MI:0915”(physical association)	0.000
RNF103		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (31): RNF103 (Two-hybrid), RNF103 (PCA), PDLIM1 (Affinity Capture-MS), PEPD (Affinity Capture-MS), ATXN2L (Affinity Capture-MS), HYOU1 (Affinity Capture-MS), COPS2 (Affinity Capture-MS), CBR1 (Affinity Capture-MS), DIS3 (Affinity Capture-MS), CTSB (Affinity Capture-MS), HADH (Affinity Capture-MS), IDH2 (Affinity Capture-MS), RNF103 (Affinity Capture-MS), RNF103 (Affinity Capture-MS), DERL1 (Affinity Capture-Western)

ESM2 similar proteins: A0A2K2A1B1, A0A3N7G677, A2YX04, B5BT18, C6L7U1, D1FP53, D1FP57, F4HVS6, F4HW65, F4I6M4, F4JBP3, O00237, O64728, Q0D8I9, Q38796, Q689G9, Q6I576, Q6LA42, Q6NPP4, Q6PUA2, Q6Z8M8, Q700C2, Q75LH6, Q7X843, Q7XIT1, Q84JU6, Q8GSA7, Q8GYU3, Q8RY95, Q8S9G8, Q8VY16, Q94BP7, Q9C9U5, Q9EPZ8, Q9FG14, Q9FMN2, Q9FPR3, Q9FY74, Q9FYG2, Q9FZ99

Diamond homologs: A0A0D1E015, A8Y4B2, E9QAU8, F1MM41, F7EP40, O00237, O54965, P0DPR2, P87237, Q06651, Q07G42, Q08CN9, Q08DI6, Q0V9R0, Q20798, Q3U2C5, Q4R6Y5, Q5DTZ6, Q5M974, Q5NCP0, Q5R476, Q5XHH7, Q5XIL0, Q641J8, Q66HG0, Q66J97, Q66KG7, Q68DV7, Q6AY01, Q6NKR1, Q6NRL6, Q6NRV8, Q6NRX0, Q6P4U6, Q6Y290, Q6ZNA4, Q6ZSG1, Q71FD5, Q7T037, Q803I8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF103	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1111 predictions. Top by Δscore:

Variant	Effect	Δscore
2:86617562:TATC:T	donor_gain	1.0000
2:86620325:CATA:C	donor_loss	1.0000
2:86620326:ATACC:A	donor_loss	1.0000
2:86620328:A:AC	donor_gain	1.0000
2:86620328:A:C	donor_loss	1.0000
2:86620328:ACCT:A	donor_loss	1.0000
2:86620329:C:CC	donor_gain	1.0000
2:86620329:CCT:C	donor_gain	1.0000
2:86620331:TGA:T	donor_gain	1.0000
2:86620465:GTCAC:G	acceptor_gain	1.0000
2:86620466:TCAC:T	acceptor_gain	1.0000
2:86620467:CAC:C	acceptor_gain	1.0000
2:86620467:CACC:C	acceptor_gain	1.0000
2:86620468:AC:A	acceptor_gain	1.0000
2:86620468:ACCT:A	acceptor_loss	1.0000
2:86620469:CC:C	acceptor_gain	1.0000
2:86620469:CCT:C	acceptor_loss	1.0000
2:86620469:CCTG:C	acceptor_loss	1.0000
2:86620470:C:CC	acceptor_gain	1.0000
2:86620470:C:T	acceptor_gain	1.0000
2:86605205:CTGA:C	donor_gain	0.9900
2:86605206:TGAT:T	donor_gain	0.9900
2:86605415:ATAT:A	acceptor_gain	0.9900
2:86605416:TAT:T	acceptor_gain	0.9900
2:86605419:C:CC	acceptor_gain	0.9900
2:86605420:T:G	acceptor_loss	0.9900
2:86612152:AACTT:A	donor_loss	0.9900
2:86612153:ACTTA:A	donor_loss	0.9900
2:86612154:CTTAC:C	donor_loss	0.9900
2:86612155:TTA:T	donor_loss	0.9900

AlphaMissense

4540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:86604040:A:G	C621R	1.000
2:86604896:A:C	N335K	1.000
2:86604896:A:T	N335K	1.000
2:86604911:G:C	S330R	1.000
2:86604911:G:T	S330R	1.000
2:86604913:T:G	S330R	1.000
2:86603916:C:T	C662Y	0.999
2:86603917:A:G	C662R	0.999
2:86603924:G:C	C659W	0.999
2:86603926:A:G	C659R	0.999
2:86603948:C:A	W651C	0.999
2:86603948:C:G	W651C	0.999
2:86603950:A:G	W651R	0.999
2:86603950:A:T	W651R	0.999
2:86603960:G:C	C647W	0.999
2:86603961:C:A	C647F	0.999
2:86603961:C:T	C647Y	0.999
2:86603962:A:G	C647R	0.999
2:86603972:A:C	F643L	0.999
2:86603972:A:T	F643L	0.999
2:86603973:A:G	F643S	0.999
2:86603974:A:G	F643L	0.999
2:86603984:A:C	C639W	0.999
2:86603985:C:T	C639Y	0.999
2:86603986:A:G	C639R	0.999
2:86604029:G:C	C624W	0.999
2:86604031:A:G	C624R	0.999
2:86604038:A:C	C621W	0.999
2:86604358:A:G	W515R	0.999
2:86604358:A:T	W515R	0.999

dbSNP variants (sampled 300 via entrez): RS1000148956 (2:86603554 T>C,G), RS1000151460 (2:86611207 C>G,T), RS1000209827 (2:86604068 C>A), RS1000402076 (2:86614811 T>C), RS1000438771 (2:86608693 C>A,G), RS1000451518 (2:86609958 T>A,C), RS1000497635 (2:86610843 G>A,C), RS1000839051 (2:86622118 C>G,T), RS1000985194 (2:86623805 C>A,G,T), RS1001078451 (2:86603312 C>G), RS1001144784 (2:86609587 T>C), RS1001187767 (2:86621836 T>C), RS1001280831 (2:86622996 G>A,C), RS1001500239 (2:86609973 C>G), RS1001515892 (2:86623210 G>T)

Disease associations

OMIM: gene MIM:602507 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007326_1	Number of sexual partners	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation	3
Air Pollutants	affects expression, affects cotreatment, decreases expression, increases abundance	2
Ozone	affects cotreatment, decreases expression, increases abundance, affects expression	2
Silver	increases expression	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
cobaltous chloride	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
seocalcitol	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
NSC 689534	affects binding, increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	increases methylation	1
Leflunomide	decreases expression	1
Acrolein	decreases expression, increases abundance, affects cotreatment	1
Arsenic	decreases expression, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Copper	affects binding, increases expression	1
Curcumin	increases expression	1
Dimethyl Sulfoxide	decreases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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