RNF122

Summary

RNF122 (ring finger protein 122, HGNC:21147) is a protein-coding gene on chromosome 8p12, encoding RING finger protein 122 (Q9H9V4). May induce necrosis and apoptosis.

The encoded protein contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. The encoded protein is localized to the endoplasmic reticulum and golgi apparatus, and may be associated with cell viability.

Source: NCBI Gene 79845 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_024787

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21147
Approved symbol	RNF122
Name	ring finger protein 122
Location	8p12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12526
Ensembl gene	ENSG00000133874
Ensembl biotype	protein_coding
OMIM	620523
Entrez	79845

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000256257, ENST00000933858, ENST00000933859

RefSeq mRNA: 1 — MANE Select: NM_024787 NM_024787

CCDS: CCDS6091

Canonical transcript exons

ENST00000256257 — 6 exons

Exon	Start	End
ENSE00000890756	33549410	33549492
ENSE00000890757	33551044	33551085
ENSE00000890758	33551344	33551389
ENSE00000890759	33558615	33558771
ENSE00001199284	33547754	33548867
ENSE00001199287	33566699	33567128

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 92.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7775 / max 169.1125, expressed in 1647 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92668	12.1899	1586
92669	0.8499	481
92667	0.4084	223
92666	0.1900	80
92665	0.1394	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left uterine tube	UBERON:0001303	92.43	gold quality
pancreatic ductal cell	CL:0002079	91.66	silver quality
right ovary	UBERON:0002118	91.47	gold quality
left ovary	UBERON:0002119	91.00	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.58	gold quality
omental fat pad	UBERON:0010414	88.54	gold quality
peritoneum	UBERON:0002358	88.49	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.87	gold quality
ganglionic eminence	UBERON:0004023	86.66	gold quality
right atrium auricular region	UBERON:0006631	85.74	gold quality
gastrocnemius	UBERON:0001388	85.35	gold quality
ovary	UBERON:0000992	85.21	gold quality
right uterine tube	UBERON:0001302	85.13	gold quality
granulocyte	CL:0000094	84.98	gold quality
upper lobe of left lung	UBERON:0008952	84.85	gold quality
apex of heart	UBERON:0002098	84.70	gold quality
cardiac atrium	UBERON:0002081	84.67	gold quality
muscle of leg	UBERON:0001383	84.62	gold quality
mucosa of stomach	UBERON:0001199	84.57	gold quality
cervix squamous epithelium	UBERON:0006922	83.87	silver quality
gall bladder	UBERON:0002110	83.75	gold quality
heart left ventricle	UBERON:0002084	82.96	gold quality
right lung	UBERON:0002167	82.83	gold quality
right adrenal gland cortex	UBERON:0035827	82.79	gold quality
cardiac ventricle	UBERON:0002082	82.68	gold quality
heart	UBERON:0000948	82.61	gold quality
cerebellar cortex	UBERON:0002129	82.56	gold quality
upper lobe of lung	UBERON:0008948	82.55	gold quality
smooth muscle tissue	UBERON:0001135	82.51	gold quality
cerebellar hemisphere	UBERON:0002245	82.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.06
E-GEOD-110499	no	140.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting RNF122, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150

Literature-anchored findings (GeneRIF, showing 2)

• Findings indicate genetic association between E3 ubiquitin ligase RNF122 and Attention Deficit Disorders with Hyperactivity (ADHD). (PMID:28710364)
• RNF122 promotes glioblastoma growth via the JAK2/STAT3/c-Myc signaling Axis. (PMID:39218810)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf122	ENSDARG00000102075
mus_musculus	Rnf122	ENSMUSG00000039328
rattus_norvegicus	Rnf122	ENSRNOG00000023473
caenorhabditis_elegans		WBGENE00015641
caenorhabditis_elegans		WBGENE00015642
caenorhabditis_elegans		WBGENE00015818
caenorhabditis_elegans		WBGENE00017589
caenorhabditis_elegans		WBGENE00020665
caenorhabditis_elegans		WBGENE00022262
caenorhabditis_elegans		WBGENE00022265

Paralogs (1): RNF24 (ENSG00000101236)

Protein

Protein identifiers

RING finger protein 122 — Q9H9V4 (reviewed: Q9H9V4)

All UniProt accessions (1): Q9H9V4

UniProt curated annotations — full annotation on UniProt →

Function. May induce necrosis and apoptosis. May play a role in cell viability.

Subcellular location. Golgi apparatus. Endoplasmic reticulum. Membrane.

Tissue specificity. Widely expressed in several tissues and cell lines.

RefSeq proteins (1): NP_079063* (*=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 (4 total): chain 1, transmembrane region 1, zinc finger region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9V4-F1	72.23	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEIN_AUTOUBIQUITINATION, MARTIN_VIRAL_GPCR_SIGNALING_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, AACTTT_UNKNOWN, GOBP_REGULATION_OF_MITOCHONDRIAL_MEMBRANE_POTENTIAL, RYTTCCTG_ETS2_B, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, IK2_01, chr8p12, DOUGLAS_BMI1_TARGETS_UP, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, PITX2_Q2

GO Biological Process (4): negative regulation of mitochondrial membrane potential (GO:0010917), positive regulation of apoptotic process (GO:0043065), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein autoubiquitination (GO:0051865)

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 (4): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
negative regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein ubiquitination	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

864 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF122	RNF125	Q96EQ8	679
RNF122	MEX3C	Q5U5Q3	596
RNF122	TRIM40	Q6P9F5	593
RNF122	TRIM4	Q9C037	582
RNF122	RNF135	Q8IUD6	577
RNF122	TRIM25	Q14258	507
RNF122	USP3	Q9Y6I4	495
RNF122	L3HYPDH	Q96EM0	475
RNF122	TXLNB	Q8N3L3	470
RNF122	FAM234A	Q9H0X4	464
RNF122	TRIM31	Q9BZY9	451
RNF122	USP4	Q13107	425
RNF122	RNF5	Q99942	423
RNF122	MARCHF5	Q9NX47	423
RNF122	RNF170	Q96K19	407

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CDS2	RNF122	psi-mi:“MI:0915”(physical association)	0.560
GPR37L1	RNF122	psi-mi:“MI:0915”(physical association)	0.560
PPGB	RNF122	psi-mi:“MI:0915”(physical association)	0.560
AQP1	RNF122	psi-mi:“MI:0915”(physical association)	0.560
RNF122	PLLP	psi-mi:“MI:0915”(physical association)	0.560
RNF122	UBE2L6	psi-mi:“MI:0915”(physical association)	0.370
MFSD14A	FAM171A2	psi-mi:“MI:0914”(association)	0.350
SLC2A10	NRP1	psi-mi:“MI:0914”(association)	0.350
SLC37A1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC7A5	KLRG2	psi-mi:“MI:0914”(association)	0.350
CDS2	RNF122	psi-mi:“MI:0915”(physical association)	0.000
GPR37L1	RNF122	psi-mi:“MI:0915”(physical association)	0.000
PPGB	RNF122	psi-mi:“MI:0915”(physical association)	0.000
AQP1	RNF122	psi-mi:“MI:0915”(physical association)	0.000
PLLP	RNF122	psi-mi:“MI:0915”(physical association)	0.000
cysK	RNF122	psi-mi:“MI:0915”(physical association)	0.000
RNF122	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (24): RNF122 (Affinity Capture-MS), DDX58 (Affinity Capture-Western), RNF122 (Affinity Capture-Western), RNF122 (Reconstituted Complex), RNF122 (Two-hybrid), RNF122 (Two-hybrid), RNF122 (Two-hybrid), GPR37L1 (Two-hybrid), AQP1 (Two-hybrid), RNF122 (Affinity Capture-RNA), RNF122 (Affinity Capture-MS), RNF122 (Affinity Capture-MS), RNF122 (Affinity Capture-MS), RNF122 (Affinity Capture-MS), RNF122 (Two-hybrid)

ESM2 similar proteins: A0PJ23, A9JR22, A9JR44, B0BLK0, B0BLK7, B0BLK9, B2C4J2, B2MW50, B2ZDY1, B6VQ60, G5EDM7, J7H5K9, O43034, O73557, P05075, P0DKL9, P18541, P19325, P27426, Q03607, Q06651, Q11107, Q17768, Q197D3, Q20082, Q27YE2, Q27YE6, Q2XNS1, Q3UKZ7, Q5R7K8, Q5UPV2, Q6BET5, Q6IUF9, Q6IV57, Q6IVU5, Q6R7D2, Q6R7D3, Q6RSS3, Q6UY62, Q6UY71

Diamond homologs: A0A0D1E015, A5WWA0, A8Y4B2, E9QAU8, F1MM41, F1QB30, F7EP40, G3X9R7, O49691, O54965, P0C035, P0DPR2, Q06651, Q07G42, Q08CN9, Q08D68, Q08DI6, Q0V9R0, Q20798, Q29RU0, Q3U2C5, Q4KLR8, Q4R6Y5, Q5DTZ6, Q5M974, Q5NCP0, Q5R476, Q5RF74, Q5SSZ7, Q5XHH7, Q5XIL0, Q641J8, Q66HG0, Q66J97, Q66KG7, Q6AY01, Q6NKR1, Q6NRL6, Q6NRV8, Q6NRX0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF122	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

682 predictions. Top by Δscore:

Variant	Effect	Δscore
8:33549361:C:CA	donor_gain	1.0000
8:33549408:A:AC	donor_gain	1.0000
8:33549409:C:CC	donor_gain	1.0000
8:33549488:GTCTG:G	acceptor_gain	1.0000
8:33549490:CTG:C	acceptor_gain	1.0000
8:33549491:TG:T	acceptor_gain	1.0000
8:33549492:GC:G	acceptor_loss	1.0000
8:33549493:C:CC	acceptor_gain	1.0000
8:33549493:CTG:C	acceptor_loss	1.0000
8:33549494:T:A	acceptor_loss	1.0000
8:33551342:ACCT:A	donor_gain	1.0000
8:33551343:CCTC:C	donor_gain	1.0000
8:33551345:T:TA	donor_gain	1.0000
8:33558610:CGCA:C	donor_loss	1.0000
8:33558612:CA:C	donor_loss	1.0000
8:33558613:ACCTG:A	donor_loss	1.0000
8:33558614:C:A	donor_loss	1.0000
8:33558767:ACACC:A	acceptor_gain	1.0000
8:33558768:CACC:C	acceptor_gain	1.0000
8:33558768:CACCC:C	acceptor_gain	1.0000
8:33558769:ACC:A	acceptor_gain	1.0000
8:33558770:CC:C	acceptor_gain	1.0000
8:33558770:CCC:C	acceptor_gain	1.0000
8:33558771:CC:C	acceptor_gain	1.0000
8:33558772:C:CC	acceptor_gain	1.0000
8:33558772:C:T	acceptor_gain	1.0000
8:33558773:T:A	acceptor_loss	1.0000
8:33558775:C:CT	acceptor_gain	1.0000
8:33558776:A:T	acceptor_gain	1.0000
8:33549409:CTTG:C	donor_gain	0.9900

AlphaMissense

1027 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:33548824:A:G	C133R	1.000
8:33548829:G:T	P131H	1.000
8:33548830:G:A	P131S	1.000
8:33548831:G:C	C130W	1.000
8:33548832:C:T	C130Y	1.000
8:33548833:A:G	C130R	1.000
8:33548852:C:A	W123C	1.000
8:33548852:C:G	W123C	1.000
8:33548854:A:G	W123R	1.000
8:33548854:A:T	W123R	1.000
8:33548866:A:G	C119R	1.000
8:33549417:G:C	H116D	1.000
8:33549418:A:C	F115L	1.000
8:33549418:A:T	F115L	1.000
8:33549419:A:G	F115S	1.000
8:33549420:A:G	F115L	1.000
8:33549424:G:C	H113Q	1.000
8:33549424:G:T	H113Q	1.000
8:33549432:A:G	C111R	1.000
8:33549473:A:G	L97P	1.000
8:33549475:A:C	C96W	1.000
8:33549476:C:G	C96S	1.000
8:33549476:C:T	C96Y	1.000
8:33549477:A:G	C96R	1.000
8:33549477:A:T	C96S	1.000
8:33549479:A:T	V95D	1.000
8:33549484:G:C	C93W	1.000
8:33549485:C:A	C93F	1.000
8:33549485:C:G	C93S	1.000
8:33549485:C:T	C93Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000127725 (8:33554846 G>A), RS1000474742 (8:33561112 C>T), RS1000537521 (8:33561452 C>T), RS1000546022 (8:33566209 T>C), RS1000591400 (8:33561759 T>G), RS1000703292 (8:33549240 T>A), RS1000864411 (8:33565701 G>A,C), RS1000895260 (8:33566054 T>C,G), RS1001060574 (8:33553275 G>C), RS1001078927 (8:33559590 C>A,T), RS1001132613 (8:33553502 A>G), RS1001304933 (8:33547650 G>A), RS1001409127 (8:33559229 C>T), RS1001529323 (8:33556659 A>G), RS1001728651 (8:33550493 A>C)

Disease associations

OMIM: gene MIM:620523 | 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
GCST007269_276	Pulse pressure	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, increases mutagenesis, increases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	affects splicing, decreases expression	1
incobotulinumtoxinA	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Ethanol	increases expression	1
Curcumin	increases expression	1
Dexamethasone	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Niclosamide	increases expression	1
Tretinoin	increases expression	1
Tunicamycin	increases expression	1
Urethane	increases expression	1
Okadaic Acid	increases expression	1
2-Propanol	increases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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