RNF215

Summary

RNF215 (ring finger protein 215, HGNC:33434) is a protein-coding gene on chromosome 22q12.2, encoding RING finger protein 215 (Q9Y6U7).

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent protein catabolic process. Predicted to be located in membrane. Predicted to be active in cytoplasm.

Source: NCBI Gene 200312 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 68 total
• MANE Select transcript: NM_001017981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33434
Approved symbol	RNF215
Name	ring finger protein 215
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099999
Ensembl biotype	protein_coding
Entrez	200312

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000215798, ENST00000332468, ENST00000382363, ENST00000421022, ENST00000431544, ENST00000463319, ENST00000473077, ENST00000619645, ENST00000630264, ENST00000631046, ENST00000949118, ENST00000949119, ENST00000949120

RefSeq mRNA: 1 — MANE Select: NM_001017981 NM_001017981

CCDS: CCDS33633

Canonical transcript exons

ENST00000382363 — 9 exons

Exon	Start	End
ENSE00000652203	30384339	30384495
ENSE00001300480	30387029	30387411
ENSE00001629490	30378821	30379622
ENSE00003485368	30386070	30386141
ENSE00003512893	30380062	30380205
ENSE00003616337	30380282	30380401
ENSE00003634173	30379711	30379813
ENSE00003657113	30385904	30385989
ENSE00003757798	30386616	30386759

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 90.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7017 / max 59.4992, expressed in 1662 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193627	3.4489	1556
193625	1.3703	884
193626	0.8825	512

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	90.52	gold quality
cerebellar hemisphere	UBERON:0002245	89.92	gold quality
cerebellar cortex	UBERON:0002129	89.71	gold quality
stromal cell of endometrium	CL:0002255	88.77	gold quality
right frontal lobe	UBERON:0002810	88.49	gold quality
apex of heart	UBERON:0002098	88.20	gold quality
cerebellum	UBERON:0002037	88.02	gold quality
body of uterus	UBERON:0009853	87.95	gold quality
endocervix	UBERON:0000458	87.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.65	gold quality
anterior cingulate cortex	UBERON:0009835	87.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.26	gold quality
right ovary	UBERON:0002118	87.25	gold quality
prefrontal cortex	UBERON:0000451	87.07	gold quality
left uterine tube	UBERON:0001303	86.87	gold quality
ectocervix	UBERON:0012249	86.27	gold quality
left ovary	UBERON:0002119	86.22	gold quality
hypothalamus	UBERON:0001898	85.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.49	gold quality
right lobe of thyroid gland	UBERON:0001119	85.11	gold quality
mucosa of stomach	UBERON:0001199	84.94	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.82	gold quality
cortical plate	UBERON:0005343	84.77	gold quality
lower esophagus	UBERON:0013473	84.77	gold quality
metanephros cortex	UBERON:0010533	84.50	gold quality
nucleus accumbens	UBERON:0001882	84.41	gold quality
tibial nerve	UBERON:0001323	84.40	gold quality
neocortex	UBERON:0001950	84.28	gold quality
frontal cortex	UBERON:0001870	84.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting RNF215, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-4263	99.18	69.25	2236
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-210-5P	98.57	64.37	832
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-558	97.50	67.16	977
HSA-MIR-10397-5P	97.31	69.06	710
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-920	95.97	63.95	811
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf215	ENSDARG00000059424
mus_musculus	Rnf215	ENSMUSG00000003581
rattus_norvegicus	Rnf215	ENSRNOG00000004940
drosophila_melanogaster	gzl	FBGN0037442
caenorhabditis_elegans		WBGENE00007666

Paralogs (9): RNF13 (ENSG00000082996), ZNRF4 (ENSG00000105428), RNF167 (ENSG00000108523), RNF130 (ENSG00000113269), RNF128 (ENSG00000133135), RNF149 (ENSG00000163162), RNF150 (ENSG00000170153), RNF133 (ENSG00000188050), RNF148 (ENSG00000235631)

Protein

Protein identifiers

RING finger protein 215 — Q9Y6U7 (reviewed: Q9Y6U7)

All UniProt accessions (7): Q9Y6U7, A0A0D9SF05, A0A0D9SFN2, A0A0D9SGK3, C9JDL7, H0Y2L4, H7C0R1

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001017981* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR051073	ZNRF3_Arkadia_E3_ligases	Family

Pfam: PF13639

UniProt features (11 total): topological domain 3, transmembrane region 2, chain 1, sequence variant 1, zinc finger region 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6U7-F1	66.68	0.05

Functional residue map

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

Glycosylation sites (1): 186

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 55 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEOLYSIS, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, MARTENS_TRETINOIN_RESPONSE_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, E2F3_UP.V1_DN, ARID5B_TARGET_GENES, GSE13547_2H_VS_12_H_ANTI_IGM_STIM_ZFX_KO_BCELL_UP, TFEB_TARGET_GENES, MIR3678_3P, MIR6734_3P

GO Biological Process (1): ubiquitin-dependent protein catabolic process (GO:0006511)

GO Molecular Function (3): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), metal ion binding (GO:0046872)

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
cation binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF215	TMPRSS12	Q86WS5	666
RNF215	ERGIC2	Q96RQ1	595
RNF215	ZNF10	P21506	584
RNF215	ASB8	Q9H765	552
RNF215	PRR9	Q5T870	544
RNF215	UBOX5	O94941	504
RNF215	ILDR1	Q86SU0	473
RNF215	RNF185	Q96GF1	447
RNF215	CCDC157	Q569K6	419
RNF215	WDFY4	Q6ZS81	405
RNF215	RFFL	Q8WZ73	380
RNF215	FBXO7	Q9Y3I1	367
RNF215	COG6	Q9Y2V7	366
RNF215	CD2BP2	O95400	360
RNF215	GPR150	Q8NGU9	357

IntAct

4 interactions, top by confidence:

A	B	Type	Score
RNF215	CAPN15	psi-mi:“MI:0915”(physical association)	0.400
KCNC4	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CHRNB4	GPR89A	psi-mi:“MI:0914”(association)	0.350
KCNC4	SMPD2	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): RNF215 (Affinity Capture-MS), RNF215 (Affinity Capture-MS), RNF215 (Affinity Capture-MS), CAPN15 (Affinity Capture-MS), RNF215 (Affinity Capture-Western), RELA (Affinity Capture-Western), RNF215 (Co-localization)

ESM2 similar proteins: A0A1W2PP97, A6NLX4, A6QNY1, P0DJK0, P12838, P13207, P22389, P22749, P23943, P29473, P29474, P55056, P70313, P79209, P97270, P98162, Q1RMT9, Q28969, Q2TAL6, Q2VPJ9, Q4TUC0, Q566C8, Q5BIR3, Q5JTB6, Q5NRP8, Q5RCS3, Q5SPX3, Q5XIX0, Q62600, Q64322, Q7TMJ8, Q7TPD7, Q7TSF4, Q80TT8, Q867D0, Q8BZT7, Q8C8N3, Q8K1T4, Q8K4Z2, Q8MJW9

Diamond homologs: A5WWA0, E9QAU8, G3X9R7, O22197, O22755, O43567, O54965, O64763, P0C034, P0CH30, P0DPR2, Q06003, Q07G42, Q08D68, Q0II22, Q0VD51, Q10R93, Q14B02, Q29RU0, Q2TA44, Q3U2C5, Q4KLR8, Q4R6Y5, Q5NCP0, Q5RCV8, Q5RF74, Q5SPX3, Q5SSZ7, Q5XF85, Q641J8, Q66HG0, Q68DV7, Q69U49, Q6AY01, Q6DIP3, Q6IRP0, Q6NML0, Q6NQG7, Q6NRX0, Q6Y290

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF215	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4321 predictions. Top by Δscore:

Variant	Effect	Δscore
22:30370317:T:A	acceptor_gain	1.0000
22:30373590:T:A	acceptor_gain	1.0000
22:30373595:A:AG	acceptor_gain	1.0000
22:30373596:G:GA	acceptor_gain	1.0000
22:30373596:GT:G	acceptor_gain	1.0000
22:30373596:GTC:G	acceptor_gain	1.0000
22:30373596:GTCT:G	acceptor_gain	1.0000
22:30373731:G:GT	donor_gain	1.0000
22:30373761:GCAG:G	donor_gain	1.0000
22:30373765:G:GC	donor_loss	1.0000
22:30373766:T:G	donor_loss	1.0000
22:30375637:G:GT	donor_gain	1.0000
22:30375637:G:T	donor_gain	1.0000
22:30376257:A:AG	acceptor_gain	1.0000
22:30376257:AGCT:A	acceptor_gain	1.0000
22:30376258:G:GA	acceptor_gain	1.0000
22:30376258:GC:G	acceptor_gain	1.0000
22:30376258:GCT:G	acceptor_gain	1.0000
22:30376258:GCTG:G	acceptor_gain	1.0000
22:30376346:GG:G	donor_gain	1.0000
22:30376347:GG:G	donor_gain	1.0000
22:30379811:CCA:C	acceptor_gain	1.0000
22:30379812:CAC:C	acceptor_gain	1.0000
22:30379814:C:CC	acceptor_gain	1.0000
22:30384334:CCCA:C	donor_loss	1.0000
22:30384336:CACC:C	donor_loss	1.0000
22:30384337:AC:A	donor_loss	1.0000
22:30384338:CCTGC:C	donor_loss	1.0000
22:30384496:C:CC	acceptor_gain	1.0000
22:30385902:A:AC	donor_gain	1.0000

AlphaMissense

2376 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:30379781:A:C	F347L	1.000
22:30379781:A:T	F347L	1.000
22:30379782:A:G	F347S	1.000
22:30379783:A:G	F347L	1.000
22:30379727:G:C	C365W	0.999
22:30379728:C:G	C365S	0.999
22:30379728:C:T	C365Y	0.999
22:30379729:A:G	C365R	0.999
22:30379729:A:T	C365S	0.999
22:30379734:G:T	P363Q	0.999
22:30379736:G:C	C362W	0.999
22:30379737:C:T	C362Y	0.999
22:30379738:A:G	C362R	0.999
22:30379755:A:G	L356P	0.999
22:30379757:C:A	W355C	0.999
22:30379757:C:G	W355C	0.999
22:30379769:A:C	C351W	0.999
22:30379770:C:T	C351Y	0.999
22:30379771:A:G	C351R	0.999
22:30379780:G:C	H348D	0.999
22:30379782:A:C	F347C	0.999
22:30379794:C:T	C343Y	0.999
22:30379795:A:G	C343R	0.999
22:30380086:G:C	C328W	0.999
22:30380088:A:G	C328R	0.999
22:30380095:A:C	C325W	0.999
22:30380096:C:T	C325Y	0.999
22:30384420:C:A	W221C	0.999
22:30384420:C:G	W221C	0.999
22:30379728:C:A	C365F	0.998

dbSNP variants (sampled 300 via entrez): RS1001464615 (22:30383540 C>G,T), RS1001552393 (22:30384213 G>A), RS1001728427 (22:30378818 A>G), RS1001809165 (22:30386277 A>G), RS1001860195 (22:30380713 A>C), RS1001927430 (22:30380994 C>T), RS1002135480 (22:30386115 G>A), RS1002524611 (22:30383214 C>T), RS1002596533 (22:30383463 C>T), RS1002607911 (22:30389015 A>G), RS1003353014 (22:30387726 C>G), RS1003552594 (22:30387517 C>T), RS1003877080 (22:30388014 C>G), RS1004103449 (22:30388507 T>C), RS1004290604 (22:30388207 G>A)

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

1 associations (top):

Study	Trait	p-value
GCST004607_193	Plateletcrit	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1

Clinical trials (associated diseases)

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