RNF222

Summary

RNF222 (ring finger protein 222, HGNC:34517) is a protein-coding gene on chromosome 17p13.1, encoding RING finger protein 222 (A6NCQ9).

Predicted to enable zinc ion binding activity. Predicted to be located in membrane.

Source: NCBI Gene 643904 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_001146684

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34517
Approved symbol	RNF222
Name	ring finger protein 222
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000189051
Ensembl biotype	protein_coding
Entrez	643904

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000344001, ENST00000399398

RefSeq mRNA: 1 — MANE Select: NM_001146684 NM_001146684

CCDS: CCDS45608

Canonical transcript exons

ENST00000399398 — 3 exons

Exon	Start	End
ENSE00001537967	8390702	8393486
ENSE00001537968	8394178	8394329
ENSE00001537969	8397695	8397827

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 92.60.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0414 / max 6.9722, expressed in 15 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164432	0.0414	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	92.60	gold quality
esophagus mucosa	UBERON:0002469	78.83	gold quality
skin of leg	UBERON:0001511	72.78	gold quality
zone of skin	UBERON:0000014	72.25	gold quality
skin of abdomen	UBERON:0001416	71.72	gold quality
vagina	UBERON:0000996	60.69	gold quality
esophagus	UBERON:0001043	57.08	gold quality
tonsil	UBERON:0002372	55.33	gold quality
placenta	UBERON:0001987	52.60	gold quality
bone marrow	UBERON:0002371	52.37	gold quality
bone marrow cell	CL:0002092	49.73	gold quality
ectocervix	UBERON:0012249	47.09	gold quality
uterine cervix	UBERON:0000002	46.67	gold quality
blood	UBERON:0000178	46.44	silver quality
granulocyte	CL:0000094	42.94	silver quality
minor salivary gland	UBERON:0001830	42.91	gold quality
skeletal muscle tissue	UBERON:0001134	42.30	gold quality
endometrium	UBERON:0001295	42.25	gold quality
saliva-secreting gland	UBERON:0001044	42.24	gold quality
sural nerve	UBERON:0015488	42.10	gold quality
colonic epithelium	UBERON:0000397	42.04	gold quality
lymph node	UBERON:0000029	41.19	gold quality
cortical plate	UBERON:0005343	39.79	gold quality
ganglionic eminence	UBERON:0004023	38.83	gold quality
vermiform appendix	UBERON:0001154	38.73	silver quality
muscle tissue	UBERON:0002385	38.71	gold quality
multicellular organism	UBERON:0000468	37.85	gold quality
urinary bladder	UBERON:0001255	36.68	gold quality
liver	UBERON:0002107	36.58	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.43

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnf222	ENSMUSG00000046490
rattus_norvegicus	Rnf222	ENSRNOG00000022964

Protein

Protein identifiers

RING finger protein 222 — A6NCQ9 (reviewed: A6NCQ9)

All UniProt accessions (1): A6NCQ9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001140156* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR027370	Znf-RING_euk	Domain
IPR042973	RNF222	Family

Pfam: PF13445

UniProt features (5 total): chain 1, transmembrane region 1, zinc finger region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NCQ9-F1	63.13	0.10

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GSE13522_WT_VS_IFNG_KO_SKIN_UP, SKP2_TARGET_GENES, MIR4728_5P, MIR6785_5P, MIR182_5P, MIR149_3P, MIR6883_5P, MIR3182, MIR6887_3P, MIR4653_5P, MIR3921, MIR337_3P, MIR4667_3P, MIR1301_3P_MIR5047

GO Biological Process (0):

GO Molecular Function (2): zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion binding	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF222	SEZ6L	Q9BYH1	574
RNF222	TMEM220	Q6QAJ8	526
RNF222	ZZEF1	O43149	477
RNF222	SAMD1	Q6SPF0	471
RNF222	PI15	O43692	455
RNF222	CUZD1	Q86UP6	432
RNF222	MUC15	Q8N387	425
RNF222	GABRP	O00591	414
RNF222	GABRD	O14764	399
RNF222	NUP210	Q8TEM1	398
RNF222	OLFML2B	Q68BL8	394
RNF222	DMGDH	Q9UI17	365
RNF222	BACE2	Q9Y5Z0	356
RNF222	ANP32E	Q9BTT0	325
RNF222	RMI2	Q96E14	318

IntAct

0 interactions, top by confidence:

BioGRID (1): RNF222 (Affinity Capture-MS)

ESM2 similar proteins: A6NCL7, A6NCQ9, A6QP29, A6QQV9, B1AVH7, B5DFA1, D2H0G5, D2H6Z0, D2H788, D3ZBM4, D4A723, E1C2W7, O95153, Q0QWG9, Q3SWY0, Q3T0Y9, Q3U0L2, Q3UV31, Q3V3A7, Q5RF77, Q60943, Q6INB3, Q6PGG2, Q7TNF8, Q7Z465, Q80TI1, Q810L3, Q8BG47, Q8BRJ3, Q8BXP5, Q8C0R7, Q8C432, Q8CEF8, Q8HYZ0, Q8N0U2, Q8N6D2, Q8N8N0, Q8NC24, Q8QZS5, Q8TED9

Diamond homologs: A6NCQ9, E7ERA6, M0QZC1, Q3UV31, Q6ZWI9, Q8CEF8, Q9D7D1, P0DH78, Q13049, Q3SWY0, Q3UIW8, Q8CH72, Q8QZS5, Q96D59, E1BD59, O16616, Q5ZMD4, Q6VVB1, Q8IWR1, Q922Y2, Q9BRZ2, Q9D241, Q5E9G4, Q5M929

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF222	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

48 predictions. Top by Δscore:

Variant	Effect	Δscore
17:8392810:T:TA	donor_gain	0.9300
17:8392801:ACG:A	donor_gain	0.8100
17:8392802:CGC:C	donor_gain	0.8100
17:8392785:C:CA	donor_gain	0.7900
17:8392811:C:A	donor_gain	0.6300
17:8392810:TCCTC:T	donor_gain	0.5700
17:8393332:TG:T	donor_gain	0.5500
17:8392818:A:T	donor_gain	0.4700
17:8392814:C:T	donor_gain	0.4300
17:8392784:T:TA	donor_gain	0.4100
17:8392802:CG:C	donor_gain	0.3800
17:8393026:C:CA	donor_gain	0.3200
17:8392482:C:A	acceptor_gain	0.3100
17:8392545:AGC:A	acceptor_loss	0.3000
17:8392546:GCCT:G	acceptor_loss	0.3000
17:8392547:CC:C	acceptor_loss	0.3000
17:8392548:C:A	acceptor_loss	0.3000
17:8392548:C:CC	acceptor_gain	0.3000
17:8392549:T:A	acceptor_loss	0.3000
17:8392803:G:C	donor_gain	0.3000
17:8392550:A:C	acceptor_loss	0.2900
17:8392852:C:CT	donor_gain	0.2800
17:8392542:C:CT	acceptor_gain	0.2700
17:8392543:C:CG	acceptor_gain	0.2700
17:8392546:G:GA	acceptor_gain	0.2500
17:8392256:C:A	acceptor_gain	0.2400
17:8392817:C:CT	donor_gain	0.2300
17:8391333:T:G	acceptor_gain	0.2200
17:8392137:CCCCT:C	acceptor_gain	0.2200
17:8392541:TCC:T	acceptor_gain	0.2200

AlphaMissense

1395 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:8393281:A:G	C61R	1.000
17:8393351:G:C	F37L	1.000
17:8393351:G:T	F37L	1.000
17:8393352:A:G	F37S	1.000
17:8393353:A:G	F37L	1.000
17:8393422:A:G	C14R	1.000
17:8393270:G:C	C64W	0.999
17:8393271:C:A	C64F	0.999
17:8393271:C:G	C64S	0.999
17:8393271:C:T	C64Y	0.999
17:8393272:A:G	C64R	0.999
17:8393272:A:T	C64S	0.999
17:8393279:G:C	C61W	0.999
17:8393280:C:G	C61S	0.999
17:8393280:C:T	C61Y	0.999
17:8393281:A:T	C61S	0.999
17:8393339:G:C	C41W	0.999
17:8393340:C:G	C41S	0.999
17:8393340:C:T	C41Y	0.999
17:8393341:A:G	C41R	0.999
17:8393341:A:T	C41S	0.999
17:8393348:G:C	C38W	0.999
17:8393349:C:T	C38Y	0.999
17:8393350:A:G	C38R	0.999
17:8393352:A:C	F37C	0.999
17:8393363:A:C	C33W	0.999
17:8393364:C:G	C33S	0.999
17:8393364:C:T	C33Y	0.999
17:8393365:A:G	C33R	0.999
17:8393365:A:T	C33S	0.999

dbSNP variants (sampled 300 via entrez): RS1000030344 (17:8391824 C>T), RS1000144632 (17:8391662 T>G), RS1000344784 (17:8397706 G>C), RS1000884238 (17:8394405 A>C), RS1001824361 (17:8391955 T>C,G), RS1002281783 (17:8398908 A>G), RS1002373338 (17:8393282 G>A), RS1002573977 (17:8398658 C>A,T), RS1002668639 (17:8397409 A>C), RS1002966863 (17:8391579 C>A,G,T), RS1003122392 (17:8396020 A>G), RS1003379897 (17:8394699 C>T), RS1003417716 (17:8395757 G>T), RS1003893042 (17:8398565 C>T), RS1004837665 (17:8391555 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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