RNF223

Summary

RNF223 (ring finger protein 223, HGNC:40020) is a protein-coding gene on chromosome 1p36.33, encoding RING finger protein 223 (E7ERA6).

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in membrane.

Source: NCBI Gene 401934 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 75 total — 1 pathogenic
• MANE Select transcript: NM_001205252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:40020
Approved symbol	RNF223
Name	ring finger protein 223
Location	1p36.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000237330
Ensembl biotype	protein_coding
Entrez	401934

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000453464

RefSeq mRNA: 1 — MANE Select: NM_001205252 NM_001205252

CCDS: CCDS53257

Canonical transcript exons

ENST00000453464 — 2 exons

Exon	Start	End
ENSE00001666214	1070967	1072575
ENSE00001707588	1074016	1074306

Expression profiles

Bgee: expression breadth broad, 55 present calls, max score 92.10.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5617 / max 100.5766, expressed in 294 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9694	3.5617	294

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	92.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.49	gold quality
esophagus mucosa	UBERON:0002469	83.28	gold quality
vagina	UBERON:0000996	67.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.51	gold quality
mucosa of transverse colon	UBERON:0004991	65.96	gold quality
skin of leg	UBERON:0001511	65.68	gold quality
zone of skin	UBERON:0000014	64.42	gold quality
skin of abdomen	UBERON:0001416	62.85	gold quality
minor salivary gland	UBERON:0001830	62.38	gold quality
saliva-secreting gland	UBERON:0001044	61.91	gold quality
placenta	UBERON:0001987	60.83	gold quality
body of stomach	UBERON:0001161	60.44	gold quality
stomach	UBERON:0000945	58.60	gold quality
esophagus	UBERON:0001043	58.02	gold quality
urinary bladder	UBERON:0001255	56.31	gold quality
transverse colon	UBERON:0001157	55.42	gold quality
mucosa of stomach	UBERON:0001199	55.42	gold quality
tonsil	UBERON:0002372	53.23	gold quality
fundus of stomach	UBERON:0001160	52.23	gold quality
islet of Langerhans	UBERON:0000006	51.63	gold quality
rectum	UBERON:0001052	48.36	gold quality
upper lobe of left lung	UBERON:0008952	47.96	gold quality
uterine cervix	UBERON:0000002	47.55	gold quality
metanephros cortex	UBERON:0010533	46.74	gold quality
lung	UBERON:0002048	45.77	gold quality
colonic epithelium	UBERON:0000397	45.10	gold quality
ectocervix	UBERON:0012249	45.03	gold quality
colon	UBERON:0001155	44.18	gold quality
kidney	UBERON:0002113	43.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.72

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnf223	ENSMUSG00000110404
rattus_norvegicus	Rnf223	ENSRNOG00000036856

Paralogs (3): RNF183 (ENSG00000165188), RNF208 (ENSG00000212864), RNF225 (ENSG00000269855)

Protein

Protein identifiers

RING finger protein 223 — E7ERA6 (reviewed: E7ERA6)

All UniProt accessions (1): E7ERA6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (1): NP_001192181* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR051435	RING_finger_E3_ubiq-ligases	Family

Pfam: PF14634

UniProt features (8 total): region of interest 2, compositionally biased region 2, 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-E7ERA6-F1	73.42	0.39

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, chr1p36, ZNF184_TARGET_GENES, ZNF592_TARGET_GENES, GOBP_PROTEIN_MODIFICATION_BY_SMALL_PROTEIN_CONJUGATION, BLANCO_MELO_BRONCHIAL_EPITHELIAL_CELLS_INFLUENZA_A_DEL_NS1_INFECTION_UP, DESCARTES_FETAL_KIDNEY_URETERIC_BUD_CELLS, DESCARTES_FETAL_LUNG_SQUAMOUS_EPITHELIAL_CELLS, DESCARTES_FETAL_PLACENTA_EXTRAVILLOUS_TROPHOBLASTS, HE_LIM_SUN_FETAL_LUNG_C1_SQUAMOUS_CELL, WP_1P36_COPY_NUMBER_VARIATION_SYNDROME, ZHANG_FH_DEFICIENT_RCC_TUMOR_VS_NORMAL_DN

GO Biological Process (1): protein ubiquitination (GO:0016567)

GO Molecular Function (3): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), 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
protein modification by small protein conjugation	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
cation binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF223	TIFAB	Q6ZNK6	698
RNF223	AADACL4	Q5VUY2	623
RNF223	TLX2	O43763	609
RNF223	RNFT1	Q5M7Z0	580
RNF223	RNFT2	Q96EX2	568
RNF223	MEAF6	Q9HAF1	519
RNF223	RNF148	Q8N7C7	507
RNF223	TMEM129	A0AVI4	505
RNF223	RNF130	Q86XS8	495
RNF223	LRTM3	Q8NDH2	489
RNF223	RNF144A	P50876	477
RNF223	RBM5	P52756	476
RNF223	RNF144B	Q7Z419	439
RNF223	WWOX	Q9NZC7	433
RNF223	NCAPD3	P42695	405

IntAct

0 interactions, top by confidence:

BioGRID (1): RNF223 (Affinity Capture-RNA)

ESM2 similar proteins: A2A9Q0, A5PKD8, A9JSM3, D4A2Q0, E7ERA6, F1SAM7, F2Z333, P0CG25, Q07303, Q0IIA6, Q1RMK9, Q24JP5, Q2MJR0, Q2WF71, Q3MIP1, Q3UV16, Q3ZCQ3, Q504Y2, Q5EBM0, Q5GH56, Q5GH64, Q5GH72, Q5RJI4, Q5SZI1, Q641Q3, Q6IEE6, Q6IQX7, Q6P6N5, Q6UKI2, Q6ZMC9, Q6ZVW7, Q86UD0, Q8IUW3, Q8IZ52, Q8K064, Q8N4K4, Q8NAC3, Q8NBR0, Q8NCL9, Q8NFR9

Diamond homologs: A6NCQ9, E7ERA6, M0QZC1, Q3UV31, Q6ZWI9, Q8CEF8, Q9D7D1, E1BD59, F6ZQ54, O60858, Q03601, Q0IIM1, Q32L60, Q3UIW8, Q503I2, Q5M7V1, Q5ZMD4, Q61510, Q7T308, Q80VI1, Q810I1, Q810I2, Q8BFW4, Q8IUD6, Q9BRZ2, Q9CYB0, Q3SWY0, Q6IMG5, Q6VVB1, Q8BR37, Q8IWR1, Q8QZS5, Q96D59, Q9D241, P0DH78, Q13049, Q8CH72, O16616, Q09623, A0A7I2V3R4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF223	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	70
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
443012	GRCh37/hg19 1p36.33-36.32(chr1:849466-2748837)x1	Pathogenic

SpliceAI

275 predictions. Top by Δscore:

Variant	Effect	Δscore
1:1074010:CCTTA:C	donor_loss	1.0000
1:1074011:CTTAC:C	donor_loss	1.0000
1:1074012:TTACC:T	donor_loss	1.0000
1:1074014:A:AT	donor_loss	1.0000
1:1074014:A:AC	donor_gain	0.9900
1:1074015:C:CC	donor_gain	0.9900
1:1074015:CCTG:C	donor_gain	0.9600
1:1072576:C:CC	acceptor_gain	0.9300
1:1072571:CTGAG:C	acceptor_gain	0.9200
1:1074014:AC:A	donor_gain	0.9000
1:1074015:CC:C	donor_gain	0.9000
1:1074015:CCT:C	donor_gain	0.8800
1:1073620:C:A	acceptor_gain	0.8700
1:1072572:TGAGC:T	acceptor_loss	0.8500
1:1072574:AGCT:A	acceptor_loss	0.8500
1:1072575:GCT:G	acceptor_loss	0.8500
1:1072576:CTGT:C	acceptor_loss	0.8500
1:1072577:T:G	acceptor_loss	0.8500
1:1072578:G:C	acceptor_loss	0.8500
1:1072683:T:A	donor_gain	0.8500
1:1074015:CCTGG:C	donor_gain	0.8400
1:1072338:C:CA	donor_gain	0.8300
1:1072579:TGGGA:T	acceptor_loss	0.8200
1:1072585:A:T	acceptor_loss	0.8200
1:1072580:GGGA:G	acceptor_loss	0.8100
1:1072595:GT:G	acceptor_loss	0.7800
1:1072596:T:A	acceptor_loss	0.7500
1:1072581:GGA:G	acceptor_loss	0.7400
1:1072584:CAGGG:C	acceptor_loss	0.7400
1:1074113:T:TA	donor_gain	0.7400

AlphaMissense

1567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:1072369:C:A	K66N	0.999
1:1072369:C:G	K66N	0.999
1:1072415:C:G	C51S	0.994
1:1072416:A:T	C51S	0.994
1:1072262:C:A	R102M	0.993
1:1072334:C:G	C78S	0.993
1:1072335:A:G	C78R	0.993
1:1072335:A:T	C78S	0.993
1:1072345:G:C	F74L	0.993
1:1072345:G:T	F74L	0.993
1:1072347:A:G	F74L	0.993
1:1072373:G:T	P65H	0.993
1:1072402:G:C	F55L	0.993
1:1072402:G:T	F55L	0.993
1:1072404:A:G	F55L	0.993
1:1072409:A:T	I53N	0.993
1:1072416:A:G	C51R	0.993
1:1072346:A:G	F74S	0.992
1:1072381:G:C	F62L	0.992
1:1072381:G:T	F62L	0.992
1:1072383:A:G	F62L	0.992
1:1072262:C:G	R102T	0.991
1:1072275:A:G	C98R	0.990
1:1072343:C:T	C75Y	0.990
1:1072344:A:G	C75R	0.990
1:1072351:G:C	H72Q	0.990
1:1072351:G:T	H72Q	0.990
1:1072409:A:G	I53T	0.990
1:1072342:G:C	C75W	0.989
1:1072358:C:T	C70Y	0.989

dbSNP variants (sampled 300 via entrez): RS1000097429 (1:1073998 G>A,C), RS1000293410 (1:1072154 T>C), RS1000412084 (1:1071191 C>T), RS1000448295 (1:1070860 C>T), RS1001843899 (1:1072953 A>G), RS1002850757 (1:1072985 A>G), RS1002903596 (1:1074808 G>A,T), RS1003470421 (1:1072241 G>A,C,T), RS1003525458 (1:1071317 G>A,C), RS1003998560 (1:1072201 C>T), RS1004024875 (1:1072276 A>G), RS1005555472 (1:1072449 G>A), RS1006220025 (1:1074234 G>C,T), RS1006340647 (1:1071373 C>G), RS1006352060 (1:1071557 C>T)

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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
sotorasib	decreases expression, affects cotreatment	1
beta-lapachone	increases expression	1
corosolic acid	increases expression	1
abrine	increases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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