RNF227

Summary

RNF227 (ring finger protein 227, HGNC:27571) is a protein-coding gene on chromosome 17p13.1, encoding RING finger protein 227 (A6NIN4).

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

Source: NCBI Gene 284023 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001358699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27571
Approved symbol	RNF227
Name	ring finger protein 227
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000179859
Ensembl biotype	protein_coding
Entrez	284023

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000324348, ENST00000635932, ENST00000640240

RefSeq mRNA: 1 — MANE Select: NM_001358699 NM_001358699

CCDS: CCDS86570

Canonical transcript exons

ENST00000324348 — 2 exons

Exon	Start	End
ENSE00001246380	7913339	7915577
ENSE00001246383	7915679	7916289

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 98.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.4178 / max 150.5887, expressed in 1263 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164331	2.5179	1033
164332	0.8999	327

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	98.75	gold quality
upper leg skin	UBERON:0004262	93.79	gold quality
oviduct epithelium	UBERON:0004804	93.79	gold quality
skin of leg	UBERON:0001511	93.43	gold quality
zone of skin	UBERON:0000014	92.39	gold quality
skin of abdomen	UBERON:0001416	91.05	gold quality
skin of hip	UBERON:0001554	88.89	gold quality
buccal mucosa cell	CL:0002336	87.28	gold quality
gingival epithelium	UBERON:0001949	83.44	gold quality
sural nerve	UBERON:0015488	80.35	gold quality
nipple	UBERON:0002030	80.34	gold quality
mammalian vulva	UBERON:0000997	79.79	gold quality
ileal mucosa	UBERON:0000331	79.23	silver quality
fallopian tube	UBERON:0003889	79.15	gold quality
cortical plate	UBERON:0005343	78.17	gold quality
gingiva	UBERON:0001828	78.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.07	gold quality
cerebellar hemisphere	UBERON:0002245	77.34	gold quality
germinal epithelium of ovary	UBERON:0001304	77.30	gold quality
cerebellar cortex	UBERON:0002129	77.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.09	gold quality
cerebellum	UBERON:0002037	76.70	gold quality
right uterine tube	UBERON:0001302	76.68	gold quality
primary visual cortex	UBERON:0002436	74.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.54	gold quality
body of uterus	UBERON:0009853	74.49	gold quality
Brodmann (1909) area 23	UBERON:0013554	74.36	gold quality
ventricular zone	UBERON:0003053	74.27	gold quality
esophagus squamous epithelium	UBERON:0006920	73.83	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	73.56	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	19.11
E-ANND-3	no	2.67
E-MTAB-5061	no	2.47

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rnf227	ENSMUSG00000043419
rattus_norvegicus	Rnf227	ENSRNOG00000021540
drosophila_melanogaster	roq	FBGN0036621

Paralogs (5): RC3H2 (ENSG00000056586), RC3H1 (ENSG00000135870), RNF182 (ENSG00000180537), RNF224 (ENSG00000233198), RNF228 (ENSG00000288658)

Protein

Protein identifiers

RING finger protein 227 — A6NIN4 (reviewed: A6NIN4)

Alternative names: Long intergenic non-protein coding RNA 2581

All UniProt accessions (3): A0A1B0GTZ6, A0A2Y9D085, A6NIN4

RefSeq proteins (1): NP_001345628* (*=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
IPR027952	DUF4632	Domain
IPR051435	RING_finger_E3_ubiq-ligases	Family

Pfam: PF13445, PF15451

UniProt features (4 total): chain 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-A6NIN4-F1	69.55	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 38 (showing top): TSENG_IRS1_TARGETS_UP, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, GOLDRATH_ANTIGEN_RESPONSE, RAMALHO_STEMNESS_DN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, CUI_TCF21_TARGETS_2_UP, CHEN_ETV5_TARGETS_TESTIS, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLACK_UP, TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_UP, ZWANG_EGF_PERSISTENTLY_UP, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, YAP1_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 (0):

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

Protein interactions and networks

STRING

58 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF227	GPR152	Q8TDT2	239
RNF227	GPR171	O14626	193
RNF227	GPR82	Q96P67	158
RNF227	GPR158	Q5T848	156
RNF227	GPR162	Q16538	141
RNF227	PNMA8A	Q86V59	116
RNF227	PNMA8C	A0A1B0GUJ8	116
RNF227	TMEM59L	Q9UK28	110
RNF227	CXorf66	Q5JRM2	72
RNF227	RPSA	P08865	72
RNF227	PPP1R26	Q5T8A7	70
RNF227	MRPS2	Q9Y399	70
RNF227	SMKR1	H3BMG3	70
RNF227	REELD1	A0A1B0GV85	65
RNF227	RPS16	P17008	51

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A286YF58, A0A494C0N9, A0A494C0Y3, A0A7I2V3R4, A2VDX9, A6NIN4, D3YXK1, G3UXB3, O15370, O15522, O35392, O70218, O70220, O89113, P0DPE3, P12980, P17542, P22091, P28283, P82976, Q04890, Q05916, Q05917, Q13461, Q14V87, Q15270, Q19A40, Q5T230, Q5VY09, Q63244, Q6F5E0, Q6SPE9, Q6SPF0, Q7RTU7, Q80WY3, Q8TD94, Q8WY41, Q8WZ71, Q91XV7, Q96Q04

Diamond homologs: A6NIN4, D2H788, D3ZBM4, Q3UIW8, Q6INB3, Q8C432, Q8N6D2, Q9DCB3, A0A7I2V3R4, O70277, O75382, Q13049, Q3T0Y9, Q6IMG5, Q8CH72, Q8K0W3, Q9FY48, Q9H0X6, Q9NXI6, Q9R1R2, A4IF63, D2GXS7, D3ZQG6, E1BD59, F7H9X2, M0QZC1, P0DH78, Q80VI1, Q8QZS5, Q9C040, Q9D7D1, Q9ESN6, Q9D241

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1204 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7916121:G:C	F25L	0.980
17:7916121:G:T	F25L	0.980
17:7916123:A:G	F25L	0.980
17:7915959:G:C	F79L	0.972
17:7915959:G:T	F79L	0.972
17:7915961:A:G	F79L	0.972
17:7916053:C:T	C48Y	0.965
17:7916134:C:G	C21S	0.963
17:7916135:A:T	C21S	0.963
17:7916052:G:C	C48W	0.961
17:7916099:G:T	R33S	0.961
17:7916134:C:T	C21Y	0.957
17:7916054:A:G	C48R	0.955
17:7915967:A:G	C77R	0.954
17:7916053:C:G	C48S	0.954
17:7916054:A:T	C48S	0.954
17:7916143:C:G	C18S	0.954
17:7916144:A:T	C18S	0.954
17:7916101:G:T	P32H	0.953
17:7916135:A:G	C21R	0.952
17:7916143:C:T	C18Y	0.952
17:7916061:G:C	H45Q	0.950
17:7916061:G:T	H45Q	0.950
17:7916133:G:C	C21W	0.948
17:7916144:A:G	C18R	0.939
17:7916122:A:G	F25S	0.935
17:7916134:C:A	C21F	0.935
17:7916143:C:A	C18F	0.934
17:7915957:C:T	C80Y	0.933
17:7915957:C:G	C80S	0.929

dbSNP variants (sampled 300 via entrez): RS1000513172 (17:7914668 A>C,G), RS1000570247 (17:7915123 G>T), RS1001115353 (17:7914246 T>A), RS1001125222 (17:7914490 T>C), RS1001518340 (17:7913296 C>T), RS1001748186 (17:7917219 G>A,C,T), RS1001802031 (17:7917551 C>T), RS1002136129 (17:7916217 G>T), RS1003181819 (17:7914471 T>TGGGAGGCGGAGGCTGCA), RS1003828165 (17:7916330 G>A), RS1004967857 (17:7913965 G>C), RS1005587607 (17:7916798 C>G,T), RS1005714059 (17:7913878 T>A,C,G), RS1005872647 (17:7914921 C>A,G,T), RS1005881409 (17:7913848 T>C)

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, increases expression	3
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
licochalcone B	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Niclosamide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tunicamycin	increases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1
Magnetite Nanoparticles	decreases methylation	1

Clinical trials (associated diseases)

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