RNF224

Summary

RNF224 (ring finger protein 224, HGNC:41912) is a protein-coding gene on chromosome 9q34.3, encoding RING finger protein 224 (P0DH78).

Predicted to enable zinc ion binding activity.

Source: NCBI Gene 643596 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 51 total — 1 pathogenic
• MANE Select transcript: NM_001190228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:41912
Approved symbol	RNF224
Name	ring finger protein 224
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000233198
Ensembl biotype	protein_coding
Entrez	643596

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000445101, ENST00000886780

RefSeq mRNA: 1 — MANE Select: NM_001190228 NM_001190228

CCDS: CCDS55356

Canonical transcript exons

ENST00000445101 — 3 exons

Exon	Start	End
ENSE00001766922	137228622	137229640
ENSE00002219094	137227502	137227861
ENSE00002285347	137228152	137228341

Expression profiles

Bgee: expression breadth ubiquitous, 117 present calls, max score 81.00.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	81.00	gold quality
pituitary gland	UBERON:0000007	77.36	gold quality
adenohypophysis	UBERON:0002196	75.04	gold quality
lower esophagus mucosa	UBERON:0035834	73.31	gold quality
esophagus mucosa	UBERON:0002469	70.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.80	gold quality
metanephros cortex	UBERON:0010533	62.60	gold quality
esophagus	UBERON:0001043	62.54	gold quality
cortex of kidney	UBERON:0001225	62.36	gold quality
saliva-secreting gland	UBERON:0001044	59.86	gold quality
adult mammalian kidney	UBERON:0000082	59.85	gold quality
right frontal lobe	UBERON:0002810	59.52	gold quality
minor salivary gland	UBERON:0001830	59.43	gold quality
mucosa of stomach	UBERON:0001199	58.78	gold quality
kidney	UBERON:0002113	58.62	gold quality
fallopian tube	UBERON:0003889	58.55	gold quality
left lobe of thyroid gland	UBERON:0001120	58.53	gold quality
body of stomach	UBERON:0001161	58.22	gold quality
thyroid gland	UBERON:0002046	58.08	gold quality
prostate gland	UBERON:0002367	57.79	gold quality
right lung	UBERON:0002167	57.41	gold quality
right lobe of thyroid gland	UBERON:0001119	57.06	gold quality
vagina	UBERON:0000996	56.57	gold quality
upper lobe of left lung	UBERON:0008952	56.13	gold quality
right atrium auricular region	UBERON:0006631	56.12	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	55.92	gold quality
fundus of stomach	UBERON:0001160	55.74	gold quality
caudate nucleus	UBERON:0001873	55.65	gold quality
body of pancreas	UBERON:0001150	55.47	gold quality
stomach	UBERON:0000945	55.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting RNF224, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-10524-5P	99.05	66.08	963
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-4490	98.51	68.47	943
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-134-3P	96.83	66.22	1001
HSA-MIR-7108-5P	96.42	66.17	598
HSA-MIR-1238-5P	94.82	67.52	493
HSA-MIR-4758-5P	94.82	67.06	499

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	rnf224	ENSDARG00000095415
mus_musculus	Rnf224	ENSMUSG00000089953
rattus_norvegicus	Rnf224	ENSRNOG00000072192
drosophila_melanogaster	roq	FBGN0036621

Paralogs (5): RC3H2 (ENSG00000056586), RC3H1 (ENSG00000135870), RNF227 (ENSG00000179859), RNF182 (ENSG00000180537), RNF228 (ENSG00000288658)

Protein

Protein identifiers

RING finger protein 224 — P0DH78 (reviewed: P0DH78)

All UniProt accessions (1): P0DH78

RefSeq proteins (1): NP_001177157* (*=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
IPR053122	RING_finger_domain	Family

Pfam: PF13445

UniProt features (2 total): chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DH78-F1	78.07	0.48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 12 (showing top): MIKKELSEN_MEF_LCP_WITH_H3K27ME3, chr9q34, GREB1_TARGET_GENES, ZNF274_TARGET_GENES, ZNF8_TARGET_GENES, AHRR_TARGET_GENES, DESCARTES_MAIN_FETAL_ERYTHROBLASTS, DESCARTES_FETAL_ADRENAL_ERYTHROBLASTS, DESCARTES_FETAL_INTESTINE_ERYTHROBLASTS, DESCARTES_FETAL_KIDNEY_ERYTHROBLASTS, DESCARTES_FETAL_PANCREAS_ERYTHROBLASTS, DESCARTES_FETAL_STOMACH_ERYTHROBLASTS

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion binding	1
cation binding	1

Protein interactions and networks

STRING

6 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RNF224	UBE2D2	P51669	0
RNF224	CYSRT1	A8MQ03	0
RNF224	SLC34A3	Q8N130	0

IntAct

0 interactions, top by confidence:

BioGRID (1): RNF224 (Reconstituted Complex)

ESM2 similar proteins: A1L515, A2A9Q0, D3YZZ2, D4A2Q0, E1BDF2, E7ERA6, F2Z333, H3BV60, O43508, O46547, O54907, P0C6B2, P0DH78, P41155, P51172, P70225, Q01113, Q13477, Q14626, Q29RT8, Q5RF19, Q5SZI1, Q5T7M4, Q5U4P2, Q63148, Q64385, Q6AZ51, Q6BAA4, Q6UWL6, Q6UXT9, Q6ZMC9, Q86UR1, Q86YD3, Q8BH06, Q8N1F8, Q8NFR9, Q96G42, Q99640, Q99M75, Q99MF4

Diamond homologs: A0A7I2V3R4, D2H788, D3ZBM4, O70277, O75382, P0DH78, Q3SWY0, Q3UIW8, Q58EC8, Q68EV7, Q6INB3, Q8C432, Q8N6D2, Q8QZS5, Q96D59, Q9BRZ2, Q9R1R2, A6NCQ9, E7ERA6, M0QZC1, Q13049, Q3UV31, Q8CEF8, Q8CH72, Q9D7D1, E1BD59, Q80VI1, Q9DCB3, A4IF63, A6NIN4, D2GXS7, D3ZQG6, F7H9X2, Q9C040, Q9ESN6, Q5ZMD4, Q810I1, Q810I2, Q8BFW4, Q5M929

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RNF224	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	49
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
830975	NC_000009.12:g.(?137139467)(137834973_?)del	Pathogenic

SpliceAI

593 predictions. Top by Δscore:

Variant	Effect	Δscore
9:137228222:T:TA	acceptor_gain	0.9800
9:137227412:GGG:G	donor_gain	0.9700
9:137227413:GGG:G	donor_gain	0.9700
9:137228617:GGCA:G	acceptor_loss	0.9700
9:137228618:GCA:G	acceptor_loss	0.9700
9:137228619:CAG:C	acceptor_loss	0.9700
9:137228620:A:AC	acceptor_loss	0.9700
9:137228620:AG:A	acceptor_gain	0.9700
9:137228621:GG:G	acceptor_gain	0.9700
9:137227519:AGTCT:A	acceptor_gain	0.9600
9:137227520:GTCTG:G	acceptor_gain	0.9600
9:137227736:TCAAG:T	donor_loss	0.9600
9:137227737:CAAG:C	donor_loss	0.9600
9:137227738:AAG:A	donor_loss	0.9600
9:137227739:AG:A	donor_loss	0.9600
9:137227740:GGT:G	donor_loss	0.9600
9:137227742:T:G	donor_loss	0.9600
9:137228235:A:G	acceptor_gain	0.9600
9:137228616:T:TA	acceptor_gain	0.9600
9:137228621:GGAT:G	acceptor_gain	0.9600
9:137227519:A:AG	acceptor_gain	0.9500
9:137227520:G:GG	acceptor_gain	0.9500
9:137227878:G:GG	donor_gain	0.9500
9:137228234:A:AG	acceptor_gain	0.9500
9:137227811:G:GT	donor_gain	0.9400
9:137227863:C:T	donor_gain	0.9400
9:137227898:G:T	donor_gain	0.9400
9:137228617:G:A	acceptor_gain	0.9400
9:137228620:A:AG	acceptor_gain	0.9400
9:137228621:G:GG	acceptor_gain	0.9400

AlphaMissense

981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:137228728:C:A	P38H	0.988
9:137228750:C:A	H45Q	0.985
9:137228750:C:G	H45Q	0.985
9:137228814:T:C	C67R	0.985
9:137228754:T:C	F47L	0.984
9:137228756:C:A	F47L	0.984
9:137228756:C:G	F47L	0.984
9:137228727:C:A	P38T	0.983
9:137228727:C:T	P38S	0.982
9:137228743:G:A	C43Y	0.982
9:137228886:T:C	F91L	0.982
9:137228888:C:A	F91L	0.982
9:137228888:C:G	F91L	0.982
9:137228730:C:A	R39S	0.981
9:137228887:T:C	F91S	0.981
9:137228823:T:A	C70S	0.979
9:137228824:G:C	C70S	0.979
9:137228823:T:C	C70R	0.978
9:137228757:T:C	C48R	0.977
9:137228814:T:A	C67S	0.977
9:137228815:G:C	C67S	0.977
9:137228742:T:A	C43S	0.975
9:137228743:G:C	C43S	0.975
9:137228767:G:A	C51Y	0.975
9:137228755:T:C	F47S	0.974
9:137228809:T:C	I65T	0.973
9:137228749:A:T	H45L	0.972
9:137228757:T:A	C48S	0.971
9:137228758:G:C	C48S	0.971
9:137228816:T:G	C67W	0.971

dbSNP variants (sampled 300 via entrez): RS1000973210 (9:137227844 A>G), RS1001318627 (9:137228131 G>A,C), RS1001645598 (9:137226022 G>A,T), RS1001752150 (9:137229795 C>A,T), RS1002605376 (9:137226829 G>A,C), RS1002657731 (9:137226957 G>A), RS1003424591 (9:137228881 C>T), RS1004147869 (9:137229316 A>G,T), RS1004573437 (9:137228650 TCGGAGGAGGGGGGCCCC>T), RS1005072533 (9:137229942 G>A,C), RS1005557803 (9:137230134 G>A), RS1005573864 (9:137226701 T>C), RS1005625448 (9:137229542 C>T), RS1005746887 (9:137228379 G>A), RS1006008549 (9:137228858 G>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:610253

GenCC curated gene-disease

Mondo (1): Kleefstra syndrome 1 (MONDO:0027407)

Orphanet (1): Kleefstra syndrome (Orphanet:261494)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563043	Kleefstra Syndrome (supp.)

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
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
Estradiol	decreases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Zearalenone	decreases expression	1

Clinical trials (associated diseases)

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