RFPL4A

Summary

RFPL4A (ret finger protein like 4A, HGNC:16449) is a protein-coding gene on chromosome 19q13.42, encoding Ret finger protein-like 4A (A6NLU0). It is a selective cancer dependency (DepMap: 20.0% of cell lines).

Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response and regulation of gene expression. Predicted to be located in female germ cell nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 342931 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• Cancer dependency (DepMap): dependent in 20.0% of screened cell lines
• MANE Select transcript: NM_001145014

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16449
Approved symbol	RFPL4A
Name	ret finger protein like 4A
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	RNF210
Ensembl gene	ENSG00000223638
Ensembl biotype	protein_coding
OMIM	612601
Entrez	342931

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000434937, ENST00000897443

RefSeq mRNA: 1 — MANE Select: NM_001145014 NM_001145014

CCDS: CCDS46201

Canonical transcript exons

ENST00000434937 — 3 exons

Exon	Start	End
ENSE00002213747	55759097	55759175
ENSE00002452029	55761792	55762086
ENSE00002522858	55762598	55763421

Expression profiles

Bgee: expression breadth broad, 47 present calls, max score 90.87.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.87	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.19	gold quality
right lobe of liver	UBERON:0001114	65.59	gold quality
granulocyte	CL:0000094	63.55	gold quality
liver	UBERON:0002107	58.24	gold quality
vermiform appendix	UBERON:0001154	48.93	gold quality
monocyte	CL:0000576	45.64	gold quality
leukocyte	CL:0000738	45.51	gold quality
testis	UBERON:0000473	44.15	gold quality
lymph node	UBERON:0000029	44.03	gold quality
right testis	UBERON:0004534	43.71	gold quality
left testis	UBERON:0004533	42.65	gold quality
smooth muscle tissue	UBERON:0001135	41.67	gold quality
islet of Langerhans	UBERON:0000006	41.09	gold quality
cortex of kidney	UBERON:0001225	40.55	gold quality
gall bladder	UBERON:0002110	40.12	gold quality
rectum	UBERON:0001052	38.94	silver quality
bone marrow cell	CL:0002092	38.47	gold quality
body of stomach	UBERON:0001161	38.28	gold quality
pancreas	UBERON:0001264	38.18	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
bone marrow	UBERON:0002371	36.90	gold quality
stomach	UBERON:0000945	36.58	gold quality
body of pancreas	UBERON:0001150	36.52	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
small intestine	UBERON:0002108	36.06	gold quality
metanephros cortex	UBERON:0010533	35.93	silver quality
transverse colon	UBERON:0001157	35.76	silver quality
small intestine Peyer’s patch	UBERON:0003454	35.76	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	964.09
E-ANND-3	no	1.63

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• The ret finger protein-like 4 gene, Rfpl4, encodes a putative E3 ubiquitin-protein ligase expressed in adult germ cells. (PMID:11850190)
• These results indicate that RFPL4A is a novel factor that increases the G1 population and decreases sensitivity to chemotherapy and thus may be a promising therapeutic target for refractory tumor conditions. (PMID:25605732)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rfpl4	ENSMUSG00000035191

Paralogs (12): CD86 (ENSG00000114013), CD274 (ENSG00000120217), CD80 (ENSG00000121594), RFPL1 (ENSG00000128250), RFPL2 (ENSG00000128253), RFPL3 (ENSG00000128276), SPRYD4 (ENSG00000176422), RNF152 (ENSG00000176641), RNF135 (ENSG00000181481), PDCD1LG2 (ENSG00000197646), RFPL4AL1 (ENSG00000229292), RFPL4B (ENSG00000251258)

Protein

Protein identifiers

Ret finger protein-like 4A — A6NLU0 (reviewed: A6NLU0)

Alternative names: RING finger protein 210

All UniProt accessions (1): A6NLU0

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with PSMB1, UBE2A and CCNB1.

Subcellular location. Cytoplasm. Nucleus.

RefSeq proteins (1): NP_001138486* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR001870	B30.2/SPRY	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR022723	RDM_domain_RFPL	Domain
IPR037960	SPRY/PRY_RFPL	Domain
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF11002, PF13765, PF15227

UniProt features (25 total): strand 16, turn 5, chain 1, domain 1, zinc finger region 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2FBE	X-RAY DIFFRACTION	2.52

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NLU0-F1	91.55	0.79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 9 (showing top): GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERSPECIES_INTERACTION_BETWEEN_ORGANISMS, GSE12507_PDC_CELL_LINE_VS_IMMATUE_T_CELL_LINE_DN, HE_LIM_SUN_FETAL_LUNG_C2_DC1_CELL, chr19q13

GO Biological Process (2): regulation of gene expression (GO:0010468), innate immune response (GO:0045087)

GO Molecular Function (4): zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
gene expression	1
regulation of macromolecule biosynthetic process	1
immune response	1
defense response to symbiont	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFPL4A	GDF9	O60383	884
RFPL4A	OOSP1	A8MZH6	526
RFPL4A	NOBOX	O60393	448
RFPL4A	H1-8	Q8IZA3	406
RFPL4A	OR10C1	Q96KK4	397
RFPL4A	ZSCAN5B	A6NJL1	393
RFPL4A	RNF113B	Q8IZP6	376
RFPL4A	OR52K1	Q8NGK4	374
RFPL4A	ZSCAN5A	Q9BUG6	371
RFPL4A	TRIM74	Q86UV6	370
RFPL4A	TRIM61	Q5EBN2	370
RFPL4A	TRIM73	Q86UV7	357
RFPL4A	TMED8	Q6PL24	348
RFPL4A	ARHGAP40	Q5TG30	348
RFPL4A	BMP15	O95972	336

IntAct

19 interactions, top by confidence:

A	B	Type	Score
RFPL4B	RFPL4A	psi-mi:“MI:0914”(association)	0.640
RFPL4A	KCNRG	psi-mi:“MI:0915”(physical association)	0.560
FAM90A1	RFPL4A	psi-mi:“MI:0914”(association)	0.530
RFPL4B	KRBA1	psi-mi:“MI:0914”(association)	0.350
RFPL4B	POTEF	psi-mi:“MI:0914”(association)	0.350
ACD	RFPL4A	psi-mi:“MI:0914”(association)	0.350
ARHGEF35	RFPL4A	psi-mi:“MI:0914”(association)	0.350
DCAF8	RFPL4A	psi-mi:“MI:0914”(association)	0.350
FOXN3	RFPL4A	psi-mi:“MI:0914”(association)	0.350
GCLM	RFPL4A	psi-mi:“MI:0914”(association)	0.350
HAUS7	RFPL4A	psi-mi:“MI:0914”(association)	0.350
MBLAC2	RFPL4A	psi-mi:“MI:0914”(association)	0.350
RDX	RFPL4A	psi-mi:“MI:0914”(association)	0.350
TCEAL1		psi-mi:“MI:0914”(association)	0.350

BioGRID (9): RFPL4A (Affinity Capture-MS), RFPL4A (Affinity Capture-MS), RFPL4A (Affinity Capture-MS), RFPL4A (Affinity Capture-MS), RFPL4A (Two-hybrid), RFPL4A (Affinity Capture-MS), RFPL4A (Affinity Capture-MS), RFPL4A (Reconstituted Complex), RFPL4A (Co-crystal Structure)

ESM2 similar proteins: A6NK02, A6NLU0, D4ABM4, F8VTS6, O00635, O19085, O77666, P14373, P15533, P62603, P86448, P86449, Q12899, Q2T9Z0, Q3UWZ0, Q495X7, Q58DK8, Q5BK82, Q5D7H7, Q5D7I6, Q5E9G4, Q5RBG2, Q5SZ99, Q5TM55, Q62158, Q62191, Q640S6, Q6AZZ1, Q6PGR9, Q7TPM3, Q7YR32, Q7YR33, Q7YR34, Q7YRV4, Q80X56, Q86WT6, Q8BVP1, Q8K243, Q8N7C3, Q8N9V2

Diamond homologs: A0A0E4BZH1, A0JN74, A4QPC6, A6NGJ6, A6NI03, A6NK02, A6NLU0, A7TZE6, A7TZF0, A7TZF3, A7XUX6, A7XUY5, A7XUZ6, A7XV04, A7XV07, A8MVZ5, B1H278, D4ABM4, F8S122, F8VTS6, O00478, O00481, O00635, O15553, O70355, O75677, O75678, O75679, P14373, P18892, P19474, P55803, P78410, Q02084, Q13410, Q1XHU0, Q27J48, Q2T9Z0, Q3UWZ0, Q495X7

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RFPL4A	ubiquitination
RFPL4A	“down-regulates quantity by destabilization”	CCNB1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

259 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55761787:TATA:T	acceptor_loss	1.0000
19:55761788:A:AG	acceptor_gain	1.0000
19:55761789:T:G	acceptor_gain	1.0000
19:55761790:A:AG	acceptor_gain	1.0000
19:55761790:AGA:A	acceptor_loss	1.0000
19:55761791:G:GA	acceptor_gain	1.0000
19:55761791:GA:G	acceptor_gain	1.0000
19:55761791:GAC:G	acceptor_gain	1.0000
19:55761791:GACA:G	acceptor_gain	1.0000
19:55761791:GACAT:G	acceptor_gain	1.0000
19:55762076:G:GT	donor_gain	1.0000
19:55762083:CAAGG:C	donor_loss	1.0000
19:55762084:AAGG:A	donor_loss	1.0000
19:55762085:AGGTA:A	donor_loss	1.0000
19:55762086:GGTA:G	donor_loss	1.0000
19:55762087:G:GG	donor_gain	1.0000
19:55762087:GTA:G	donor_loss	1.0000
19:55762088:T:G	donor_loss	1.0000
19:55762594:A:AG	acceptor_gain	1.0000
19:55762594:ACAGT:A	acceptor_gain	1.0000
19:55762595:C:G	acceptor_gain	1.0000
19:55762596:A:AG	acceptor_gain	1.0000
19:55762596:AGT:A	acceptor_gain	1.0000
19:55762596:AGTG:A	acceptor_gain	1.0000
19:55762597:G:GA	acceptor_gain	1.0000
19:55762597:GT:G	acceptor_gain	1.0000
19:55762597:GTG:G	acceptor_gain	1.0000
19:55762597:GTGG:G	acceptor_gain	1.0000
19:55759172:AGAGG:A	donor_loss	0.9900
19:55759173:GAG:G	donor_gain	0.9900

AlphaMissense

1904 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:55762768:T:A	W153R	0.985
19:55762768:T:C	W153R	0.985
19:55762711:T:C	F134L	0.984
19:55762713:C:A	F134L	0.984
19:55762713:C:G	F134L	0.984
19:55762798:T:A	W163R	0.982
19:55762798:T:C	W163R	0.982
19:55762867:T:C	F186L	0.982
19:55762869:C:A	F186L	0.982
19:55762869:C:G	F186L	0.982
19:55762996:T:C	F229L	0.981
19:55762998:T:A	F229L	0.981
19:55762998:T:G	F229L	0.981
19:55762770:G:C	W153C	0.979
19:55762770:G:T	W153C	0.979
19:55762080:T:C	F94L	0.975
19:55762082:T:A	F94L	0.975
19:55762082:T:G	F94L	0.975
19:55762815:C:G	C168W	0.970
19:55762868:T:C	F186S	0.970
19:55762808:G:A	G166D	0.965
19:55762814:G:A	C168Y	0.965
19:55762807:G:C	G166R	0.963
19:55762730:T:A	V140D	0.958
19:55762800:G:C	W163C	0.958
19:55762800:G:T	W163C	0.958
19:55762813:T:C	C168R	0.958
19:55762735:G:C	G142R	0.955
19:55763032:T:C	F241L	0.953
19:55763034:C:A	F241L	0.953

dbSNP variants (sampled 300 via entrez): RS1000767045 (19:55761898 A>G), RS1000913246 (19:55756306 T>C), RS1001261630 (19:55762212 C>A,G), RS1001592790 (19:55758351 T>C), RS1001625332 (19:55757673 C>G,T), RS1004053153 (19:55756893 C>A,T), RS1004940480 (19:55761363 T>A), RS1005132839 (19:55755891 A>G), RS1005377636 (19:55760912 G>A), RS1005724727 (19:55757585 G>A), RS1006680293 (19:55755646 G>T), RS1008217264 (19:55756336 C>T), RS1009106190 (19:55760627 T>A,G), RS1010028197 (19:55757301 C>G,T), RS1010562611 (19:55760127 C>T)

Disease associations

OMIM: gene MIM:612601 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001850_4	Major depressive disorder	3.000000e-06
GCST001850_49	Major depressive disorder	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	affects reaction, increases expression	1
methyleugenol	increases expression	1
propionaldehyde	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
zinc chromate	increases abundance, increases expression	1
gallium arsenide	increases expression	1
pentanal	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
Aldehydes	increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Silver	increases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Thapsigargin	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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