RFPL4B

Summary

RFPL4B (ret finger protein like 4B, HGNC:33264) is a protein-coding gene on chromosome 6q21, encoding Ret finger protein-like 4B (Q6ZWI9).

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

Source: NCBI Gene 442247 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_001013734

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33264
Approved symbol	RFPL4B
Name	ret finger protein like 4B
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	RNF211
Ensembl gene	ENSG00000251258
Ensembl biotype	protein_coding
Entrez	442247

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000441065, ENST00000962225

RefSeq mRNA: 1 — MANE Select: NM_001013734 NM_001013734

CCDS: CCDS34515

Canonical transcript exons

ENST00000441065 — 3 exons

Exon	Start	End
ENSE00002289141	112347330	112347407
ENSE00002304888	112349604	112351294
ENSE00003577974	112349193	112349321

Expression profiles

Bgee: expression breadth broad, 21 present calls, max score 88.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2470 / max 127.1286, expressed in 68 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69328	0.2470	68

Top tissues by expression

122 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	88.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.80	gold quality
placenta	UBERON:0001987	54.97	gold quality
testis	UBERON:0000473	53.96	gold quality
right testis	UBERON:0004534	53.11	gold quality
left testis	UBERON:0004533	52.40	gold quality
colonic epithelium	UBERON:0000397	41.39	gold quality
ventricular zone	UBERON:0003053	40.14	gold quality
ganglionic eminence	UBERON:0004023	37.56	silver quality
cortical plate	UBERON:0005343	36.47	gold quality
smooth muscle tissue	UBERON:0001135	36.46	silver quality
bone marrow cell	CL:0002092	36.16	gold quality
cortex of kidney	UBERON:0001225	35.69	silver quality
metanephros cortex	UBERON:0010533	35.01	gold quality
kidney	UBERON:0002113	34.87	gold quality
gall bladder	UBERON:0002110	34.85	silver quality
adult mammalian kidney	UBERON:0000082	33.63	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
calcaneal tendon	UBERON:0003701	32.89	gold quality
vermiform appendix	UBERON:0001154	32.68	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
prefrontal cortex	UBERON:0000451	31.01	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
islet of Langerhans	UBERON:0000006	29.88	gold quality
superior frontal gyrus	UBERON:0002661	29.88	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.83	gold quality
thoracic aorta	UBERON:0001515	29.41	silver quality
endometrium	UBERON:0001295	29.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting RFPL4B, 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-5193	100.00	67.26	1744
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-3152-3P	99.10	66.35	678

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rfpl4b	ENSMUSG00000094311
rattus_norvegicus	AABR07045341.1	ENSRNOG00000058648

Paralogs (12): CD86 (ENSG00000114013), CD274 (ENSG00000120217), CD80 (ENSG00000121594), RFPL1 (ENSG00000128250), RFPL2 (ENSG00000128253), RFPL3 (ENSG00000128276), SPRYD4 (ENSG00000176422), RNF152 (ENSG00000176641), RNF135 (ENSG00000181481), PDCD1LG2 (ENSG00000197646), RFPL4A (ENSG00000223638), RFPL4AL1 (ENSG00000229292)

Protein

Protein identifiers

Ret finger protein-like 4B — Q6ZWI9 (reviewed: Q6ZWI9)

Alternative names: RING finger protein 211

All UniProt accessions (1): Q6ZWI9

RefSeq proteins (1): NP_001013756* (*=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
IPR017907	Znf_RING_CS	Conserved_site
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF13765, PF15227

UniProt features (5 total): chain 1, domain 1, zinc finger region 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZWI9-F1	83.42	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, MIR570_3P, MIR1283, MIR101_3P, MIR4699_3P, MIR6817_3P, MIR146A_3P, MIR6830_3P, MIR5193, MIR6818_3P, MIR3152_3P

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 (1): 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 anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

378 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFPL4B	KHDC1L	Q5JSQ8	544
RFPL4B	PRAMEF25	A6NGN4	520
RFPL4B	A0A096LNW4	A0A096LNW4	506
RFPL4B	KHDC1	Q4VXA5	479
RFPL4B	PRAMEF15	P0DUQ1	479
RFPL4B	ZSCAN4	Q8NAM6	473
RFPL4B	CLPSL1	A2RUU4	449
RFPL4B	PRAMEF1	O95521	448
RFPL4B	MBD3L2	Q8NHZ7	447
RFPL4B	MBD3L3	A6NE82	446
RFPL4B	GOLGA6B	A6NDN3	439
RFPL4B	MBD3L5	A6NJ08	415
RFPL4B	DUX4L2	P0CJ85	400
RFPL4B	PRAMEF2	O60811	397
RFPL4B	CT45A10	P0DMU9	392

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RFPL4B	RFPL4A	psi-mi:“MI:0914”(association)	0.640
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

BioGRID (107): YEATS2 (Affinity Capture-MS), SALL2 (Affinity Capture-MS), SALL1 (Affinity Capture-MS), ZKSCAN1 (Affinity Capture-MS), ZNF324 (Affinity Capture-MS), ZZZ3 (Affinity Capture-MS), ZNF784 (Affinity Capture-MS), TAB1 (Affinity Capture-MS), CSRP2BP (Affinity Capture-MS), MIOS (Affinity Capture-MS), ZMYM6 (Affinity Capture-MS), RFPL4A (Affinity Capture-MS), POLR2J (Affinity Capture-MS), PER1 (Affinity Capture-MS), LRIF1 (Affinity Capture-MS)

ESM2 similar proteins: A6NK02, A6NLU0, D4ABM4, F8RKW2, F8VTS6, O75677, O75678, O75679, P15533, P62603, Q2T9Z0, Q3UWZ0, Q495X7, Q5BK82, Q5E9G4, Q5RBG2, Q5RKG6, Q5SZ99, Q62191, Q640S6, Q6AZZ1, Q6PGR9, Q6UX41, Q6UXE8, Q6ZWI9, Q7TPM3, Q7YR32, Q80X56, Q810I1, Q810I2, Q865W2, Q86WT6, Q86XT4, Q8BVP1, Q8C006, Q8K243, Q8N7C3, Q8N9V2, Q8R0K2, Q8VH31

Diamond homologs: A0A3B3IT33, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, B0BLU1, C9J1S8, I1YAP6, O00478, O00481, O15344, O75677, O75678, O75679, O76064, P0CI25, P0CI26, P18892, P19474, P62603, P86448, P86449, Q13410, Q2HJ46, Q3C1V9, Q3TL54, Q4KLN8, Q5EBN2, Q5PQN2, Q5R4I2, Q5R996, Q61510, Q62556, Q6INS5, Q6MFY8, Q6UX41, Q6UXE8, Q6ZWI9, Q7T308

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	RFPL4B	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

308 predictions. Top by Δscore:

Variant	Effect	Δscore
6:112347404:CAAGG:C	donor_loss	1.0000
6:112347406:AG:A	donor_gain	1.0000
6:112347407:GG:G	donor_gain	1.0000
6:112347407:GGT:G	donor_loss	1.0000
6:112347408:G:GA	donor_loss	1.0000
6:112347408:G:GG	donor_gain	1.0000
6:112349183:T:A	acceptor_gain	1.0000
6:112349191:A:AG	acceptor_gain	1.0000
6:112349191:AGAG:A	acceptor_gain	1.0000
6:112349192:G:GG	acceptor_gain	1.0000
6:112349192:GA:G	acceptor_gain	1.0000
6:112349192:GAGG:G	acceptor_gain	1.0000
6:112349318:CTAGG:C	donor_loss	1.0000
6:112349321:GGT:G	donor_loss	1.0000
6:112349322:G:GC	donor_loss	1.0000
6:112349323:T:A	donor_loss	1.0000
6:112347403:TCAAG:T	donor_gain	0.9900
6:112347405:AAGGT:A	donor_loss	0.9900
6:112349186:A:AG	acceptor_gain	0.9900
6:112349187:C:G	acceptor_gain	0.9900
6:112349188:T:A	acceptor_gain	0.9900
6:112349189:GCAG:G	acceptor_loss	0.9900
6:112349190:CA:C	acceptor_loss	0.9900
6:112349191:A:C	acceptor_loss	0.9900
6:112349192:G:GA	acceptor_loss	0.9900
6:112349192:GAGGA:G	acceptor_gain	0.9900
6:112349306:G:GT	donor_gain	0.9900
6:112349322:G:GG	donor_gain	0.9900
6:112349590:A:AG	acceptor_gain	0.9900
6:112349601:TAG:T	acceptor_loss	0.9900

AlphaMissense

1748 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:112350366:T:C	F220L	0.957
6:112350368:T:A	F220L	0.957
6:112350368:T:G	F220L	0.957
6:112350246:T:C	F180L	0.917
6:112350248:C:A	F180L	0.917
6:112350248:C:G	F180L	0.917
6:112349796:T:C	F30L	0.912
6:112349798:C:A	F30L	0.912
6:112349798:C:G	F30L	0.912
6:112350152:G:C	W148C	0.905
6:112350152:G:T	W148C	0.905
6:112350129:T:C	F141L	0.899
6:112350131:C:A	F141L	0.899
6:112350131:C:G	F141L	0.899
6:112350369:T:C	F221L	0.890
6:112350371:T:A	F221L	0.890
6:112350371:T:G	F221L	0.890
6:112350150:T:A	W148R	0.889
6:112350150:T:C	W148R	0.889
6:112350438:T:C	F244L	0.885
6:112350440:C:A	F244L	0.885
6:112350440:C:G	F244L	0.885
6:112350180:T:A	W158R	0.884
6:112350180:T:C	W158R	0.884
6:112350336:T:C	F210L	0.884
6:112350338:C:A	F210L	0.884
6:112350338:C:G	F210L	0.884
6:112350334:T:C	I209T	0.862
6:112350367:T:C	F220S	0.842
6:112350253:T:C	I182T	0.814

dbSNP variants (sampled 300 via entrez): RS1000052819 (6:112349101 C>G), RS1001982859 (6:112351415 A>G), RS1002551619 (6:112346438 A>C), RS1002581104 (6:112347184 T>C), RS1002612069 (6:112347345 C>A,G,T), RS1003564796 (6:112347512 A>T), RS1004919165 (6:112348494 C>T), RS1004952002 (6:112348829 T>G), RS1005786440 (6:112345699 T>C), RS1006171182 (6:112345532 T>G), RS1007739254 (6:112347292 G>A), RS1009140480 (6:112348393 T>C), RS1009166941 (6:112348700 C>A,G,T), RS1009519942 (6:112348054 A>T), RS1010190175 (6:112350726 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

3 associations (top):

Study	Trait	p-value
GCST005170_52	Intraocular pressure	1.000000e-08
GCST011517_3	joint destruction in rheumatoid arthritis (rapid vs slow)	1.000000e-06
GCST90000654_40	Central corneal thickness	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0005413	joint damage measurement
EFO:0005213	central corneal thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9384825	Metabolism/PK	3	o-desmethyltramadol;tramadol

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9384825	RFPL4B	3	1.50	1	o-desmethyltramadol;tramadol

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
abrine	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1

Clinical trials (associated diseases)

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