RFPL3

Summary

RFPL3 (ret finger protein like 3, HGNC:9980) is a protein-coding gene on chromosome 22q12.3, encoding Ret finger protein-like 3 (O75679). (Microbial infection) Stimulates the activity of Human Immunodeficiency Virus 1/HIV-1 pre-integration complex.

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 nucleus. Predicted to be active in cytoplasm.

Source: NCBI Gene 10738 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_001098535

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9980
Approved symbol	RFPL3
Name	ret finger protein like 3
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	RNF120
Ensembl gene	ENSG00000128276
Ensembl biotype	protein_coding
OMIM	605970
Entrez	10738

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000249007, ENST00000397468

RefSeq mRNA: 2 — MANE Select: NM_001098535 NM_001098535, NM_006604

CCDS: CCDS13904, CCDS43011

Canonical transcript exons

ENST00000249007 — 2 exons

Exon	Start	End
ENSE00000879968	32360252	32361161
ENSE00001750025	32357867	32358444

Expression profiles

Bgee: expression breadth broad, 78 present calls, max score 87.87.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.87	gold quality
buccal mucosa cell	CL:0002336	86.98	silver quality
pancreatic ductal cell	CL:0002079	80.02	gold quality
sperm	CL:0000019	72.57	silver quality
male germ cell	CL:0000015	70.78	silver quality
ileal mucosa	UBERON:0000331	68.86	gold quality
CA1 field of hippocampus	UBERON:0003881	68.65	gold quality
diaphragm	UBERON:0001103	68.48	gold quality
tibialis anterior	UBERON:0001385	67.56	gold quality
middle temporal gyrus	UBERON:0002771	66.75	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	65.70	gold quality
postcentral gyrus	UBERON:0002581	65.63	silver quality
hair follicle	UBERON:0002073	65.42	gold quality
Brodmann (1909) area 23	UBERON:0013554	65.34	silver quality
periodontal ligament	UBERON:0008266	64.63	silver quality
decidua	UBERON:0002450	63.74	gold quality
parietal lobe	UBERON:0001872	63.73	silver quality
choroid plexus epithelium	UBERON:0003911	62.13	gold quality
cranial nerve II	UBERON:0000941	61.50	silver quality
pons	UBERON:0000988	60.47	silver quality
right testis	UBERON:0004534	60.34	gold quality
testis	UBERON:0000473	59.40	gold quality
left testis	UBERON:0004533	59.40	gold quality
deltoid	UBERON:0001476	59.18	silver quality
superior frontal gyrus	UBERON:0002661	59.14	silver quality
mucosa of urinary bladder	UBERON:0001259	57.79	gold quality
upper leg skin	UBERON:0004262	56.79	gold quality
lateral nuclear group of thalamus	UBERON:0002736	56.47	gold quality
epithelium of mammary gland	UBERON:0003244	56.46	gold quality
mammary duct	UBERON:0001765	56.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	55.09
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting RFPL3, 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-3646	100.00	73.56	5283
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-943	97.81	64.42	694
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-600	97.07	66.73	1259
HSA-MIR-4256	96.22	67.70	669
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-11181-5P	96.12	67.46	665
HSA-MIR-571	95.38	66.54	671

Literature-anchored findings (GeneRIF, showing 6)

• the human RFPL1,2,3 genes have a role in neocortex development (PMID:18656177)
• RFPL3 is a potential stimulator of human immunodeficiency virus, type 1 (HIV-1) preintegration complex integration. (PMID:25107902)
• These results demonstrate that RFPL3 is an important cellular factor which promotes lung cancer growth by activating hTERT expression (PMID:25481043)
• RFPL3 and CBP have roles in upregulating hTERT activity and promoting lung cancer growth (PMID:26318425)
• EGF significantly upregulated RFPL3 and hTERT protein levels in the nonsmall cell lung cancer cells. RFPL3 and hTERT proteins upregulation by EGF were attenuated by pretreatment with AG1478 and erlotinib. EGF promoted proliferation and inhibited apoptosis; PD98059 decreased RFPL3 and hTERT protein expression; and RFPL3 overexpression increased the expression of hTERT and related MEKpathway proteins (PMID:29749533)
• Importin 13 promotes NSCLC progression by mediating RFPL3 nuclear translocation and hTERT expression upregulation. (PMID:33082305)

Cross-species orthologs

0 orthologs

Paralogs (12): CD86 (ENSG00000114013), CD274 (ENSG00000120217), CD80 (ENSG00000121594), RFPL1 (ENSG00000128250), RFPL2 (ENSG00000128253), SPRYD4 (ENSG00000176422), RNF152 (ENSG00000176641), RNF135 (ENSG00000181481), PDCD1LG2 (ENSG00000197646), RFPL4A (ENSG00000223638), RFPL4AL1 (ENSG00000229292), RFPL4B (ENSG00000251258)

Protein

Protein identifiers

Ret finger protein-like 3 — O75679 (reviewed: O75679)

All UniProt accessions (1): O75679

UniProt curated annotations — full annotation on UniProt →

Function. (Microbial infection) Stimulates the activity of Human Immunodeficiency Virus 1/HIV-1 pre-integration complex.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed during neurogenesis in differentiating human embryonic stem cells and in the developing human neocortex.

Isoforms (2)

UniProt ID	Names	Canonical?
O75679-1	1	yes
O75679-2	2

RefSeq proteins (2): NP_001092005, NP_006595 (=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 (8 total): sequence variant 4, chain 1, domain 1, zinc finger region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75679-F1	85.53	0.63

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, CERIBELLI_GENES_INACTIVE_AND_BOUND_BY_NFY, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, MIR4422, MIR4496, MIR600, MIR4432, MIR571, GSE1432_CTRL_VS_IFNG_24H_MICROGLIA_UP, chr22q12, SCHERER_PBMC_YF_VAX_AGE_18_40YO_4_TO_7DY_UP

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

358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFPL3	PAX6	P26367	668
RFPL3	PRAMEF13	Q5VWM6	547
RFPL3	PRAMEF11	O60813	537
RFPL3	OR1N2	Q8NGR9	505
RFPL3	PRAMEF12	O95522	434
RFPL3	FGF2	P09038	423
RFPL3	OR5J2	Q8NH18	411
RFPL3	PRAMEF1	O95521	403
RFPL3	PRAMEF2	O60811	402
RFPL3	RNF175	Q8N4F7	377
RFPL3	ANKDD1B	A6NHY2	375
RFPL3	KHDC1L	Q5JSQ8	370
RFPL3	BPIFC	Q8NFQ6	370
RFPL3	SLC5A4	Q9NY91	366
RFPL3	TRIM48	Q8IWZ4	352

IntAct

38 interactions, top by confidence:

A	B	Type	Score
RFPL3	HSPB2	psi-mi:“MI:0915”(physical association)	0.600
UBE2I	RFPL3	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	LNX1	psi-mi:“MI:0915”(physical association)	0.560
LNX1	RFPL3	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	POF1B	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	PFDN4	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	SLAIN1	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	C3orf62	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	RGP1	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	EIF1AX	psi-mi:“MI:0915”(physical association)	0.560
RFPL3	RFPL1	psi-mi:“MI:0914”(association)	0.530
ECE1	RFPL3	psi-mi:“MI:0915”(physical association)	0.370
RFPL3	RFPL2	psi-mi:“MI:0914”(association)	0.350
RFPL3	POF1B	psi-mi:“MI:0915”(physical association)	0.000
RFPL3	PFDN4	psi-mi:“MI:0915”(physical association)	0.000
RFPL3	HSPB2	psi-mi:“MI:0915”(physical association)	0.000
SLAIN1	RFPL3	psi-mi:“MI:0915”(physical association)	0.000
RFPL3	C3orf62	psi-mi:“MI:0915”(physical association)	0.000
RFPL3	DDIT4L	psi-mi:“MI:0915”(physical association)	0.000
RGP1	RFPL3	psi-mi:“MI:0915”(physical association)	0.000
RFPL3	EIF1AX	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): RFPL3 (Two-hybrid), LNX1 (Two-hybrid), TLK2 (Affinity Capture-MS), DAB2IP (Affinity Capture-MS), ASNSD1 (Affinity Capture-MS), RFPL1 (Affinity Capture-MS), RFPL2 (Affinity Capture-MS), CREBBP (Affinity Capture-Western), RFPL1 (Affinity Capture-MS), RFPL2 (Affinity Capture-MS), ASNSD1 (Affinity Capture-MS), DAB2IP (Affinity Capture-MS), TLK2 (Affinity Capture-MS), RFPL3 (Two-hybrid), RFPL3 (Two-hybrid)

ESM2 similar proteins: A0A0E4BZH1, A4QPC6, A7TZE6, A8K4G0, A8MVZ5, O00478, O00481, O00635, O70355, O75677, O75679, P14373, P18892, P19474, P55803, P78410, Q13410, Q1XHU0, Q3ZEE5, Q58DK8, Q5BN31, Q5C8U1, Q5D7H8, Q5D7I0, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7J2, Q5R7W8, Q5R996, Q61885, Q62158, Q62191, Q62556, Q6MFZ5, Q6MG97, Q6UX41, Q6UXE8, Q6UXG8, Q7KYR7

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”	RFPL3	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

520 predictions. Top by Δscore:

Variant	Effect	Δscore
22:32358138:A:AG	acceptor_gain	1.0000
22:32358148:T:TA	acceptor_gain	1.0000
22:32358149:G:A	acceptor_gain	1.0000
22:32358152:A:AG	acceptor_gain	1.0000
22:32358152:AGTG:A	acceptor_gain	1.0000
22:32358153:G:GA	acceptor_gain	1.0000
22:32358153:GTGG:G	acceptor_gain	1.0000
22:32358441:CAAGG:C	donor_loss	1.0000
22:32358442:AAGG:A	donor_loss	1.0000
22:32358443:AGGTA:A	donor_loss	1.0000
22:32358444:GGT:G	donor_loss	1.0000
22:32358445:G:GG	donor_gain	1.0000
22:32358445:GTAA:G	donor_loss	1.0000
22:32360248:A:AG	acceptor_gain	1.0000
22:32360248:ACAGT:A	acceptor_gain	1.0000
22:32360249:C:G	acceptor_gain	1.0000
22:32360249:CAGT:C	acceptor_loss	1.0000
22:32360250:A:AG	acceptor_gain	1.0000
22:32360250:AGT:A	acceptor_gain	1.0000
22:32360250:AGTG:A	acceptor_gain	1.0000
22:32360251:G:GA	acceptor_gain	1.0000
22:32360251:GT:G	acceptor_gain	1.0000
22:32360251:GTG:G	acceptor_gain	1.0000
22:32360251:GTGG:G	acceptor_gain	1.0000
22:32360251:GTGGA:G	acceptor_gain	1.0000
22:32354987:G:GT	donor_gain	0.9900
22:32358135:T:TA	acceptor_gain	0.9900
22:32358139:C:G	acceptor_gain	0.9900
22:32358152:AGT:A	acceptor_gain	0.9900
22:32358153:GT:G	acceptor_gain	0.9900

AlphaMissense

2084 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:32358438:T:C	F123L	0.963
22:32358440:C:A	F123L	0.963
22:32358440:C:G	F123L	0.963
22:32360686:T:C	F270L	0.956
22:32360688:C:A	F270L	0.956
22:32360688:C:G	F270L	0.956
22:32360521:T:C	F215L	0.955
22:32360523:C:A	F215L	0.955
22:32360523:C:G	F215L	0.955
22:32360650:T:C	F258L	0.945
22:32360652:T:A	F258L	0.945
22:32360652:T:G	F258L	0.945
22:32360452:T:A	W192R	0.937
22:32360452:T:C	W192R	0.937
22:32360620:T:C	F248L	0.925
22:32360622:T:A	F248L	0.925
22:32360622:T:G	F248L	0.925
22:32360424:G:C	W182C	0.916
22:32360424:G:T	W182C	0.916
22:32360401:T:C	F175L	0.909
22:32360403:T:A	F175L	0.909
22:32360403:T:G	F175L	0.909
22:32360653:T:C	F259L	0.904
22:32360655:T:A	F259L	0.904
22:32360655:T:G	F259L	0.904
22:32360722:T:C	F282L	0.903
22:32360724:T:A	F282L	0.903
22:32360724:T:G	F282L	0.903
22:32360422:T:A	W182R	0.898
22:32360422:T:C	W182R	0.898

dbSNP variants (sampled 300 via entrez): RS1000079594 (22:32358515 T>A,G), RS1000201332 (22:32354326 T>A,C), RS1000587950 (22:32355456 C>G,T), RS1001199618 (22:32358876 T>A,C), RS1001408569 (22:32355075 C>CT), RS1001554403 (22:32353768 G>A), RS1002079833 (22:32353903 C>T), RS1002203903 (22:32360113 T>C), RS1002501151 (22:32355990 T>C), RS1003176699 (22:32356975 G>C), RS1003244840 (22:32361322 C>T), RS1003277427 (22:32361487 T>C,G), RS1004638249 (22:32354348 A>G), RS1004710236 (22:32354473 C>T), RS1005415743 (22:32353018 G>A,C)

Disease associations

OMIM: gene MIM:605970 | 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
GCST005756_10	Dimensional psychopathology (Negative)	7.000000e-07
GCST005758_7	Dimensional psychopathology (Arousal)	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009096	negative domain measurement
EFO:0009099	arousal domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Vorinostat	affects cotreatment, decreases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

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