RFPL1

Summary

RFPL1 (ret finger protein like 1, HGNC:9977) is a protein-coding gene on chromosome 22q12.2, encoding Ret finger protein-like 1 (O75677). Negatively regulates the G2-M phase transition, possibly by promoting cyclin B1/CCNB1 and CDK1 proteasomal degradation and thereby preventing their accumulation during interphase.

Predicted to enable ubiquitin protein ligase activity. Involved in negative regulation of G2/M transition of mitotic cell cycle and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Located in cytoplasm.

Source: NCBI Gene 5988 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_021026

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9977
Approved symbol	RFPL1
Name	ret finger protein like 1
Location	22q12.2
Locus type	gene with protein product
Status	Approved
Aliases	RNF78
Ensembl gene	ENSG00000128250
Ensembl biotype	protein_coding
OMIM	605968
Entrez	5988

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000354373

RefSeq mRNA: 2 — MANE Select: NM_021026 NM_001393612, NM_021026

CCDS: CCDS13857

Canonical transcript exons

ENST00000354373 — 2 exons

Exon	Start	End
ENSE00000879737	29438583	29439164
ENSE00000879738	29441542	29442455

Expression profiles

Bgee: expression breadth broad, 67 present calls, max score 81.96.

Top tissues by expression

278 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	81.96	gold quality
endometrium epithelium	UBERON:0004811	70.72	gold quality
prefrontal cortex	UBERON:0000451	67.73	gold quality
Brodmann (1909) area 10	UBERON:0013541	66.68	gold quality
cortical plate	UBERON:0005343	61.36	gold quality
cerebellar vermis	UBERON:0004720	60.61	gold quality
lower lobe of lung	UBERON:0008949	60.34	silver quality
frontal cortex	UBERON:0001870	58.62	gold quality
decidua	UBERON:0002450	56.55	gold quality
neocortex	UBERON:0001950	56.33	gold quality
sperm	CL:0000019	54.09	silver quality
male germ cell	CL:0000015	54.04	silver quality
Brodmann (1909) area 9	UBERON:0013540	52.95	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	51.61	gold quality
right testis	UBERON:0004534	51.42	gold quality
quadriceps femoris	UBERON:0001377	51.37	gold quality
prostate gland	UBERON:0002367	51.22	gold quality
cerebral cortex	UBERON:0000956	51.09	gold quality
left testis	UBERON:0004533	50.90	gold quality
right frontal lobe	UBERON:0002810	50.87	gold quality
vastus lateralis	UBERON:0001379	50.81	gold quality
primary visual cortex	UBERON:0002436	50.77	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
right adrenal gland cortex	UBERON:0035827	50.33	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
cingulate cortex	UBERON:0003027	49.54	gold quality
anterior cingulate cortex	UBERON:0009835	49.37	gold quality
thymus	UBERON:0002370	49.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	714.91
E-ANND-3	no	1.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PAX6

miRNA regulators (miRDB)

21 targeting RFPL1, 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-432-3P	100.00	67.86	705
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-649	97.96	67.21	704
HSA-MIR-4432	97.80	67.87	705
HSA-MIR-600	97.07	66.73	1259
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-4433B-5P	95.91	66.56	727
HSA-MIR-571	95.38	66.54	671

Literature-anchored findings (GeneRIF, showing 2)

• the human RFPL1,2,3 genes have a role in neocortex development (PMID:18656177)
• hRFPL1 antiproliferative activity led to an increased cell population in G(2)/M phase and specific cyclin B1 and Cdc2 downregulations. (PMID:20725088)

Cross-species orthologs

0 orthologs

Paralogs (12): CD86 (ENSG00000114013), CD274 (ENSG00000120217), CD80 (ENSG00000121594), RFPL2 (ENSG00000128253), RFPL3 (ENSG00000128276), SPRYD4 (ENSG00000176422), RNF152 (ENSG00000176641), RNF135 (ENSG00000181481), PDCD1LG2 (ENSG00000197646), RFPL4A (ENSG00000223638), RFPL4AL1 (ENSG00000229292), RFPL4B (ENSG00000251258)

Protein

Protein identifiers

Ret finger protein-like 1 — O75677 (reviewed: O75677)

Alternative names: RING finger protein 78

All UniProt accessions (1): O75677

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates the G2-M phase transition, possibly by promoting cyclin B1/CCNB1 and CDK1 proteasomal degradation and thereby preventing their accumulation during interphase.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Seems to be expressed in prostate and less abundantly in adult brain, fetal liver, and fetal kidney.

Post-translational modifications. Phosphorylated by PKC and CDK1. The antiproliferative effect seems to be positively regulated by PKC phosphorylation and negatively by CDK1 phosphorylation.

Domain organisation. The B30.2/SPRY domain is required for the negative regulation of cell proliferation.

RefSeq proteins (2): NP_001380541, NP_066306* (*=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 (14 total): mutagenesis site 5, sequence variant 5, chain 1, domain 1, sequence conflict 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75677-F1	84.97	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (5):

Position	Phenotype
200	no effect on cell proliferation.
287	increased cell proliferation, reduced apoptosis and lack of cyclin b1/ccnb1 and cdk1 degradation.
287	reduced phosphorylation by cdk1.
65–124	increased cell proliferation.
200	reduced phosphorylation by pkc, increased cell proliferation, reduced apoptosis and lack of cyclin b1/ccnb1 and cdk1 deg

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 75 (showing top): GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CELL_CYCLE_G2_M_PHASE_TRANSITION, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, MODULE_99, GOBP_NEGATIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MITOTIC_CELL_CYCLE

GO Biological Process (4): regulation of gene expression (GO:0010468), negative regulation of G2/M transition of mitotic cell cycle (GO:0010972), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), 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
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
negative regulation of mitotic cell cycle phase transition	1
negative regulation of cell cycle G2/M phase transition	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic 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

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFPL1	PAX6	P26367	712
RFPL1	GDF9	O60383	638
RFPL1	FOXL2NB	Q6ZUU3	582
RFPL1	PRAMEF12	O95522	557
RFPL1	PRAMEF1	O95521	531
RFPL1	KCNA6	P17658	522
RFPL1	MBD3L2	Q8NHZ7	506
RFPL1	PRAMEF13	Q5VWM6	503
RFPL1	PRAMEF11	O60813	501
RFPL1	PRAMEF2	O60811	476
RFPL1	ZSCAN4	Q8NAM6	475
RFPL1	FAM187B	Q17R55	474
RFPL1	PRAMEF25	A6NGN4	473
RFPL1	KCNA1	Q09470	467
RFPL1	A0A096LNW4	A0A096LNW4	448
RFPL1	KHDC1L	Q5JSQ8	448

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RFPL3	RFPL1	psi-mi:“MI:0914”(association)	0.530
ECE1	RFPL1	psi-mi:“MI:0915”(physical association)	0.370
RFPL1	CCT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): RFPL1 (Affinity Capture-MS), RFPL1 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), RFPL1 (Affinity Capture-MS), RFPL1 (Positive Genetic)

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”	RFPL1	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

139 predictions. Top by Δscore:

Variant	Effect	Δscore
22:29439162:AAGGT:A	donor_loss	1.0000
22:29439163:AGG:A	donor_loss	1.0000
22:29439164:GGTG:G	donor_loss	1.0000
22:29439165:GTGA:G	donor_loss	1.0000
22:29441538:A:AG	acceptor_gain	1.0000
22:29441538:ACAGT:A	acceptor_gain	1.0000
22:29441539:C:G	acceptor_gain	1.0000
22:29441539:CAGT:C	acceptor_loss	1.0000
22:29441540:A:AC	acceptor_loss	1.0000
22:29441540:A:AG	acceptor_gain	1.0000
22:29441540:AGT:A	acceptor_gain	1.0000
22:29441540:AGTG:A	acceptor_gain	1.0000
22:29441541:G:GT	acceptor_gain	1.0000
22:29441541:GT:G	acceptor_gain	1.0000
22:29441541:GTG:G	acceptor_gain	1.0000
22:29441541:GTGG:G	acceptor_gain	1.0000
22:29441541:GTGGA:G	acceptor_gain	1.0000
22:29439148:G:GT	donor_gain	0.9900
22:29439154:G:GT	donor_gain	0.9900
22:29439166:T:A	donor_loss	0.9900
22:29441542:T:TA	acceptor_gain	0.9900
22:29441543:G:A	acceptor_gain	0.9900
22:29439165:G:GG	donor_gain	0.9700
22:29441538:ACAG:A	acceptor_gain	0.9700
22:29441540:A:C	acceptor_gain	0.9700
22:29441541:G:T	acceptor_gain	0.9700
22:29439158:TTCCA:T	donor_gain	0.9600
22:29441536:TCACA:T	acceptor_gain	0.9600
22:29441537:CACA:C	acceptor_gain	0.9600
22:29441539:CAGTG:C	acceptor_gain	0.9600

AlphaMissense

2102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:29441811:T:C	F215L	0.936
22:29441813:C:A	F215L	0.936
22:29441813:C:G	F215L	0.936
22:29439158:T:C	F123L	0.931
22:29439160:C:A	F123L	0.931
22:29439160:C:G	F123L	0.931
22:29441655:T:C	F163L	0.931
22:29441657:T:A	F163L	0.931
22:29441657:T:G	F163L	0.931
22:29441976:T:C	F270L	0.918
22:29441978:C:A	F270L	0.918
22:29441978:C:G	F270L	0.918
22:29441940:T:C	F258L	0.907
22:29441942:T:A	F258L	0.907
22:29441942:T:G	F258L	0.907
22:29441742:T:A	W192R	0.902
22:29441742:T:C	W192R	0.902
22:29441910:T:C	F248L	0.866
22:29441912:T:A	F248L	0.866
22:29441912:T:G	F248L	0.866
22:29441943:T:C	F259L	0.852
22:29441945:T:A	F259L	0.852
22:29441945:T:G	F259L	0.852
22:29441744:G:C	W192C	0.836
22:29441744:G:T	W192C	0.836
22:29441691:T:C	F175L	0.823
22:29441693:T:A	F175L	0.823
22:29441693:T:G	F175L	0.823
22:29441712:T:A	W182R	0.808
22:29441712:T:C	W182R	0.808

dbSNP variants (sampled 300 via entrez): RS1000006377 (22:29393655 A>G), RS1000030631 (22:29386908 C>G), RS1000115030 (22:29388015 GTTT>G,GTT,GTTTT), RS1000256682 (22:29417340 T>C), RS1000409444 (22:29411499 T>G), RS1000493192 (22:29417636 C>A), RS1000569936 (22:29433495 A>C), RS1000631698 (22:29391826 T>C), RS1000698486 (22:29390031 C>G), RS1000718578 (22:29398205 C>G,T), RS1000744123 (22:29439404 C>A,G,T), RS1000831460 (22:29432874 G>C), RS1000863333 (22:29416302 A>G), RS1000882441 (22:29432580 A>C,G), RS1000901436 (22:29426653 G>T)

Disease associations

OMIM: gene MIM:605968 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000555_7	Carotid atherosclerosis in HIV infection	2.000000e-06

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
propionaldehyde	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Lead	affects expression	1
Testosterone	affects cotreatment, increases expression	1
Tretinoin	increases expression	1

Clinical trials (associated diseases)

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