RFPL2

Summary

RFPL2 (ret finger protein like 2, HGNC:9979) is a protein-coding gene on chromosome 22q12.3, encoding Ret finger protein-like 2 (O75678).

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 10739 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_001394555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9979
Approved symbol	RFPL2
Name	ret finger protein like 2
Location	22q12.3
Locus type	gene with protein product
Status	Approved
Aliases	RNF79
Ensembl gene	ENSG00000128253
Ensembl biotype	protein_coding
OMIM	605969
Entrez	10739

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000248983, ENST00000400237, ENST00000489846, ENST00000626996, ENST00000628378, ENST00000652607

RefSeq mRNA: 14 — MANE Select: NM_001394555 NM_001098527, NM_001159545, NM_001159546, NM_001364982, NM_001364983, NM_001364984, NM_001364985, NM_001364986, NM_001394554, NM_001394555, NM_001394556, NM_001394557, NM_001394558, NM_001394559

CCDS: CCDS43009

Canonical transcript exons

ENST00000652607 — 5 exons

Exon	Start	End
ENSE00001542121	32190438	32191352
ENSE00003568523	32202333	32202550
ENSE00003663985	32194345	32194490
ENSE00003748730	32192902	32193192
ENSE00003847275	32204707	32205073

Expression profiles

Bgee: expression breadth ubiquitous, 103 present calls, max score 89.86.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	89.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.47	gold quality
primary visual cortex	UBERON:0002436	79.83	gold quality
right frontal lobe	UBERON:0002810	78.70	gold quality
middle temporal gyrus	UBERON:0002771	78.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.06	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.23	gold quality
Brodmann (1909) area 23	UBERON:0013554	76.16	gold quality
sperm	CL:0000019	75.11	silver quality
endothelial cell	CL:0000115	74.88	gold quality
anterior cingulate cortex	UBERON:0009835	74.73	gold quality
cingulate cortex	UBERON:0003027	74.62	gold quality
frontal cortex	UBERON:0001870	73.67	gold quality
occipital lobe	UBERON:0002021	73.62	gold quality
neocortex	UBERON:0001950	73.26	gold quality
prefrontal cortex	UBERON:0000451	73.20	gold quality
male germ cell	CL:0000015	73.08	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.96	gold quality
hypothalamus	UBERON:0001898	72.73	gold quality
cerebral cortex	UBERON:0000956	72.25	gold quality
prostate gland	UBERON:0002367	71.18	gold quality
telencephalon	UBERON:0001893	70.66	gold quality
cerebellar hemisphere	UBERON:0002245	70.66	gold quality
cerebellar cortex	UBERON:0002129	70.56	gold quality
nucleus accumbens	UBERON:0001882	70.38	gold quality
caudate nucleus	UBERON:0001873	70.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.13	gold quality
superior frontal gyrus	UBERON:0002661	70.05	gold quality
putamen	UBERON:0001874	69.85	gold quality
cerebellum	UBERON:0002037	69.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting RFPL2, 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-548N	99.98	71.94	4170
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-629-3P	99.85	67.99	1875
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-8061	99.63	69.44	1411
HSA-MIR-298	99.63	67.56	1916
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-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-3169	96.40	67.58	698
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-8083	95.93	67.55	694

Literature-anchored findings (GeneRIF, showing 1)

• the human RFPL1,2,3 genes have a role in neocortex development (PMID:18656177)

Cross-species orthologs

0 orthologs

Paralogs (12): CD86 (ENSG00000114013), CD274 (ENSG00000120217), CD80 (ENSG00000121594), RFPL1 (ENSG00000128250), RFPL3 (ENSG00000128276), SPRYD4 (ENSG00000176422), RNF152 (ENSG00000176641), RNF135 (ENSG00000181481), PDCD1LG2 (ENSG00000197646), RFPL4A (ENSG00000223638), RFPL4AL1 (ENSG00000229292), RFPL4B (ENSG00000251258)

Protein

Protein identifiers

Ret finger protein-like 2 — O75678 (reviewed: O75678)

Alternative names: RING finger protein 79

All UniProt accessions (2): O75678, A0A0D9SGA4

UniProt curated annotations — full annotation on UniProt →

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

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be due to intron retention.

Isoforms (3)

UniProt ID	Names	Canonical?
O75678-1	1	yes
O75678-2	2
O75678-3	3

RefSeq proteins (14): NP_001091997, NP_001153017, NP_001153018, NP_001351911, NP_001351912, NP_001351913, NP_001351914, NP_001351915, NP_001381483, NP_001381484, NP_001381485, NP_001381486, NP_001381487, NP_001381488 (=MANE)

Domains & families (InterPro)

ID	Name	Type
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): sequence variant 7, splice variant 4, chain 1, domain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75678-F1	74.14	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, P53_DN.V2_UP, PRC1_BMI_UP.V1_UP, PRC2_EED_DN.V1_UP, ELF2_TARGET_GENES, ZNF418_TARGET_GENES, MIR4422, MIR369_3P, MIR4496, MIR4700_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

426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFPL2	PAX6	P26367	647
RFPL2	PRAMEF1	O95521	602
RFPL2	PRAMEF13	Q5VWM6	531
RFPL2	ZSCAN4	Q8NAM6	522
RFPL2	MBD3L2	Q8NHZ7	518
RFPL2	PRAMEF11	O60813	507
RFPL2	PRAMEF2	O60811	506
RFPL2	PRAMEF12	O95522	502
RFPL2	KHDC1L	Q5JSQ8	478
RFPL2	KHDC1	Q4VXA5	476
RFPL2	PRAMEF25	A6NGN4	475
RFPL2	TRIM48	Q8IWZ4	471
RFPL2	A0A096LNW4	A0A096LNW4	450
RFPL2	DUX4L2	P0CJ85	450
RFPL2	PRAMEF15	P0DUQ1	447

IntAct

6 interactions, top by confidence:

A	B	Type	Score
RFPL3	RFPL1	psi-mi:“MI:0914”(association)	0.530
ECE1	RFPL2	psi-mi:“MI:0915”(physical association)	0.370
RFPL2	BACH1	psi-mi:“MI:0914”(association)	0.350
RFPL3	RFPL2	psi-mi:“MI:0914”(association)	0.350
RFPL2	HSPA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (40): PHLPP1 (Affinity Capture-MS), ZNF507 (Affinity Capture-MS), TTC5 (Affinity Capture-MS), BACH1 (Affinity Capture-MS), PASK (Affinity Capture-MS), MIOS (Affinity Capture-MS), DYRK1A (Affinity Capture-MS), CBWD1 (Affinity Capture-MS), DMWD (Affinity Capture-MS), RB1 (Affinity Capture-MS), MDM2 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), RFPL2 (Affinity Capture-MS), RFPL2 (Affinity Capture-MS), BACH1 (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”	RFPL2	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	66
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

656 predictions. Top by Δscore:

Variant	Effect	Δscore
22:32191348:ATCCA:A	acceptor_gain	1.0000
22:32191349:TCCA:T	acceptor_gain	1.0000
22:32191350:CCA:C	acceptor_gain	1.0000
22:32191350:CCAC:C	acceptor_gain	1.0000
22:32191351:CA:C	acceptor_gain	1.0000
22:32191351:CAC:C	acceptor_gain	1.0000
22:32191352:AC:A	acceptor_loss	1.0000
22:32191353:C:CC	acceptor_gain	1.0000
22:32191355:G:C	acceptor_gain	1.0000
22:32191355:G:GC	acceptor_gain	1.0000
22:32192896:CCTTA:C	donor_loss	1.0000
22:32192897:CTTAC:C	donor_loss	1.0000
22:32192898:TTA:T	donor_loss	1.0000
22:32192899:TACCT:T	donor_loss	1.0000
22:32192900:A:AC	donor_gain	1.0000
22:32192900:A:AT	donor_loss	1.0000
22:32192900:AC:A	donor_gain	1.0000
22:32192901:C:CA	donor_gain	1.0000
22:32192901:CC:C	donor_gain	1.0000
22:32193188:GTCCA:G	acceptor_gain	1.0000
22:32193189:TCCA:T	acceptor_gain	1.0000
22:32193190:CCA:C	acceptor_gain	1.0000
22:32193190:CCAC:C	acceptor_gain	1.0000
22:32193191:CA:C	acceptor_gain	1.0000
22:32193191:CAC:C	acceptor_gain	1.0000
22:32193193:C:CC	acceptor_gain	1.0000
22:32193194:T:A	acceptor_loss	1.0000
22:32193197:C:CT	acceptor_gain	1.0000
22:32193197:C:T	acceptor_gain	1.0000
22:32193198:A:T	acceptor_gain	1.0000

AlphaMissense

2488 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:32191237:A:C	F224L	0.982
22:32191237:A:T	F224L	0.982
22:32191239:A:G	F224L	0.982
22:32190916:G:C	F331L	0.981
22:32190916:G:T	F331L	0.981
22:32190918:A:G	F331L	0.981
22:32191081:G:C	F276L	0.980
22:32191081:G:T	F276L	0.980
22:32191083:A:G	F276L	0.980
22:32191152:A:G	W253R	0.978
22:32191152:A:T	W253R	0.978
22:32192906:G:C	F184L	0.976
22:32192906:G:T	F184L	0.976
22:32192908:A:G	F184L	0.976
22:32190952:A:C	F319L	0.974
22:32190952:A:T	F319L	0.974
22:32190954:A:G	F319L	0.974
22:32191180:C:A	W243C	0.972
22:32191180:C:G	W243C	0.972
22:32191182:A:G	W243R	0.967
22:32191182:A:T	W243R	0.967
22:32191135:G:C	C258W	0.964
22:32191150:C:A	W253C	0.962
22:32191150:C:G	W253C	0.962
22:32191082:A:G	F276S	0.952
22:32191201:A:C	F236L	0.950
22:32191201:A:T	F236L	0.950
22:32191203:A:G	F236L	0.950
22:32191119:G:T	R264S	0.946
22:32191142:C:T	G256E	0.945

dbSNP variants (sampled 300 via entrez): RS1000461985 (22:32195355 G>A), RS1000614537 (22:32206259 T>A,C), RS1000735980 (22:32205012 G>A), RS1000745025 (22:32199517 C>A,T), RS1000773034 (22:32206457 T>A), RS1001102729 (22:32204771 C>G,T), RS1001521163 (22:32195522 C>A,T), RS1001597855 (22:32198756 C>G,T), RS1001630322 (22:32198927 G>A,T), RS1001733333 (22:32189949 T>A), RS1001805570 (22:32190152 G>A), RS1001958419 (22:32200941 C>A,G), RS1002035544 (22:32195704 C>A,T), RS1002093744 (22:32204166 C>G,T), RS1002632089 (22:32197196 C>T)

Disease associations

OMIM: gene MIM:605969 | 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
GCST003773_10	Loneliness (multivariate analysis)	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007865	loneliness measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	3
Vorinostat	affects cotreatment, decreases expression	2
Tretinoin	decreases expression, increases expression	2
propionaldehyde	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
CGP 52608	increases reaction, affects binding	1
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
jinfukang	affects cotreatment, increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Lead	affects expression	1
Cyclosporine	decreases methylation	1
Cadmium Chloride	increases expression	1
Acrylamide	increases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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