LONRF2

Summary

LONRF2 (LON peptidase N-terminal domain and ring finger 2, HGNC:24788) is a protein-coding gene on chromosome 2q11.2, encoding LON peptidase N-terminal domain and RING finger protein 2 (Q1L5Z9).

Predicted to enable misfolded protein binding activity; ribonucleoprotein complex binding activity; and ubiquitin protein ligase activity. Predicted to act upstream of or within several processes, including motor behavior; neuron differentiation; and protein quality control for misfolded or incompletely synthesized proteins. Predicted to be located in cytoplasm.

Source: NCBI Gene 164832 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 121 total
• Druggable target: yes
• MANE Select transcript: NM_198461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24788
Approved symbol	LONRF2
Name	LON peptidase N-terminal domain and ring finger 2
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ45273, RNF192
Ensembl gene	ENSG00000170500
Ensembl biotype	protein_coding
Entrez	164832

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000393437, ENST00000409647

RefSeq mRNA: 2 — MANE Select: NM_198461 NM_001371783, NM_198461

CCDS: CCDS2046, CCDS92818

Canonical transcript exons

ENST00000393437 — 12 exons

Exon	Start	End
ENSE00000963954	100295432	100295553
ENSE00000963955	100294229	100294387
ENSE00001072219	100298836	100298950
ENSE00001215796	100299226	100299319
ENSE00001297366	100290258	100290420
ENSE00001312093	100302921	100303043
ENSE00001318782	100286914	100287063
ENSE00001377226	100300644	100300787
ENSE00001390834	100299717	100299918
ENSE00001515297	100271875	100284492
ENSE00001689804	100321415	100322501
ENSE00003567966	100309107	100309225

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 98.65.

FANTOM5 (CAGE): breadth broad, TPM avg 6.2442 / max 114.0187, expressed in 532 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29914	2.6668	398
29916	2.5963	457
29917	0.2837	157
29915	0.1795	129
29919	0.1491	83
29918	0.1442	84
29920	0.1386	73
29913	0.0859	49

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.65	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.13	gold quality
middle temporal gyrus	UBERON:0002771	97.64	gold quality
germinal epithelium of ovary	UBERON:0001304	97.54	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.44	gold quality
endothelial cell	CL:0000115	97.18	gold quality
postcentral gyrus	UBERON:0002581	96.78	gold quality
oviduct epithelium	UBERON:0004804	96.68	gold quality
parietal lobe	UBERON:0001872	96.64	gold quality
superior vestibular nucleus	UBERON:0007227	96.50	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.37	gold quality
entorhinal cortex	UBERON:0002728	96.16	gold quality
pons	UBERON:0000988	96.13	gold quality
superior frontal gyrus	UBERON:0002661	96.01	gold quality
substantia nigra pars compacta	UBERON:0001965	95.35	gold quality
cerebellar vermis	UBERON:0004720	95.15	gold quality
caput epididymis	UBERON:0004358	94.83	gold quality
left uterine tube	UBERON:0001303	94.65	gold quality
lateral globus pallidus	UBERON:0002476	94.53	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.83	gold quality
cauda epididymis	UBERON:0004360	93.75	gold quality
medulla oblongata	UBERON:0001896	93.49	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.13	gold quality
left ventricle myocardium	UBERON:0006566	92.94	gold quality
fallopian tube	UBERON:0003889	92.55	gold quality
occipital lobe	UBERON:0002021	91.77	gold quality
adult organism	UBERON:0007023	91.64	gold quality
epithelial cell of pancreas	CL:0000083	91.35	gold quality
ventral tegmental area	UBERON:0002691	91.19	gold quality
primary visual cortex	UBERON:0002436	90.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	13.41
E-ANND-3	yes	6.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

291 targeting LONRF2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4745-5P	99.98	65.95	1028

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch1073-440b2.1	ENSDARG00000089138
mus_musculus	Lonrf2	ENSMUSG00000048814
rattus_norvegicus	Lonrf2	ENSRNOG00000023312
drosophila_melanogaster	CG32369	FBGN0052369
caenorhabditis_elegans		WBGENE00011365

Paralogs (2): LONRF1 (ENSG00000154359), LONRF3 (ENSG00000175556)

Protein

Protein identifiers

LON peptidase N-terminal domain and RING finger protein 2 — Q1L5Z9 (reviewed: Q1L5Z9)

Alternative names: Neuroblastoma apoptosis-related protease, RING finger protein 192

All UniProt accessions (1): Q1L5Z9

Isoforms (2)

UniProt ID	Names	Canonical?
Q1L5Z9-1	1	yes
Q1L5Z9-2	2

RefSeq proteins (2): NP_001358712, NP_940863* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR003111	Lon_prtase_N	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR015947	PUA-like_sf	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR019734	TPR_rpt	Repeat
IPR046336	Lon_prtase_N_sf	Homologous_superfamily

Pfam: PF02190, PF13432, PF13923

UniProt features (18 total): repeat 6, sequence variant 3, region of interest 2, compositionally biased region 2, chain 1, splice variant 1, sequence conflict 1, domain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q1L5Z9-F1	78.97	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_BEHAVIOR, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_CELL_DIFFERENTIATION_IN_SPINAL_CORD, GOBP_SPINAL_CORD_MOTOR_NEURON_DIFFERENTIATION, GOBP_VENTRAL_SPINAL_CORD_DEVELOPMENT, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_NEURON_APOPTOTIC_PROCESS, AFP1_Q6, GOBP_CELL_PROJECTION_ORGANIZATION, VECCHI_GASTRIC_CANCER_EARLY_DN

GO Biological Process (7): protein quality control for misfolded or incompletely synthesized proteins (GO:0006515), spinal cord motor neuron differentiation (GO:0021522), neuron projection development (GO:0031175), negative regulation of neuron apoptotic process (GO:0043524), neuromuscular process (GO:0050905), neuron apoptotic process (GO:0051402), motor behavior (GO:0061744)

GO Molecular Function (6): zinc ion binding (GO:0008270), ribonucleoprotein complex binding (GO:0043021), misfolded protein binding (GO:0051787), 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
protein catabolic process	1
cell differentiation in spinal cord	1
ventral spinal cord development	1
central nervous system neuron differentiation	1
neuron development	1
plasma membrane bounded cell projection organization	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
nervous system process	1
apoptotic process	1
behavior	1
transition metal ion binding	1
protein-containing complex binding	1
protein 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

720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LONRF2	AFF3	P51826	651
LONRF2	CHST10	O43529	612
LONRF2	NFX1	Q12986	527
LONRF2	SUPT16H	Q9Y5B9	521
LONRF2	MYO9A	B2RTY4	496
LONRF2	MVB12B	Q9H7P6	483
LONRF2	SYNCRIP	O60506	481
LONRF2	PPP4C	P33172	466
LONRF2	PDZRN4	Q6ZMN7	464
LONRF2	ZDHHC15	Q96MV8	462
LONRF2	RPL22	P35268	456
LONRF2	HDAC4	P56524	450
LONRF2	SUDS3	Q9H7L9	445
LONRF2	GNAO1	P09471	442
LONRF2	ADAD1	Q96M93	439

IntAct

84 interactions, top by confidence:

A	B	Type	Score
DPYSL5	DPYSL4	psi-mi:“MI:0914”(association)	0.640
CASP6	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
DMWD	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
FGFR3	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
LONRF2	GFAP	psi-mi:“MI:0915”(physical association)	0.560
GRIN2C	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
LONRF2	GSN	psi-mi:“MI:0915”(physical association)	0.560
LAMP2	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
LONRF2	PMP22	psi-mi:“MI:0915”(physical association)	0.560
TSC1	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
LONRF2	CCT5	psi-mi:“MI:0915”(physical association)	0.560
LONRF2	HTRA2	psi-mi:“MI:0915”(physical association)	0.560
CYCS	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
PRPF40A	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
LONRF2	JPH3	psi-mi:“MI:0915”(physical association)	0.560
SPRED1	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
HTT	LONRF2	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	LONRF2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (41): LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (PCA), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS), LONRF2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6ASZ5, A0JN53, A4IG66, D3Z8X7, D3ZND0, G3X992, O00750, O08836, O70576, P0DKR2, Q15021, Q1JQC5, Q1L5Z9, Q1LWH4, Q1LXZ7, Q2YD98, Q3T1I9, Q3TV65, Q3UJU9, Q4R5Q4, Q5EAU9, Q5JTW2, Q5R6Z1, Q5TC12, Q61249, Q66H15, Q6NY52, Q6P5E6, Q6PBQ2, Q6PI26, Q80TE0, Q80V31, Q80XC6, Q8BIW9, Q8BM55, Q8K2Z4, Q8R3L2, Q8VDP4, Q8WVB6, Q92574

Diamond homologs: A0A3B3IT33, A0JN74, A4QPC6, A6NCK2, A6NDI0, A6NGJ6, A6NI03, A6NLI5, A6NLU0, B1H278, B6VQ60, C9J1S8, D4ABM4, F6ZQ54, F8VTS6, I1YAP6, O00478, O00481, O15344, O70583, O75677, O75678, O75679, O76064, P0CI25, P0CI26, P18892, P19474, P82458, P86448, P86449, Q02398, Q03605, Q13410, Q14258, Q1L5Z9, Q1XHT8, Q2HJ46, Q2T9Z0, Q3TL54

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	LONRF2	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1876 predictions. Top by Δscore:

Variant	Effect	Δscore
2:100284312:C:CA	donor_gain	1.0000
2:100284488:TTACT:T	acceptor_gain	1.0000
2:100284489:TACT:T	acceptor_gain	1.0000
2:100284490:ACT:A	acceptor_gain	1.0000
2:100284491:CT:C	acceptor_gain	1.0000
2:100284491:CTC:C	acceptor_gain	1.0000
2:100284492:TCT:T	acceptor_gain	1.0000
2:100284492:TCTG:T	acceptor_loss	1.0000
2:100284493:C:CC	acceptor_gain	1.0000
2:100284493:C:G	acceptor_gain	1.0000
2:100284493:C:T	acceptor_loss	1.0000
2:100284494:T:A	acceptor_loss	1.0000
2:100290253:CTTAC:C	donor_loss	1.0000
2:100290254:TTAC:T	donor_loss	1.0000
2:100290255:TA:T	donor_loss	1.0000
2:100290256:A:AC	donor_gain	1.0000
2:100290256:AC:A	donor_gain	1.0000
2:100290256:ACCT:A	donor_loss	1.0000
2:100290257:C:CA	donor_gain	1.0000
2:100290257:CC:C	donor_gain	1.0000
2:100290257:CCT:C	donor_gain	1.0000
2:100290257:CCTT:C	donor_gain	1.0000
2:100290417:AAGC:A	acceptor_gain	1.0000
2:100290418:AGC:A	acceptor_gain	1.0000
2:100290419:GC:G	acceptor_gain	1.0000
2:100290420:CC:C	acceptor_gain	1.0000
2:100290421:C:CC	acceptor_gain	1.0000
2:100295430:A:AC	donor_gain	1.0000
2:100295431:C:CT	donor_gain	1.0000
2:100295554:C:CC	acceptor_gain	1.0000

AlphaMissense

4885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:100298865:A:G	C483R	1.000
2:100298907:A:G	C469R	1.000
2:100298908:A:C	F468L	1.000
2:100298908:A:T	F468L	1.000
2:100298910:A:G	F468L	1.000
2:100299242:A:G	C449R	1.000
2:100284465:A:G	W700R	0.999
2:100284465:A:T	W700R	0.999
2:100290327:G:C	F617L	0.999
2:100290327:G:T	F617L	0.999
2:100290328:A:G	F617S	0.999
2:100290329:A:G	F617L	0.999
2:100294289:C:G	R566T	0.999
2:100294294:C:A	M564I	0.999
2:100294294:C:G	M564I	0.999
2:100294294:C:T	M564I	0.999
2:100294295:A:C	M564R	0.999
2:100294295:A:G	M564T	0.999
2:100294295:A:T	M564K	0.999
2:100294298:A:G	L563P	0.999
2:100294315:A:C	F557L	0.999
2:100294315:A:T	F557L	0.999
2:100294317:A:G	F557L	0.999
2:100295470:C:A	R520S	0.999
2:100295470:C:G	R520S	0.999
2:100295471:C:A	R520M	0.999
2:100298854:G:C	C486W	0.999
2:100298855:C:G	C486S	0.999
2:100298855:C:T	C486Y	0.999
2:100298856:A:G	C486R	0.999

dbSNP variants (sampled 300 via entrez): RS1000062968 (2:100273765 G>C), RS1000112383 (2:100314897 G>A), RS1000147394 (2:100303962 T>C), RS1000246426 (2:100290553 G>A,T), RS1000298191 (2:100273059 A>G,T), RS1000310471 (2:100278721 G>A), RS1000410477 (2:100321891 A>G), RS1000422393 (2:100284832 T>C), RS1000487177 (2:100302576 T>G), RS1000686373 (2:100282957 A>T), RS1000701748 (2:100290798 T>C), RS1000767054 (2:100296180 C>A), RS1000789378 (2:100307208 C>A,T), RS1000831228 (2:100297541 G>A,C), RS1000841916 (2:100307485 G>A)

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

17 associations (top):

Study	Trait	p-value
GCST005316_183	Intelligence (MTAG)	5.000000e-13
GCST005316_185	Intelligence (MTAG)	1.000000e-11
GCST005316_186	Intelligence (MTAG)	3.000000e-09
GCST005316_188	Intelligence (MTAG)	9.000000e-11
GCST005316_285	Intelligence (MTAG)	7.000000e-16
GCST005528_3	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	8.000000e-07
GCST006269_1048	General cognitive ability	2.000000e-08
GCST006269_779	General cognitive ability	2.000000e-09
GCST006922_7	Regular attendance at a religious group	3.000000e-11
GCST007044_6	Extremely high intelligence	5.000000e-11
GCST007155_1	Household income	2.000000e-08
GCST008129_7	Body mass index	2.000000e-12
GCST009523_10	Household income	3.000000e-09
GCST009523_9	Household income	3.000000e-09
GCST009524_160	Household income (MTAG)	5.000000e-12
GCST009524_341	Household income (MTAG)	7.000000e-13
GCST90014325_35	Asthma	5.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009592	social interaction measurement
EFO:0009695	household income
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066138 (PROTEIN-PROTEIN INTERACTION)

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

CTD chemical–gene interactions

34 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, increases reaction	4
Valproic Acid	affects expression, increases expression, increases methylation	3
bisphenol A	affects cotreatment, affects methylation, increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Lead	affects expression, increases expression	2
Nickel	decreases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
trichostatin A	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
torcetrapib	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Vorinostat	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	increases methylation	1
Tetrachlorodibenzodioxin	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5609548	Binding	PROTAC activity at LONRF2/VHL in human Jurkat cells assessed as degradation of LONRF2 measured at 0.1 to 5 uM after 6 hrs incubation by Western blotting analysis	Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7). — Eur J Med Chem

Clinical trials (associated diseases)

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