LONRF3

Summary

LONRF3 (LON peptidase N-terminal domain and ring finger 3, HGNC:21152) is a protein-coding gene on chromosome Xq24, encoding LON peptidase N-terminal domain and RING finger protein 3 (Q496Y0).

The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. Multiple alternatively spliced transcript variants have been suggested, but their full length natures are not clear.

Source: NCBI Gene 79836 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 176 total
• MANE Select transcript: NM_001031855

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21152
Approved symbol	LONRF3
Name	LON peptidase N-terminal domain and ring finger 3
Location	Xq24
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22612
Ensembl gene	ENSG00000175556
Ensembl biotype	protein_coding
Entrez	79836

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000304778, ENST00000371628, ENST00000422289, ENST00000439603, ENST00000472173, ENST00000481285, ENST00000961937

RefSeq mRNA: 3 — MANE Select: NM_001031855 NM_001031855, NM_001289109, NM_024778

CCDS: CCDS14575, CCDS35374, CCDS76014

Canonical transcript exons

ENST00000371628 — 11 exons

Exon	Start	End
ENSE00001280342	119013039	119013201
ENSE00002169620	118974618	118975597
ENSE00002309959	119017535	119018355
ENSE00003467615	118978345	118978463
ENSE00003469638	118989408	118989672
ENSE00003486110	119006121	119006235
ENSE00003491185	118990470	118990560
ENSE00003494930	119009126	119009247
ENSE00003525679	119014207	119014356
ENSE00003607786	119011815	119011973
ENSE00003672126	118982821	118982943

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 81.56.

FANTOM5 (CAGE): breadth broad, TPM avg 1.9735 / max 76.5200, expressed in 632 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197374	1.6533	604
197375	0.3202	129

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	81.56	gold quality
muscle of leg	UBERON:0001383	79.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.76	gold quality
right lobe of thyroid gland	UBERON:0001119	79.64	gold quality
left lobe of thyroid gland	UBERON:0001120	78.75	gold quality
thyroid gland	UBERON:0002046	78.31	gold quality
calcaneal tendon	UBERON:0003701	77.99	gold quality
islet of Langerhans	UBERON:0000006	76.76	gold quality
muscle organ	UBERON:0001630	75.75	gold quality
right lobe of liver	UBERON:0001114	75.70	gold quality
upper lobe of left lung	UBERON:0008952	75.08	gold quality
upper lobe of lung	UBERON:0008948	74.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	74.47	gold quality
rectum	UBERON:0001052	74.28	gold quality
liver	UBERON:0002107	74.17	gold quality
mucosa of stomach	UBERON:0001199	73.51	gold quality
pancreas	UBERON:0001264	73.42	gold quality
superficial temporal artery	UBERON:0001614	72.74	gold quality
cerebellar cortex	UBERON:0002129	72.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.60	gold quality
popliteal artery	UBERON:0002250	72.53	gold quality
cerebellar hemisphere	UBERON:0002245	72.51	gold quality
tibial artery	UBERON:0007610	72.50	gold quality
body of pancreas	UBERON:0001150	72.35	gold quality
lower lobe of lung	UBERON:0008949	72.30	silver quality
right hemisphere of cerebellum	UBERON:0014890	72.28	gold quality
tibialis anterior	UBERON:0001385	72.27	silver quality
hair follicle	UBERON:0002073	72.16	gold quality
monocyte	CL:0000576	71.87	gold quality
leukocyte	CL:0000738	71.86	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.34
E-MTAB-6075	no	48.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

64 targeting LONRF3, 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-126-5P	100.00	72.71	3180
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lonrf3	ENSMUSG00000016239
rattus_norvegicus	Lonrf3	ENSRNOG00000013092
drosophila_melanogaster	CG32369	FBGN0052369
caenorhabditis_elegans		WBGENE00011365

Paralogs (2): LONRF1 (ENSG00000154359), LONRF2 (ENSG00000170500)

Protein

Protein identifiers

LON peptidase N-terminal domain and RING finger protein 3 — Q496Y0 (reviewed: Q496Y0)

Alternative names: RING finger protein 127

All UniProt accessions (3): Q496Y0, B3KUN7, H0Y7Q8

Isoforms (3)

UniProt ID	Names	Canonical?
Q496Y0-1	1	yes
Q496Y0-2	2
Q496Y0-3	3

RefSeq proteins (3): NP_001027026, NP_001276038, NP_079054 (=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
IPR018957	Znf_C3HC4_RING-type	Domain
IPR019734	TPR_rpt	Repeat
IPR046336	Lon_prtase_N_sf	Homologous_superfamily

Pfam: PF00097, PF02190, PF13923

UniProt features (16 total): repeat 4, splice variant 3, compositionally biased region 2, zinc finger region 2, region of interest 2, chain 1, sequence variant 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q496Y0-F1	75.03	0.52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 184 (showing top): RNGTGGGC_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, PEREZ_TP63_TARGETS, GCANCTGNY_MYOD_Q6, CEBP_Q2, CATRRAGC_UNKNOWN, MCAATNNNNNGCG_UNKNOWN, GATA3_01, USF_01, TGANTCA_AP1_C, WEST_ADRENOCORTICAL_CARCINOMA_VS_ADENOMA_UP, PEREZ_TP53_AND_TP63_TARGETS, USF_02, HAND1E47_01, NFE2_01

GO Biological Process (0):

GO Molecular Function (3): zinc ion binding (GO:0008270), 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
transition metal ion binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

626 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LONRF3	PER3	P56645	522
LONRF3	NPAS2	Q99743	517
LONRF3	PER2	O15055	486
LONRF3	BMAL1	O00327	481
LONRF3	ZCCHC18	P0CG32	480
LONRF3	NFIL3	Q16649	459
LONRF3	C22orf31	O95567	447
LONRF3	HAPSTR1	Q14CZ0	414
LONRF3	RNF223	E7ERA6	400
LONRF3	DCAF12L2	Q5VW00	378
LONRF3	GCSAML	Q5JQS6	370
LONRF3	MTMR8	Q96EF0	369
LONRF3	ZNF71	Q9NQZ8	360
LONRF3	PRODH2	Q9UF12	355
LONRF3	CLVS2	Q5SYC1	339

IntAct

30 interactions, top by confidence:

A	B	Type	Score
NOTCH2NLA	LONRF3	psi-mi:“MI:0915”(physical association)	0.560
APPBP2	LONRF3	psi-mi:“MI:0915”(physical association)	0.560
LONRF3	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
LONRF3	TRAF2	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	LONRF3	psi-mi:“MI:0915”(physical association)	0.560
CTAG1A	LONRF3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	LONRF3	psi-mi:“MI:0915”(physical association)	0.560
DES	LONRF3	psi-mi:“MI:0915”(physical association)	0.560
DMD	UTRN	psi-mi:“MI:0914”(association)	0.530
LONRF3	PHB1	psi-mi:“MI:0915”(physical association)	0.520
APBB1	SSPOP	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
RFPL4B	KRBA1	psi-mi:“MI:0914”(association)	0.350
AGO3	AP3B1	psi-mi:“MI:0914”(association)	0.350
PRDM11	LONRF3	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350
SLC31A1	DENND11	psi-mi:“MI:0914”(association)	0.350
LONRF3	CTAG1A	psi-mi:“MI:0915”(physical association)	0.000
LONRF3	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
LONRF3	DES	psi-mi:“MI:0915”(physical association)	0.000
PHB1	LONRF3	psi-mi:“MI:0915”(physical association)	0.000
ENO1	LONRF3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): LONRF3 (Two-hybrid), NOTCH2NL (Two-hybrid), LONRF3 (Affinity Capture-MS), LONRF3 (Affinity Capture-MS), LONRF3 (Affinity Capture-MS), LONRF3 (Affinity Capture-MS), LONRF3 (Affinity Capture-MS), LONRF3 (Affinity Capture-RNA), LONRF3 (Co-fractionation), LONRF3 (Affinity Capture-RNA), LONRF3 (Two-hybrid), CTAG1B (Two-hybrid), CYSRT1 (Two-hybrid), CTAG1A (Two-hybrid), LONRF3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JXN2, A2AWP8, O88842, O95267, P29590, P52734, P98174, Q1LY10, Q29RM4, Q2TBA3, Q3TAA7, Q3U0J8, Q3UTZ3, Q496Y0, Q4VX76, Q568M3, Q58D15, Q5BIM1, Q5JSP0, Q5R5M3, Q5R5T1, Q5REJ9, Q5W0U4, Q68FF6, Q69Z89, Q69ZK0, Q6PFY8, Q7TNM2, Q7Z4K8, Q7Z5H3, Q7Z6J4, Q80V85, Q8BY35, Q8BZ52, Q8C190, Q8N1F8, Q8TCU6, Q8WVR3, Q96JH8, Q99N48

Diamond homologs: A2ZLU6, A4K2V0, A5PKG6, A6HD62, D3ZSP7, D7REX8, E4NKF8, E9Q735, F1RBN2, F8RP11, O13754, O13797, O14217, O16259, O35814, O54981, O80742, O81902, O88196, P0C6E7, P0CT30, P15705, P25638, P31948, P53041, P53042, P53804, Q07617, Q0IMG9, Q0JL44, Q14139, Q15785, Q32PZ3, Q388N2, Q3KRD5, Q3ZBR5, Q3ZBZ8, Q43468, Q496Y0, Q4R8N7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	LONRF3	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	9
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2160 predictions. Top by Δscore:

Variant	Effect	Δscore
X:118975585:GCAGT:G	donor_gain	1.0000
X:118975589:T:G	donor_gain	1.0000
X:118975593:GTTGG:G	donor_gain	1.0000
X:118975594:T:G	donor_gain	1.0000
X:118975596:GG:G	donor_gain	1.0000
X:118975597:GG:G	donor_gain	1.0000
X:118975598:G:GG	donor_gain	1.0000
X:118978343:A:AG	acceptor_gain	1.0000
X:118978344:G:GG	acceptor_gain	1.0000
X:119009121:T:G	acceptor_gain	1.0000
X:119009122:GTA:G	acceptor_loss	1.0000
X:119009124:A:AG	acceptor_gain	1.0000
X:119009124:AGT:A	acceptor_gain	1.0000
X:119009125:G:GT	acceptor_gain	1.0000
X:119009125:GT:G	acceptor_gain	1.0000
X:119009125:GTG:G	acceptor_gain	1.0000
X:119009125:GTGC:G	acceptor_gain	1.0000
X:119009125:GTGCT:G	acceptor_gain	1.0000
X:119009228:G:GT	donor_gain	1.0000
X:119009229:A:T	donor_gain	1.0000
X:119009234:G:GT	donor_gain	1.0000
X:119009243:TCTAA:T	donor_gain	1.0000
X:119009244:C:G	donor_gain	1.0000
X:119009245:TAA:T	donor_gain	1.0000
X:119009245:TAAGT:T	donor_loss	1.0000
X:119009246:AA:A	donor_gain	1.0000
X:119009248:G:GG	donor_gain	1.0000
X:119009248:G:T	donor_loss	1.0000
X:119009249:T:A	donor_loss	1.0000
X:119017529:TTGCA:T	acceptor_loss	1.0000

AlphaMissense

4952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:118975252:T:C	C158R	1.000
X:118975261:T:C	C161R	1.000
X:118975312:T:C	C178R	1.000
X:118975313:G:A	C178Y	1.000
X:118975528:G:C	G250R	1.000
X:118978375:G:C	R283P	1.000
X:118990544:T:A	C467S	1.000
X:118990544:T:C	C467R	1.000
X:118990545:G:C	C467S	1.000
X:118990546:C:G	C467W	1.000
X:118990553:T:C	C470R	1.000
X:118990554:G:A	C470Y	1.000
X:118990555:T:G	C470W	1.000
X:119006135:C:A	P477Q	1.000
X:119006138:T:A	V478D	1.000
X:119006153:G:A	G483E	1.000
X:119006161:T:C	F486L	1.000
X:119006163:T:A	F486L	1.000
X:119006163:T:G	F486L	1.000
X:119006164:T:C	C487R	1.000
X:119006165:G:A	C487Y	1.000
X:119006166:C:G	C487W	1.000
X:119006173:T:C	C490R	1.000
X:119006175:C:G	C490W	1.000
X:119006206:T:C	C501R	1.000
X:119011837:T:C	F559L	1.000
X:119011839:C:A	F559L	1.000
X:119011839:C:G	F559L	1.000
X:119011904:T:C	L581P	1.000
X:119011913:G:C	R584P	1.000

dbSNP variants (sampled 300 via entrez): RS1000045871 (X:118972635 C>A,T), RS1000076628 (X:119008467 T>C), RS1000103568 (X:118976359 G>A), RS1000109108 (X:119006910 A>G), RS1000164477 (X:118995867 A>G), RS1000333328 (X:118987773 A>G), RS1000374926 (X:118999087 G>A,T), RS1000395803 (X:119012873 C>A), RS1000427184 (X:118998741 A>C,G), RS1000428865 (X:119004613 T>C), RS1000598424 (X:119011141 A>G), RS1000677455 (X:119006401 T>C), RS1000742082 (X:119003980 C>T), RS1000769308 (X:119014487 T>C,G), RS1000828340 (X:118977908 A>G)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation	6
Benzo(a)pyrene	affects methylation, increases expression	2
Estradiol	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
trichostatin A	increases expression	1
arsenite	increases methylation, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
monomethylarsonous acid	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Vorinostat	increases expression	1
Leflunomide	increases expression	1

Clinical trials (associated diseases)

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