RLF

Summary

RLF (RLF zinc finger, HGNC:10025) is a protein-coding gene on chromosome 1p34.2, encoding Zinc finger protein Rlf (Q13129). May be involved in transcriptional regulation.

Predicted to enable DNA binding activity and DNA-binding transcription activator activity, RNA polymerase II-specific. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of heterochromatin formation. Located in extracellular exosome.

Source: NCBI Gene 6018 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 203 total
• MANE Select transcript: NM_012421

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10025
Approved symbol	RLF
Name	RLF zinc finger
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	ZNF292L, Zn-15L
Ensembl gene	ENSG00000117000
Ensembl biotype	protein_coding
OMIM	180610
Entrez	6018

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000372771

RefSeq mRNA: 1 — MANE Select: NM_012421 NM_012421

CCDS: CCDS448

Canonical transcript exons

ENST00000372771 — 8 exons

Exon	Start	End
ENSE00001042832	40222574	40222710
ENSE00001122724	40231517	40231658
ENSE00001122759	40202412	40202614
ENSE00001192043	40190772	40190853
ENSE00001192049	40189055	40189209
ENSE00001458614	40235792	40240921
ENSE00001458617	40161387	40161636
ENSE00003461548	40195632	40195764

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 92.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3719 / max 654.4916, expressed in 1790 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2346	15.7248	1788
2345	0.5743	282
2347	0.0728	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	92.83	gold quality
cartilage tissue	UBERON:0002418	92.53	gold quality
calcaneal tendon	UBERON:0003701	90.07	gold quality
ventricular zone	UBERON:0003053	89.86	gold quality
sperm	CL:0000019	89.62	gold quality
endothelial cell	CL:0000115	88.44	gold quality
cortical plate	UBERON:0005343	87.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.90	gold quality
male germ cell	CL:0000015	86.23	gold quality
embryo	UBERON:0000922	86.13	gold quality
ganglionic eminence	UBERON:0004023	85.99	gold quality
middle temporal gyrus	UBERON:0002771	84.47	gold quality
Brodmann (1909) area 23	UBERON:0013554	84.46	gold quality
oocyte	CL:0000023	83.94	gold quality
amniotic fluid	UBERON:0000173	83.94	gold quality
adrenal tissue	UBERON:0018303	83.82	gold quality
esophagus squamous epithelium	UBERON:0006920	83.31	gold quality
choroid plexus epithelium	UBERON:0003911	83.03	gold quality
bone marrow	UBERON:0002371	82.88	gold quality
primary visual cortex	UBERON:0002436	82.21	gold quality
buccal mucosa cell	CL:0002336	82.11	silver quality
skin of abdomen	UBERON:0001416	81.61	gold quality
tibial artery	UBERON:0007610	81.51	gold quality
popliteal artery	UBERON:0002250	81.50	gold quality
oviduct epithelium	UBERON:0004804	81.35	gold quality
skin of leg	UBERON:0001511	81.29	gold quality
cerebellar cortex	UBERON:0002129	81.13	gold quality
cerebellar hemisphere	UBERON:0002245	81.10	gold quality
gastrocnemius	UBERON:0001388	80.99	gold quality
squamous epithelium	UBERON:0006914	80.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-17	no	851.42
E-CURD-112	no	2.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
FOS	Activation
MYL2
NPPA
RLF
SF1

Upstream regulators (CollecTRI, top): HESX1, MYCL, NR0B1, NR5A1, RBPJ, RLF

miRNA regulators (miRDB)

84 targeting RLF, 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-4262	100.00	73.26	3931
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
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-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-498-3P	99.91	71.27	1114

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rlf	ENSDARG00000063553
mus_musculus	Rlf	ENSMUSG00000049878
rattus_norvegicus	Rlf	ENSRNOG00000027921

Paralogs (2): ZNF654 (ENSG00000175105), ZNF292 (ENSG00000188994)

Protein

Protein identifiers

Zinc finger protein Rlf — Q13129 (reviewed: Q13129)

Alternative names: Rearranged L-myc fusion gene protein, Zn-15-related protein

All UniProt accessions (1): Q13129

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation.

Subunit / interactions. Interacts with RIT1 and RIT2.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed in fetal and adult tissues.

Miscellaneous. In some small cell lung carcinoma (SCLC) cell lines, there is an intrachromosomal rearrangements at 1p32 fusing the first exon of the RLF gene with L-myc.

Similarity. Belongs to the krueppel C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_036553* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR052251	GH-ZnFinger_Regulators	Family
IPR057986	TPR_Rlf/292/654	Domain
IPR058902	Znf_C2H2_ZNF292/Rlf	Domain

Pfam: PF00096, PF25420, PF25580, PF26218

UniProt features (48 total): zinc finger region 14, compositionally biased region 9, region of interest 7, cross-link 7, sequence variant 6, modified residue 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13129-F1	57.48	0.07

Functional residue map

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

Post-translational modifications (10): 41, 632, 634, 622, 839, 1423, 1599, 1611, 1696, 1762

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, BROWNE_HCMV_INFECTION_4HR_UP, MODULE_97, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MODULE_182, USF_01, chr1p34, MODULE_123, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, USF_02, CDPCR3HD_01, USF2_Q6, CHEN_HOXA5_TARGETS_9HR_UP, MYC_Q2

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), negative regulation of heterochromatin formation (GO:0031452), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (6): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
positive regulation of gene expression	1
regulation of heterochromatin formation	1
heterochromatin formation	1
negative regulation of heterochromatin organization	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

844 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RLF	MYCL	P12524	804
RLF	CFAP144	A6NL82	566
RLF	POU2AF3	A8K830	565
RLF	RLN3	Q8WXF3	552
RLF	RLN1	P04808	546
RLF	WBP1L	Q9NX94	498
RLF	FBXL17	Q9UF56	495
RLF	HIGD1A	Q9Y241	476
RLF	PNMA8B	Q9ULN7	473
RLF	C21orf91	Q9NYK6	466
RLF	ANKRD18B	A2A2Z9	445
RLF	KLHL7	Q8IXQ5	443
RLF	UAP1	Q16222	441
RLF	UFC1	Q9Y3C8	419
RLF	SMCHD1	A6NHR9	408

IntAct

43 interactions, top by confidence:

A	B	Type	Score
NFIC	NFIB	psi-mi:“MI:2364”(proximity)	0.690
RIT1	RLF	psi-mi:“MI:0915”(physical association)	0.510
Rit2	RLF	psi-mi:“MI:0915”(physical association)	0.510
	RLF	psi-mi:“MI:0915”(physical association)	0.510
RLF		psi-mi:“MI:0915”(physical association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
PRPF40A	RLF	psi-mi:“MI:0915”(physical association)	0.370
RLF	GCH1	psi-mi:“MI:0915”(physical association)	0.370
Cbx1		psi-mi:“MI:0914”(association)	0.350
ALB	CDC45	psi-mi:“MI:0914”(association)	0.350
TRIM11	BTN3A3	psi-mi:“MI:0914”(association)	0.350
CBX5	ZNF568	psi-mi:“MI:0914”(association)	0.350
CBX1	EXOC5	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TRIM11	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
CCT8L2	DVL2	psi-mi:“MI:0914”(association)	0.350
CBX3	ZNF324	psi-mi:“MI:0914”(association)	0.350
TRIM11	LYPLA1	psi-mi:“MI:0914”(association)	0.350
	PHF20L1	psi-mi:“MI:0914”(association)	0.350
CBX3	MYL12B	psi-mi:“MI:0914”(association)	0.350
CBX5	ZNF292	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
KLF16	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (77): RLF (Synthetic Lethality), RLF (Proximity Label-MS), RLF (Proximity Label-MS), RLF (Biochemical Activity), RLF (Affinity Capture-MS), RLF (Affinity Capture-MS), RLF (Affinity Capture-RNA), RLF (Affinity Capture-MS), RLF (Affinity Capture-MS), RLF (Two-hybrid), RLF (Affinity Capture-MS), RLF (Affinity Capture-Western), RLF (Affinity Capture-MS), RLF (Affinity Capture-RNA), RLF (Affinity Capture-MS)

ESM2 similar proteins: A0A0M3U1B0, A0A1L8EYB2, A0JMF7, A1L2Y1, A2ALV5, A9JRX0, B2GUZ2, D3ZSP7, F1QB81, O35892, O70608, O75113, P23497, P70347, Q0P5X5, Q13129, Q16533, Q2T9I9, Q3U1D0, Q5CZC0, Q5H9M0, Q5REF4, Q5RHB5, Q5SW75, Q5T4T6, Q5T5J6, Q5XG69, Q5ZLE9, Q60664, Q63HN8, Q7M6U3, Q7Z4H7, Q80VH0, Q8BVK9, Q8C263, Q8CCC3, Q8NA03, Q90WN7, Q92844, Q96QP1

Diamond homologs: O60281, O60315, Q13129, Q8IZM8, Q9DAU9, Q9R0G7, Q9Z2U2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RLF	“up-regulates activity”	RIT1	binding
RLF	“up-regulates activity”	RIN1	binding
Ub:E2	“up-regulates activity”	RLF	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 51 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
ChAHP complex assembly	5	24.2×	4e-04
Formation of the beta-catenin:TCF transactivating complex	5	15.8×	1e-03
Activation of anterior HOX genes in hindbrain development during early embryogenesis	6	14.4×	4e-04
Regulation of endogenous retroelements by KRAB-ZFP proteins	5	14.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
DNA replication	5	16.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	185
Likely benign	7
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1434 predictions. Top by Δscore:

Variant	Effect	Δscore
1:40189053:A:AG	acceptor_gain	1.0000
1:40189054:G:GA	acceptor_gain	1.0000
1:40189201:A:G	donor_gain	1.0000
1:40189205:GTACT:G	donor_gain	1.0000
1:40189210:G:GG	donor_gain	1.0000
1:40190380:T:G	donor_gain	1.0000
1:40190771:GGA:G	acceptor_gain	1.0000
1:40190853:GGTG:G	donor_loss	1.0000
1:40190854:G:GG	donor_gain	1.0000
1:40190854:GTGA:G	donor_loss	1.0000
1:40190855:T:G	donor_loss	1.0000
1:40195626:TTCTA:T	acceptor_loss	1.0000
1:40195627:TCTAG:T	acceptor_loss	1.0000
1:40195628:CTAG:C	acceptor_loss	1.0000
1:40195629:TAGGA:T	acceptor_loss	1.0000
1:40195630:AGG:A	acceptor_loss	1.0000
1:40195631:G:A	acceptor_loss	1.0000
1:40195631:GGA:G	acceptor_gain	1.0000
1:40195760:GGAAG:G	donor_gain	1.0000
1:40195761:GAAGG:G	donor_gain	1.0000
1:40195762:AAGGT:A	donor_loss	1.0000
1:40195763:AGG:A	donor_loss	1.0000
1:40195764:GGTAA:G	donor_loss	1.0000
1:40195765:GTAAG:G	donor_loss	1.0000
1:40195766:T:A	donor_loss	1.0000
1:40202410:A:AG	acceptor_gain	1.0000
1:40202411:G:GG	acceptor_gain	1.0000
1:40202611:GGAG:G	donor_gain	1.0000
1:40202612:GAGG:G	donor_gain	1.0000
1:40222707:CTTGG:C	donor_loss	1.0000

AlphaMissense

12735 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:40235943:T:C	L414P	1.000
1:40236066:T:C	L455P	1.000
1:40236081:A:T	K460I	1.000
1:40236082:A:C	K460N	1.000
1:40236082:A:T	K460N	1.000
1:40236089:T:A	W463R	1.000
1:40236089:T:C	W463R	1.000
1:40236091:G:C	W463C	1.000
1:40236091:G:T	W463C	1.000
1:40236107:T:C	F469L	1.000
1:40236108:T:C	F469S	1.000
1:40236109:T:A	F469L	1.000
1:40236109:T:G	F469L	1.000
1:40236110:T:A	W470R	1.000
1:40236110:T:C	W470R	1.000
1:40236112:G:C	W470C	1.000
1:40236112:G:T	W470C	1.000
1:40236126:T:C	L475S	1.000
1:40236350:T:A	W550R	1.000
1:40236350:T:C	W550R	1.000
1:40236352:G:C	W550C	1.000
1:40236352:G:T	W550C	1.000
1:40236354:T:C	L551P	1.000
1:40236371:T:A	C557S	1.000
1:40236371:T:C	C557R	1.000
1:40236372:G:A	C557Y	1.000
1:40236372:G:C	C557S	1.000
1:40236372:G:T	C557F	1.000
1:40236373:T:G	C557W	1.000
1:40236380:T:A	C560S	1.000

dbSNP variants (sampled 300 via entrez): RS1000006821 (1:40167195 A>G), RS1000101124 (1:40178953 G>A,C), RS1000104688 (1:40232615 A>G), RS1000163052 (1:40200955 A>G), RS1000167709 (1:40203622 T>C), RS1000251585 (1:40216180 A>G), RS1000404726 (1:40196529 A>G), RS1000424794 (1:40190229 CA>C,CAA), RS1000454565 (1:40187422 A>G), RS1000632469 (1:40205553 G>A,C,T), RS1000646988 (1:40179436 T>G), RS1000656184 (1:40193352 T>C), RS1000680111 (1:40240105 T>C), RS1000692764 (1:40220682 G>A), RS1000855543 (1:40214936 A>AC)

Disease associations

OMIM: gene MIM:180610 | 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Arsenic	increases abundance, increases expression, decreases expression	3
cobaltous chloride	increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Cisplatin	affects cotreatment, decreases expression, increases expression	2
Oxygen	increases expression	2
Quercetin	increases expression, increases phosphorylation	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
TAK-243	decreases sumoylation	1
chloroacetaldehyde	affects expression	1
bisphenol A	affects methylation	1
sodium arsenate	increases abundance, increases expression	1
titanium dioxide	increases methylation	1
arsenite	affects binding, decreases reaction	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
cupric oxide	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases expression, increases abundance	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
Rosiglitazone	increases expression	1
Temozolomide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_2058	HCC33	Cancer cell line	Male

Clinical trials (associated diseases)

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