RTL3

Summary

RTL3 (retrotransposon Gag like 3, HGNC:22997) is a protein-coding gene on chromosome Xq21.1, encoding Retrotransposon Gag-like protein 3 (Q8N8U3). May function as a transcriptional regulator.

This gene is a member of a family of gag-related retrotransposon genes. These genes appear to have lost the ability to retrotranspose; however, their open reading frames have remained intact, which may indicate that these genes have acquired new functions in the cell.

Source: NCBI Gene 203430 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_152694

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22997
Approved symbol	RTL3
Name	retrotransposon Gag like 3
Location	Xq21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38865, Mar3, Mart3, ZHC5, SIRH9
Ensembl gene	ENSG00000179300
Ensembl biotype	protein_coding
OMIM	301130
Entrez	203430

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000321110, ENST00000870570

RefSeq mRNA: 1 — MANE Select: NM_152694 NM_152694

CCDS: CCDS14440

Canonical transcript exons

ENST00000321110 — 2 exons

Exon	Start	End
ENSE00001242156	78659261	78659328
ENSE00001242165	78656068	78658648

Expression profiles

Bgee: expression breadth broad, 74 present calls, max score 64.14.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	64.14	gold quality
right coronary artery	UBERON:0001625	63.54	gold quality
ascending aorta	UBERON:0001496	63.17	gold quality
thoracic aorta	UBERON:0001515	62.69	gold quality
tibia	UBERON:0000979	62.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	61.92	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.90	gold quality
lower esophagus	UBERON:0013473	61.82	gold quality
calcaneal tendon	UBERON:0003701	60.26	gold quality
apex of heart	UBERON:0002098	59.70	gold quality
aorta	UBERON:0000947	59.13	gold quality
upper leg skin	UBERON:0004262	57.45	silver quality
smooth muscle tissue	UBERON:0001135	57.31	gold quality
coronary artery	UBERON:0001621	56.77	gold quality
popliteal artery	UBERON:0002250	56.57	gold quality
tibial artery	UBERON:0007610	56.52	gold quality
left coronary artery	UBERON:0001626	56.46	gold quality
tendon	UBERON:0000043	54.67	gold quality
muscle layer of sigmoid colon	UBERON:0035805	54.35	gold quality
descending thoracic aorta	UBERON:0002345	51.92	gold quality
esophagus	UBERON:0001043	48.74	gold quality
layer of synovial tissue	UBERON:0007616	48.59	silver quality
body of uterus	UBERON:0009853	48.18	gold quality
deltoid	UBERON:0001476	47.99	gold quality
tendon of biceps brachii	UBERON:0008188	47.79	gold quality
saphenous vein	UBERON:0007318	46.94	silver quality
heart	UBERON:0000948	46.84	gold quality
myometrium	UBERON:0001296	46.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	46.30	silver quality
heart left ventricle	UBERON:0002084	46.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting RTL3, 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-6740-5P	100.00	65.64	932
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-380-3P	99.89	70.18	1978
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-936	98.87	70.51	1124
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-513B-3P	98.76	68.12	1577

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rtl3	ENSMUSG00000047686
rattus_norvegicus	Rtl3	ENSRNOG00000002429

Paralogs (10): RTL8C (ENSG00000134590), LDOC1 (ENSG00000182195), RTL4 (ENSG00000187823), RTL6 (ENSG00000188636), RTL8A (ENSG00000203950), RTL8B (ENSG00000212747), RTL10 (ENSG00000215012), PEG10 (ENSG00000242265), RTL5 (ENSG00000242732), RTL1 (ENSG00000254656)

Protein

Protein identifiers

Retrotransposon Gag-like protein 3 — Q8N8U3 (reviewed: Q8N8U3)

Alternative names: Zinc finger CCHC domain-containing protein 5

All UniProt accessions (1): Q8N8U3

UniProt curated annotations — full annotation on UniProt →

Function. May function as a transcriptional regulator. Plays a role in postnatal myogenesis, may be involved in the regulation of satellite cells self-renewal.

Subcellular location. Nucleus.

Miscellaneous. RTL3 is one of at least 11 genes called Mar or Mart related to long terminal repeat retrotransposons. They do not correspond to functional retrotransposons, but rather to neofunctionalized retrotransposons genes.

RefSeq proteins (1): NP_689907* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR032549	RTL1/1-8/LDOC_capsid-like	Domain
IPR032567	RTL1-rel	Family
IPR036875	Znf_CCHC_sf	Homologous_superfamily

Pfam: PF00098, PF16297

UniProt features (8 total): region of interest 3, compositionally biased region 2, chain 1, zinc finger region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8U3-F1	59.48	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 64 (showing top): AAGCAAT_MIR137, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, HFH4_01, OCT1_06, AACTTT_UNKNOWN, P300_01, P53_DECAMER_Q2, ISRE_01, AR_01, TGGAAA_NFAT_Q4_01, CTGTTAC_MIR194, P53_02, PR_01, chrXq21

GO Biological Process (0):

GO Molecular Function (3): nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), 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
binding	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RTL3	RTL6	Q6ICC9	747
RTL3	RTL8B	Q17RB0	541
RTL3	VPS29	Q9UBQ0	423
RTL3	RTL9	Q8NET4	387
RTL3	TMEM217	Q8N7C4	361
RTL3	TMEM217B	A0A494BZU4	360
RTL3	PNMA5	Q96PV4	353
RTL3	SEPTIN4	O43236	348
RTL3	RTL5	Q5HYW3	343
RTL3	OR10V1	Q8NGI7	323
RTL3	OR4F16	Q6IEY1	323
RTL3	OR8K5	Q8NH50	322
RTL3	RTL4	Q6ZR62	321
RTL3	ERICH6	Q7L0X2	315
RTL3	OR10G8	Q8NGN5	311

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A6NKG5, B0BAX9, G2TRT2, O12157, P03161, P03364, P0C2I8, P0C2J2, P0C2J4, P0C2J6, P0C691, P0CX59, P0CX60, P0CX61, P0CX62, P17192, P19558, P22281, P25383, P30028, P61511, P61512, P85051, Q03483, Q03964, Q04215, Q09T00, Q0R5R4, Q12217, Q12260, Q12266, Q12293, Q12391, Q12392, Q12439, Q12470, Q1PD56, Q3URY0, Q4R7E8, Q52QI2

Diamond homologs: A6NKG5, A6ZKI3, O95751, Q17QF6, Q17RB0, Q1JQ94, Q505G4, Q6ICC9, Q6SEH4, Q6SEH5, Q7M732, Q7TN75, Q7TPY9, Q86TG7, Q8N8U3, Q9BWD3, Q32KG4, Q52QI2, Q5DTT4, Q5HYW3, Q3URY0, Q6ZR62, Q6P1Y1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

166 predictions. Top by Δscore:

Variant	Effect	Δscore
X:78658647:CA:C	acceptor_gain	0.9800
X:78659274:AGT:A	donor_gain	0.9800
X:78658649:C:CC	acceptor_gain	0.9700
X:78658645:TACA:T	acceptor_gain	0.9600
X:78659256:GTTAC:G	donor_loss	0.9000
X:78659257:TTAC:T	donor_loss	0.9000
X:78659259:ACC:A	donor_loss	0.9000
X:78659260:CCATT:C	donor_gain	0.9000
X:78659254:ACGTT:A	donor_loss	0.8800
X:78658646:ACA:A	acceptor_gain	0.8700
X:78658647:CAC:C	acceptor_gain	0.8700
X:78659259:A:AC	donor_gain	0.8700
X:78659260:C:CC	donor_gain	0.8700
X:78659274:A:AC	donor_gain	0.8600
X:78658315:GGGCC:G	acceptor_gain	0.8500
X:78658647:CACT:C	acceptor_loss	0.8500
X:78658648:ACTG:A	acceptor_loss	0.8500
X:78658649:CTG:C	acceptor_loss	0.8500
X:78658650:T:A	acceptor_loss	0.8500
X:78659274:AGTC:A	donor_gain	0.8200
X:78658423:T:G	acceptor_gain	0.8100
X:78658644:ATACA:A	acceptor_gain	0.7800
X:78659261:C:G	donor_loss	0.7800
X:78659275:G:C	donor_gain	0.7500
X:78658378:C:G	acceptor_gain	0.7400
X:78658681:C:CC	acceptor_gain	0.6800
X:78658316:GGCCT:G	acceptor_gain	0.6600
X:78658317:GCCTG:G	acceptor_gain	0.6600
X:78659254:A:AC	donor_gain	0.6300
X:78659255:C:CC	donor_gain	0.6300

AlphaMissense

3114 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:78657689:G:C	F244L	0.884
X:78657689:G:T	F244L	0.884
X:78657691:A:G	F244L	0.884
X:78657338:A:C	F361L	0.870
X:78657338:A:T	F361L	0.870
X:78657340:A:G	F361L	0.870
X:78657659:G:C	F254L	0.863
X:78657659:G:T	F254L	0.863
X:78657661:A:G	F254L	0.863
X:78657587:A:C	F278L	0.859
X:78657587:A:T	F278L	0.859
X:78657589:A:G	F278L	0.859
X:78657548:G:C	F291L	0.809
X:78657548:G:T	F291L	0.809
X:78657550:A:G	F291L	0.809
X:78657473:A:C	F316L	0.792
X:78657473:A:T	F316L	0.792
X:78657475:A:G	F316L	0.792
X:78657392:G:C	F343L	0.783
X:78657392:G:T	F343L	0.783
X:78657394:A:G	F343L	0.783
X:78657497:G:C	F308L	0.767
X:78657497:G:T	F308L	0.767
X:78657499:A:G	F308L	0.767
X:78657059:A:C	F454L	0.730
X:78657059:A:T	F454L	0.730
X:78657061:A:G	F454L	0.730
X:78657585:A:T	V279D	0.704
X:78657339:A:G	F361S	0.693
X:78657267:A:G	L385P	0.673

dbSNP variants (sampled 300 via entrez): RS1000025896 (X:78656274 C>A,T), RS1000373115 (X:78660189 T>A), RS1000407413 (X:78659779 G>T), RS1002048498 (X:78658393 T>C), RS1002696082 (X:78659472 A>T), RS1004787763 (X:78656925 T>C), RS1005207203 (X:78656590 C>T), RS1005213474 (X:78660699 C>T), RS1006561068 (X:78655764 C>A), RS1006826872 (X:78658117 C>A), RS1007212706 (X:78660751 G>A), RS1007389054 (X:78659316 G>T), RS1008498499 (X:78660378 A>G), RS1008975501 (X:78657365 C>G,T), RS1009338275 (X:78655657 G>A)

Disease associations

OMIM: gene MIM:301130 | 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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
potassium chromate(VI)	affects cotreatment, decreases expression	2
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Estradiol	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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