RTL6

Summary

RTL6 (retrotransposon Gag like 6, HGNC:13343) is a protein-coding gene on chromosome 22q13.31, encoding Retrotransposon Gag-like protein 6 (Q6ICC9).

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_032287

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13343
Approved symbol	RTL6
Name	retrotransposon Gag like 6
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	dJ1033E15.2, DKFZp761O17121, Mart6, Mar6, SIRH3
Ensembl gene	ENSG00000188636
Ensembl biotype	protein_coding
OMIM	621006
Entrez	84247

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000341255

RefSeq mRNA: 1 — MANE Select: NM_032287 NM_032287

CCDS: CCDS33662

Canonical transcript exons

ENST00000341255 — 2 exons

Exon	Start	End
ENSE00001365955	44492583	44497811
ENSE00001408791	44498044	44498233

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 98.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.4012 / max 133.9063, expressed in 1763 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194537	6.7861	1611
194535	6.4686	1571
194539	1.2774	769
194538	0.8291	530
194536	0.5155	259
194540	0.3035	129
194534	0.2210	87

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.77	gold quality
tibialis anterior	UBERON:0001385	96.88	gold quality
cortical plate	UBERON:0005343	95.83	gold quality
ileal mucosa	UBERON:0000331	95.78	gold quality
epithelial cell of pancreas	CL:0000083	95.66	gold quality
left ventricle myocardium	UBERON:0006566	95.08	gold quality
ganglionic eminence	UBERON:0004023	94.96	gold quality
pancreatic ductal cell	CL:0002079	94.70	silver quality
oviduct epithelium	UBERON:0004804	94.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.52	gold quality
middle temporal gyrus	UBERON:0002771	93.84	gold quality
ventricular zone	UBERON:0003053	93.66	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.36	gold quality
postcentral gyrus	UBERON:0002581	92.19	gold quality
kidney epithelium	UBERON:0004819	92.19	gold quality
entorhinal cortex	UBERON:0002728	91.97	gold quality
germinal epithelium of ovary	UBERON:0001304	91.92	gold quality
superior frontal gyrus	UBERON:0002661	91.55	gold quality
parietal lobe	UBERON:0001872	91.43	gold quality
medial globus pallidus	UBERON:0002477	90.48	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.39	gold quality
cerebellar vermis	UBERON:0004720	90.07	gold quality
sperm	CL:0000019	89.43	gold quality
prefrontal cortex	UBERON:0000451	89.17	gold quality
deltoid	UBERON:0001476	88.79	silver quality
parietal pleura	UBERON:0002400	88.78	gold quality
temporal lobe	UBERON:0001871	88.66	gold quality
tendon of biceps brachii	UBERON:0008188	88.46	gold quality
frontal cortex	UBERON:0001870	88.38	gold quality
globus pallidus	UBERON:0001875	88.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting RTL6, 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-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-6748-5P	100.00	65.81	1057
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rtl6	ENSMUSG00000055745
rattus_norvegicus	Rtl6	ENSRNOG00000064516

Paralogs (10): RTL8C (ENSG00000134590), RTL3 (ENSG00000179300), LDOC1 (ENSG00000182195), RTL4 (ENSG00000187823), RTL8A (ENSG00000203950), RTL8B (ENSG00000212747), RTL10 (ENSG00000215012), PEG10 (ENSG00000242265), RTL5 (ENSG00000242732), RTL1 (ENSG00000254656)

Protein

Protein identifiers

Retrotransposon Gag-like protein 6 — Q6ICC9 (reviewed: Q6ICC9)

Alternative names: Leucine zipper protein down-regulated in cancer cells-like, Mammalian retrotransposon-derived protein 6, Protein LDOC1L

All UniProt accessions (1): Q6ICC9

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. RTL6 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.

Similarity. Belongs to the LDOC1 family.

RefSeq proteins (1): NP_115663* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032549	RTL1/1-8/LDOC_capsid-like	Domain

Pfam: PF16297

UniProt features (6 total): region of interest 2, compositionally biased region 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ICC9-F1	78.37	0.47

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, CCCAGAG_MIR326, CTTTGTA_MIR524, CUI_TCF21_TARGETS_2_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_MAGENTA_DN, chr22q13, CHEN_METABOLIC_SYNDROM_NETWORK, MEISSNER_NPC_HCP_WITH_H3K4ME2, FOSTER_KDM1A_TARGETS_DN, CHUNG_BLISTER_CYTOTOXICITY_UP, MIR1323, MIR29B_3P_MIR29C_3P, MIR29A_3P

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RTL6	RTL9	Q8NET4	810
RTL6	RTL4	Q6ZR62	771
RTL6	RTL3	Q8N8U3	747
RTL6	RTL1	A6NKG5	597
RTL6	PNMA6A	P0CW24	506
RTL6	RAPH1	Q70E73	470
RTL6	SLC25A6	P12236	442
RTL6	PNMA8A	Q86V59	422
RTL6	ZCCHC3	Q9NUD5	407
RTL6	PNMA1	Q8ND90	403
RTL6	XKRX	Q6PP77	373
RTL6	ZCCHC12	Q6PEW1	358
RTL6	RTL5	Q5HYW3	356
RTL6	PEG10	Q86TG7	339
RTL6	LMAN2L	Q9H0V9	306

IntAct

16 interactions, top by confidence:

A	B	Type	Score
STX18	NBAS	psi-mi:“MI:0914”(association)	0.810
DDIT3	DDIT3	psi-mi:“MI:0914”(association)	0.590
MAFF	GAPDHS	psi-mi:“MI:0914”(association)	0.530
PPFIBP2	SNAP29	psi-mi:“MI:0914”(association)	0.530
SHARPIN	MAP3K7	psi-mi:“MI:0914”(association)	0.350
STX18	NBAS	psi-mi:“MI:0914”(association)	0.350
BATF3	TARSL2	psi-mi:“MI:0914”(association)	0.350
GOPC	ZBTB5	psi-mi:“MI:0914”(association)	0.350
BATF3	TARS3	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
DDIT3	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
RTL6	uxaC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): LDOC1L (Affinity Capture-RNA), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-RNA), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS), LDOC1L (Affinity Capture-MS)

ESM2 similar proteins: A6NKG5, A6QLK5, F4HT77, O95751, P03334, P03336, P0CG32, P0DOH3, P11269, P21416, P21435, P23090, P26806, P26807, P29168, P32594, Q08DL1, Q12173, Q17QF6, Q27ID9, Q2F7I9, Q2F7J2, Q2KIT6, Q505G4, Q52QI2, Q5HZA3, Q5R486, Q6ICC9, Q6PEW1, Q6SEH4, Q6SEH5, Q7K1U0, Q7M732, Q7TN75, Q7TPY9, Q86TG7, Q8BHK0, Q8C1C8, Q8JZW8, Q8ND90

Diamond homologs: A6NKG5, A6ZKI3, O95751, Q17QF6, Q17RB0, Q1JQ94, Q505G4, Q6ICC9, Q6SEH4, Q6SEH5, Q7M732, Q7TN75, Q7TPY9, Q86TG7, Q8N8U3, Q9BWD3, Q32KG4, Q52QI2, Q5DTT4, Q5HYW3, Q5R6M8, Q7L3V2, Q6P1Y1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

155 predictions. Top by Δscore:

Variant	Effect	Δscore
22:44498039:CGTA:C	donor_loss	0.9900
22:44498040:GTACC:G	donor_loss	0.9900
22:44498041:TA:T	donor_loss	0.9900
22:44498042:A:C	donor_loss	0.9900
22:44498043:C:A	donor_loss	0.9900
22:44498038:GCGTA:G	donor_loss	0.9800
22:44496986:T:TA	donor_gain	0.9700
22:44498042:A:AC	donor_gain	0.9000
22:44498043:C:CC	donor_gain	0.9000
22:44497757:A:AC	donor_gain	0.8800
22:44497758:C:CC	donor_gain	0.8800
22:44497810:CC:C	acceptor_gain	0.7900
22:44497811:CC:C	acceptor_gain	0.7900
22:44497811:CCTGG:C	acceptor_loss	0.7800
22:44497812:C:CG	acceptor_loss	0.7800
22:44496816:C:CT	donor_gain	0.7600
22:44496817:T:TT	donor_gain	0.7600
22:44497588:C:CT	acceptor_gain	0.7600
22:44497588:C:T	acceptor_gain	0.7300
22:44497812:C:CC	acceptor_gain	0.6900
22:44494554:A:C	acceptor_gain	0.6600
22:44497809:GCC:G	acceptor_gain	0.6300
22:44497810:CCC:C	acceptor_gain	0.6300
22:44497809:GCCCT:G	acceptor_gain	0.6200
22:44494562:C:CT	acceptor_gain	0.6000
22:44497807:GGGCC:G	acceptor_gain	0.5800
22:44497808:GGCCC:G	acceptor_gain	0.5800
22:44497820:T:TC	acceptor_gain	0.5800
22:44497810:CCCT:C	acceptor_gain	0.5700
22:44498043:CCTGG:C	donor_gain	0.5700

AlphaMissense

1524 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:44497050:G:C	F169L	0.999
22:44497050:G:T	F169L	0.999
22:44497051:A:G	F169S	0.999
22:44497052:A:G	F169L	0.999
22:44497104:C:A	W151C	0.999
22:44497104:C:G	W151C	0.999
22:44497167:G:C	F130L	0.999
22:44497167:G:T	F130L	0.999
22:44497169:A:G	F130L	0.999
22:44497212:G:C	F115L	0.999
22:44497212:G:T	F115L	0.999
22:44497213:A:G	F115S	0.999
22:44497214:A:G	F115L	0.999
22:44497242:A:C	F105L	0.999
22:44497242:A:T	F105L	0.999
22:44497243:A:G	F105S	0.999
22:44497244:A:G	F105L	0.999
22:44497106:A:G	W151R	0.998
22:44497106:A:T	W151R	0.998
22:44497126:A:G	L144P	0.998
22:44497140:G:C	F139L	0.998
22:44497140:G:T	F139L	0.998
22:44497142:A:G	F139L	0.998
22:44497168:A:G	F130S	0.998
22:44497243:A:C	F105C	0.998
22:44497138:A:G	L140P	0.997
22:44497168:A:C	F130C	0.997
22:44497191:G:C	F122L	0.997
22:44497191:G:T	F122L	0.997
22:44497193:A:G	F122L	0.997

dbSNP variants (sampled 300 via entrez): RS1000635163 (22:44494480 TCC>T), RS1000640909 (22:44498421 C>A,G,T), RS1000721586 (22:44492693 C>T), RS1000742902 (22:44493106 G>A), RS1001013708 (22:44499221 A>T), RS1001316272 (22:44496227 G>A,C), RS1001685723 (22:44495954 G>A,C), RS1002923756 (22:44494806 G>A), RS1003009998 (22:44496687 G>A), RS1003338658 (22:44498056 G>C,T), RS1003589197 (22:44493136 C>T), RS1004084564 (22:44497466 A>C), RS1005147319 (22:44492474 C>G), RS1005419886 (22:44497822 A>C), RS1005497000 (22:44496443 C>T)

Disease associations

OMIM: gene MIM:621006 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003542_170	Night sleep phenotypes	7.000000e-06
GCST005316_269	Intelligence (MTAG)	1.000000e-08
GCST006296_7	Response to ziprazidone in schizophrenia	2.000000e-07
GCST009524_41	Household income (MTAG)	8.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0009695	household income

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases abundance, increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	increases expression	1
Estradiol	increases expression	1
Smoke	increases expression	1
Valproic Acid	decreases expression, increases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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