RTL8A

Summary

RTL8A (retrotransposon Gag like 8A, HGNC:24514) is a protein-coding gene on chromosome Xq26.3, encoding Retrotransposon Gag-like protein 8A (Q9BWD3).

At a glance

• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001078172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24514
Approved symbol	RTL8A
Name	retrotransposon Gag like 8A
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564B147, MAR8A, CXX1b, SIRH6
Ensembl gene	ENSG00000203950
Ensembl biotype	protein_coding
Entrez	26071

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000370775, ENST00000518153, ENST00000520964, ENST00000522309

RefSeq mRNA: 2 — MANE Select: NM_001078172 NM_001078172, NM_001134321

CCDS: CCDS43998

Canonical transcript exons

ENST00000370775 — 1 exons

Exon	Start	End
ENSE00001453601	135050932	135052135

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 97.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 89.3692 / max 911.1634, expressed in 1802 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200612	88.2785	1802
200610	0.9411	466
200611	0.1496	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.16	gold quality
lower esophagus	UBERON:0013473	97.02	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.02	gold quality
cortical plate	UBERON:0005343	96.99	gold quality
popliteal artery	UBERON:0002250	96.95	gold quality
tibial artery	UBERON:0007610	96.95	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.90	gold quality
right coronary artery	UBERON:0001625	96.86	gold quality
lower esophagus mucosa	UBERON:0035834	96.84	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.75	gold quality
left coronary artery	UBERON:0001626	96.74	gold quality
aorta	UBERON:0000947	96.63	gold quality
thoracic aorta	UBERON:0001515	96.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.51	gold quality
ascending aorta	UBERON:0001496	96.49	gold quality
adenohypophysis	UBERON:0002196	96.49	gold quality
body of uterus	UBERON:0009853	96.49	gold quality
ectocervix	UBERON:0012249	96.42	gold quality
endocervix	UBERON:0000458	96.33	gold quality
descending thoracic aorta	UBERON:0002345	96.26	gold quality
left uterine tube	UBERON:0001303	96.15	gold quality
esophagus	UBERON:0001043	96.14	gold quality
stromal cell of endometrium	CL:0002255	96.12	gold quality
mucosa of stomach	UBERON:0001199	96.06	gold quality
ventricular zone	UBERON:0003053	96.02	gold quality
right ovary	UBERON:0002118	95.99	gold quality
right adrenal gland	UBERON:0001233	95.89	gold quality
anterior cingulate cortex	UBERON:0009835	95.89	gold quality
left ovary	UBERON:0002119	95.88	gold quality
left adrenal gland cortex	UBERON:0035825	95.87	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.12
E-MTAB-6058	no	186.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting RTL8A, 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-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-4492	99.87	68.25	3611
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-4477A	98.83	69.75	2952

Literature-anchored findings (GeneRIF, showing 1)

• RTL8 promotes nuclear localization of UBQLN2 to subnuclear compartments associated with protein quality control. (PMID:35247097)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rtl8c	ENSMUSG00000051851
mus_musculus	Rtl8b	ENSMUSG00000067924
mus_musculus	Rtl8a	ENSMUSG00000067925
rattus_norvegicus	Rtl8a	ENSRNOG00000062466

Paralogs (10): RTL8C (ENSG00000134590), RTL3 (ENSG00000179300), LDOC1 (ENSG00000182195), RTL4 (ENSG00000187823), RTL6 (ENSG00000188636), RTL8B (ENSG00000212747), RTL10 (ENSG00000215012), PEG10 (ENSG00000242265), RTL5 (ENSG00000242732), RTL1 (ENSG00000254656)

Protein

Protein identifiers

Retrotransposon Gag-like protein 8A — Q9BWD3 (reviewed: Q9BWD3)

Alternative names: Mammalian retrotransposon derived protein 8A

All UniProt accessions (1): Q9BWD3

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. RTL8A 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 FAM127 family.

RefSeq proteins (2): NP_001071640, NP_001127793 (=MANE)

Domains & families (InterPro)

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

Pfam: PF16297

UniProt features (2 total): chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWD3-F1	87.91	0.72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): BLALOCK_ALZHEIMERS_DISEASE_DN, chrXq26, FORTSCHEGGER_PHF8_TARGETS_DN, ZNF618_TARGET_GENES, MIR6825_5P, MIR892C_5P, MIR34A_5P, MIR449A, LET_7A_2_3P, LET_7G_3P, MIR4768_3P, MIR6719_3P, MIR7152_3P, GSE1460_INTRATHYMIC_T_PROGENITOR_VS_THYMIC_STROMAL_CELL_DN, GSE1460_DP_THYMOCYTE_VS_THYMIC_STROMAL_CELL_DN

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RTL8A	RTL5	Q5HYW3	528
RTL8A	MOSPD1	Q9UJG1	485
RTL8A	ZNF606	Q8WXB4	374
RTL8A	RTL9	Q8NET4	370
RTL8A	B3GALT6	Q96L58	359
RTL8A	HAUS7	Q99871	357
RTL8A	ZIK1	Q3SY52	352
RTL8A	IRGQ	Q8WZA9	352
RTL8A	FOXN2	P32314	351
RTL8A	TCAF1	Q9Y4C2	326
RTL8A	SYCP2	Q9BX26	323
RTL8A	PRRG1	O14668	323
RTL8A	IRF2BP1	Q8IU81	295
RTL8A	TTC12	Q9H892	288
RTL8A	ZCCHC3	Q9NUD5	284

IntAct

25 interactions, top by confidence:

A	B	Type	Score
PEG10	RTL8C	psi-mi:“MI:0914”(association)	0.700
PEG10	RTL8A	psi-mi:“MI:0915”(physical association)	0.700
UBQLN1	RTL8A	psi-mi:“MI:0915”(physical association)	0.670
RTL8A	UBQLN1	psi-mi:“MI:0915”(physical association)	0.670
PEG10	RTL8C	psi-mi:“MI:0914”(association)	0.670
RTL8A	CCDC102B	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	RTL8A	psi-mi:“MI:0915”(physical association)	0.560
CCDC102B	RTL8A	psi-mi:“MI:0915”(physical association)	0.560
RTL8A	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
SLC1A3	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SLC39A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
RTL8A	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
RTL8A	PEG10	psi-mi:“MI:0915”(physical association)	0.000
PEG10	RTL8A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): UBQLN1 (Two-hybrid), CCDC102B (Two-hybrid), FAM127B (Affinity Capture-MS), UBQLN1 (Two-hybrid), FAM127B (Affinity Capture-MS), FAM127B (Affinity Capture-RNA), FAM127B (Two-hybrid), FAM127B (Two-hybrid), PEG10 (Two-hybrid), FAM127B (Affinity Capture-MS), FAM127B (Affinity Capture-MS), FAM127B (Affinity Capture-MS), FAM127B (Affinity Capture-MS), FAM127B (Affinity Capture-MS), FAM127B (Affinity Capture-MS)

ESM2 similar proteins: A6QLK5, A6ZKI3, D2HBJ8, O15519, O94955, O95751, P0CW24, P10272, Q0V9G5, Q17QF6, Q17RB0, Q1JQ94, Q2TBA3, Q5RD56, Q5RER6, Q5XGZ2, Q63053, Q6NTR6, Q6P5G6, Q6SEH4, Q6SEH5, Q70Z35, Q7JV70, Q7K1U0, Q7LC44, Q7TPY9, Q86TG7, Q8AWC3, Q8C1C8, Q8CA95, Q8N165, Q8N635, Q8ND90, Q8QZR7, Q8TCU6, Q8VHZ4, Q8WNV3, Q96PV4, Q9BWD3, Q9BYG7

Diamond homologs: A6NKG5, A6ZKI3, O95751, Q17QF6, Q17RB0, Q1JQ94, Q52QI2, Q5DTZ0, Q5HYW3, Q6SEH4, Q6SEH5, Q7M732, Q7TPY9, Q9BWD3, Q505G4, Q6ICC9, Q7TN75, Q86TG7, Q8N8U3, Q32KG4, Q5DTT4, Q5R6M8, Q7L3V2, Q6P1Y1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

281 predictions. Top by Δscore:

Variant	Effect	Δscore
X:135051853:T:TA	donor_gain	1.0000
X:135051761:C:CA	donor_gain	0.9800
X:135051780:T:TA	donor_gain	0.9800
X:135051783:T:TA	donor_gain	0.9800
X:135051774:T:TA	donor_gain	0.9700
X:135051849:T:A	donor_gain	0.9700
X:135051867:A:AC	donor_gain	0.9600
X:135051874:A:AC	donor_gain	0.9600
X:135051875:C:CC	donor_gain	0.9600
X:135051805:T:TA	donor_gain	0.9300
X:135051787:C:CA	donor_gain	0.8400
X:135051797:G:GT	donor_gain	0.7700
X:135051369:C:CC	acceptor_gain	0.7600
X:135051808:T:C	donor_gain	0.7300
X:135051472:TGC:T	donor_gain	0.6600
X:135051765:G:GA	donor_gain	0.6600
X:135051791:T:TA	donor_gain	0.6300
X:135051729:C:A	donor_gain	0.6200
X:135051919:T:A	donor_gain	0.6200
X:135051366:GGTC:G	acceptor_loss	0.6100
X:135051368:TCT:T	acceptor_loss	0.6100
X:135051369:C:G	acceptor_loss	0.6100
X:135051370:T:A	acceptor_loss	0.6100
X:135051911:CGTCA:C	donor_loss	0.6100
X:135051912:GTCAC:G	donor_loss	0.6100
X:135051913:TCAC:T	donor_loss	0.6100
X:135051914:CAC:C	donor_loss	0.6100
X:135051915:ACC:A	donor_loss	0.6100
X:135051916:C:A	donor_loss	0.6100
X:135051917:C:G	donor_loss	0.6000

AlphaMissense

740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:135051935:G:C	F58L	0.997
X:135051935:G:T	F58L	0.997
X:135051937:A:G	F58L	0.997
X:135052010:A:C	F33L	0.997
X:135052010:A:T	F33L	0.997
X:135052012:A:G	F33L	0.997
X:135051794:A:C	F105L	0.996
X:135051794:A:T	F105L	0.996
X:135051796:A:G	F105L	0.996
X:135051908:G:C	F67L	0.996
X:135051908:G:T	F67L	0.996
X:135051910:A:G	F67L	0.996
X:135051980:G:C	F43L	0.996
X:135051980:G:T	F43L	0.996
X:135051982:A:G	F43L	0.996
X:135051818:G:C	F97L	0.994
X:135051818:G:T	F97L	0.994
X:135051820:A:G	F97L	0.994
X:135051872:C:A	W79C	0.992
X:135051872:C:G	W79C	0.992
X:135051874:A:G	W79R	0.992
X:135051874:A:T	W79R	0.992
X:135051819:A:G	F97S	0.991
X:135051981:A:G	F43S	0.990
X:135051894:A:G	L72P	0.989
X:135052005:C:A	G35V	0.989
X:135052005:C:T	G35E	0.989
X:135051897:C:G	R71P	0.987
X:135051906:A:G	L68P	0.985
X:135051936:A:G	F58S	0.985

dbSNP variants (sampled 300 via entrez): RS1000679334 (X:135050683 C>T), RS1004861671 (X:135051465 C>A,T), RS1005529590 (X:135053538 T>C), RS1005715241 (X:135052409 G>T), RS1006914166 (X:135050765 C>T), RS1007209315 (X:135052328 C>A,G,T), RS1007302874 (X:135050745 A>C), RS1014268150 (X:135052412 C>A,G), RS1014397700 (X:135052940 T>G), RS1014748446 (X:135052638 C>G,T), RS1014862655 (X:135053607 T>C), RS1015297885 (X:135053583 A>G), RS1017177432 (X:135051479 G>A,C), RS1018468304 (X:135053945 A>G), RS1019492052 (X:135052340 T>C)

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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
microcystin RR	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Dexamethasone	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Selenium	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Vitamin E	increases expression, affects cotreatment, decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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