RTL8C

Summary

RTL8C (retrotransposon Gag like 8C, HGNC:2569) is a protein-coding gene on chromosome Xq26.3, encoding Retrotransposon Gag-like protein 8C (A6ZKI3).

Predicted to be located in plasma membrane.

Source: NCBI Gene 8933 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001078171

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2569
Approved symbol	RTL8C
Name	retrotransposon Gag like 8C
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	Mart8, Mar8, MAR8C, SIRH5
Ensembl gene	ENSG00000134590
Ensembl biotype	protein_coding
OMIM	300213
Entrez	8933

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000257013, ENST00000464369, ENST00000495563

RefSeq mRNA: 1 — MANE Select: NM_001078171 NM_001078171

CCDS: CCDS43997

Canonical transcript exons

ENST00000257013 — 1 exons

Exon	Start	End
ENSE00000921629	135032355	135033546

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 216.9141 / max 2438.9187, expressed in 1800 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197621	189.7396	1799
197620	20.0912	1757
197624	3.3872	1178
197622	2.5028	1145
197623	1.1933	776

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	99.53	gold quality
frontal pole	UBERON:0002795	99.45	gold quality
right frontal lobe	UBERON:0002810	99.34	gold quality
prefrontal cortex	UBERON:0000451	99.31	gold quality
hypothalamus	UBERON:0001898	99.30	gold quality
apex of heart	UBERON:0002098	99.27	gold quality
cingulate cortex	UBERON:0003027	99.27	gold quality
anterior cingulate cortex	UBERON:0009835	99.27	gold quality
amygdala	UBERON:0001876	99.21	gold quality
nucleus accumbens	UBERON:0001882	99.17	gold quality
heart left ventricle	UBERON:0002084	99.16	gold quality
cardiac ventricle	UBERON:0002082	99.15	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.13	gold quality
left ventricle myocardium	UBERON:0006566	99.12	gold quality
frontal cortex	UBERON:0001870	99.10	gold quality
adenohypophysis	UBERON:0002196	99.08	gold quality
caudate nucleus	UBERON:0001873	99.04	gold quality
spinal cord	UBERON:0002240	99.04	gold quality
right coronary artery	UBERON:0001625	99.02	gold quality
right atrium auricular region	UBERON:0006631	99.01	gold quality
temporal lobe	UBERON:0001871	98.99	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.99	gold quality
left coronary artery	UBERON:0001626	98.98	gold quality
neocortex	UBERON:0001950	98.98	gold quality
cardiac atrium	UBERON:0002081	98.97	gold quality
middle frontal gyrus	UBERON:0002702	98.97	gold quality
coronary artery	UBERON:0001621	98.95	gold quality
lower esophagus	UBERON:0013473	98.94	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	11.48
E-HCAD-25	yes	7.39
E-CURD-112	yes	6.57
E-MTAB-7303	no	650.53
E-MTAB-7052	no	202.47
E-MTAB-6678	no	3.64
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

44 targeting RTL8C, 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-3925-3P	100.00	69.95	1237
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-142-3P	99.62	71.30	974
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3960	99.41	66.11	96
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6868-5P	99.06	65.69	1284

Literature-anchored findings (GeneRIF, showing 3)

• Sequence-Selective Covalent CaaX-Box Receptors Prevent Farnesylation of Oncogenic Ras Proteins and Impact MAPK/PI3 K Signaling. (PMID:33899342)
• Evaluation of expression level and methylation profile of CXX1 gene in breast cancer tissue blocks. (PMID:34916361)
• 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): RTL3 (ENSG00000179300), 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 8C — A6ZKI3 (reviewed: A6ZKI3, O15255)

Alternative names: Mammalian retrotransposon derived protein 8C

All UniProt accessions (1): A6ZKI3

UniProt curated annotations — full annotation on UniProt →

Miscellaneous. RTL8C 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 (1): NP_001071639* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032549	RTL1/1-8/LDOC_capsid-like	Domain
IPR031771	CAAX_1	Family

Pfam: PF15895, PF16297

UniProt features (8 total): chain 2, sequence variant 2, propeptide 1, region of interest 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6ZKI3-F1	89.00	0.71
AF-O15255-F1	36.51	0.00

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 (2): 206, 206

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, TIEN_INTESTINE_PROBIOTICS_24HR_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, SUZUKI_RESPONSE_TO_TSA_AND_DECITABINE_1A, CHEN_HOXA5_TARGETS_9HR_DN, ACEVEDO_LIVER_CANCER_UP, LIEN_BREAST_CARCINOMA_METAPLASTIC_VS_DUCTAL_UP, CONCANNON_APOPTOSIS_BY_EPOXOMICIN_DN, BLALOCK_ALZHEIMERS_DISEASE_DN, ZHENG_GLIOBLASTOMA_PLASTICITY_UP, STEIN_ESRRA_TARGETS_UP, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_UP, KIM_ALL_DISORDERS_OLIGODENDROCYTE_NUMBER_CORR_UP, KIM_BIPOLAR_DISORDER_OLIGODENDROCYTE_DENSITY_CORR_UP, KIM_ALL_DISORDERS_CALB1_CORR_UP

GO Biological Process (0):

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

GO Cellular Component (1): plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

666 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RTL8C	RTL4	Q6ZR62	675
RTL8C	RTL5	Q5HYW3	672
RTL8C	RTL9	Q8NET4	606
RTL8C	CLLU1-AS1	Q5K130	433
RTL8C	IHO1	Q8IYA8	366
RTL8C	TCAF1	Q9Y4C2	364
RTL8C	MCRIP2	Q9BUT9	360
RTL8C	MOSPD1	Q9UJG1	315
RTL8C	SEZ6L	Q9BYH1	306
RTL8C	PPID	Q08752	306
RTL8C	TCEAL2	Q9H3H9	299
RTL8C	H0YL38	H0YL38	290
RTL8C	RABEPK	Q7Z6M1	287
RTL8C	ZNF280D	Q6N043	285
RTL8C	ZCCHC3	Q9NUD5	284

IntAct

92 interactions, top by confidence:

A	B	Type	Score
RTL8C	UBQLN1	psi-mi:“MI:0915”(physical association)	0.720
UBQLN1	RTL8C	psi-mi:“MI:0915”(physical association)	0.720
PEG10	RTL8C	psi-mi:“MI:0914”(association)	0.700
RTL8C	PEG10	psi-mi:“MI:0915”(physical association)	0.700
RTL8C	PEG10	psi-mi:“MI:0915”(physical association)	0.670
PEG10	RTL8C	psi-mi:“MI:0915”(physical association)	0.670
PEG10	RTL8C	psi-mi:“MI:0914”(association)	0.670
UBQLN1	RTL8C	psi-mi:“MI:0915”(physical association)	0.560
RTL8C	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
RTL8C	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
RTL8C	REL	psi-mi:“MI:0915”(physical association)	0.560
RTL8C	GPANK1	psi-mi:“MI:0915”(physical association)	0.560
RTL8C	CDKN2B	psi-mi:“MI:0915”(physical association)	0.560
RTL8C	LMO2	psi-mi:“MI:0915”(physical association)	0.560
RTL8C	CCDC102B	psi-mi:“MI:0915”(physical association)	0.560
RTL8C	SAMD11	psi-mi:“MI:0915”(physical association)	0.560
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
OTC	RTL8C	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
THTPA	RTL8C	psi-mi:“MI:0914”(association)	0.530

BioGRID (73): PEG10 (Two-hybrid), UBQLN1 (Two-hybrid), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (Affinity Capture-MS), FAM127A (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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

188 predictions. Top by Δscore:

Variant	Effect	Δscore
X:135032643:A:T	donor_gain	0.9900
X:135032708:G:GT	donor_gain	0.9800
X:135032730:G:GT	donor_gain	0.9800
X:135032711:G:GT	donor_gain	0.9700
X:135032690:C:T	donor_gain	0.9600
X:135032717:G:GT	donor_gain	0.9400
X:135032638:G:GT	donor_gain	0.9300
X:135032616:A:AG	donor_gain	0.9200
X:135032617:G:GG	donor_gain	0.9200
X:135032624:A:AG	donor_gain	0.9100
X:135032686:G:GT	donor_gain	0.8600
X:135032642:G:GT	donor_gain	0.8500
X:135032704:G:GT	donor_gain	0.8400
X:135032705:G:T	donor_gain	0.7700
X:135032700:G:GT	donor_gain	0.7400
X:135032726:G:GT	donor_gain	0.7300
X:135032684:A:G	donor_gain	0.7100
X:135032730:G:T	donor_gain	0.6800
X:135032727:C:T	donor_gain	0.6700
X:135032731:G:GT	donor_gain	0.6400
X:135032573:A:T	donor_gain	0.6300
X:135032571:TGAAG:T	donor_loss	0.6000
X:135032572:GAAGG:G	donor_loss	0.6000
X:135032573:AAG:A	donor_loss	0.6000
X:135032574:AGGT:A	donor_loss	0.6000
X:135032575:G:C	donor_loss	0.6000
X:135032576:G:T	donor_loss	0.6000
X:135032577:T:A	donor_loss	0.6000
X:135032705:G:GT	donor_gain	0.6000
X:135032689:G:GG	donor_gain	0.5900

AlphaMissense

738 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002500077 (X:135032061 T>C), RS1005620804 (X:135033979 T>C), RS1006304346 (X:135031980 G>C,T), RS1006397701 (X:135031373 A>G), RS1007148345 (X:135032811 C>G,T), RS1007559937 (X:135030831 G>A,C), RS1007943245 (X:135030373 G>A), RS1008124276 (X:135030906 A>G), RS1008570047 (X:135030743 C>A,T), RS1009339972 (X:135031202 G>A), RS1010564631 (X:135032579 A>G), RS1011212743 (X:135033687 A>G), RS1011973149 (X:135031504 T>A), RS1012829950 (X:135032296 G>A,C), RS1015953125 (X:135030909 G>A)

Disease associations

OMIM: gene MIM:300213 | 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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	increases expression	2
Aflatoxin B1	increases expression, decreases methylation	2
sodium arsenite	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
MT19c compound	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Doxorubicin	decreases expression	1
Fluorouracil	affects response to substance	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Potassium Dichromate	increases expression	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Tunicamycin	decreases expression	1
Valproic Acid	increases expression	1
Vitamin E	increases expression	1
Antirheumatic Agents	increases expression	1
Acrylamide	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3GD	Abcam HEK293T RTL8C KO	Transformed cell line	Female

Clinical trials (associated diseases)

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