L1TD1

Summary

L1TD1 (LINE1 type transposase domain containing 1, HGNC:25595) is a protein-coding gene on chromosome 1p31.3, encoding LINE-1 type transposase domain-containing protein 1 (Q5T7N2).

Predicted to enable single-stranded RNA binding activity. Predicted to be involved in retrotransposition. Located in intracellular membrane-bounded organelle.

Source: NCBI Gene 54596 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_019079

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25595
Approved symbol	L1TD1
Name	LINE1 type transposase domain containing 1
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10884, ECAT11
Ensembl gene	ENSG00000240563
Ensembl biotype	protein_coding
OMIM	621222
Entrez	54596

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 20 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000498273, ENST00000717380, ENST00000928897, ENST00000928898, ENST00000928899, ENST00000928901, ENST00000928902, ENST00000928903, ENST00000928904, ENST00000928905, ENST00000928906, ENST00000928907, ENST00000928908, ENST00000928909, ENST00000928910, ENST00000928911, ENST00000928912, ENST00000928913, ENST00000928914, ENST00000928915, ENST00000928916

RefSeq mRNA: 2 — MANE Select: NM_019079 NM_001164835, NM_019079

CCDS: CCDS619

Canonical transcript exons

ENST00000498273 — 4 exons

Exon	Start	End
ENSE00001850840	62206519	62207636
ENSE00001944644	62196435	62196528
ENSE00001952571	62209783	62212328
ENSE00004032375	62194849	62194921

Expression profiles

Bgee: expression breadth broad, 86 present calls, max score 94.76.

FANTOM5 (CAGE): breadth broad, TPM avg 22.0576 / max 1568.1954, expressed in 349 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3133	21.2413	341
3140	0.3562	73
3132	0.1634	65
3141	0.0987	42
3131	0.0732	33
3139	0.0687	34
3142	0.0562	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.11	gold quality
placenta	UBERON:0001987	83.14	gold quality
vermiform appendix	UBERON:0001154	72.88	gold quality
mucosa of transverse colon	UBERON:0004991	71.11	gold quality
testis	UBERON:0000473	68.19	gold quality
leukocyte	CL:0000738	64.94	gold quality
monocyte	CL:0000576	64.93	gold quality
right testis	UBERON:0004534	64.83	gold quality
left testis	UBERON:0004533	64.40	gold quality
colonic epithelium	UBERON:0000397	63.83	gold quality
transverse colon	UBERON:0001157	63.40	gold quality
sural nerve	UBERON:0015488	61.52	silver quality
granulocyte	CL:0000094	60.10	gold quality
tibial nerve	UBERON:0001323	60.00	gold quality
rectum	UBERON:0001052	58.04	gold quality
spleen	UBERON:0002106	54.95	gold quality
lung	UBERON:0002048	54.51	gold quality
colon	UBERON:0001155	54.50	gold quality
ventricular zone	UBERON:0003053	53.78	gold quality
calcaneal tendon	UBERON:0003701	53.49	gold quality
smooth muscle tissue	UBERON:0001135	52.47	gold quality
right adrenal gland	UBERON:0001233	51.67	gold quality
upper lobe of left lung	UBERON:0008952	51.43	gold quality
intestine	UBERON:0000160	51.35	gold quality
lymph node	UBERON:0000029	50.98	gold quality
gall bladder	UBERON:0002110	50.77	gold quality
adrenal tissue	UBERON:0018303	50.70	gold quality
adrenal gland	UBERON:0002369	49.82	gold quality
islet of Langerhans	UBERON:0000006	49.64	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	1307.36
E-MTAB-9388	yes	304.74
E-GEOD-125970	yes	10.74
E-ANND-3	yes	3.86
E-GEOD-137537	no	3.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NANOG, POU5F1, SOX2

miRNA regulators (miRDB)

39 targeting L1TD1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-548AV-3P	99.43	68.50	1721
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-3152-3P	99.10	66.35	678
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-4317	98.49	67.09	987
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-3680-5P	98.06	66.20	394
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-1279	97.83	67.50	1898

Literature-anchored findings (GeneRIF, showing 24)

• LINE-1 hypomethylation is significantly associated with CpG island hypermethylation in EF+ gastritis. (PMID:18842996)
• there was no significant association of LINE-1 methylation with case status, although reduced LINE-1 methylation was associated with increased risk of bladder cancer among never smokers (PMID:21445976)
• L1TD1 is a downstream target of Nanog and represents a useful marker for identifying undifferentiated hESC (PMID:21559406)
• L1TD1 is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4, suggesting that L1TD1 has an important role in the regulation of stemness. (PMID:22162396)
• LINE-1 hypomethylation in gastric cancer is associated with shorter survival, suggesting that it has potential for use as a prognostic biomarker. (PMID:23179365)
• Paternal methylation aberrations at imprinting control regions of DLK1-GTL2, MEST (PEG1), and ZAC (PLAGL1) and global methylation levels are not associated with idiopathic recurrent spontaneous miscarriages. (PMID:23415968)
• LINE-1 methylation was evaluated, a statistical difference was seen amongst groups and a slight hypomethylated state in the AgP samples was observed. (PMID:24769218)
• L1TD1 may have become incorporated into pluripotency maintenance in some lineages. (PMID:25211013)
• we show that L1TD1 is a part of the pluripotency interactome network of OCT4, SOX2, and NANOG, bridging nuclear and cytoplasmic regulation and highlighting the importance of RNA biology in pluripotency. (PMID:25702638)
• L1TD1 depletion reduced medulloblastoma cell viability, cell proliferation, downregulated expression of the neural stem cell markers and induced apoptosis. (PMID:26159230)
• SPAG6 and L1TD1 are tumor-specifically methylated in NSCLCs and that DNA methylation is involved in the transcriptional regulation of these genes. Moreover, in vitro as well as in vivo experiments revealed tumor-cell growth suppressing properties of L1TD1 in NSCLC cells. (PMID:28093071)
• this study shows that LINE1 contributes to autoimmunity through both RIG-I- and MDA5-mediated RNA sensing pathways (PMID:29525183)
• The authors propose a model in which RNase H2 degrades the LINE-1 RNA after reverse transcription, allowing retrotransposition to be completed. This also explains how LINE-1 elements can retrotranspose efficiently without their own RNase H activity. (PMID:29959219)
• Study results identify increased expression of L1TD1 as a prognostic marker predicting longer disease-free survival in colon cancer patients. (PMID:31337362)
• Hepatitis C virus infection restricts human LINE-1 retrotransposition in hepatoma cells. (PMID:33872335)
• The Rhox gene cluster suppresses germline LINE1 transposition. (PMID:34083437)
• Structural dissection of sequence recognition and catalytic mechanism of human LINE-1 endonuclease. (PMID:34554261)
• Maternal LINE-1 DNA Methylation in Early Spontaneous Preterm Birth. (PMID:34727781)
• LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint. (PMID:35169076)
• MxB inhibits long interspersed element type 1 retrotransposition. (PMID:35171907)
• The differential expression of long interspersed nuclear elements-1 as a marker for hypomethylation in Merkel cell carcinoma. (PMID:35596537)
• LINE-1 hypomethylation is associated with poor outcomes in locoregionally advanced oropharyngeal cancer. (PMID:36503584)
• Identification and characterization of the long non-coding RNA NFIA-AS2 as a novel locus for body mass index in American Indians. (PMID:36806387)
• Dissolution of ribonucleoprotein condensates by the embryonic stem cell protein L1TD1. (PMID:38165001)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	L1td1	ENSMUSG00000087166
rattus_norvegicus	L1td1	ENSRNOG00000050670

Protein

Protein identifiers

LINE-1 type transposase domain-containing protein 1 — Q5T7N2 (reviewed: Q5T7N2)

Alternative names: Embryonic stem cell-associated protein 11

All UniProt accessions (1): Q5T7N2

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the transposase 22 family.

RefSeq proteins (2): NP_001158307, NP_061952* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004244	Transposase_22	Family
IPR035300	L1_dsRBD	Domain
IPR042566	L1_C	Homologous_superfamily
IPR043636	L1_RRM_dom	Domain

Pfam: PF02994, PF17490

UniProt features (37 total): modified residue 13, sequence variant 7, compositionally biased region 4, helix 3, region of interest 2, turn 2, strand 2, initiator methionine 1, chain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3SOO	X-RAY DIFFRACTION	2.73
2LR6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T7N2-F1	56.06	0.13

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 (13): 2, 149, 154, 472, 476, 478, 518, 561, 573, 640, 648, 665, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOMF_SINGLE_STRANDED_RNA_BINDING, BENPORATH_ES_1, HAMAI_APOPTOSIS_VIA_TRAIL_UP, YAUCH_HEDGEHOG_SIGNALING_PARACRINE_UP, HATADA_METHYLATED_IN_LUNG_CANCER_UP, HUTTMANN_B_CLL_POOR_SURVIVAL_UP, MIKKELSEN_MEF_HCP_WITH_H3_UNMETHYLATED, GOBP_TRANSPOSITION, LEE_NEURAL_CREST_STEM_CELL_UP, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, IL15_UP.V1_UP, JAK2_DN.V1_UP, KRAS.600.LUNG.BREAST_UP.V1_UP, GSE13522_WT_VS_IFNG_KO_SKIN_UP

GO Biological Process (1): retrotransposition (GO:0032197)

GO Molecular Function (2): single-stranded RNA binding (GO:0003727), protein binding (GO:0005515)

GO Cellular Component (1): ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transposition	1
RNA binding	1
binding	1
protein-containing complex	1

Protein interactions and networks

STRING

2953 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
L1TD1	LIN28A	Q9H9Z2	725
L1TD1	POU5F1	P31359	560
L1TD1	C11orf96	Q7Z7L8	471
L1TD1	OR7G2	Q8NG99	396
L1TD1	OR10R2	Q8NGX6	377
L1TD1	PPP1R21	Q6ZMI0	370
L1TD1	DPPA4	Q7L190	367
L1TD1	SPAG6	O75602	342
L1TD1	NBPF19	A0A087WUL8	329
L1TD1	NANOG	Q9H9S0	324
L1TD1	DRC8	Q5VUJ9	323
L1TD1	ANKRD65	E5RJM6	319
L1TD1	ZSCAN10	Q96SZ4	315
L1TD1	SOX2	P48431	305
L1TD1	UTF1	Q5T230	300

IntAct

23 interactions, top by confidence:

A	B	Type	Score
L1TD1	HNRNPA2B1	psi-mi:“MI:0915”(physical association)	0.560
SOX2	POU5F1	psi-mi:“MI:0914”(association)	0.560
L1TD1	KPNA2	psi-mi:“MI:0914”(association)	0.460
KPNA2	POU5F1	psi-mi:“MI:0914”(association)	0.460
L1TD1	PARP1	psi-mi:“MI:0403”(colocalization)	0.460
L1TD1	PARP1	psi-mi:“MI:0914”(association)	0.460
ZNF512B	L1TD1	psi-mi:“MI:0915”(physical association)	0.370
L1TD1	PPP1R12C	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
L1TD1	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
L1TD1	SRSF3	psi-mi:“MI:0914”(association)	0.350
KPNA2	PARP1	psi-mi:“MI:0403”(colocalization)	0.350
GAPDH	KPNA2	psi-mi:“MI:0403”(colocalization)	0.350
L1TD1	SOX2	psi-mi:“MI:0914”(association)	0.350
L1TD1	PSMD11	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
KRT27	CCDC88B	psi-mi:“MI:0914”(association)	0.350
CSNK2B	TUBAL3	psi-mi:“MI:0914”(association)	0.350

BioGRID (28): LIN28A (Affinity Capture-Western), DHX9 (Affinity Capture-Western), KIF5B (Affinity Capture-MS), TCOF1 (Affinity Capture-MS), KAT6A (Affinity Capture-MS), CBX4 (Affinity Capture-MS), EIF3I (Affinity Capture-MS), TRIM28 (Affinity Capture-MS), TRIOBP (Affinity Capture-MS), DCTN3 (Affinity Capture-MS), POLR1A (Affinity Capture-MS), BBS9 (Affinity Capture-MS), MRPL4 (Affinity Capture-MS), PPP1R12C (Affinity Capture-MS), UACA (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GR13, A1KXM5, A1Z7A8, A2AEY4, A4FU49, A6NE01, A6X8Z9, B0QZF7, E1JH25, E9PVX6, E9Q0C6, E9Q7D5, F6XZJ7, O14100, P22575, P35663, P46013, P88825, Q05860, Q06813, Q13127, Q2YDJ5, Q32MG2, Q3UZB0, Q4QY64, Q4R729, Q53TS8, Q5BI31, Q5JRM2, Q5R7U0, Q5SRN2, Q5T7N2, Q66H17, Q6AXV6, Q70KF4, Q7TSG5, Q810T2, Q8BUY8, Q8IWC1, Q8N3K9

Diamond homologs: P11260, Q587J6, Q5T7N2, Q9UN81

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

419 predictions. Top by Δscore:

Variant	Effect	Δscore
1:62209769:T:TA	acceptor_gain	1.0000
1:62209774:A:AG	acceptor_gain	1.0000
1:62209775:A:AG	acceptor_gain	1.0000
1:62209780:CAGG:C	acceptor_loss	1.0000
1:62209781:A:AG	acceptor_gain	1.0000
1:62209781:AG:A	acceptor_gain	1.0000
1:62209782:G:GT	acceptor_gain	1.0000
1:62209782:GG:G	acceptor_gain	1.0000
1:62209782:GGA:G	acceptor_gain	1.0000
1:62209782:GGAT:G	acceptor_gain	1.0000
1:62209782:GGATA:G	acceptor_gain	1.0000
1:62194918:CCAG:C	donor_loss	0.9900
1:62194921:GGTAA:G	donor_loss	0.9900
1:62194922:G:A	donor_loss	0.9900
1:62209776:C:G	acceptor_gain	0.9900
1:62209780:CAGGA:C	acceptor_gain	0.9900
1:62209781:AGGAT:A	acceptor_gain	0.9900
1:62194917:GCCAG:G	donor_gain	0.9800
1:62196525:CTTGG:C	donor_loss	0.9800
1:62196526:TTGG:T	donor_loss	0.9800
1:62196527:TGGTA:T	donor_loss	0.9800
1:62196528:GGTA:G	donor_loss	0.9800
1:62196529:G:A	donor_loss	0.9800
1:62196529:G:GG	donor_gain	0.9800
1:62196530:T:G	donor_loss	0.9800
1:62209779:TCAGG:T	acceptor_gain	0.9800
1:62196433:A:AG	acceptor_gain	0.9700
1:62196434:G:GG	acceptor_gain	0.9700
1:62207635:GG:G	donor_gain	0.9700
1:62207636:GG:G	donor_gain	0.9700

AlphaMissense

5781 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:62211193:T:A	W807R	0.998
1:62211193:T:C	W807R	0.998
1:62211084:A:C	K770N	0.996
1:62211084:A:T	K770N	0.996
1:62211186:A:C	R804S	0.996
1:62211186:A:T	R804S	0.996
1:62211195:G:C	W807C	0.996
1:62211195:G:T	W807C	0.996
1:62210881:C:A	R703S	0.995
1:62210885:T:C	L704S	0.995
1:62211047:G:C	R758T	0.995
1:62211048:A:C	R758S	0.995
1:62211048:A:T	R758S	0.995
1:62211149:T:C	L792S	0.994
1:62210882:G:C	R703P	0.993
1:62210891:G:A	G706E	0.993
1:62211065:T:C	F764S	0.993
1:62211147:G:C	R791S	0.993
1:62211147:G:T	R791S	0.993
1:62211185:G:C	R804T	0.993
1:62211194:G:C	W807S	0.993
1:62211242:T:C	I823T	0.993
1:62211265:T:C	F831L	0.993
1:62211266:T:C	F831S	0.993
1:62211267:T:A	F831L	0.993
1:62211267:T:G	F831L	0.993
1:62211292:T:C	F840L	0.993
1:62211294:T:A	F840L	0.993
1:62211294:T:G	F840L	0.993
1:62210959:T:C	F729L	0.992

dbSNP variants (sampled 300 via entrez): RS1000066997 (1:62207185 GAAATCGCAA>G), RS1000224873 (1:62193782 C>A), RS1000523340 (1:62198359 G>A,T), RS1000672510 (1:62205889 G>A), RS1000695546 (1:62207745 T>A), RS1001075859 (1:62195589 C>G), RS1001248737 (1:62195226 G>A), RS1001368633 (1:62212343 T>C,G), RS1001414030 (1:62197497 T>G), RS1001678791 (1:62194871 T>C), RS1001714378 (1:62208991 G>A), RS1001814000 (1:62199627 C>T), RS1001922261 (1:62197397 T>A,C), RS1002090167 (1:62210006 C>A,G), RS1002098045 (1:62199877 A>T)

Disease associations

OMIM: gene MIM:621222 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006109_1	Lip morphology	9.000000e-06
GCST006920_5	Regular attendance at a gym or sports club	1.000000e-08
GCST007552_31	Colorectal cancer	4.000000e-08
GCST009391_729	Metabolite levels	1.000000e-06
GCST011053_5	Neuroblastoma (pediatric)	6.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0009774	serine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases expression, affects cotreatment	6
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	affects expression, increases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
bisphenol A	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Decitabine	decreases methylation	1
Panobinostat	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Fluorouracil	affects reaction, decreases expression	1
Rotenone	increases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SV18	HAP1 L1TD1 (-) 1	Cancer cell line	Male
CVCL_SV19	HAP1 L1TD1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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