LEUTX

Summary

LEUTX (leucine twenty homeobox, HGNC:31953) is a protein-coding gene on chromosome 19q13.2, encoding Paired-like homeodomain transcription factor LEUTX (A8MZ59). Paired-like homeobox transcription factor involved in embryogenesis.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 342900 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 24 total
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.05 (LoF-tolerant), LOEUF 1.84 (unconstrained)
• MANE Select transcript: NM_001382345

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31953
Approved symbol	LEUTX
Name	leucine twenty homeobox
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213921
Ensembl biotype	protein_coding
OMIM	618701
Entrez	342900

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000638280

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 2: 1, TSL 3: 1

ENST00000638280, ENST00000396841

RefSeq mRNA: 2 — MANE Select: NM_001382345 NM_001143832, NM_001382345

CCDS: CCDS92615

Canonical transcript exons

ENST00000638280 — 3 exons

Exon	Start	End
ENSE00003803257	39785698	39786291
ENSE00003806262	39778854	39778927
ENSE00003810096	39784527	39784678

Expression profiles

Bgee: expression breadth tissue_specific, 9 present calls, max score 97.16.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, colonic epithelium, ventricular zone, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LEUTX is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	eqtl	1.1e-07	+0.42	19:39784269:G:A

Top tissues by expression

showing 100 of 125 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.61	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
smooth muscle tissue	UBERON:0001135	29.47	silver quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
placenta	UBERON:0001987	28.66	silver quality
monocyte	CL:0000576	28.39	silver quality
leukocyte	CL:0000738	28.32	silver quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	27.00	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	24.98	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
pancreas	UBERON:0001264	24.17	gold quality
rectum	UBERON:0001052	24.16	silver quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
gastrocnemius	UBERON:0001388	23.78	gold quality
frontal cortex	UBERON:0001870	23.74	gold quality
kidney	UBERON:0002113	23.19	gold quality
calcaneal tendon	UBERON:0003701	23.08	gold quality
endometrium	UBERON:0001295	22.90	gold quality
right lobe of liver	UBERON:0001114	22.36	gold quality
lower esophagus mucosa	UBERON:0035834	22.15	gold quality
heart left ventricle	UBERON:0002084	22.01	gold quality
cortex of kidney	UBERON:0001225	21.85	gold quality
myometrium	UBERON:0001296	21.65	gold quality
body of pancreas	UBERON:0001150	21.36	gold quality
heart	UBERON:0000948	21.24	gold quality
tibial artery	UBERON:0007610	21.20	gold quality
popliteal artery	UBERON:0002250	21.19	gold quality
adult mammalian kidney	UBERON:0000082	21.10	gold quality
uterine cervix	UBERON:0000002	20.73	gold quality
granulocyte	CL:0000094	20.63	gold quality
stomach	UBERON:0000945	20.58	gold quality
esophagus mucosa	UBERON:0002469	20.44	gold quality
esophagus	UBERON:0001043	20.30	gold quality
apex of heart	UBERON:0002098	20.28	gold quality
multicellular organism	UBERON:0000468	19.92	silver quality
mucosa of transverse colon	UBERON:0004991	19.91	gold quality
lung	UBERON:0002048	19.71	gold quality
right atrium auricular region	UBERON:0006631	19.63	gold quality
thoracic aorta	UBERON:0001515	19.54	gold quality
ascending aorta	UBERON:0001496	19.53	gold quality
body of stomach	UBERON:0001161	19.46	gold quality
intestine	UBERON:0000160	19.45	gold quality
colon	UBERON:0001155	19.43	gold quality
right coronary artery	UBERON:0001625	19.38	gold quality
lower esophagus	UBERON:0013473	19.30	gold quality
lower esophagus muscularis layer	UBERON:0035833	19.28	gold quality
cerebellum	UBERON:0002037	19.25	gold quality
cerebellar cortex	UBERON:0002129	19.13	gold quality
small intestine	UBERON:0002108	19.12	gold quality
thoracic mammary gland	UBERON:0005200	19.04	gold quality
left coronary artery	UBERON:0001626	19.00	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	18.95	gold quality
cerebellar hemisphere	UBERON:0002245	18.89	gold quality
fundus of stomach	UBERON:0001160	18.84	gold quality
ovary	UBERON:0000992	18.79	gold quality
transverse colon	UBERON:0001157	18.76	gold quality
right adrenal gland cortex	UBERON:0035827	18.68	gold quality
saliva-secreting gland	UBERON:0001044	18.64	gold quality
right adrenal gland	UBERON:0001233	18.63	gold quality
Ammon’s horn	UBERON:0001954	18.62	gold quality
muscle layer of sigmoid colon	UBERON:0035805	18.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	18.53	gold quality
adipose tissue	UBERON:0001013	18.51	gold quality
subcutaneous adipose tissue	UBERON:0002190	18.47	gold quality
fallopian tube	UBERON:0003889	18.43	gold quality
putamen	UBERON:0001874	18.37	gold quality
descending thoracic aorta	UBERON:0002345	18.35	gold quality
mucosa of stomach	UBERON:0001199	18.29	gold quality
adrenal tissue	UBERON:0018303	18.25	gold quality
omental fat pad	UBERON:0010414	18.23	gold quality
temporal lobe	UBERON:0001871	18.21	gold quality
prostate gland	UBERON:0002367	18.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	18.12	gold quality
amygdala	UBERON:0001876	17.98	gold quality
zone of skin	UBERON:0000014	17.92	gold quality
substantia nigra	UBERON:0002038	17.91	gold quality
left ovary	UBERON:0002119	17.78	gold quality
nucleus accumbens	UBERON:0001882	17.75	gold quality
skin of abdomen	UBERON:0001416	17.70	gold quality
skin of leg	UBERON:0001511	17.70	gold quality
minor salivary gland	UBERON:0001830	17.60	gold quality
ectocervix	UBERON:0012249	17.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

HPA expression

RNA tissue specificity: Not detected

28 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Cerebellum	tissue	8.9
Olfactory bulb	tissue	6.2
Amygdala	tissue	5.3
Cerebral cortex	tissue	5.0
Basal ganglia	tissue	5.0
Corpus callosum	tissue	5.0
Occipital cortex	tissue	5.0
Insular cortex	tissue	4.7
Ventral pallidum	tissue	4.6
Cingulate cortex	tissue	4.6
Prefrontal cortex	tissue	4.5
Somatosensory cortex	tissue	4.4
Temporal cortex	tissue	4.4
Hippocampal formation	tissue	4.3
Entorhinal cortex	tissue	4.3
Retrosplenial cortex	tissue	4.2
Motor cortex	tissue	4.1
Substantia nigra	tissue	3.7
Putamen	tissue	3.6
Medulla oblongata	tissue	3.1
Periaqueductal gray	tissue	3.0
Hypothalamus	tissue	2.8
Spinal cord	tissue	2.7
Septum	tissue	2.7
Midbrain	tissue	2.6
Superior colliculi	tissue	2.3
Pons	tissue	2.2
Thalamus	tissue	1.7

Brain sub-regions (HPA Brain Atlas): detected in 6; highest nTPM — White matter (5.0), Dorsal hippocampus (4.2), Ventral hippocampus (3.9), Subiculum (3.4), Ventral spinal cord (2.7).

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2597.1	LEUTX	Paired-related HD

JASPAR matrix evidence (PMIDs): PMID:27578796

Functional genomics

gnomAD constraint: pLI 0.0455, LOEUF 1.84, missense Z 0.273 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000638280 — one region, missense o/e 0.97.

Literature-anchored findings (GeneRIF, showing 2)

• Rapid Evolution of the Embryonically Expressed Homeobox Gene LEUTX within Primates. (PMID:37232378)
• Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion. (PMID:38500181)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Dbx	FBGN0261723

Paralogs (3): DBX1 (ENSG00000109851), HLX (ENSG00000136630), DBX2 (ENSG00000185610)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Encephalitozoon cuniculi GB-M1	Q8SW51	46.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FBL	protein-coding	2091
FCGBP	protein-coding	8857
DYRK1B	protein-coding	9149
LGALS14	protein-coding	56891
MIR6719	ncRNA	102465974
CLC	protein-coding	1178

Protein

Protein identifiers

Paired-like homeodomain transcription factor LEUTX — A8MZ59 (reviewed: A8MZ59)

Alternative names: Leucine-twenty homeobox, Paired-like homeobox transcription factor LEUTX

All UniProt accessions (1): A8MZ59

UniProt curated annotations — full annotation on UniProt →

Function. Paired-like homeobox transcription factor involved in embryogenesis. May act as a regulator of embryo genome activation. Binds to a 36 bp DNA elements containing a 5’-TAATCC-3’ sequence motif, referred to as EEA motif (EGA-enriched Alu-motif), present in the promoters of target genes activated in early embryos. Inactive transcriptional activity.

Subcellular location. Nucleus.

Domain organisation. The homeobox contain essential residues (Ile-54, Lys-57, Ala-61) for binding to the 5’-TAATCC-3’ motif of the targe gene promoters. The homeobox is incomplete and cannot bind to the 36 bp motif found in the promoters of the target genes. The 9aaTAD motif is a conserved putative nine amino acid transactivation motifs in C-terminus of the LEUTX region.

Similarity. Belongs to the paired homeobox family.

Isoforms (2)

UniProt ID	Names	Canonical?
A8MZ59-2	1, LEUTX.n	yes
A8MZ59-1	2, LEUTX.R

RefSeq proteins (2): NP_001137304, NP_001369274* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site

Pfam: PF00046

UniProt features (17 total): short sequence motif 4, site 3, mutagenesis site 2, sequence conflict 2, region of interest 2, chain 1, DNA-binding region 1, splice variant 1, compositionally biased region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MZ59-F1	68.84	0.29

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Helix-turn-helix domains

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli; nucleoplasm

Antibody reliability (HPA): IH uncertain · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3)

Position	Role
57	required for binding to the 5’-taatcc-3’ sequence
61	required for binding to the 5’-taatcc-3’ sequence
54	required for binding to the 5’-taatcc-3’ sequence

Mutagenesis-validated functional residues (2)

Position	Phenotype
54	increased transcriptional activity; when associated with ala-61-val, restores wild-type transcriptional activity.
61	abolished catalytic activity; when associated with ile-54-thr, restores wild-type transcriptional activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-9819196	Zygotic genome activation (ZGA)	curated
R-HSA-1266738	Developmental Biology	—
R-HSA-9816359	Maternal to zygotic transition (MZT)	—

MSigDB gene sets: 14 (showing top): KUUSELO_PANCREATIC_CANCER_19Q13_AMPLIFICATION, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, WP_PREIMPLANTATION_EMBRYO, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, REACTOME_MATERNAL_TO_ZYGOTIC_TRANSITION_MZT, REACTOME_ZYGOTIC_GENOME_ACTIVATION_ZGA, PULVER_FOREY_PERTURB_ATTRITION_S, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, chr19q13, GOCC_CHROMATIN, FLORIO_NEOCORTEX_BASAL_RADIAL_GLIA_UP, FLORIO_HUMAN_NEOCORTEX

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Maternal to zygotic transition (MZT)	1
Developmental Biology	1

GO top-level categories

16 GO namespaces:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

showing 15 of 444 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LEUTX	DPRX	A6NFQ7	807
LEUTX	DUXB	A0A1W2PPF3	756
LEUTX	DUX4L2	P0CJ85	750
LEUTX	TPRX1	Q8N7U7	747
LEUTX	KHDC1L	Q5JSQ8	739
LEUTX	DUXA	A6NLW8	734
LEUTX	TRIM43	Q96BQ3	702
LEUTX	PRAMEF1	O95521	677
LEUTX	ZSCAN4	Q8NAM6	659
LEUTX	MBD3L2	Q8NHZ7	655
LEUTX	KHDC1	Q4VXA5	630
LEUTX	NUTM2A	Q8IVF1	606
LEUTX	PRAMEF2	O60811	570
LEUTX	MBD3L3	A6NE82	550
LEUTX	NUTM1	Q86Y26	548

IntAct

Human interaction partners of LEUTX in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 45 partners by confidence:

Partner	Interaction type	MIscore	Records
AGPAT4	physical association	0.560	3
AIG1	physical association	0.560	3
AQP2	physical association	0.560	3
AQP3	physical association	0.560	3
ASGR1	physical association	0.560	3
C1QL4	physical association	0.560	3
CDS2	physical association	0.560	3
CMTM3	physical association	0.560	3
CMTM5	physical association	0.560	3
CNIH1	physical association	0.560	3
CNIH3	physical association	0.560	3
CXCL9	physical association	0.560	3
EMP3	physical association	0.560	3
ENTPD3	physical association	0.560	3
FAM24B	physical association	0.560	3
FZD7	physical association	0.560	3
GOSR2	physical association	0.560	3
KIR2DL3	physical association	0.560	3
LAT	physical association	0.560	3
MRPL57	physical association	0.560	3
MS4A1	physical association	0.560	3
NAPB	physical association	0.560	3
NDRG4	physical association	0.560	3
OLFM4	physical association	0.560	3
PLP1	physical association	0.560	3
PNLIPRP1	physical association	0.560	3
PRB1	physical association	0.560	3
SLC13A3	physical association	0.560	3
SLC30A8	physical association	0.560	3
SLC41A2	physical association	0.560	3

BioGRID (47 interactions; top human partners by supporting records): AGPAT4 (Two-hybrid), AIG1 (Two-hybrid), AQP2 (Two-hybrid), AQP3 (Two-hybrid), ASGR1 (Two-hybrid), C1GALT1 (Two-hybrid), C1QL4 (Two-hybrid), C3orf52 (Two-hybrid), CDS2 (Two-hybrid), CMTM3 (Two-hybrid), CMTM5 (Two-hybrid), CNIH1 (Two-hybrid), CNIH3 (Two-hybrid), CXCL9 (Two-hybrid), EMP3 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for LEUTX: 24 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	3
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 30 predictions of 216):

Position(s)	Effect	Δscore	Sites
19:39785696–39785697	acceptor_loss	1.0000	5
19:39778928–39778929	donor_loss	0.9900	5
19:39784652	donor_gain	0.9900
19:39785697	acceptor_loss	0.9800
19:39784525–39784526	acceptor_loss	0.9600	6
19:39784511	acceptor_loss	0.9400
19:39784313	donor_gain	0.9300
19:39784513	acceptor_loss	0.9300
19:39784679–39784680	donor_loss	0.9300	5
19:39784678–39784680	donor_loss	0.9200	4

AlphaMissense

178 missense substitutions predicted likely pathogenic (of 1,279 scored), across 47 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N58	8	0.935	0.973
F56	7	0.961	0.991
W55	7	0.897	0.946
F15	7	0.896	0.972
D48	7	0.689	0.875
K57	6	0.884	0.981
P33	6	0.861	0.951
R12	6	0.838	0.929
Q19	6	0.830	0.901
K62	6	0.793	0.923
T13	6	0.727	0.901
K53	5	0.795	0.907
V52	5	0.780	0.924
L23	5	0.737	0.965
A42	4	0.856	0.965
L47	4	0.834	0.920
Q59	4	0.791	0.946
V51	4	0.752	0.815
W155	4	0.748	0.793
S34	4	0.731	0.739

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:618701 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST006976_86	Macular thickness	5e-17

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.