LIAT1

Summary

LIAT1 (ligand of ATE1, HGNC:33800) is a protein-coding gene on chromosome 17p13.3, encoding Protein LIAT1 (Q6ZQX7). Participates in nucleolar liquid-liquid phase separation (LLPS) through its N-terminal intrinsically disordered region (IDR).

Predicted to enable molecular condensate scaffold activity. Predicted to be involved in membraneless organelle assembly and protein arginylation. Predicted to be located in cytoplasm and nucleus. Predicted to be active in nucleolus.

Source: NCBI Gene 400566 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 49 total — 1 pathogenic
• MANE Select transcript: NM_001013672

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33800
Approved symbol	LIAT1
Name	ligand of ATE1
Location	17p13.3
Locus type	gene with protein product
Status	Approved
Aliases	LOC400566
Ensembl gene	ENSG00000187624
Ensembl biotype	protein_coding
Entrez	400566

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000360127, ENST00000491373, ENST00000571106, ENST00000575151, ENST00000629953

RefSeq mRNA: 1 — MANE Select: NM_001013672 NM_001013672

CCDS: CCDS32519

Canonical transcript exons

ENST00000360127 — 2 exons

Exon	Start	End
ENSE00001528657	413148	414666
ENSE00002438832	410325	410646

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.4909 / max 281.4770, expressed in 1451 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158680	5.4909	1451

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.49	gold quality
right testis	UBERON:0004534	95.14	gold quality
testis	UBERON:0000473	94.75	gold quality
right uterine tube	UBERON:0001302	94.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.22	gold quality
nucleus accumbens	UBERON:0001882	82.98	gold quality
superior frontal gyrus	UBERON:0002661	81.58	gold quality
putamen	UBERON:0001874	81.55	gold quality
caudate nucleus	UBERON:0001873	81.49	gold quality
mucosa of transverse colon	UBERON:0004991	81.25	gold quality
hypothalamus	UBERON:0001898	79.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.72	gold quality
cortex of kidney	UBERON:0001225	79.64	gold quality
fallopian tube	UBERON:0003889	79.51	gold quality
primary visual cortex	UBERON:0002436	79.31	gold quality
right frontal lobe	UBERON:0002810	79.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.10	gold quality
Ammon’s horn	UBERON:0001954	78.90	gold quality
anterior cingulate cortex	UBERON:0009835	78.81	gold quality
pituitary gland	UBERON:0000007	78.34	gold quality
adult mammalian kidney	UBERON:0000082	78.34	gold quality
cerebral cortex	UBERON:0000956	78.30	gold quality
brain	UBERON:0000955	77.99	gold quality
temporal lobe	UBERON:0001871	77.89	gold quality
amygdala	UBERON:0001876	77.86	gold quality
kidney	UBERON:0002113	77.78	gold quality
metanephros cortex	UBERON:0010533	77.73	gold quality
adenohypophysis	UBERON:0002196	77.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.18

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting LIAT1, 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-4789-3P	99.99	70.75	2484
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-1304-5P	98.90	68.58	1054
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4751	98.80	64.95	525
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-15A-3P	97.47	65.08	527
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-8069	97.05	66.79	718
HSA-MIR-591	96.29	68.16	611
HSA-MIR-5186	94.63	66.76	627
HSA-MIR-6765-5P	94.51	62.65	164
HSA-MIR-3672	94.46	65.67	646
HSA-MIR-6864-3P	94.46	65.97	625

Literature-anchored findings (GeneRIF, showing 1)

• The Ligand of Ate1 is intrinsically disordered and participates in nucleolar phase separation regulated by Jumonji Domain Containing 6. (PMID:33443146)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Liat1	ENSMUSG00000053783
rattus_norvegicus	Liat1	ENSRNOG00000025287

Protein

Protein identifiers

Protein LIAT1 — Q6ZQX7 (reviewed: Q6ZQX7)

Alternative names: Ligand of ATE1 protein

All UniProt accessions (4): A0A0H4IV28, H7C5B9, I3L0T0, Q6ZQX7

UniProt curated annotations — full annotation on UniProt →

Function. Participates in nucleolar liquid-liquid phase separation (LLPS) through its N-terminal intrinsically disordered region (IDR). May be involved in ATE1-mediated N-terminal arginylation.

Subunit / interactions. Self-associates (via Lys-rich domain); targets LIAT1 to the nucleolus. Interacts with ATE1; it is not a substrate of ATE1, the interaction takes place in the cytoplasm and seems to increase ATE1 arginyltransferase activity. Interacts with JMJD6 and MRPS14.

Subcellular location. Nucleus. Nucleolus. Cytoplasm.

Post-translational modifications. Post-translationally modified by JMJD6 lysyl-hydroxylase activity at its Lys-rich domain, which inhibits its self-association and nucleolar localization.

Domain organisation. LIAT1 proteins of some primates, from macaques to humans, contain tandem repeats of a 10-residue sequence, whereas LIAT1 proteins of other mammals contain a single copy of this motif. Quantities of these repeats are, in general, different in LIAT1 of different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in the gibbon, gorilla, orangutan, bonobo, neanderthal, and human LIAT1, respectively. The N-terminal intrinsically disordered region (IDR) facilitates its liquid-liquid phase separation (LLPS) in the nucleolus. In the IDR, the lysine-rich domain mediates self-association and targeting to the nucleolus.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6ZQX7-1	1	yes
Q6ZQX7-2	2
Q6ZQX7-3	3
Q6ZQX7-4	4

RefSeq proteins (1): NP_001013694* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038794	LIAT1	Family

UniProt features (40 total): repeat 20, region of interest 6, compositionally biased region 4, splice variant 4, sequence conflict 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZQX7-F1	46.92	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 72 (showing top): GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ORGANELLE_ASSEMBLY, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, ACEVEDO_LIVER_CANCER_UP, GOBP_PROTEIN_CATABOLIC_PROCESS, GOBP_PROTEOLYSIS, GOCC_NUCLEOLUS, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, KOYAMA_SEMA3B_TARGETS_DN, PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_7, HHEX_TARGET_GENES, HOXA10_TARGET_GENES, HOXB4_TARGET_GENES, HOXB6_TARGET_GENES

GO Biological Process (2): protein arginylation (GO:0016598), membraneless organelle assembly (GO:0140694)

GO Molecular Function (2): molecular condensate scaffold activity (GO:0140693), protein binding (GO:0005515)

GO Cellular Component (3): nucleolus (GO:0005730), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ubiquitin-dependent protein catabolic process	1
protein modification process	1
organelle assembly	1
protein-macromolecule adaptor activity	1
binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

800 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIAT1	KRT7	P08729	960
LIAT1	CDX2	Q99626	904
LIAT1	KRT19	P08727	877
LIAT1	KRT5	P13647	824
LIAT1	NAPSA	O96009	815
LIAT1	SYP	P08247	812
LIAT1	PIP	P12273	810
LIAT1	KRT18	P05783	801
LIAT1	PAX8	Q06710	791
LIAT1	CEACAM5	P06731	788
LIAT1	NKX2-1	P43699	781
LIAT1	MUC2	Q02817	776
LIAT1	KRT8	P05787	720
LIAT1	MME	P08473	719
LIAT1	MUC6	Q6W4X9	716

IntAct

3 interactions, top by confidence:

A	B	Type	Score
JMJD6	LIAT1	psi-mi:“MI:0915”(physical association)	0.370
AGBL3	CLIC3	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): C17orf97 (Proximity Label-MS), C17orf97 (Proximity Label-MS), C17orf97 (Affinity Capture-MS), C17orf97 (Affinity Capture-MS), C17orf97 (Affinity Capture-MS), JMJD6 (Two-hybrid)

ESM2 similar proteins: A0A087WUL8, A0A0J9YWL9, A0A0J9YY54, A0A0U1RQI7, A6NJ88, A6QL64, B4DH59, D3ZVV1, E9Q6E9, F1LWT0, O04492, O88799, P0DKJ7, P0DKJ8, P0DKL2, P0DPF3, P18583, P53353, Q08AG5, Q0P6D6, Q2EG98, Q3BBV2, Q4ZJZ1, Q5HY64, Q5JPF3, Q5QGU6, Q5TAG4, Q5TI25, Q5XHX6, Q6P3W6, Q6P902, Q6XPR3, Q6ZQX7, Q86T75, Q86VE3, Q86VQ3, Q8N2N9, Q8N660, Q8N693, Q96EQ9

Diamond homologs: Q6ZQX7, Q810M6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	17
Likely benign	27
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4076090	GRCh37/hg19 17p13.3(chr17:124606-643426)x1	Pathogenic

SpliceAI

294 predictions. Top by Δscore:

Variant	Effect	Δscore
17:410612:G:GT	donor_gain	1.0000
17:410612:G:T	donor_gain	0.9500
17:413146:A:AG	acceptor_gain	0.9500
17:413147:G:GG	acceptor_gain	0.9500
17:410592:A:T	donor_gain	0.9400
17:410613:A:T	donor_gain	0.9400
17:410591:G:GT	donor_gain	0.9300
17:410615:G:GT	donor_gain	0.9300
17:410618:G:GT	donor_gain	0.9100
17:410642:GGACG:G	donor_gain	0.9100
17:410643:GACGG:G	donor_gain	0.9100
17:410636:C:T	donor_gain	0.9000
17:410647:G:GA	donor_loss	0.9000
17:410648:TAAGA:T	donor_loss	0.9000
17:410647:G:GG	donor_gain	0.8900
17:413143:A:AG	acceptor_gain	0.8900
17:413144:G:GG	acceptor_gain	0.8900
17:410632:C:A	donor_gain	0.8700
17:410649:A:AG	donor_loss	0.8700
17:413140:CTCA:C	acceptor_loss	0.8700
17:413141:TCA:T	acceptor_loss	0.8700
17:413142:CAG:C	acceptor_loss	0.8700
17:413144:G:GA	acceptor_loss	0.8700
17:413145:CAG:C	acceptor_loss	0.8700
17:413146:A:AT	acceptor_loss	0.8700
17:413147:G:T	acceptor_loss	0.8700
17:413200:T:G	acceptor_gain	0.8500
17:410643:GACG:G	donor_gain	0.8300
17:413147:GAT:G	acceptor_gain	0.8300
17:413210:A:G	acceptor_gain	0.8300

AlphaMissense

2795 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1002193203 (17:408562 A>G), RS1002390008 (17:412818 A>G), RS1002744307 (17:413030 G>A), RS1002989598 (17:410731 C>A,T), RS1003020281 (17:410486 C>G,T), RS1003326505 (17:411844 A>G), RS1003813177 (17:411561 A>C,G), RS1003992915 (17:410054 C>T), RS1004025399 (17:409880 G>A), RS1005511553 (17:412324 G>C), RS1005905238 (17:408624 C>T), RS1006000706 (17:413473 G>A,C), RS1006335281 (17:408983 C>A), RS1006647711 (17:411232 A>G), RS1006963818 (17:411021 C>T)

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

3 associations (top):

Study	Trait	p-value
GCST012227_388	Hip circumference adjusted for BMI	3.000000e-08
GCST90020026_268	Hip index	4.000000e-11
GCST90020028_1508	Hip circumference adjusted for BMI	3.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	increases expression, decreases expression, increases abundance	2
bisphenol F	decreases methylation	1
butyraldehyde	decreases expression	1
ferrous chloride	decreases expression	1
pentanal	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
jinfukang	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Cannabidiol	increases expression	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	affects expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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