LIX1

Summary

LIX1 (limb and CNS expressed 1, HGNC:18581) is a protein-coding gene on chromosome 5q15, encoding Protein limb expression 1 homolog (Q8N485).

Predicted to be involved in autophagosome maturation. Predicted to be active in cytoplasm.

Source: NCBI Gene 167410 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_153234

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18581
Approved symbol	LIX1
Name	limb and CNS expressed 1
Location	5q15
Locus type	gene with protein product
Status	Approved
Aliases	Lft
Ensembl gene	ENSG00000145721
Ensembl biotype	protein_coding
OMIM	610466
Entrez	167410

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000274382, ENST00000512378, ENST00000942939

RefSeq mRNA: 1 — MANE Select: NM_153234 NM_153234

CCDS: CCDS4088

Canonical transcript exons

ENST00000274382 — 6 exons

Exon	Start	End
ENSE00000971854	97107360	97107500
ENSE00000971855	97105190	97105285
ENSE00000971856	97096810	97096887
ENSE00001159857	97124466	97124629
ENSE00001230951	97091867	97095035
ENSE00001230958	97142495	97142611

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 92.06.

FANTOM5 (CAGE): breadth broad, TPM avg 7.8369 / max 1350.0957, expressed in 296 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
62713	6.1219	261
62716	1.1991	210
62714	0.4878	143
62715	0.0280	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral globus pallidus	UBERON:0002476	92.06	gold quality
caudate nucleus	UBERON:0001873	88.90	gold quality
nucleus accumbens	UBERON:0001882	88.83	gold quality
corpus callosum	UBERON:0002336	88.75	gold quality
medulla oblongata	UBERON:0001896	88.46	gold quality
amygdala	UBERON:0001876	88.37	gold quality
superior vestibular nucleus	UBERON:0007227	87.94	gold quality
globus pallidus	UBERON:0001875	87.78	gold quality
medial globus pallidus	UBERON:0002477	87.56	gold quality
ventral tegmental area	UBERON:0002691	86.62	gold quality
substantia nigra	UBERON:0002038	86.41	gold quality
putamen	UBERON:0001874	86.32	gold quality
hypothalamus	UBERON:0001898	86.31	gold quality
spinal cord	UBERON:0002240	86.22	gold quality
midbrain	UBERON:0001891	85.64	gold quality
inferior vagus X ganglion	UBERON:0005363	85.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.19	gold quality
substantia nigra pars reticulata	UBERON:0001966	85.08	gold quality
temporal lobe	UBERON:0001871	85.02	gold quality
Ammon’s horn	UBERON:0001954	83.92	gold quality
anterior cingulate cortex	UBERON:0009835	82.60	gold quality
telencephalon	UBERON:0001893	82.42	gold quality
entorhinal cortex	UBERON:0002728	81.71	gold quality
secondary oocyte	CL:0000655	81.32	gold quality
substantia nigra pars compacta	UBERON:0001965	81.31	gold quality
oocyte	CL:0000023	80.89	gold quality
forebrain	UBERON:0001890	80.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.37	gold quality
dorsal plus ventral thalamus	UBERON:0001897	80.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.21	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	1052.10
E-MTAB-10018	yes	230.38
E-MTAB-7316	yes	24.81
E-GEOD-93593	yes	18.82
E-MTAB-8271	yes	7.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

154 targeting LIX1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583

Literature-anchored findings (GeneRIF, showing 3)

• Data show that mutations in LIX1 do not contribute significantly to the cause of motor neuron diseases in the human population. (PMID:18395445)
• LIX1 regulates YAP activity and controls gastrointestinal cancer cell plasticity. (PMID:32633461)
• Single Nucleotide Polymorphism and mRNA Expression of LTF in Oral Squamous Cell Carcinoma. (PMID:36360322)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lix1	ENSDARG00000052154
mus_musculus	Lix1	ENSMUSG00000047786
rattus_norvegicus	Lix1	ENSRNOG00000012988
drosophila_melanogaster	lft	FBGN0032230

Paralogs (2): EPG5 (ENSG00000152223), LIX1L (ENSG00000271601)

Protein

Protein identifiers

Protein limb expression 1 homolog — Q8N485 (reviewed: Q8N485)

All UniProt accessions (2): D6RID5, Q8N485

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the LIX1 family.

RefSeq proteins (1): NP_694966* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029270	LIX1	Family
IPR051436	Autophagy-related_EPG5	Family

Pfam: PF14954

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N485-F1	85.93	0.65

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 132 (showing top): TAL1ALPHAE47_01, CHX10_01, AAAYRNCTG_UNKNOWN, GOBP_MACROAUTOPHAGY, EVI1_05, IRF7_01, GATA6_01, WTGAAAT_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_DN, HP1SITEFACTOR_Q6, GATA1_03, AACTTT_UNKNOWN, HAND1E47_01, GATA1_02, GATA4_Q3

GO Biological Process (1): autophagosome maturation (GO:0097352)

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

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
macroautophagy	1
protein-containing complex disassembly	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

632 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIX1	LNPEP	Q9UIQ6	866
LIX1	TFRC	P02786	548
LIX1	SCARA5	Q6ZMJ2	516
LIX1	TMEM255A	Q5JRV8	469
LIX1	SMN1	Q16637	468
LIX1	ISOC1	Q96CN7	459
LIX1	LHX2	P50458	459
LIX1	RASGEF1C	Q8N431	457
LIX1	CUX2	O14529	444
LIX1	FAM174A	Q8TBP5	438
LIX1	LHX6	Q9UPM6	433
LIX1	RIOK2	Q9BVS4	432
LIX1	LHX3	Q9UBR4	426
LIX1	ISL1	P20663	425
LIX1	PLCH1	Q4KWH8	421

IntAct

16 interactions, top by confidence:

A	B	Type	Score
TSACC	LIX1	psi-mi:“MI:0915”(physical association)	0.560
EMSY	LIX1	psi-mi:“MI:0915”(physical association)	0.560
LIX1	FAM110A	psi-mi:“MI:0915”(physical association)	0.560
LIX1	TSACC	psi-mi:“MI:0915”(physical association)	0.560
LIX1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
APPL2	LIX1	psi-mi:“MI:0915”(physical association)	0.490
LIX1	DOK4	psi-mi:“MI:0915”(physical association)	0.370
EMSY	LIX1	psi-mi:“MI:0915”(physical association)	0.000
FAM110A	LIX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): LIX1 (Two-hybrid), LIX1 (Two-hybrid), LIX1 (Two-hybrid), C11orf30 (Two-hybrid), TSACC (Two-hybrid)

ESM2 similar proteins: A1DL98, A1XIQ0, A2AVJ0, A4UHQ4, F1QGC8, O36381, O74982, O76616, O88738, P02890, P02891, P02892, P06435, P0CZ24, P16420, P32774, P35259, P49408, P68969, Q0GBX8, Q14BA6, Q1KN21, Q1T763, Q1X6Y6, Q1X709, Q1X711, Q20A00, Q2GKJ2, Q3E744, Q3TDK6, Q58DR0, Q5PQ44, Q5REH8, Q5VYS4, Q5XX03, Q5ZK14, Q66T64, Q6WB97, Q6X1D3, Q6X1D7

Diamond homologs: Q5PQQ7, Q6P566, Q8BQ89, Q8IVB5, Q8N485, Q8UVV7, Q9VKY1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1351 predictions. Top by Δscore:

Variant	Effect	Δscore
5:97105185:GGTAC:G	donor_loss	1.0000
5:97105186:GTACC:G	donor_loss	1.0000
5:97105187:TA:T	donor_loss	1.0000
5:97105188:ACC:A	donor_loss	1.0000
5:97105189:C:CA	donor_loss	1.0000
5:97105284:CC:C	acceptor_gain	1.0000
5:97105284:CCCT:C	acceptor_gain	1.0000
5:97105285:CC:C	acceptor_gain	1.0000
5:97105286:C:CC	acceptor_gain	1.0000
5:97105286:C:CG	acceptor_loss	1.0000
5:97105286:C:T	acceptor_gain	1.0000
5:97105287:T:C	acceptor_gain	1.0000
5:97105287:T:TC	acceptor_gain	1.0000
5:97107358:A:AC	donor_gain	1.0000
5:97107359:C:CC	donor_gain	1.0000
5:97107359:CG:C	donor_gain	1.0000
5:97107379:T:TA	donor_gain	1.0000
5:97107499:CACT:C	acceptor_gain	1.0000
5:97107502:T:C	acceptor_gain	1.0000
5:97107502:T:TC	acceptor_gain	1.0000
5:97118382:AAGTT:A	donor_gain	1.0000
5:97124460:TCTTA:T	donor_loss	1.0000
5:97124461:CTTAC:C	donor_loss	1.0000
5:97124462:TTA:T	donor_loss	1.0000
5:97124463:TAC:T	donor_loss	1.0000
5:97124464:ACC:A	donor_loss	1.0000
5:97124625:GTTCA:G	acceptor_gain	1.0000
5:97124626:TTCA:T	acceptor_gain	1.0000
5:97124627:TCA:T	acceptor_gain	1.0000
5:97124628:CA:C	acceptor_gain	1.0000

AlphaMissense

1856 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:97096857:A:G	W172R	1.000
5:97096857:A:T	W172R	1.000
5:97096865:A:G	L169P	1.000
5:97094845:A:T	I251K	0.999
5:97094969:A:G	W210R	0.999
5:97094969:A:T	W210R	0.999
5:97096855:C:A	W172C	0.999
5:97096855:C:G	W172C	0.999
5:97096862:A:G	L170S	0.999
5:97096870:G:C	F167L	0.999
5:97096870:G:T	F167L	0.999
5:97096871:A:G	F167S	0.999
5:97096872:A:G	F167L	0.999
5:97105193:A:C	F160L	0.999
5:97105193:A:T	F160L	0.999
5:97105195:A:G	F160L	0.999
5:97105227:A:G	L149P	0.999
5:97105240:A:C	Y145D	0.999
5:97107412:A:G	I112T	0.999
5:97107451:A:G	L99P	0.999
5:97107454:G:T	A98D	0.999
5:97107463:G:T	A95D	0.999
5:97124476:C:T	G79D	0.999
5:97124478:A:C	F78L	0.999
5:97124478:A:T	F78L	0.999
5:97124480:A:G	F78L	0.999
5:97094842:A:C	L252W	0.998
5:97094845:A:C	I251R	0.998
5:97094872:A:G	L242P	0.998
5:97096844:A:G	L176P	0.998

dbSNP variants (sampled 300 via entrez): RS1000014188 (5:97134939 G>C), RS1000131662 (5:97105711 C>A), RS1000131706 (5:97141805 A>G), RS1000169578 (5:97114846 T>G), RS1000208626 (5:97131906 A>C,T), RS1000261441 (5:97128669 A>C), RS1000280169 (5:97121565 C>T), RS1000304939 (5:97125481 T>C), RS1000482757 (5:97142036 A>G), RS1000620888 (5:97123288 G>A,T), RS1000640742 (5:97123794 T>C), RS1000671712 (5:97124136 A>G), RS1000678539 (5:97114618 G>A,T), RS1000953412 (5:97144001 C>A), RS1001063302 (5:97091979 T>C)

Disease associations

OMIM: gene MIM:610466 | 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

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	4
trichostatin A	affects cotreatment, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Zoledronic Acid	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Ethinyl Estradiol	affects expression	1
Lead	affects expression	1
Niclosamide	decreases expression	1
Silicon Dioxide	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Cyclosporine	decreases expression	1
Genistein	affects expression	1

Clinical trials (associated diseases)

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