LIX1L

Summary

LIX1L (limb and CNS expressed 1 like, HGNC:28715) is a protein-coding gene on chromosome 1q21.1, encoding LIX1-like protein (Q8IVB5).

Predicted to be involved in autophagosome maturation. Predicted to act upstream of or within actin cytoskeleton organization; gene expression; and mitral valve development. Predicted to be active in cytoplasm.

Source: NCBI Gene 128077 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 49 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_153713

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28715
Approved symbol	LIX1L
Name	limb and CNS expressed 1 like
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC46719
Ensembl gene	ENSG00000271601
Ensembl biotype	protein_coding
Entrez	128077

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000604000, ENST00000854709, ENST00000854710, ENST00000854711

RefSeq mRNA: 1 — MANE Select: NM_153713 NM_153713

CCDS: CCDS72873

Canonical transcript exons

ENST00000604000 — 6 exons

Exon	Start	End
ENSE00002690833	145936908	145936985
ENSE00002696751	145957636	145958017
ENSE00002699070	145937604	145937699
ENSE00002712634	145947619	145947782
ENSE00002733008	145942713	145942853
ENSE00003535336	145933423	145936552

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 97.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.1742 / max 158.2742, expressed in 1701 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14163	24.1640	1692
14164	2.7391	1338
14165	1.1985	868
14162	0.6836	442
14161	0.3889	183

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	97.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.60	gold quality
left ventricle myocardium	UBERON:0006566	97.09	gold quality
urethra	UBERON:0000057	96.65	gold quality
saphenous vein	UBERON:0007318	96.10	gold quality
superficial temporal artery	UBERON:0001614	95.94	gold quality
layer of synovial tissue	UBERON:0007616	95.66	gold quality
tibia	UBERON:0000979	95.26	gold quality
parietal pleura	UBERON:0002400	95.05	gold quality
seminal vesicle	UBERON:0000998	94.96	gold quality
tendon of biceps brachii	UBERON:0008188	94.91	gold quality
synovial joint	UBERON:0002217	94.42	gold quality
deltoid	UBERON:0001476	94.41	gold quality
oviduct epithelium	UBERON:0004804	94.41	gold quality
trigeminal ganglion	UBERON:0001675	94.21	gold quality
lower lobe of lung	UBERON:0008949	94.20	gold quality
pericardium	UBERON:0002407	94.08	gold quality
dorsal root ganglion	UBERON:0000044	94.05	gold quality
germinal epithelium of ovary	UBERON:0001304	93.76	gold quality
visceral pleura	UBERON:0002401	93.58	gold quality
upper arm skin	UBERON:0004263	93.54	gold quality
quadriceps femoris	UBERON:0001377	93.32	gold quality
vena cava	UBERON:0004087	93.28	gold quality
medial globus pallidus	UBERON:0002477	93.27	gold quality
ventricular zone	UBERON:0003053	93.23	gold quality
cauda epididymis	UBERON:0004360	93.21	gold quality
myocardium	UBERON:0002349	93.20	gold quality
vastus lateralis	UBERON:0001379	92.99	gold quality
penis	UBERON:0000989	92.95	gold quality
globus pallidus	UBERON:0001875	92.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-109979	yes	424.13
E-ANND-3	yes	5.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

171 targeting LIX1L, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593

Literature-anchored findings (GeneRIF, showing 1)

• LIX1L is an RNA-binding protein, with implications for therapeutic approaches for targeting LIX1L in LIX1L-expressing cancer cells. (PMID:26310847)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lix1l	ENSMUSG00000049288
rattus_norvegicus	Lix1l	ENSRNOG00000021213
drosophila_melanogaster	lft	FBGN0032230

Paralogs (2): LIX1 (ENSG00000145721), EPG5 (ENSG00000152223)

Protein

Protein identifiers

LIX1-like protein — Q8IVB5 (reviewed: Q8IVB5)

All UniProt accessions (1): Q8IVB5

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the LIX1 family.

RefSeq proteins (1): NP_714924* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029270	LIX1	Family
IPR051436	Autophagy-related_EPG5	Family

Pfam: PF14954

UniProt features (4 total): compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVB5-F1	79.82	0.55

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, CREL_01, HERNANDEZ_MITOTIC_ARREST_BY_DOCETAXEL_1_UP, GOBP_MACROAUTOPHAGY, AACWWCAANK_UNKNOWN, NFKB_Q6, SRF_Q5_01, NFKB_C, GGGNNTTTCC_NFKB_Q6_01, TGGNNNNNNKCCAR_UNKNOWN, RYTTCCTG_ETS2_B, HAND1E47_01, GATA4_Q3, ACEVEDO_LIVER_CANCER_UP, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM

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

GO Molecular Function (0):

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
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIX1L	POLR3GL	Q9BT43	580
LIX1L	ANKRD35	Q8N283	526
LIX1L	PEX11B	O96011	513
LIX1L	ANKRD34A	Q69YU3	480
LIX1L	NUDT17	P0C025	447
LIX1L	NBPF20	P0DPF2	445
LIX1L	NBPF11	Q86T75	445
LIX1L	MOB1B	Q7L9L4	435
LIX1L	DISP2	A7MBM2	428
LIX1L	OSCP1	Q8WVF1	403
LIX1L	TATDN1	Q6P1N9	400
LIX1L	ITGA10	O75578	396
LIX1L	RASSF2	P50749	371
LIX1L	RBM8A	Q9Y5S9	370
LIX1L	ACP6	Q9NPH0	351

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CAPNS2	CAPN1	psi-mi:“MI:0914”(association)	0.640
CAPNS2	CAPNS1	psi-mi:“MI:0914”(association)	0.530
LIX1L	NONO	psi-mi:“MI:0915”(physical association)	0.400
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
GPD2	TTC19	psi-mi:“MI:0914”(association)	0.350
LIX1L	FAT4	psi-mi:“MI:0914”(association)	0.350
CAPNS2	FLOT1	psi-mi:“MI:0914”(association)	0.350
LIX1L		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): LIX1L (Affinity Capture-RNA), LIX1L (Affinity Capture-RNA), LIX1L (Affinity Capture-MS), LIX1L (Co-fractionation), LIX1L (Co-fractionation), LIX1L (Co-fractionation), LIX1L (Affinity Capture-MS), LIX1L (Proximity Label-MS), DCHS1 (Affinity Capture-MS), LIX1L (Affinity Capture-MS), LIX1L (Affinity Capture-MS), FAT4 (Affinity Capture-MS), LIX1L (Affinity Capture-MS), LIX1L (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1L020, A1L3F4, A7X8B3, A7X8B5, A7X8B7, A7X8B9, A7X8C2, A7X8C4, A7X8C7, A7X8C9, A7X8D2, A7X8D4, A7XW25, O97775, O97776, O97952, O97960, P06401, P10275, P84550, P84551, P89463, Q01JD1, Q05A36, Q0VDT2, Q3UE17, Q5PQQ7, Q5U5Q3, Q69Z36, Q6QT55, Q6ZK57, Q6ZN04, Q71FD5, Q7RTV3, Q7TSJ6, Q7XQN1, Q7XT42, Q84SL2, Q86XN8, Q8BQ89

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

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	0
Likely pathogenic	1
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
545146	NC_000001.11:g.(?145601945)(146048346_?)del	Likely pathogenic

SpliceAI

996 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145936551:GGA:G	acceptor_gain	1.0000
1:145936551:GGAGG:G	acceptor_gain	1.0000
1:145936552:AGGAG:A	acceptor_gain	1.0000
1:145936553:TAGGA:T	acceptor_loss	1.0000
1:145936554:CTAG:C	acceptor_loss	1.0000
1:145936555:A:AG	acceptor_gain	1.0000
1:145936555:ACTAG:A	acceptor_gain	1.0000
1:145936904:T:G	donor_loss	1.0000
1:145936905:GT:G	donor_loss	1.0000
1:145936908:CAGG:C	donor_loss	1.0000
1:145937613:TTG:T	donor_gain	1.0000
1:145937705:A:AG	acceptor_gain	1.0000
1:145937714:T:A	acceptor_gain	1.0000
1:145942709:T:G	donor_loss	1.0000
1:145942710:G:GG	donor_gain	1.0000
1:145942710:GT:G	donor_loss	1.0000
1:145942711:TG:T	donor_loss	1.0000
1:145942712:AT:A	donor_gain	1.0000
1:145942713:AATGT:A	donor_loss	1.0000
1:145942714:TAATG:T	donor_loss	1.0000
1:145942852:G:GG	acceptor_gain	1.0000
1:145942852:GT:G	acceptor_gain	1.0000
1:145942852:GTTTT:G	acceptor_gain	1.0000
1:145942853:A:AG	acceptor_gain	1.0000
1:145947781:G:GA	acceptor_gain	1.0000
1:145947781:GT:G	acceptor_gain	1.0000
1:145947782:A:AG	acceptor_gain	1.0000
1:145936551:G:GT	acceptor_gain	0.9900
1:145936551:GG:G	acceptor_gain	0.9900
1:145936552:A:AG	acceptor_gain	0.9900

AlphaMissense

2173 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145936376:C:A	K316N	1.000
1:145936376:C:G	K316N	1.000
1:145936389:A:G	L312P	1.000
1:145936393:C:T	E311K	1.000
1:145936398:C:T	G309D	1.000
1:145936486:A:G	W280R	1.000
1:145936486:A:T	W280R	1.000
1:145936495:C:G	A277P	1.000
1:145936497:A:C	M276R	1.000
1:145936497:A:G	M276T	1.000
1:145936497:A:T	M276K	1.000
1:145936537:A:C	Y263D	1.000
1:145936537:A:G	Y263H	1.000
1:145936545:A:G	L260S	1.000
1:145936548:A:T	V259E	1.000
1:145936929:C:A	R250S	1.000
1:145936929:C:G	R250S	1.000
1:145936930:C:A	R250M	1.000
1:145936932:C:A	M249I	1.000
1:145936932:C:G	M249I	1.000
1:145936932:C:T	M249I	1.000
1:145936933:A:G	M249T	1.000
1:145936942:A:G	L246P	1.000
1:145936942:A:T	L246H	1.000
1:145936944:G:C	S245R	1.000
1:145936944:G:T	S245R	1.000
1:145936946:T:G	S245R	1.000
1:145936948:C:A	G244V	1.000
1:145936950:A:C	N243K	1.000
1:145936950:A:T	N243K	1.000

dbSNP variants (sampled 300 via entrez): RS1000266708 (1:145939865 C>T), RS1000606035 (1:145938415 G>A), RS1000906360 (1:145946325 A>T), RS1000964074 (1:145952900 C>T), RS1000992049 (1:145952650 C>T), RS1001123053 (1:145945638 C>G,T), RS1001289187 (1:145959756 G>A), RS1001612439 (1:145947191 T>A), RS1001643622 (1:145946778 T>C), RS1001877989 (1:145952197 C>A,G,T), RS1001944442 (1:145945167 T>C), RS1001945860 (1:145953871 C>T), RS1001980470 (1:145944769 T>C), RS1002205921 (1:145939268 T>C), RS1002308703 (1:145959646 T>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:181500

GenCC curated gene-disease

Mondo (1): schizophrenia (MONDO:0005090)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

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

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	2
Aflatoxin B1	decreases methylation	2
Particulate Matter	affects cotreatment, decreases expression, increases abundance	2
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
1-Butanol	affects cotreatment, decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1VW	Abcam HeLa LIX1L KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety