LZTS3

Summary

LZTS3 (leucine zipper tumor suppressor family member 3, HGNC:30139) is a protein-coding gene on chromosome 20p13, encoding Leucine zipper putative tumor suppressor 3 (O60299). May be involved in promoting the maturation of dendritic spines, probably via regulating SIPA1L1 levels at the postsynaptic density of synapses.

Predicted to enable PDZ domain binding activity. Predicted to be involved in protein homooligomerization; regulation of dendritic spine morphogenesis; and regulation of postsynapse assembly. Predicted to be located in postsynaptic density. Predicted to be active in dendritic spine and glutamatergic synapse.

Source: NCBI Gene 9762 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_001365618

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30139
Approved symbol	LZTS3
Name	leucine zipper tumor suppressor family member 3
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	ProSAPiP1, KIAA0552
Ensembl gene	ENSG00000088899
Ensembl biotype	protein_coding
OMIM	610484
Entrez	9762

Gene structure

Transcript identifiers

Ensembl transcripts: 37 — 37 protein_coding

ENST00000329152, ENST00000337576, ENST00000360342, ENST00000645462, ENST00000875471, ENST00000875472, ENST00000875473, ENST00000875474, ENST00000875475, ENST00000875476, ENST00000875477, ENST00000875478, ENST00000875479, ENST00000875480, ENST00000875481, ENST00000875482, ENST00000927879, ENST00000927880, ENST00000927881, ENST00000927882, ENST00000927883, ENST00000927884, ENST00000927885, ENST00000927886, ENST00000927887, ENST00000927888, ENST00000927889, ENST00000927890, ENST00000927891, ENST00000927892, ENST00000943289, ENST00000943290, ENST00000943291, ENST00000943292, ENST00000943293, ENST00000943294, ENST00000943295

RefSeq mRNA: 8 — MANE Select: NM_001365618 NM_001282533, NM_001365618, NM_001367609, NM_001388189, NM_001388190, NM_001388191, NM_001388192, NM_001388193

CCDS: CCDS13049, CCDS63218

Canonical transcript exons

ENST00000337576 — 5 exons

Exon	Start	End
ENSE00000858724	3166705	3167181
ENSE00001322554	3165497	3166360
ENSE00001405874	3167738	3167961
ENSE00001550366	3162617	3165152
ENSE00003729687	3173455	3173549

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5629 / max 165.8181, expressed in 1105 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186129	5.3428	1067
186130	0.1969	79
208975	0.0233	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	99.11	gold quality
cerebellar vermis	UBERON:0004720	99.01	gold quality
middle frontal gyrus	UBERON:0002702	98.82	gold quality
paraflocculus	UBERON:0005351	98.82	gold quality
CA1 field of hippocampus	UBERON:0003881	98.61	gold quality
postcentral gyrus	UBERON:0002581	98.39	gold quality
parietal lobe	UBERON:0001872	98.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.35	gold quality
cerebellum	UBERON:0002037	98.26	gold quality
cerebellar cortex	UBERON:0002129	98.25	gold quality
cerebellar hemisphere	UBERON:0002245	98.24	gold quality
entorhinal cortex	UBERON:0002728	98.04	gold quality
superior frontal gyrus	UBERON:0002661	97.95	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.80	gold quality
frontal pole	UBERON:0002795	97.77	gold quality
lateral globus pallidus	UBERON:0002476	97.50	gold quality
orbitofrontal cortex	UBERON:0004167	97.48	gold quality
primary visual cortex	UBERON:0002436	97.39	gold quality
occipital lobe	UBERON:0002021	97.16	gold quality
right frontal lobe	UBERON:0002810	97.10	gold quality
middle temporal gyrus	UBERON:0002771	96.74	gold quality
frontal cortex	UBERON:0001870	96.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.46	gold quality
prefrontal cortex	UBERON:0000451	96.39	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.37	gold quality
nucleus accumbens	UBERON:0001882	96.10	gold quality
neocortex	UBERON:0001950	96.08	gold quality
cerebral cortex	UBERON:0000956	95.86	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.66

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• We thus propose a model where ProSAP/Shank proteins are in the center of a postsynaptic signaling pathway that is disrupted in several neuropsychiatric disorders. (PMID:21840719)
• Long non-coding RNA (lncRNA) PGM5P4-AS1 inhibits lung cancer progression by up-regulating leucine zipper tumor suppressor (LZTS3) through sponging microRNA miR-1275. (PMID:33315502)
• LZTS3/TAGLN Suppresses Cancer Progression in Human Colorectal Adenocarcinoma Through Regulating Cell Proliferation, Migration, and Actin Cytoskeleton. (PMID:37806182)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lzts3b	ENSDARG00000058558
danio_rerio	lzts3a	ENSDARG00000098751
mus_musculus	Lzts3	ENSMUSG00000037703
rattus_norvegicus	Lzts3	ENSRNOG00000021231
drosophila_melanogaster	CG15365	FBGN0030077
caenorhabditis_elegans		WBGENE00018033

Paralogs (2): LZTS1 (ENSG00000061337), LZTS2 (ENSG00000107816)

Protein

Protein identifiers

Leucine zipper putative tumor suppressor 3 — O60299 (reviewed: O60299)

Alternative names: ProSAP-interacting protein 1

All UniProt accessions (1): O60299

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in promoting the maturation of dendritic spines, probably via regulating SIPA1L1 levels at the postsynaptic density of synapses.

Subunit / interactions. Interacts (via C-terminus) with SHANK3 (via PDZ domain). Interacts (via coiled coil) with SIPA1L1. Can form homooligomers.

Subcellular location. Synapse. Postsynaptic density. Cell projection. Dendritic spine. Dendrite. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the LZTS3 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60299-1	1	yes
O60299-2	2

RefSeq proteins (8): NP_001269462, NP_001352547, NP_001354538, NP_001375118, NP_001375119, NP_001375120, NP_001375121, NP_001375122 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR045329	LZTS	Family

Pfam: PF06818

UniProt features (18 total): compositionally biased region 7, region of interest 4, modified residue 2, coiled-coil region 2, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60299-F1	65.40	0.38

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 (2): 316, 318

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, CACCAGC_MIR138, BROWNE_HCMV_INFECTION_12HR_UP, MODULE_66, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_DENDRITE_MORPHOGENESIS, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, MODULE_99, CORRE_MULTIPLE_MYELOMA_UP, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY

GO Biological Process (1): regulation of dendritic spine morphogenesis (GO:0061001)

GO Molecular Function (0):

GO Cellular Component (7): cytoskeleton (GO:0005856), postsynaptic density (GO:0014069), dendritic spine (GO:0043197), synapse (GO:0045202), cytoplasm (GO:0005737), dendrite (GO:0030425), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of neuron projection development	1
regulation of anatomical structure morphogenesis	1
dendritic spine morphogenesis	1
regulation of postsynapse organization	1
intracellular membraneless organelle	1
asymmetric synapse	1
postsynaptic specialization	1
dendrite	1
neuron spine	1
postsynapse	1
cell junction	1
intracellular anatomical structure	1
neuron projection	1
dendritic tree	1

Protein interactions and networks

STRING

312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LZTS3	SHANK3	Q9BYB0	953
LZTS3	SIPA1L1	O43166	911
LZTS3	UBOX5	O94941	619
LZTS3	PTPRA	P18433	520
LZTS3	RNF32	Q9H0A6	520
LZTS3	RPP40	O75818	491
LZTS3	GNRH2	O43555	477
LZTS3	PRAP1	Q96NZ9	457
LZTS3	ZNF366	Q8N895	448
LZTS3	SIPA1L2	Q9P2F8	443
LZTS3	ZNF367	Q7RTV3	439
LZTS3	DDRGK1	Q96HY6	403
LZTS3	THNSL2	Q86YJ6	396
LZTS3	TMEM184B	Q9Y519	395
LZTS3	SMYD1	Q8NB12	375

IntAct

18 interactions, top by confidence:

A	B	Type	Score
CCDC6	LZTS3	psi-mi:“MI:0914”(association)	0.530
DYRK1B	BMAL1	psi-mi:“MI:0914”(association)	0.530
LZTS3	SHANK3	psi-mi:“MI:0915”(physical association)	0.370
DYRK1A	SEC16A	psi-mi:“MI:0914”(association)	0.350
ODF2	ELAPOR2	psi-mi:“MI:0914”(association)	0.350
CDK5RAP2	SPTBN2	psi-mi:“MI:0914”(association)	0.350
WWP2	CCDC85C	psi-mi:“MI:0914”(association)	0.350
LZTS3	SIPA1L1	psi-mi:“MI:0914”(association)	0.350
ESR2	PSMD11	psi-mi:“MI:0914”(association)	0.350
CEP128	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
CEP135	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
NINL	CCDC66	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (32): LZTS3 (Proximity Label-MS), LZTS3 (Proximity Label-MS), LZTS3 (Proximity Label-MS), LZTS3 (Affinity Capture-MS), LZTS3 (Affinity Capture-MS), LZTS3 (Affinity Capture-MS), LZTS3 (Affinity Capture-MS), LZTS3 (Affinity Capture-MS), LZTS3 (Affinity Capture-MS), LZTS3 (Two-hybrid), DYRK1B (Affinity Capture-MS), SIPA1L3 (Affinity Capture-MS), USP7 (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), DYRK1A (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3QA39, A1YB07, A2A6T1, A2A9T0, A2AHG0, A5PKL7, A6NKD9, A7MCY6, B8A5S6, D3ZD05, E1BEQ5, E1U8D0, E9Q6B2, F1MRK3, G3V735, O14529, O60299, O75145, O94964, P60469, Q1LZH7, Q3LUD4, Q3UIL6, Q499E4, Q5JTD0, Q5RCR6, Q5XIA0, Q62036, Q63ZY3, Q6DG50, Q6IQ23, Q6NZT2, Q6PDH0, Q86UU1, Q86X02, Q8BX02, Q8C7U1, Q8IY63, Q8K1Q4, Q8K371

Diamond homologs: A0A1L8GUX5, A0A1L8GXY6, A2AHG0, O15049, O60299, P60853, Q3LUD3, Q3LUD4, Q5U4W1, Q5ZLT3, Q6DIS8, Q8C7U1, Q8CFC9, Q8K1Q4, Q91YU6, Q9Y250, A5PKL7, Q9BRK4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1195 predictions. Top by Δscore:

Variant	Effect	Δscore
20:3165153:C:CA	acceptor_loss	1.0000
20:3165154:T:A	acceptor_loss	1.0000
20:3165498:T:TA	donor_gain	1.0000
20:3165499:C:A	donor_gain	1.0000
20:3165506:A:AC	donor_gain	1.0000
20:3165506:AGTTT:A	donor_gain	1.0000
20:3165507:G:C	donor_gain	1.0000
20:3165510:T:A	donor_gain	1.0000
20:3165148:CACAC:C	acceptor_gain	0.9900
20:3165149:ACAC:A	acceptor_gain	0.9900
20:3165150:CAC:C	acceptor_gain	0.9900
20:3165150:CACC:C	acceptor_gain	0.9900
20:3165153:C:CC	acceptor_gain	0.9900
20:3165158:C:CT	acceptor_gain	0.9900
20:3165159:A:T	acceptor_gain	0.9900
20:3165164:CAGG:C	acceptor_gain	0.9900
20:3165165:A:T	acceptor_gain	0.9900
20:3165502:A:AC	donor_gain	0.9900
20:3165503:C:CC	donor_gain	0.9900
20:3165576:T:TA	donor_gain	0.9900
20:3166055:G:C	donor_gain	0.9900
20:3166865:T:TC	acceptor_gain	0.9900
20:3167182:C:CC	acceptor_gain	0.9900
20:3165151:AC:A	acceptor_gain	0.9800
20:3165152:CC:C	acceptor_gain	0.9800
20:3165491:CCGCA:C	donor_loss	0.9800
20:3165492:CGCA:C	donor_loss	0.9800
20:3165493:GCAC:G	donor_loss	0.9800
20:3165494:CA:C	donor_loss	0.9800
20:3165495:A:T	donor_loss	0.9800

AlphaMissense

4305 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:3164620:A:G	L619P	1.000
20:3164629:T:G	Q616P	1.000
20:3164632:T:C	Y615C	1.000
20:3164633:A:C	Y615D	1.000
20:3164633:A:G	Y615H	1.000
20:3164649:C:A	K609N	1.000
20:3164649:C:G	K609N	1.000
20:3164661:C:A	W605C	1.000
20:3164661:C:G	W605C	1.000
20:3164663:A:G	W605R	1.000
20:3164663:A:T	W605R	1.000
20:3165109:A:G	L456P	1.000
20:3165112:T:G	Q455P	1.000
20:3165117:C:A	K453N	1.000
20:3165117:C:G	K453N	1.000
20:3165119:T:C	K453E	1.000
20:3165121:A:G	L452P	1.000
20:3165124:A:G	L451P	1.000
20:3165130:A:C	I449S	1.000
20:3165130:A:G	I449T	1.000
20:3165136:C:T	G447D	1.000
20:3165141:C:A	K445N	1.000
20:3165141:C:G	K445N	1.000
20:3165145:T:G	Q444P	1.000
20:3165500:C:A	W440C	1.000
20:3165500:C:G	W440C	1.000
20:3165501:C:G	W440S	1.000
20:3165502:A:G	W440R	1.000
20:3165502:A:T	W440R	1.000
20:3166325:C:A	K165N	1.000

dbSNP variants (sampled 300 via entrez): RS1000252118 (20:3172938 C>T), RS1000302802 (20:3173257 GGCC>G), RS1000384379 (20:3169135 G>A), RS1000656697 (20:3174175 G>C), RS1000777077 (20:3172954 T>A), RS1000865626 (20:3167256 G>A,C,T), RS1000876226 (20:3162174 A>G), RS1001168385 (20:3168458 C>G,T), RS1002226564 (20:3170157 C>A,G,T), RS1002376949 (20:3164042 T>C), RS1002694243 (20:3164877 C>G), RS1002771385 (20:3171513 C>G,T), RS1002837901 (20:3164368 T>C,G), RS1002907794 (20:3172570 C>A,G,T), RS1003271161 (20:3166750 G>A)

Disease associations

OMIM: gene MIM:610484 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_59	Refractive error	6.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	affects expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
abrine	increases expression	1
jinfukang	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Lead	affects expression	1
Tobacco Smoke Pollution	affects expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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