SNAI3

Summary

SNAI3 (snail family transcriptional repressor 3, HGNC:18411) is a protein-coding gene on chromosome 16q24.2, encoding Zinc finger protein SNAI3 (Q3KNW1). Seems to inhibit myoblast differentiation.

SNAI3 is a member of the SNAIL gene family, named for the Drosophila snail gene, which plays roles in mesodermal formation during embryogenesis (Katoh and Katoh, 2003 [PubMed 12579345]).

Source: NCBI Gene 333929 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_178310

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18411
Approved symbol	SNAI3
Name	snail family transcriptional repressor 3
Location	16q24.2
Locus type	gene with protein product
Status	Approved
Aliases	SMUC, Zfp293
Ensembl gene	ENSG00000185669
Ensembl biotype	protein_coding
OMIM	612741
Entrez	333929

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000332281

RefSeq mRNA: 1 — MANE Select: NM_178310 NM_178310

CCDS: CCDS32505

Canonical transcript exons

ENST00000332281 — 3 exons

Exon	Start	End
ENSE00001291498	88681094	88681714
ENSE00001316000	88686331	88686507
ENSE00001319784	88677688	88678629

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 90.66.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0936 / max 81.2498, expressed in 540 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
158562	1.4831	449
158561	0.6105	254

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.66	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.44	gold quality
granulocyte	CL:0000094	85.12	gold quality
blood	UBERON:0000178	79.82	gold quality
muscle of leg	UBERON:0001383	78.99	gold quality
gastrocnemius	UBERON:0001388	78.65	gold quality
leukocyte	CL:0000738	77.22	gold quality
monocyte	CL:0000576	76.68	gold quality
skeletal muscle tissue	UBERON:0001134	75.81	gold quality
apex of heart	UBERON:0002098	74.82	gold quality
muscle tissue	UBERON:0002385	73.57	gold quality
spleen	UBERON:0002106	72.77	gold quality
biceps brachii	UBERON:0001507	70.80	silver quality
secondary oocyte	CL:0000655	70.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	68.26	silver quality
lymph node	UBERON:0000029	68.11	gold quality
vermiform appendix	UBERON:0001154	67.75	gold quality
bone marrow cell	CL:0002092	67.27	silver quality
body of stomach	UBERON:0001161	67.27	gold quality
prefrontal cortex	UBERON:0000451	66.97	gold quality
anterior cingulate cortex	UBERON:0009835	66.12	gold quality
heart left ventricle	UBERON:0002084	66.04	gold quality
adrenal tissue	UBERON:0018303	65.71	gold quality
small intestine Peyer’s patch	UBERON:0003454	65.37	gold quality
cardiac ventricle	UBERON:0002082	65.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.70	gold quality
right frontal lobe	UBERON:0002810	64.65	gold quality
stomach	UBERON:0000945	64.18	gold quality
mucosa of transverse colon	UBERON:0004991	63.77	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.58

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1559.1	SNAI3	More than 3 adjacent zinc fingers
MA1559.2	SNAI3	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:23762348

Upstream regulators (CollecTRI, top): RUNX2

miRNA regulators (miRDB)

48 targeting SNAI3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-760	98.81	66.65	1392

Literature-anchored findings (GeneRIF, showing 2)

• SNAI1, SNAI2, SNAI3 show unequal oncogenic potential, strictly correlating with their ability to promote epithelial-to-mesenchymal transition. (PMID:24638100)
• PAK5-stabilized Smuc confers renal cell carcinoma metastasis. (PMID:34586742)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Snai3	ENSMUSG00000006587
rattus_norvegicus	Snai3	ENSRNOG00000013586
drosophila_melanogaster	wor	FBGN0001983

Paralogs (36): ZBTB32 (ENSG00000011590), SNAI2 (ENSG00000019549), PRDM1 (ENSG00000057657), PRDM6 (ENSG00000061455), ZNF76 (ENSG00000065029), PATZ1 (ENSG00000100105), MAZ (ENSG00000103495), ZBTB16 (ENSG00000109906), ZNF451 (ENSG00000112200), ZBTB45 (ENSG00000119574), ZNF410 (ENSG00000119725), SNAI1 (ENSG00000124216), ZNF384 (ENSG00000126746), ZBTB1 (ENSG00000126804), VEZF1 (ENSG00000136451), PRDM14 (ENSG00000147596), ZNF276 (ENSG00000158805), ZNF362 (ENSG00000160094), ZNF653 (ENSG00000161914), ZNF281 (ENSG00000162702), ZNF148 (ENSG00000163848), ZNF143 (ENSG00000166478), HIC2 (ENSG00000169635), PRDM10 (ENSG00000170325), ZNF296 (ENSG00000170684), ZNF692 (ENSG00000171163), ZNF575 (ENSG00000176472), HIC1 (ENSG00000177374), ZBTB18 (ENSG00000179456), ZBTB42 (ENSG00000179627), ZBTB20 (ENSG00000181722), ZBTB7C (ENSG00000184828), ZFP91 (ENSG00000186660), MTF1 (ENSG00000188786), SCRT2 (ENSG00000215397), SCRT1 (ENSG00000261678)

Protein

Protein identifiers

Zinc finger protein SNAI3 — Q3KNW1 (reviewed: Q3KNW1)

Alternative names: Protein snail homolog 3, Zinc finger protein 293

All UniProt accessions (1): Q3KNW1

UniProt curated annotations — full annotation on UniProt →

Function. Seems to inhibit myoblast differentiation. Transcriptional repressor of E-box-dependent transactivation of downstream myogenic bHLHs genes. Binds preferentially to the canonical E-box sequences 5’-CAGGTG-3’ and 5’-CACCTG-3'.

Subcellular location. Nucleus.

Domain organisation. Binds E-box via C2H2-type zinc finger domain.

Similarity. Belongs to the snail C2H2-type zinc-finger protein family.

RefSeq proteins (1): NP_840101* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002355	Cu_oxidase_Cu_BS	Binding_site
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR050527

Pfam: PF00096

UniProt features (7 total): zinc finger region 5, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3KNW1-F1	59.95	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 105 (showing top): NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, MARSON_BOUND_BY_FOXP3_STIMULATED, NADELLA_PRKAR1A_TARGETS_UP, GOMF_COPPER_ION_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, LI_INDUCED_T_TO_NATURAL_KILLER_DN, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_C, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, WAKABAYASHI_ADIPOGENESIS_PPARG_RXRA_BOUND_8D, FOSTER_KDM1A_TARGETS_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY

GO Biological Process (3): regulation of DNA-templated transcription (GO:0006355), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (10): 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 transcription repressor activity, RNA polymerase II-specific (GO:0001227), copper ion binding (GO:0005507), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
transition metal ion binding	2
transcription cis-regulatory region binding	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription regulator activity	1
cation binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNAI3	TWIST1	Q15672	560
SNAI3	TWIST2	Q8WVJ9	559
SNAI3	CDH1	P12830	538
SNAI3	SNAI2	O43623	513
SNAI3	SMAD2	Q15796	511
SNAI3	SMAD4	Q13485	505
SNAI3	CDH2	P19022	467
SNAI3	KDM3A	Q9Y4C1	397
SNAI3	FOXC2	Q99958	377
SNAI3	RNF166	Q96A37	365
SNAI3	A0A0A6YYJ0	A0A0A6YYJ0	358
SNAI3	TMEFF1	Q8IYR6	355
SNAI3	GNG11	P50152	330
SNAI3	FN1	P02751	320
SNAI3	CTNNB1	P35222	316

IntAct

6 interactions, top by confidence:

A	B	Type	Score
SNAI3	TJP2	psi-mi:“MI:0915”(physical association)	0.400
SNAI3	STRN3	psi-mi:“MI:0914”(association)	0.350
ecfT	SNAI3	psi-mi:“MI:0915”(physical association)	0.000
	SNAI3	psi-mi:“MI:0915”(physical association)	0.000
SNAI3	dmsB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): STRN3 (Affinity Capture-MS), TJP2 (Affinity Capture-MS), STRIP1 (Affinity Capture-MS), TJP2 (Affinity Capture-MS), STRN3 (Affinity Capture-MS), SNAI3 (Affinity Capture-MS), SNAI3 (Affinity Capture-RNA), TJP2 (Affinity Capture-MS), HDAC2 (Affinity Capture-Western), HDAC1 (Affinity Capture-Western), Sin3a (Affinity Capture-Western), SNAI3 (Affinity Capture-Western), SNAI3 (Affinity Capture-Western), SNAI3 (Affinity Capture-Western)

ESM2 similar proteins: A3KN32, A6NM28, A8K8V0, E9PYI1, O75467, O95201, P10072, P10075, P10078, P10754, P28698, P30373, P52736, Q0VCC5, Q14929, Q16587, Q17QR7, Q29RZ4, Q3KNW1, Q3TDE8, Q3US17, Q58DK7, Q5RJR4, Q5T619, Q5TEC3, Q5U4E2, Q62396, Q68H95, Q6AW86, Q6PGE4, Q6ZMY9, Q7Z398, Q7Z7K2, Q8BI73, Q8BIF9, Q8BIQ3, Q8BKK5, Q8JZL0, Q8N393, Q8R0T2

Diamond homologs: O08954, O43623, P08044, P19382, P25932, P97469, Q3KNW1, Q3MHQ4, Q91924, O95863, Q02085, Q9QY31

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RUNX2	“up-regulates quantity by expression”	SNAI3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

505 predictions. Top by Δscore:

Variant	Effect	Δscore
16:88678625:CTCCC:C	acceptor_gain	1.0000
16:88678627:CCC:C	acceptor_gain	1.0000
16:88678628:CC:C	acceptor_gain	1.0000
16:88678628:CCC:C	acceptor_gain	1.0000
16:88678629:CCTG:C	acceptor_gain	1.0000
16:88678630:C:CC	acceptor_gain	1.0000
16:88678630:CT:C	acceptor_loss	1.0000
16:88678631:T:G	acceptor_loss	1.0000
16:88681091:TACC:T	donor_loss	1.0000
16:88681093:CC:C	donor_loss	1.0000
16:88686325:CAGTA:C	donor_loss	1.0000
16:88686327:GTA:G	donor_loss	1.0000
16:88686328:TA:T	donor_loss	1.0000
16:88686330:CCT:C	donor_gain	1.0000
16:88686330:CCTCT:C	donor_gain	1.0000
16:88678626:TCCC:T	acceptor_gain	0.9900
16:88678627:CCCC:C	acceptor_gain	0.9900
16:88678630:C:T	acceptor_gain	0.9900
16:88681089:CCTA:C	donor_loss	0.9900
16:88681712:TTT:T	acceptor_gain	0.9900
16:88681713:TTC:T	acceptor_loss	0.9900
16:88681714:TCTAG:T	acceptor_loss	0.9900
16:88681715:C:CC	acceptor_gain	0.9900
16:88681715:CTAG:C	acceptor_loss	0.9900
16:88681716:T:C	acceptor_loss	0.9900
16:88686332:T:TA	donor_gain	0.9900
16:88678632:G:GC	acceptor_gain	0.9800
16:88681710:GATTT:G	acceptor_gain	0.9800
16:88681713:TT:T	acceptor_gain	0.9800
16:88681723:G:GC	acceptor_gain	0.9800

AlphaMissense

1867 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:88678589:A:C	F246L	1.000
16:88678589:A:T	F246L	1.000
16:88678591:A:G	F246L	1.000
16:88681137:G:C	F218L	1.000
16:88681137:G:T	F218L	1.000
16:88681139:A:G	F218L	1.000
16:88678505:G:C	F274L	0.999
16:88678505:G:T	F274L	0.999
16:88678507:A:G	F274L	0.999
16:88678562:A:C	H255Q	0.999
16:88678562:A:T	H255Q	0.999
16:88678572:A:G	L252P	0.999
16:88678590:A:G	F246S	0.999
16:88681098:G:C	H231Q	0.999
16:88681098:G:T	H231Q	0.999
16:88681110:A:C	H227Q	0.999
16:88681110:A:T	H227Q	0.999
16:88681176:G:C	H205Q	0.999
16:88681176:G:T	H205Q	0.999
16:88681188:G:C	H201Q	0.999
16:88681188:G:T	H201Q	0.999
16:88681198:A:G	L198P	0.999
16:88681217:A:C	Y192D	0.999
16:88681238:A:G	C185R	0.999
16:88678550:G:C	H259Q	0.998
16:88678550:G:T	H259Q	0.998
16:88678564:G:C	H255D	0.998
16:88678564:G:T	H255N	0.998
16:88678591:A:T	F246I	0.998
16:88678612:A:G	C239R	0.998

dbSNP variants (sampled 300 via entrez): RS1000023767 (16:88688459 T>G), RS1000170032 (16:88686842 A>C), RS1000216828 (16:88683765 C>T), RS1000306676 (16:88679066 A>T), RS1000565822 (16:88683963 A>G), RS1000791606 (16:88680328 C>G), RS1000865659 (16:88679295 A>C), RS1001030782 (16:88687384 C>T), RS1001145104 (16:88687705 A>C), RS1001366854 (16:88684360 G>A), RS1001668554 (16:88679526 C>T), RS1001796706 (16:88684085 C>T), RS1001909920 (16:88679394 C>T), RS1002128458 (16:88688456 A>G), RS1002319508 (16:88688064 G>A,C,T)

Disease associations

OMIM: gene MIM:612741 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003479_9	Hair color	1.000000e-07
GCST004525_2	Subclinical trait of interstitial lung disease (basilar peel-core ratio of high attentuation areas on CT scan)	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007627	airway imaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	increases expression, increases methylation, affects cotreatment	2
Estradiol	increases expression, decreases expression, affects cotreatment	2
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	increases expression	1
3-nitrobenzanthrone	increases expression	1
entinostat	increases expression	1
nutlin 3	increases expression, affects cotreatment	1
jinfukang	increases expression, affects cotreatment	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	decreases expression, affects cotreatment	1
Rosiglitazone	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Calcitriol	affects cotreatment, increases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Testosterone	affects cotreatment, increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A6K2	SEES3-1V human SNAI3, clone1	Embryonic stem cell	Male
CVCL_A6K3	SEES3-1V human SNAI3, clone2	Embryonic stem cell	Male
CVCL_A6K4	SEES3-1V human SNAI3, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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