GSE1

Summary

GSE1 (Gse1 coiled-coil protein, HGNC:28979) is a protein-coding gene on chromosome 16q24.1, encoding Genetic suppressor element 1 (Q14687).

This gene encodes a proline-rich protein with coiled coil domains that may be a subunit of a BRAF35-HDAC (BHC) histone deacetylase complex. This gene may function as an oncogene in breast cancer and enhanced expression of the encoded protein has been observed in breast cancer patients.

Source: NCBI Gene 23199 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 447 total
• MANE Select transcript: NM_014615

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28979
Approved symbol	GSE1
Name	Gse1 coiled-coil protein
Location	16q24.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000131149
Ensembl biotype	protein_coding
OMIM	616886
Entrez	23199

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 5 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000253458, ENST00000393243, ENST00000405402, ENST00000411612, ENST00000412692, ENST00000438180, ENST00000469381, ENST00000471070, ENST00000479488, ENST00000495192, ENST00000496345, ENST00000562659, ENST00000568080, ENST00000574293, ENST00000635906, ENST00000637419, ENST00000880623, ENST00000880624, ENST00000880625, ENST00000912462

RefSeq mRNA: 3 — MANE Select: NM_014615 NM_001134473, NM_001278184, NM_014615

CCDS: CCDS10952, CCDS45539, CCDS62007

Canonical transcript exons

ENST00000253458 — 16 exons

Exon	Start	End
ENSE00000897849	85665015	85665128
ENSE00001399414	85633914	85634132
ENSE00001399788	85613322	85613398
ENSE00002207675	85657277	85657604
ENSE00002208941	85655726	85655917
ENSE00002210831	85656343	85656665
ENSE00002224848	85661146	85661765
ENSE00002272723	85662981	85663093
ENSE00002292885	85663344	85663614
ENSE00002302897	85654794	85654991
ENSE00002304022	85654278	85654450
ENSE00003463959	85665976	85666347
ENSE00003466294	85648552	85648751
ENSE00003473405	85668140	85668424
ENSE00003485591	85670995	85671098
ENSE00003849029	85672405	85676200

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.60.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.3018 / max 474.2394, expressed in 1799 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155411	10.2882	1218
155364	3.4661	1126
155384	3.1534	1073
155385	3.1276	843
155410	2.6789	836
155386	2.4789	645
155387	1.6696	558
155406	1.5930	516
155408	1.1724	589
155363	0.9802	600

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	97.60	gold quality
caput epididymis	UBERON:0004358	96.52	gold quality
ganglionic eminence	UBERON:0004023	96.40	gold quality
pylorus	UBERON:0001166	96.23	gold quality
placenta	UBERON:0001987	96.03	gold quality
thymus	UBERON:0002370	95.96	gold quality
cardia of stomach	UBERON:0001162	95.88	gold quality
trabecular bone tissue	UBERON:0002483	95.63	gold quality
lower lobe of lung	UBERON:0008949	95.62	gold quality
cauda epididymis	UBERON:0004360	95.42	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.15	gold quality
cortical plate	UBERON:0005343	95.14	gold quality
pituitary gland	UBERON:0000007	94.93	gold quality
adenohypophysis	UBERON:0002196	94.31	gold quality
endometrium epithelium	UBERON:0004811	94.28	gold quality
nipple	UBERON:0002030	94.09	gold quality
secondary oocyte	CL:0000655	93.87	gold quality
sural nerve	UBERON:0015488	93.82	gold quality
decidua	UBERON:0002450	93.67	gold quality
right lobe of thyroid gland	UBERON:0001119	93.40	gold quality
embryo	UBERON:0000922	93.35	gold quality
body of pancreas	UBERON:0001150	93.28	gold quality
left lobe of thyroid gland	UBERON:0001120	93.05	gold quality
fundus of stomach	UBERON:0001160	92.99	gold quality
gluteal muscle	UBERON:0002000	92.96	gold quality
thyroid gland	UBERON:0002046	92.78	gold quality
right ovary	UBERON:0002118	92.60	gold quality
cardiac muscle of right atrium	UBERON:0003379	92.59	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.48	gold quality
left ovary	UBERON:0002119	92.44	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.96
E-CURD-112	yes	7.05
E-CURD-114	yes	6.67
E-MTAB-6386	no	512.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

193 targeting GSE1, 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-4262	100.00	73.26	3931
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 5)

• In this study, we reported that GSE1 is overexpression in breast cancer and silencing of GSE1 significantly suppressed breast cancer cells proliferation, migration and invasion. (PMID:26828271)
• High GSE1 expression is associated with gastric cancer growth and metastasis. (PMID:29367342)
• Overexpression of GSE1 Related to Trastuzumab Resistance in Gastric Cancer Cells. (PMID:33623790)
• GSE1 links the HDAC1/CoREST co-repressor complex to DNA damage. (PMID:37878419)
• GSE1 promotes the proliferation and migration of lung adenocarcinoma cells by downregulating KLF6 expression. (PMID:38886911)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gse1b	ENSDARG00000062020
mus_musculus	Gse1	ENSMUSG00000031822
rattus_norvegicus	Gse1	ENSRNOG00000017489

Protein

Protein identifiers

Genetic suppressor element 1 — Q14687 (reviewed: Q14687)

All UniProt accessions (6): Q14687, A0A1B0GUL3, A0A1B0GUX8, C9JLW9, H0Y613, H7C3B5

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I.

Induction. Negatively regulated by miR-489-5p.

Isoforms (3)

UniProt ID	Names	Canonical?
Q14687-1	1	yes
Q14687-2	2
Q14687-3	3

RefSeq proteins (3): NP_001127945, NP_001265113, NP_055430* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022207	GSE-like	Domain
IPR042337	GSE1	Family

Pfam: PF12540

UniProt features (47 total): compositionally biased region 14, modified residue 14, region of interest 10, sequence variant 3, coiled-coil region 2, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14687-F1	55.37	0.08

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 (14): 10, 84, 95, 305, 433, 496, 739, 766, 826, 828, 857, 907, 909, 1101

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 321 (showing top): RNGTGGGC_UNKNOWN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, FARMER_BREAST_CANCER_CLUSTER_7, PAX4_01, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, KAAB_FAILED_HEART_ATRIUM_DN, GAANYNYGACNY_UNKNOWN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, AREB6_01, TGACCTY_ERR1_Q2, LHX3_01, GGGTGGRR_PAX4_03, AAAYRNCTG_UNKNOWN

GO Biological Process (3): in utero embryonic development (GO:0001701), placenta development (GO:0001890), gene expression (GO:0010467)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chordate embryonic development	1
animal organ development	1
macromolecule biosynthetic process	1
binding	1

Protein interactions and networks

STRING

972 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GSE1	HDAC1	Q13547	872
GSE1	HMG20B	Q9P0W2	853
GSE1	RCOR1	Q9UKL0	826
GSE1	ZMYM2	Q9UBW7	753
GSE1	KDM1A	O60341	751
GSE1	HMG20A	Q9NP66	734
GSE1	ZMYM3	Q14202	683
GSE1	GTF2I	P78347	677
GSE1	RCOR3	Q9P2K3	660
GSE1	HDAC2	Q92769	646
GSE1	PHF21A	Q96BD5	621
GSE1	KMT2D	O14686	430
GSE1	CREBBP	Q92793	415
GSE1	KMT2C	Q8NEZ4	402
GSE1	KDM6A	O15550	399

IntAct

196 interactions, top by confidence:

A	B	Type	Score
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
KDM1A	HDAC1	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
LLGL2	PRKCI	psi-mi:“MI:0914”(association)	0.890
GSE1	RCOR3	psi-mi:“MI:0915”(physical association)	0.860
RCOR3	GSE1	psi-mi:“MI:0915”(physical association)	0.860
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
GOLGA2	GSE1	psi-mi:“MI:0915”(physical association)	0.830
GSE1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.830
SNAI1	KDM1A	psi-mi:“MI:0914”(association)	0.830
HDAC1	TNRC18	psi-mi:“MI:0914”(association)	0.790
GSE1	C1orf94	psi-mi:“MI:0915”(physical association)	0.780
C1orf94	GSE1	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (227): GSE1 (Two-hybrid), GSE1 (Two-hybrid), GSE1 (Two-hybrid), GSE1 (Two-hybrid), GSE1 (Two-hybrid), RCOR3 (Two-hybrid), C1orf94 (Two-hybrid), TEKT4 (Two-hybrid), C6orf165 (Two-hybrid), GSE1 (Affinity Capture-MS), GSE1 (Affinity Capture-MS), GSE1 (Affinity Capture-MS), GSE1 (Affinity Capture-MS), NUDT18 (Two-hybrid), GSE1 (Two-hybrid)

ESM2 similar proteins: A0A087WPF7, A0A0R4IBL7, O09000, O54972, O70305, O75081, O75376, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q05AQ8, Q14157, Q14687, Q1LY51, Q2VPM4, Q3U3C9, Q4KKX4, Q4VCS5, Q566L4, Q5F3B1, Q5SFM8, Q5T6F2, Q60722, Q60974, Q61286, Q62655, Q6DIH5, Q7ZWN6, Q7ZXS3, Q80X50, Q86YP4, Q8BZ47, Q8CHY6, Q8IXK0, Q8VHG2

Diamond homologs: Q14687, Q1LWL6, Q3U3C9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 149 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Deactivation of the beta-catenin transactivating complex	5	12.4×	6e-03
Regulation of PTEN gene transcription	6	11.4×	4e-03
Negative Regulation of CDH1 Gene Transcription	8	10.2×	6e-04
Factors involved in megakaryocyte development and platelet production	8	5.7×	7e-03
mRNA Splicing - Major Pathway	9	5.2×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
cell fate commitment	6	12.6×	9e-04
cartilage development	6	10.7×	2e-03
inner ear morphogenesis	5	10.7×	5e-03
positive regulation of miRNA transcription	5	10.3×	5e-03
anatomical structure morphogenesis	10	9.9×	2e-05
regulation of alternative mRNA splicing, via spliceosome	5	8.7×	1e-02
transcription by RNA polymerase II	15	7.5×	6e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	377
Likely benign	27
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3469 predictions. Top by Δscore:

Variant	Effect	Δscore
16:85633909:TTCA:T	acceptor_loss	1.0000
16:85633910:TCAG:T	acceptor_loss	1.0000
16:85633911:CA:C	acceptor_loss	1.0000
16:85633912:A:AG	acceptor_gain	1.0000
16:85633912:AGG:A	acceptor_loss	1.0000
16:85633913:G:GA	acceptor_gain	1.0000
16:85633913:GGC:G	acceptor_gain	1.0000
16:85633913:GGCA:G	acceptor_gain	1.0000
16:85633913:GGCAT:G	acceptor_gain	1.0000
16:85634130:GAG:G	donor_gain	1.0000
16:85634133:GT:G	donor_loss	1.0000
16:85634134:T:A	donor_loss	1.0000
16:85648550:A:AG	acceptor_gain	1.0000
16:85648550:AG:A	acceptor_gain	1.0000
16:85648551:G:GG	acceptor_gain	1.0000
16:85648551:GG:G	acceptor_gain	1.0000
16:85648747:GGCAG:G	donor_gain	1.0000
16:85648748:GCAGG:G	donor_gain	1.0000
16:85648749:CAGGT:C	donor_loss	1.0000
16:85648752:G:T	donor_loss	1.0000
16:85648753:T:A	donor_loss	1.0000
16:85654276:AG:A	acceptor_gain	1.0000
16:85654277:GG:G	acceptor_gain	1.0000
16:85654277:GGAT:G	acceptor_gain	1.0000
16:85654451:G:GG	donor_gain	1.0000
16:85654792:A:AG	acceptor_gain	1.0000
16:85654793:G:GG	acceptor_gain	1.0000
16:85654953:C:G	donor_gain	1.0000
16:85655722:ACAG:A	acceptor_gain	1.0000
16:85655724:A:AG	acceptor_gain	1.0000

AlphaMissense

7873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:85634106:T:C	L67P	1.000
16:85648702:T:A	I126N	1.000
16:85648705:C:A	A127D	1.000
16:85666297:T:C	F1027S	1.000
16:85634097:T:C	L64P	0.999
16:85634099:C:A	R65S	0.999
16:85634100:G:C	R65P	0.999
16:85634106:T:A	L67H	0.999
16:85634108:G:C	A68P	0.999
16:85634109:C:A	A68D	0.999
16:85648696:T:A	V124E	0.999
16:85648702:T:C	I126T	0.999
16:85648702:T:G	I126S	0.999
16:85663354:T:C	F795S	0.999
16:85663567:T:C	F866S	0.999
16:85666284:T:C	F1023L	0.999
16:85666285:T:C	F1023S	0.999
16:85666285:T:G	F1023C	0.999
16:85666286:T:A	F1023L	0.999
16:85666286:T:G	F1023L	0.999
16:85666296:T:C	F1027L	0.999
16:85666297:T:G	F1027C	0.999
16:85666298:C:A	F1027L	0.999
16:85666298:C:G	F1027L	0.999
16:85666299:C:G	H1028D	0.999
16:85666305:T:C	S1030P	0.999
16:85666312:T:C	L1032P	0.999
16:85668376:T:A	W1123R	0.999
16:85668376:T:C	W1123R	0.999
16:85634084:T:C	F60L	0.998

dbSNP variants (sampled 300 via entrez): RS1000003078 (16:85175928 G>T), RS1000005002 (16:85351871 T>C), RS1000006062 (16:85255413 T>C), RS1000008514 (16:85281782 G>A), RS1000010849 (16:85380405 C>G), RS1000016207 (16:85307769 A>C,G), RS1000020972 (16:85568600 G>A), RS1000023613 (16:85573647 C>A), RS1000023662 (16:85649124 T>C), RS1000025339 (16:85268692 T>G), RS1000025841 (16:85509305 G>A,C,T), RS1000028283 (16:85291376 G>T), RS1000041815 (16:85397150 G>A), RS1000043111 (16:85201674 A>G), RS1000048619 (16:85343158 C>G,T)

Disease associations

OMIM: gene MIM:616886 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

18 associations (top):

Study	Trait	p-value
GCST002337_160	Amyotrophic lateral sclerosis (sporadic)	7.000000e-06
GCST002930_8	Cobalt levels	3.000000e-06
GCST004603_242	Platelet count	4.000000e-12
GCST004616_72	Platelet distribution width	4.000000e-18
GCST005991_39	Platelet count	2.000000e-11
GCST006613_108	Triglycerides	2.000000e-08
GCST009615_18	Triglyceride levels x loop diuretics use interaction	3.000000e-07
GCST012490_439	Femur bone mineral density x serum urate levels interaction	3.000000e-08
GCST012490_88	Femur bone mineral density x serum urate levels interaction	3.000000e-10
GCST90002379_178	Basophil count	5.000000e-09
GCST90002380_38	Basophil percentage of white cells	4.000000e-11
GCST90002381_99	Eosinophil count	1.000000e-14
GCST90002382_402	Eosinophil percentage of white cells	1.000000e-19
GCST90002382_403	Eosinophil percentage of white cells	4.000000e-13
GCST90002395_230	Mean platelet volume	7.000000e-14
GCST90002401_570	Platelet distribution width	7.000000e-51
GCST90002401_571	Platelet distribution width	2.000000e-10
GCST90002402_471	Platelet count	3.000000e-17

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007984	platelet component distribution width
EFO:0004530	triglyceride measurement
EFO:0004531	urate measurement
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, affects methylation	4
methylmercuric chloride	increases expression, affects cotreatment	3
Tetrachlorodibenzodioxin	decreases expression	3
entinostat	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Tretinoin	increases expression	2
Valproic Acid	increases methylation, affects expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
ON 01910	affects expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1YM	HAP1 GSE1 (-) 1	Cancer cell line	Male
CVCL_E1YN	HAP1 GSE1 (-) 2	Cancer cell line	Male
CVCL_E1YP	HAP1 GSE1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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