TUSC1

Summary

TUSC1 (tumor suppressor candidate 1, HGNC:31010) is a protein-coding gene on chromosome 9p21.2, encoding Tumor suppressor candidate gene 1 protein (Q2TAM9).

This gene is located within the region of chromosome 9p that harbors tumor suppressor genes critical in carcinogenesis. It is an intronless gene which is downregulated in non-small-cell lung cancer and small-cell lung cancer cell lines, suggesting that it may play a role in lung tumorigenesis.

Source: NCBI Gene 286319 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_001004125

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31010
Approved symbol	TUSC1
Name	tumor suppressor candidate 1
Location	9p21.2
Locus type	gene with protein product
Status	Approved
Aliases	TSG-9, CCDC89B
Ensembl gene	ENSG00000198680
Ensembl biotype	protein_coding
OMIM	610529
Entrez	286319

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000358022

RefSeq mRNA: 1 — MANE Select: NM_001004125 NM_001004125

CCDS: CCDS34999

Canonical transcript exons

ENST00000358022 — 1 exons

Exon	Start	End
ENSE00001408181	25676969	25678444

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5294 / max 88.3745, expressed in 1508 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100304	4.8820	1420
100305	3.5528	1272
100303	0.0946	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	98.52	silver quality
pancreatic ductal cell	CL:0002079	97.54	gold quality
upper arm skin	UBERON:0004263	97.00	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.70	gold quality
endothelial cell	CL:0000115	96.63	silver quality
adult organism	UBERON:0007023	96.36	gold quality
kidney epithelium	UBERON:0004819	96.14	gold quality
left ventricle myocardium	UBERON:0006566	96.11	gold quality
vena cava	UBERON:0004087	95.95	gold quality
ileal mucosa	UBERON:0000331	95.83	gold quality
saphenous vein	UBERON:0007318	95.80	gold quality
gingival epithelium	UBERON:0001949	95.71	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.28	gold quality
nipple	UBERON:0002030	94.94	gold quality
sperm	CL:0000019	94.88	gold quality
corpus epididymis	UBERON:0004359	94.81	gold quality
parietal pleura	UBERON:0002400	94.65	gold quality
parotid gland	UBERON:0001831	94.57	gold quality
epithelium of mammary gland	UBERON:0003244	94.47	gold quality
oviduct epithelium	UBERON:0004804	94.47	gold quality
mammary duct	UBERON:0001765	94.43	gold quality
gingiva	UBERON:0001828	94.43	gold quality
middle temporal gyrus	UBERON:0002771	94.41	gold quality
nasal cavity epithelium	UBERON:0005384	93.62	gold quality
tibialis anterior	UBERON:0001385	93.57	gold quality
pericardium	UBERON:0002407	93.44	gold quality
caput epididymis	UBERON:0004358	93.30	gold quality
myocardium	UBERON:0002349	93.15	gold quality
renal medulla	UBERON:0000362	92.80	gold quality
layer of synovial tissue	UBERON:0007616	92.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

69 targeting TUSC1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-6715B-5P	99.64	69.63	1420

Literature-anchored findings (GeneRIF, showing 7)

• TUSC1 may play a role in lung tumorigenesis (PMID:15208665)
• Results support TUSC1 has tumor suppressor activity as a candidate tumor suppressor gene located on chromosome 9p. (PMID:23776618)
• TUSC1 is a candidate tumor suppressor gene and intragenic hypermethylation is one of the suppressive mechanisms that regulate TUSC1 transcription in hepatocellular carcinoma. (PMID:24366000)
• Results suggested that reduced expression of TUSC1 mRNA was related to poor prognosis and TUSC1 is a putative tumor suppressor gene that is suppressed through intragenic hypermethylation in gastric cancer. (PMID:24700496)
• The expression of TUSC1 is significantly decreased in glioblastoma brain tumor tissues. (PMID:26897357)
• TUSC1 single nucleotide polymorphisms were significantly correlated with azoospermia and/or oligozoospermia in a Japanese population. (PMID:28975488)
• Circular RNA circ_0065378 upregulates tumor suppressor candidate 1 by competitively binding with miR-4701-5p to alleviate colorectal cancer progression. (PMID:35434854)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tusc1	ENSMUSG00000054000
rattus_norvegicus	Tusc1	ENSRNOG00000066328

Protein

Protein identifiers

Tumor suppressor candidate gene 1 protein — Q2TAM9 (reviewed: Q2TAM9)

Alternative names: TSG-9

All UniProt accessions (1): Q2TAM9

UniProt curated annotations — full annotation on UniProt →

Tissue specificity. Widely expressed at low level. Expressed at higher level in testis, weakly expressed in muscle, colon, lung and spleen. Not detected in 3 non small cell lung carcinoma (NSCLC) cell lines with homozygous deletion of the 9p region, while it is down-regulated in 3 other tumor cell lines.

RefSeq proteins (1): NP_001004125* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043450	CCDC89-like	Family

UniProt features (11 total): region of interest 3, compositionally biased region 3, coiled-coil region 2, chain 1, sequence variant 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2TAM9-F1	69.75	0.42

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 (1): 150

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, FIGUEROA_AML_METHYLATION_CLUSTER_6_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, NFE2L1_TARGET_GENES, UBN1_TARGET_GENES, ZNF768_TARGET_GENES, MIR1277_5P, MIR548N, MIR6074, MIR4760_5P, MIR877_3P, MIR8061

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TUSC1	RFX8	Q6ZV50	486
TUSC1	IZUMO3	Q5VZ72	435
TUSC1	ZNF197	O14709	413
TUSC1	LINGO2	Q7L985	387
TUSC1	LRRC19	Q9H756	384
TUSC1	SMIM15	Q7Z3B0	376
TUSC1	KRT85	P78386	368
TUSC1	RSU1	Q15404	367
TUSC1	DTHD1	Q6ZMT9	357
TUSC1	ST7	Q9NRC1	351
TUSC1	ERP29	P30040	316
TUSC1	CDKN2B	P42772	315
TUSC1	IFNW1	P05000	312
TUSC1	FNDC4	Q9H6D8	308
TUSC1	KRTAP3-3	Q9BYR6	305

IntAct

11 interactions, top by confidence:

A	B	Type	Score
SMN1	GEMIN2	psi-mi:“MI:0914”(association)	0.960
PRMT8	SYNCRIP	psi-mi:“MI:0914”(association)	0.830
GGPS1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
TACC3	HSPA8	psi-mi:“MI:0914”(association)	0.530
P		psi-mi:“MI:0914”(association)	0.350
EIF3D	EIF3CL	psi-mi:“MI:0914”(association)	0.350
	NFIB	psi-mi:“MI:0914”(association)	0.350
	RPS10-NUDT3	psi-mi:“MI:0914”(association)	0.350
ORF66	RALGAPA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): TUSC1 (Affinity Capture-MS), TUSC1 (Affinity Capture-MS), TUSC1 (Affinity Capture-MS), TUSC1 (Affinity Capture-MS), TUSC1 (Affinity Capture-MS), TUSC1 (Affinity Capture-MS), TUSC1 (Affinity Capture-MS), TUSC1 (Affinity Capture-MS), TUSC1 (Affinity Capture-MS), TUSC1 (Proximity Label-MS), TUSC1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8I5KY20, A2A9T0, A2IDD5, B0BNK9, B8ZZ34, C9JI98, C9JLR9, F5GYI3, O18734, P0CG25, P84157, Q0IIA6, Q0PHV7, Q0X0E2, Q13387, Q1RMK9, Q2M3D2, Q2TAM9, Q3ZCQ3, Q4VA45, Q673H1, Q69YZ2, Q6NS60, Q6P6N5, Q6PJ61, Q7Z6J2, Q80ZJ8, Q810I0, Q86SX3, Q86UD0, Q86XT2, Q8BNN1, Q8IUW3, Q8N4Y2, Q8N6N2, Q8QZV0, Q8R4T5, Q8TF61, Q8VCR9, Q8WXF8

Diamond homologs: Q2TAM9, Q673H1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	55
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

36 predictions. Top by Δscore:

Variant	Effect	Δscore
9:25677756:T:TA	donor_gain	0.5000
9:25677666:A:AC	donor_gain	0.4800
9:25677667:C:CC	donor_gain	0.4800
9:25677738:T:TA	donor_gain	0.4800
9:25677667:CCGG:C	donor_gain	0.4500
9:25677828:T:TA	donor_gain	0.4400
9:25677660:CCTCT:C	donor_loss	0.4300
9:25677661:CTCTC:C	donor_loss	0.4300
9:25677662:TCTCA:T	donor_loss	0.4300
9:25677663:CTCAC:C	donor_loss	0.4300
9:25677664:TCACC:T	donor_loss	0.4300
9:25677665:CAC:C	donor_loss	0.4300
9:25677666:A:AG	donor_loss	0.4300
9:25677667:C:A	donor_loss	0.4300
9:25677659:GCCTC:G	donor_loss	0.4200
9:25677668:C:G	donor_loss	0.4100
9:25678003:T:TA	acceptor_gain	0.4100
9:25677753:T:TA	donor_gain	0.3700
9:25677852:AGGGC:A	donor_gain	0.3600
9:25677978:AAAG:A	donor_gain	0.3400
9:25677876:T:TA	donor_gain	0.3000
9:25677822:A:C	donor_gain	0.2900
9:25677980:AG:A	donor_gain	0.2900
9:25677622:G:C	donor_gain	0.2800
9:25678004:C:A	acceptor_gain	0.2700
9:25678113:G:A	donor_gain	0.2600
9:25678047:T:TA	donor_gain	0.2400
9:25677563:C:CT	donor_gain	0.2300
9:25677712:C:A	donor_gain	0.2200
9:25677936:G:A	donor_gain	0.2200

AlphaMissense

1338 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:25678127:A:C	F65L	0.996
9:25678127:A:T	F65L	0.996
9:25678129:A:G	F65L	0.996
9:25678014:A:G	L103P	0.993
9:25678035:A:G	L96P	0.993
9:25677989:G:C	F111L	0.992
9:25677989:G:T	F111L	0.992
9:25677991:A:G	F111L	0.992
9:25678010:C:A	K104N	0.992
9:25678010:C:G	K104N	0.992
9:25678022:G:C	N100K	0.992
9:25678022:G:T	N100K	0.992
9:25678024:T:C	N100D	0.992
9:25678001:G:C	N107K	0.991
9:25678001:G:T	N107K	0.991
9:25678003:T:C	N107D	0.991
9:25678128:A:G	F65S	0.991
9:25678043:G:C	N93K	0.988
9:25678043:G:T	N93K	0.988
9:25678128:A:C	F65C	0.988
9:25678020:C:G	R101P	0.986
9:25678099:C:G	A75P	0.986
9:25677990:A:G	F111S	0.985
9:25678002:T:A	N107I	0.985
9:25678045:T:C	N93D	0.985
9:25678108:G:C	H72D	0.985
9:25678023:T:A	N100I	0.984
9:25678023:T:C	N100S	0.984
9:25678026:T:A	E99V	0.984
9:25678119:A:G	L68P	0.984

dbSNP variants (sampled 300 via entrez): RS1000105701 (9:25677790 C>A), RS1001349385 (9:25680308 T>A), RS1001817360 (9:25677307 A>G,T), RS1002186121 (9:25677038 C>G,T), RS1002452698 (9:25679496 TA>T), RS1003316152 (9:25678067 C>A,T), RS1004621047 (9:25679522 G>A,T), RS1004693220 (9:25678307 C>T), RS1004745914 (9:25678499 C>G,T), RS1005759737 (9:25679463 G>A,T), RS1006428859 (9:25678277 C>A,G,T), RS1006703758 (9:25678403 G>A,T), RS1006879584 (9:25679672 G>A,C,T), RS1007074996 (9:25677749 C>G), RS1007777325 (9:25678113 G>A,C)

Disease associations

OMIM: gene MIM:610529 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000889_1	Entorhinal cortical thickness (Alzheimer’s disease interaction)	8.000000e-06
GCST001524_25	Visceral adipose tissue/subcutaneous adipose tissue ratio	6.000000e-06
GCST001540_4	Male fertility	6.000000e-06
GCST002049_6	Sleep quality	9.000000e-06
GCST002120_12	Metabolite levels (Dihydroxy docosatrienoic acid)	8.000000e-06
GCST002550_10	Allergic rhinitis	6.000000e-07
GCST002759_33	Motion sickness	9.000000e-09
GCST008597_2	Fish intake frequency	9.000000e-06
GCST009277_11	Subjective response to placebo treatment in childhood asthma (change in cough/wheeze)	3.000000e-06
GCST009391_617	Metabolite levels	5.000000e-06
GCST010724_17	HOMA-B (corrected for HOMA-IR)	4.000000e-07
GCST010989_148	Body size at age 10	6.000000e-09
GCST012307_13	Bipolar disorder x sex interaction	2.000000e-07

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004840	cortical thickness
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0004802	family size
EFO:0004803	male fertility
EFO:0005275	dihydroxy docosatrienoic acid measurement
EFO:0006928	motion sickness
EFO:0010139	fish consumption measurement
EFO:0008344	response to placebo
EFO:0010068	respiratory symptom change measurement
EFO:0009793	isoleucine measurement
EFO:0004469	HOMA-B
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	2
bisphenol F	affects cotreatment, increases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
sodium arsenite	decreases expression	1
ferrous chloride	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Dactinomycin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Endosulfan	increases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Phthalic Acids	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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