TCERG1

Summary

TCERG1 (transcription elongation regulator 1, HGNC:15630) is a protein-coding gene on chromosome 5q32, encoding Transcription elongation regulator 1 (O14776). Transcription factor that binds RNA polymerase II and inhibits the elongation of transcripts from target promoters. It is a selective cancer dependency (DepMap: 45.7% of cell lines).

This gene encodes a nuclear protein that regulates transcriptional elongation and pre-mRNA splicing. The encoded protein interacts with the hyperphosphorylated C-terminal domain of RNA polymerase II via multiple FF domains, and with the pre-mRNA splicing factor SF1 via a WW domain. Alternative splicing results in multiple transcripts variants encoding different isoforms.

Source: NCBI Gene 10915 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 139 total — 1 pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 45.7% of screened cell lines
• MANE Select transcript: NM_001382548

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15630
Approved symbol	TCERG1
Name	transcription elongation regulator 1
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	CA150, Urn1
Ensembl gene	ENSG00000113649
Ensembl biotype	protein_coding
OMIM	605409
Entrez	10915

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 13 protein_coding, 7 retained_intron, 6 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000296702, ENST00000394421, ENST00000503741, ENST00000504116, ENST00000505285, ENST00000506524, ENST00000507175, ENST00000509787, ENST00000509810, ENST00000510724, ENST00000511077, ENST00000513298, ENST00000514567, ENST00000514719, ENST00000515203, ENST00000549332, ENST00000679501, ENST00000707167, ENST00000707168, ENST00000875793, ENST00000875794, ENST00000914696, ENST00000914697, ENST00000914698, ENST00000914699, ENST00000914700, ENST00000914701, ENST00000914702, ENST00000949116

RefSeq mRNA: 16 — MANE Select: NM_001382548 NM_001040006, NM_001382548, NM_001400077, NM_001400082, NM_001400083, NM_001400084, NM_001400085, NM_001400092, NM_001400093, NM_001400094, NM_001400095, NM_001400096, NM_001400097, NM_001400098, NM_001400099, NM_006706

CCDS: CCDS4282, CCDS43379, CCDS93799

Canonical transcript exons

ENST00000679501 — 23 exons

Exon	Start	End
ENSE00000766804	146468341	146468403
ENSE00001918127	146510441	146511961
ENSE00002084450	146447333	146447408
ENSE00003466104	146470636	146470748
ENSE00003470356	146455056	146455281
ENSE00003490616	146507873	146507956
ENSE00003491627	146463551	146463793
ENSE00003494938	146469544	146469744
ENSE00003540066	146457183	146457335
ENSE00003540188	146482592	146482727
ENSE00003547517	146498536	146498686
ENSE00003548393	146478493	146478653
ENSE00003549945	146479855	146479911
ENSE00003566451	146471488	146471576
ENSE00003576316	146503824	146504006
ENSE00003579124	146458884	146459337
ENSE00003593152	146480028	146480094
ENSE00003614902	146503375	146503539
ENSE00003615604	146509145	146509245
ENSE00003653709	146483540	146483629
ENSE00003675552	146492920	146493038
ENSE00003688904	146507028	146507207
ENSE00003910324	146481150	146481200

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 97.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.0031 / max 453.7683, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59221	49.8382	1820
59222	2.8815	1366
59225	2.1054	1005
59223	0.1780	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.92	gold quality
right uterine tube	UBERON:0001302	97.86	gold quality
sural nerve	UBERON:0015488	97.75	gold quality
cerebellar hemisphere	UBERON:0002245	97.72	gold quality
ventricular zone	UBERON:0003053	97.58	gold quality
cerebellar cortex	UBERON:0002129	97.55	gold quality
calcaneal tendon	UBERON:0003701	96.92	gold quality
embryo	UBERON:0000922	96.61	gold quality
ganglionic eminence	UBERON:0004023	96.61	gold quality
tibial nerve	UBERON:0001323	96.53	gold quality
cortical plate	UBERON:0005343	96.50	gold quality
left ovary	UBERON:0002119	96.49	gold quality
right ovary	UBERON:0002118	96.46	gold quality
adenohypophysis	UBERON:0002196	96.42	gold quality
skin of abdomen	UBERON:0001416	96.17	gold quality
body of uterus	UBERON:0009853	96.13	gold quality
adrenal tissue	UBERON:0018303	95.93	gold quality
left uterine tube	UBERON:0001303	95.80	gold quality
mucosa of stomach	UBERON:0001199	95.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.67	gold quality
skin of leg	UBERON:0001511	95.62	gold quality
right frontal lobe	UBERON:0002810	95.60	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.57	gold quality
ectocervix	UBERON:0012249	95.40	gold quality
body of pancreas	UBERON:0001150	95.37	gold quality
transverse colon	UBERON:0001157	95.34	gold quality
cerebellum	UBERON:0002037	95.33	gold quality
metanephros cortex	UBERON:0010533	95.32	gold quality
right testis	UBERON:0004534	95.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SF1

miRNA regulators (miRDB)

107 targeting TCERG1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
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-223-3P	99.99	70.14	1140
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3671	99.90	73.04	3897

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 45.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 19)

• Specific alleles in GluR6 and CA150 locus were only observed in HD patients. (PMID:12821179)
• Results suggest an essential role of WW/FF domain-containing factors such as FBP11 and CA150 in pre-mRNA splicing that likely occurs in concert with transcription in vivo. (PMID:15456888)
• CA150 is a co-repressor of C/EBP proteins and provides a possible mechanism for how C/EBPalpha can repress transcription of specific genes (PMID:16644732)
• Sequences located at both the amino and carboxyl regions of CA150 are required to assemble transcription/splicing complexes, which may be involved in the coupling of those processes. (PMID:16782886)
• GRIN2A and TCERG1 may show true association with residual age of onset for Huntington’s disease in genetic association tests in 443 affected people from a large set of kindreds from Venezuela. (PMID:17018562)
• The interferon consensus sequence-binding protein (ICSBP/IRF8) represses PTPN13 gene transcription in differentiating myeloid cells (PMID:18187414)
• Data provide the first crystal structure of an FF domain and insights into the tandem nature of the FF domains and suggest that, in addition to protein binding, FF domains might be involved in DNA binding. (PMID:19660470)
• Data gave a model for FF domain organization within tandem arrays suggests a general mechanism by which individual FF domains can manoeuvre to achieve optimal recognition of flexible binding partners, such as the intrinsically-disordered phosphoCTD (PMID:19715701)
• mutation of the SUMO acceptor lysine residues enhanced TCERG1 transcriptional activity, indicating that SUMO modification negatively regulates TCERG1 transcriptional activity (PMID:20215116)
• TCERG1 can inhibit C/EBPalpha activity regardless of the latter’s location in the nucleus (PMID:21503969)
• We propose that TCERG1 modulates the elongation rate of RNAPII to relieve pausing, thereby activating the proapoptotic Bcl-x(S) 5’ splice site. (PMID:22158966)
• The FF4 and FF5 domains of transcription elongation regulator 1 (TCERG1) target proteins to the periphery of speckles. (PMID:22453921)
• Specific interaction of the transcription elongation regulator TCERG1 with RNA polymerase II requires simultaneous phosphorylation at Ser2, Ser5, and Ser7 within the carboxyl-terminal domain repeat. (PMID:23436654)
• This study reveals that TCERG1 regulates HIV-1 transcriptional elongation by increasing the elongation rate of RNAPII and phosphorylation of Ser 2 within the carboxyl-terminal domain. (PMID:24165037)
• The QA repeat domain of TCERG1 is required for relocalization of CEBPalpha. (PMID:26264132)
• TCERG1 sensitizes a cell to apoptotic agents, thus promoting apoptosis by regulating the alternative splicing of both the Bcl-x and Fas/CD95 genes. (PMID:26462236)
• TCERG1 binds independently to elongation and splicing complexes, thus performing their coupling by transient interactions rather than by stable association with one or the other complexes. (PMID:26873599)
• TCERG1 affects expression of multiple mRNAs involved in neuron projection development. (PMID:27844289)
• Results of this study suggest that TCERG1 plays an important role in Cajal body formation and snRNP biogenesis. (PMID:31636114)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tcerg1a	ENSDARG00000098822
mus_musculus	Tcerg1	ENSMUSG00000024498
rattus_norvegicus	Tcerg1	ENSRNOG00000018849

Paralogs (2): ARHGAP5 (ENSG00000100852), TCERG1L (ENSG00000176769)

Protein

Protein identifiers

Transcription elongation regulator 1 — O14776 (reviewed: O14776)

Alternative names: TATA box-binding protein-associated factor 2S, Transcription factor CA150

All UniProt accessions (5): O14776, A0A7P0T8N8, A0AA34QVF9, A0AA34QVU1, G3V220

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds RNA polymerase II and inhibits the elongation of transcripts from target promoters. Regulates transcription elongation in a TATA box-dependent manner. Necessary for TAT-dependent activation of the human immunodeficiency virus type 1 (HIV-1) promoter.

Subunit / interactions. Binds formin. Interacts (via the second WW domain) with TREX1 (via proline-rich region). Binds RNA polymerase II, HD and SF1.

Subcellular location. Nucleus.

Tissue specificity. Detected in brain neurons.

Domain organisation. The FF domains bind the phosphorylated C-terminus of the largest subunit of RNA polymerase II, probably mediate interaction with HTATSF1 and preferentially bind peptides with the consensus sequence DE-[FWY]-DE. The WW domains bind Pro-rich domains.

Induction. Up-regulated in brain tissue from patients with Huntington disease.

Isoforms (2)

UniProt ID	Names	Canonical?
O14776-1	1	yes
O14776-2	2

RefSeq proteins (16): NP_001035095, NP_001369477, NP_001387006, NP_001387011, NP_001387012, NP_001387013, NP_001387014, NP_001387021, NP_001387022, NP_001387023, NP_001387024, NP_001387025, NP_001387026, NP_001387027, NP_001387028, NP_006697 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR002713	FF_domain	Domain
IPR036020	WW_dom_sf	Homologous_superfamily
IPR036517	FF_domain_sf	Homologous_superfamily
IPR045148	TCRG1-like	Family
IPR057565	WW_TCRG1_3rd	Domain

Pfam: PF00397, PF01846, PF23517

UniProt features (92 total): helix 23, strand 15, turn 10, domain 9, modified residue 9, compositionally biased region 7, region of interest 6, coiled-coil region 3, cross-link 3, mutagenesis site 3, chain 1, short sequence motif 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
3Q1I	X-RAY DIFFRACTION	1.4
4FQG	X-RAY DIFFRACTION	2
3HFH	X-RAY DIFFRACTION	2.7
8Q7N	ELECTRON MICROSCOPY	3.1
9R3D	ELECTRON MICROSCOPY	3.12
7ABF	ELECTRON MICROSCOPY	3.9
8QO9	ELECTRON MICROSCOPY	5.29
7ABG	ELECTRON MICROSCOPY	7.8
9R8V	ELECTRON MICROSCOPY	8.5
2DK7	SOLUTION NMR
2DOD	SOLUTION NMR
2DOE	SOLUTION NMR
2DOF	SOLUTION NMR
2E71	SOLUTION NMR
2KIQ	SOLUTION NMR
2KIS	SOLUTION NMR
2MW9	SOLUTION NMR
2MWA	SOLUTION NMR
2MWB	SOLUTION NMR
2MWD	SOLUTION NMR
2MWE	SOLUTION NMR
2MWF	SOLUTION NMR
2N4R	SOLUTION NMR
2N4S	SOLUTION NMR
2N4T	SOLUTION NMR
2N4U	SOLUTION NMR
2N4V	SOLUTION NMR
2N4W	SOLUTION NMR
2NNT	SOLID-STATE NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14776-F1	69.35	0.30

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 (12): 11, 20, 28, 30, 41, 48, 638, 834, 933, 503, 507, 608

Mutagenesis-validated functional residues (3):

Position	Phenotype
148–150	reduces repression of transcription by 35%. reduces repression of transcription by 63%; when associated with 446-aaa-448
446–448	loss of interaction with sf1. reduces repression of transcription by 35%. reduces repression of transcription by 63%; wh
545–547	no effect.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 251 (showing top): MORF_DNMT1, GNF2_MSH2, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, TATTATA_MIR374, TGACCTY_ERR1_Q2, MORF_HDAC2, PUJANA_CHEK2_PCC_NETWORK, MUELLER_PLURINET, CATRRAGC_UNKNOWN, ONKEN_UVEAL_MELANOMA_UP, MYCMAX_01, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_DN

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), mRNA processing (GO:0006397), RNA splicing (GO:0008380), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), negative regulation of transcription elongation by RNA polymerase II (GO:0034244), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (11): transcription elongation factor activity (GO:0003711), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), identical protein binding (GO:0042802), ubiquitin-like protein conjugating enzyme binding (GO:0044390), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), RNA polymerase binding (GO:0070063), protein binding (GO:0005515), proline-rich region binding (GO:0070064)

GO Cellular Component (3): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
RNA processing	2
transcription elongation by RNA polymerase II	2
regulation of transcription elongation by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
transcription regulator activity	2
transcription coregulator activity	2
protein binding	2
enzyme binding	2
mRNA metabolic process	1
positive regulation of DNA-templated transcription, elongation	1
positive regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription, elongation	1
nucleic acid binding	1
DNA-binding transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

2204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCERG1	HTT	P42858	924
TCERG1	SF3B4	Q15427	780
TCERG1	SNRPC	P09234	773
TCERG1	HTATSF1	O43719	758
TCERG1	TDRD3	Q9H7E2	753
TCERG1	CARM1	Q86X55	641
TCERG1	SMNDC1	O75940	629
TCERG1	SF1	Q15637	532
TCERG1	PRPF40A	O75400	524
TCERG1	SRSF2	Q01130	523
TCERG1	RBM8A	Q9Y5S9	519
TCERG1	SNRPB	P14678	504
TCERG1	GTF2F2	P13984	498
TCERG1	GRIK2	Q13002	497
TCERG1	U2AF2	P26368	470

IntAct

120 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TCERG1	TCERG1	psi-mi:“MI:0407”(direct interaction)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
HTT	TCERG1	psi-mi:“MI:0915”(physical association)	0.550
TCERG1	HTT	psi-mi:“MI:0915”(physical association)	0.550
SLC35B1	PGRMC1	psi-mi:“MI:0914”(association)	0.530
BARD1	TCERG1	psi-mi:“MI:0915”(physical association)	0.510
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
TCERG1	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
NR1I2	TCERG1	psi-mi:“MI:0915”(physical association)	0.400
BUB1B	TCERG1	psi-mi:“MI:0915”(physical association)	0.400
TCERG1	DHRS2	psi-mi:“MI:0915”(physical association)	0.400
NOL8	TCERG1	psi-mi:“MI:0915”(physical association)	0.400
LMCD1	TCERG1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (262): TCERG1 (Affinity Capture-MS), TCERG1 (Biochemical Activity), TCERG1 (Reconstituted Complex), TCERG1 (Affinity Capture-MS), TCERG1 (Co-fractionation), TCERG1L (Co-fractionation), TCERG1 (Affinity Capture-MS), SF1 (Reconstituted Complex), U2AF2 (Reconstituted Complex), HSPA1B (Affinity Capture-MS), SNRPA1 (Affinity Capture-MS), TCERG1 (Affinity Capture-MS), TCERG1 (Affinity Capture-MS), TCERG1 (Affinity Capture-MS), TCERG1 (Affinity Capture-MS)

ESM2 similar proteins: B6EUA9, B9DFV2, F4HY56, F4IUY8, F4JCC1, F4JP52, F4K2F0, F4KIA8, O04539, O14176, O14776, O75400, P34600, P51115, Q0JDM0, Q2T9I5, Q32SG5, Q3MHS2, Q5BJ56, Q5T8P6, Q5TUF1, Q5XI29, Q5XIN3, Q60520, Q6NV83, Q6NZN0, Q75LL6, Q7KRW8, Q7ZTQ5, Q8BTV2, Q8CGF7, Q8LPQ9, Q8N684, Q8RY18, Q8TAQ2, Q8VY15, Q96ST3, Q9C5J3, Q9C7C4, Q9C7E7

Diamond homologs: B6EUA9, F4JCC1, O14776, Q3B807, Q5U4Q0, Q7ZUK7, Q8CGF7, Q924H7, Q9BTA9, O75400, Q5VWI1, Q6NWY9, Q80W14, Q9R1C7, P34600, O04425

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 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
mRNA Polyadenylation	15	14.8×	2e-11
mRNA Splicing	11	13.6×	5e-08
mRNA Splicing - Major Pathway	22	13.5×	2e-16
Processing of Capped Intron-Containing Pre-mRNA	13	12.0×	7e-09
SARS-CoV-1-host interactions	6	11.8×	7e-04
mRNA 3’-end processing	5	11.1×	4e-03
SARS-CoV-1 Infection	6	9.6×	2e-03
Dengue Virus-Host Interactions	17	8.7×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	6	33.7×	9e-06
mRNA splicing, via spliceosome	20	16.5×	4e-16
regulation of alternative mRNA splicing, via spliceosome	6	13.2×	1e-03
RNA splicing	11	8.7×	2e-05
mRNA processing	11	7.8×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	96
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
998159	NM_001382548.1(TCERG1):c.192del (p.Pro65fs)	Pathogenic

SpliceAI

3395 predictions. Top by Δscore:

Variant	Effect	Δscore
5:146447405:TCAG:T	donor_loss	1.0000
5:146447406:CAGG:C	donor_loss	1.0000
5:146447409:G:GA	donor_loss	1.0000
5:146447410:T:G	donor_loss	1.0000
5:146455051:TGCA:T	acceptor_loss	1.0000
5:146455052:GCA:G	acceptor_loss	1.0000
5:146455054:A:AG	acceptor_gain	1.0000
5:146455054:A:G	acceptor_loss	1.0000
5:146455054:AG:A	acceptor_gain	1.0000
5:146455054:AGGAT:A	acceptor_gain	1.0000
5:146455055:G:A	acceptor_loss	1.0000
5:146455055:G:GA	acceptor_gain	1.0000
5:146455055:GG:G	acceptor_gain	1.0000
5:146455055:GGA:G	acceptor_gain	1.0000
5:146455055:GGAT:G	acceptor_gain	1.0000
5:146455055:GGATG:G	acceptor_gain	1.0000
5:146455281:GGT:G	donor_loss	1.0000
5:146455283:T:G	donor_loss	1.0000
5:146456869:G:GT	donor_gain	1.0000
5:146457170:T:TA	acceptor_gain	1.0000
5:146457172:T:TA	acceptor_gain	1.0000
5:146457178:A:AG	acceptor_gain	1.0000
5:146457179:A:G	acceptor_gain	1.0000
5:146457180:CAGAG:C	acceptor_loss	1.0000
5:146457181:A:AG	acceptor_gain	1.0000
5:146457181:A:AT	acceptor_loss	1.0000
5:146457182:G:GA	acceptor_gain	1.0000
5:146457182:GA:G	acceptor_gain	1.0000
5:146457182:GAGA:G	acceptor_gain	1.0000
5:146457182:GAGAC:G	acceptor_gain	1.0000

AlphaMissense

7296 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:146457306:T:A	W137R	1.000
5:146457306:T:C	W137R	1.000
5:146457308:G:C	W137C	1.000
5:146457308:G:T	W137C	1.000
5:146457310:T:A	V138D	1.000
5:146458887:T:G	Y148D	1.000
5:146458890:T:G	Y149D	1.000
5:146458893:T:G	Y150D	1.000
5:146458900:C:A	A152D	1.000
5:146458920:T:A	W159R	1.000
5:146458920:T:C	W159R	1.000
5:146458922:G:C	W159C	1.000
5:146458922:G:T	W159C	1.000
5:146458945:T:A	V167D	1.000
5:146469648:T:A	W435R	1.000
5:146469648:T:C	W435R	1.000
5:146469650:G:C	W435C	1.000
5:146469650:G:T	W435C	1.000
5:146469681:T:C	Y446H	1.000
5:146469681:T:G	Y446D	1.000
5:146469684:T:G	Y447D	1.000
5:146469687:T:G	Y448D	1.000
5:146469714:T:A	W457R	1.000
5:146469714:T:C	W457R	1.000
5:146469716:G:C	W457C	1.000
5:146469716:G:T	W457C	1.000
5:146471542:C:T	P523S	1.000
5:146471543:C:A	P523Q	1.000
5:146471546:T:A	V524D	1.000
5:146471548:G:C	A525P	1.000

dbSNP variants (sampled 300 via entrez): RS1000018874 (5:146445389 G>A,T), RS1000053478 (5:146452657 T>C), RS1000079418 (5:146496666 A>T), RS1000083994 (5:146452871 G>A), RS1000159995 (5:146479563 G>A), RS1000230116 (5:146461500 G>T), RS1000442150 (5:146512436 A>G), RS1000451112 (5:146496333 C>G), RS1000570099 (5:146506687 T>C,G), RS1000585121 (5:146456398 C>A), RS1000651191 (5:146471120 G>A), RS1000660638 (5:146490645 T>C,G), RS1000774562 (5:146512114 C>A,T), RS1000789667 (5:146508549 A>G,T), RS1000841271 (5:146493843 T>A,G)

Disease associations

OMIM: gene MIM:605409 | disease phenotypes: MIM:114500

GenCC curated gene-disease

Mondo (1): colorectal cancer (MONDO:0005575)

Orphanet (1): NON RARE IN EUROPE: Colorectal cancer (Orphanet:466667)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008359_7	Response to cognitive-behavioural therapy in anxiety disorder	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724602 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.27	Kd	53.22	nM	CHEMBL5653589
7.06	ED50	87.63	nM	CHEMBL5653589
6.46	IC50	350	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149563: Binding affinity to human TCERG1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0532	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178982: Inhibition of TCERG1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.3500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression, decreases methylation	7
Cadmium Chloride	decreases expression, increases abundance, increases expression, decreases methylation	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Vorinostat	decreases expression	2
Cisplatin	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
beta-lapachone	decreases expression	1
methylparaben	increases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment	1
isobutyl alcohol	increases expression, affects cotreatment, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
nutlin 3	increases secretion, affects cotreatment	1
bisphenol S	affects expression	1
jinfukang	affects cotreatment, decreases expression	1
PP242	decreases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Arsenic	increases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Cannabidiol	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression, increases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Diethylstilbestrol	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652605	Binding	Binding affinity to human TCERG1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TR79	HAP1 TCERG1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00114829	PHASE4	UNKNOWN	Preoperative Assessment of Colon Tumor
NCT00114842	PHASE4	COMPLETED	Magnetic Resonance (MR) Colonography With Fecal Tagging
NCT00114946	PHASE4	TERMINATED	A Study to Compare Two Avastin-Based Treatment Regimens for the Treatment of Metastatic Colorectal Cancer
NCT00122720	PHASE4	COMPLETED	The Effect of Darbepoetin Upon Rehabilitation for Colorectal Cancer Surgery
NCT00129870	PHASE4	TERMINATED	CONCEPT: Comparison of Oxaliplatin vs Conventional Methods With Calcium/Magnesium in First-Line Metastatic Colorectal Cancer
NCT00138060	PHASE4	COMPLETED	Toxicity/Benefit Ratio Optimization of Chemotherapy in Colorectal Cancer (CRC) Patients by Determination of Individual Genotypic Determinants
NCT00216424	PHASE4	TERMINATED	Capecitabine (Xeloda) and Radiation for Patients With Rectosigmoid Carcinoma
NCT00327093	PHASE4	TERMINATED	Elaboration of a Model for Predicting Efficacy of Monoclonal Antibodies (Cetuximab and Bevacizumab) in Patients With Colorectal Cancer and Liver Metastases
NCT00332943	PHASE4	COMPLETED	MR Colonography With Fecal Tagging. Barium vs. BariumFerumoxsil
NCT00441311	PHASE4	COMPLETED	Dissemination of Colorectal Cancer Screening to Primary Care Physicians
NCT00460837	PHASE4	WITHDRAWN	Comparison of Bowel Preparation in Virtual Colonoscopy (VC) - Patient Experience
NCT00473980	PHASE4	COMPLETED	Preoperative Non-steroidal Anti-inflammatory Drugs(NSAID) to Colorectal Cancer Patients
NCT00488904	PHASE4	COMPLETED	Omega-3 Fatty Acids and Postoperative Complications After Colorectal Surgery
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00502671	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) as Adjuvant Monotherapy in Patients With Colon Cancer.
NCT00559676	PHASE4	COMPLETED	Study of Biomarkers in Patients Undergoing Chemotherapy for Metastatic Colorectal Cancer
NCT00577031	PHASE4	COMPLETED	OBELIX Study: A Study of Avastin (Bevacizumab) in Combination With XELOX in Patients With Metastatic Cancer of the Colon or Rectum.
NCT00626054	PHASE4	COMPLETED	Comparison of Two Methods of Administration of a PEG Solution
NCT00812864	PHASE4	COMPLETED	Pharmacokinetic Study of Capecitabine in Elderly Cancer Patient (≥ 75 Years)
NCT00868569	PHASE4	UNKNOWN	Transhepatic Arterial Chemotherapy (TAC) Versus Transcatheter Arterial Chemoembolization (TACE) Plus Folfox4 as the Treatment of Unresectable Liver Metastasis of Colorectal Cancer
NCT00868816	PHASE4	COMPLETED	Oxaliplatine Based Adjuvant Chemotherapy for Stage II/III Colorectal Cancer: 8 Cycles Versus 12 Cycles
NCT00874406	PHASE4	UNKNOWN	Preoperative Transhepatic Arterial Chemotherapy (TAC) in the Treatment of Liver Metastasis of Resectable Colorectal Cancer
NCT00928928	PHASE4	COMPLETED	Oxidative Stress Markers in Open and Laparoscopic Colectomy for Cancer
NCT00942461	PHASE4	COMPLETED	Inflammatory Response in Laparoscopic and Open Colectomy
NCT01023633	PHASE4	UNKNOWN	OPTIMOX1 in Chinese mCRC Patients
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01315990	PHASE4	UNKNOWN	FOLFIRI in Combination With Cetuximab in the First-line Treatment of Metastatic Colorectal Cancer Including a Regular Dermal Prophylaxis to Prevent Acneiforme Follicular Exanthema
NCT01493713	PHASE4	COMPLETED	Correlation Between RECIST, Morphologic Response by CT- Histopathologic Response in Hepatic Metastasis Secondary to Colorectal Cancer
NCT01609660	PHASE4	COMPLETED	Impact of Probiotics on the Intestinal Microbiota
NCT01641458	PHASE4	COMPLETED	Pharmacology-driven Dosing of Fluoropyrimidines in Cancer Patients
NCT01689792	PHASE4	COMPLETED	A Multi-centre Study Comparing the Polyp Detection Rate of Two Different Types of Bowel Preparation: a 2-litre Solution (MOVIPREP®) Versus a Hyperosmotic and Stimulant Combined Low Volume Bowel Preparation (Sodium Picosulfate and Magnesium Citrate)
NCT01695772	PHASE4	COMPLETED	A Study of Bevacizumab Plus 5-Flurouracil (5-FU) Based Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Previously Untreated Unresectable Liver-Only Metastases From Colorectal Cancer
NCT01695863	PHASE4	COMPLETED	Efficacy and Patient Satisfaction of Miralax and Gatorade Versus Movi Prep
NCT01706822	PHASE4	TERMINATED	Radial Reload Laparoscopic LAR Case Series
NCT01740947	PHASE4	TERMINATED	Does Administration of Antibiotics in Patients Undergoing Surgery for Colorectal Cancer Result in Less Complications and Better Prognosis?
NCT01831310	PHASE4	COMPLETED	Nutrition for Colorectal Cancer Patients and Neutrophil Functions
NCT01841294	PHASE4	UNKNOWN	NK Activity Modulation Induced by Intravenous Lidocaine During Colorectal Laparoscopic Surgery
NCT01959061	PHASE4	UNKNOWN	Efficacy and Safety of Raltitrexed-based Transarterial Chemoembolisation(TACE)for Colorectal Cancer Liver Metastases
NCT02032953	PHASE4	UNKNOWN	Enhancing the Anabolic Effect of Perioperative Nutrition With Insulin While Maintaining Normoglycemia
NCT02567331	PHASE4	COMPLETED	A Study of Capecitabine (Xeloda) in Patients With Metastatic Colorectal Cancer