TCP10L

Summary

TCP10L (t-complex 10 like, HGNC:11657) is a protein-coding gene on chromosome 21q22.11, encoding T-complex protein 10A homolog 1 (Q8TDR4). May be involved in transcriptional regulation.

Enables DNA-binding transcription factor binding activity; identical protein binding activity; and transcription corepressor activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus.

Source: NCBI Gene 140290 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_144659

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11657
Approved symbol	TCP10L
Name	t-complex 10 like
Location	21q22.11
Locus type	gene with protein product
Status	Approved
Aliases	PRED77
Ensembl gene	ENSG00000242220
Ensembl biotype	protein_coding
OMIM	608365
Entrez	140290

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 7 protein_coding, 6 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000300258, ENST00000334165, ENST00000472557, ENST00000491828, ENST00000582575, ENST00000673667, ENST00000673699, ENST00000673776, ENST00000673787, ENST00000673793, ENST00000673907, ENST00000674032, ENST00000674055, ENST00000674141, ENST00000674156, ENST00000897540, ENST00000897541

RefSeq mRNA: 1 — MANE Select: NM_144659 NM_144659

CCDS: CCDS13616

Canonical transcript exons

ENST00000300258 — 5 exons

Exon	Start	End
ENSE00001108404	32573721	32576923
ENSE00003705877	32584161	32584305
ENSE00003707956	32582200	32582415
ENSE00003844444	32585421	32585523
ENSE00003897287	32578694	32578831

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4431 / max 240.4283, expressed in 58 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190186	0.2264	10
190188	0.1579	46
190185	0.0263	3
190187	0.0211	6
190184	0.0114	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.95	gold quality
right testis	UBERON:0004534	97.52	gold quality
testis	UBERON:0000473	96.62	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.90	gold quality
right lobe of liver	UBERON:0001114	78.92	gold quality
liver	UBERON:0002107	77.04	gold quality
cerebellar hemisphere	UBERON:0002245	70.89	gold quality
cerebellar cortex	UBERON:0002129	70.88	gold quality
cerebellum	UBERON:0002037	70.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.74	gold quality
right uterine tube	UBERON:0001302	70.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.83	gold quality
corpus callosum	UBERON:0002336	66.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.26	gold quality
right frontal lobe	UBERON:0002810	65.96	gold quality
caudate nucleus	UBERON:0001873	65.81	gold quality
nucleus accumbens	UBERON:0001882	65.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	65.63	gold quality
anterior cingulate cortex	UBERON:0009835	64.38	gold quality
Ammon’s horn	UBERON:0001954	64.27	gold quality
putamen	UBERON:0001874	64.24	gold quality
brain	UBERON:0000955	64.16	gold quality
hypothalamus	UBERON:0001898	63.75	gold quality
temporal lobe	UBERON:0001871	63.73	gold quality
amygdala	UBERON:0001876	63.73	gold quality
colonic epithelium	UBERON:0000397	62.85	gold quality
cerebral cortex	UBERON:0000956	62.85	gold quality
apex of heart	UBERON:0002098	62.84	gold quality
substantia nigra	UBERON:0002038	62.66	gold quality
right ovary	UBERON:0002118	62.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

53 targeting TCP10L, 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-10401-5P	99.99	65.79	948
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-29A-5P	99.08	68.59	1813
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-5590-5P	98.81	68.78	969
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-4680-3P	98.64	68.60	2093

Literature-anchored findings (GeneRIF, showing 7)

• The result revealed that TCP10L expressed specifically in the human liver and testis (PMID:14586771)
• Data suggest that the biological function of the interaction between T-complex protein 10-like and MAD4 may be to maintain the differentiation state in liver cells. (PMID:15469726)
• The specific expression pattern of TCP10L and interaction with DAPK-3 implies that TCP10L might play crucially important roles in spermatogenesis through its interaction with DAPK-3. (PMID:15910542)
• Overexpression of TCP10L in hepatocellular carcinoma cells suppressed colony formation, inhibited cell cycle progression through G0/G1 phase, and attenuated cell growth in vivo. (PMID:24565846)
• TCP10L stabilizes MAD1 protein level through direct interaction, and they cooperatively regulate cell cycle progression. (PMID:26698869)
• Inactivating Frameshift Mutations of HACD4 and TCP10L Tumor Suppressor Genes in Colorectal and Gastric Cancers. (PMID:29532408)
• TCP10L negatively regulates alpha-fetoprotein expression in hepatocellular carcinoma. (PMID:32438969)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tcp10c	ENSMUSG00000052469
mus_musculus	Tcp10b	ENSMUSG00000055602
mus_musculus	Tcp10a	ENSMUSG00000071322
rattus_norvegicus	Tcp10b	ENSRNOG00000013374
drosophila_melanogaster	Sas-4	FBGN0011020

Paralogs (1): CPAP (ENSG00000151849)

Protein

Protein identifiers

T-complex protein 10A homolog 1 — Q8TDR4 (reviewed: Q8TDR4)

Alternative names: TCP10-like

All UniProt accessions (6): A0A669KAW6, A0A669KB91, A0A669KBD0, Q8TDR4, J3KTL9, V9GY77

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation. Has in vitro transcription inhibition activity. Acts as a tumor suppressor in hepatocellular carcinoma (HCC) cells.

Subunit / interactions. Self-associates (via leucine zipper). Interacts (via leucine zipper) with ZIPK/DAPK3 (via leucine zipper). Interacts with MAD4.

Subcellular location. Nucleus.

Tissue specificity. Expressed in liver and testis. Expressed in the seminiferous tubules (at protein level).

Similarity. Belongs to the TCP10 family.

RefSeq proteins (1): NP_653260* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026581	TCP10L/CENPJ	Family

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDR4-F1	67.44	0.28

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (2):

Position	Phenotype
89	disrupts self-association.
82	greatly decreases in vitro transcription inhibition activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): IVANOVA_HEMATOPOIESIS_MATURE_CELL, WANG_RESPONSE_TO_BEXAROTENE_UP, chr21q22, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, GOMF_TRANSCRIPTION_FACTOR_BINDING, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY, MORI_SMALL_PRE_BII_LYMPHOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, JOHNSTONE_PARVB_TARGETS_3_DN, BRUINS_UVC_RESPONSE_EARLY_LATE, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, FORTSCHEGGER_PHF8_TARGETS_UP, GOMF_TRANSCRIPTION_COREGULATOR_ACTIVITY

GO Biological Process (1): negative regulation of transcription by RNA polymerase II (GO:0000122)

GO Molecular Function (4): transcription corepressor activity (GO:0003714), identical protein binding (GO:0042802), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
transcription coregulator activity	1
protein binding	1
transcription factor binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

889 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCP10L	FKBP15	Q5T1M5	487
TCP10L	UACA	Q9BZF9	473
TCP10L	BBS10	Q8TAM1	455
TCP10L	CEP295	Q9C0D2	442
TCP10L	REEP1	Q9H902	433
TCP10L	APTX	Q7Z2E3	425
TCP10L	GSDMB	Q8TAX9	418
TCP10L	C20orf96	Q9NUD7	415
TCP10L	DFFA	O00273	410
TCP10L	CYP8B1	Q9UNU6	404
TCP10L	TSACC	Q96A04	401
TCP10L	POTED	Q86YR6	393
TCP10L	HACD4	Q5VWC8	373
TCP10L	POC1B	Q8TC44	358
TCP10L	CATSPERG	Q6ZRH7	355

IntAct

129 interactions, top by confidence:

A	B	Type	Score
GRIPAP1	TCP10L	psi-mi:“MI:0915”(physical association)	0.740
PRPH	TCP10L	psi-mi:“MI:0915”(physical association)	0.720
TCP10L	PRPH	psi-mi:“MI:0915”(physical association)	0.720
TCP10L	DAPK3	psi-mi:“MI:0915”(physical association)	0.670
DAPK3	TCP10L	psi-mi:“MI:0915”(physical association)	0.670
TCP10L	MXD4	psi-mi:“MI:0915”(physical association)	0.660
MXD4	TCP10L	psi-mi:“MI:0915”(physical association)	0.660
MXD4	TCP10L	psi-mi:“MI:0403”(colocalization)	0.660
LMO1	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
TCEANC	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
CDR2L	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
MAPK9	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
CCDC102B	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
MFAP1	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
NCK2	TCP10L	psi-mi:“MI:0915”(physical association)	0.560
LMO3	TCP10L	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (104): TCP10L (Two-hybrid), GRIPAP1 (Affinity Capture-MS), PPP1R21 (Affinity Capture-MS), TBCK (Affinity Capture-MS), KIF20B (Affinity Capture-MS), TCP10L (Affinity Capture-MS), CRYZL1 (Affinity Capture-MS), RNF20 (Affinity Capture-MS), SH3KBP1 (Affinity Capture-MS), FBXO28 (Affinity Capture-MS), PICK1 (Affinity Capture-MS), NIN (Affinity Capture-MS), USP4 (Affinity Capture-MS), MLLT10 (Affinity Capture-MS), RNF40 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA9, A0JNH1, A1L170, A2TJV2, A6H7B4, A6NFA0, A6NGY1, A6X8Z5, A7YY35, B2RQL2, D3Z1D3, M0RD54, P43359, Q05860, Q0VF49, Q1RMX6, Q1RN00, Q2M1Z3, Q32LI3, Q3URK1, Q5EBJ4, Q5M831, Q5RJL0, Q62100, Q640N3, Q64256, Q642A3, Q66H53, Q66LM6, Q68D20, Q68DA7, Q68US1, Q6AXN6, Q6AYA8, Q6IR42, Q711Q0, Q80VY2, Q86UF4, Q8IY42, Q8TDR4

Diamond homologs: Q569L8, Q68US1, Q8TDR4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1447 predictions. Top by Δscore:

Variant	Effect	Δscore
21:32501413:A:AG	acceptor_gain	1.0000
21:32501414:G:GG	acceptor_gain	1.0000
21:32514809:TGCA:T	acceptor_loss	1.0000
21:32514810:GCAG:G	acceptor_loss	1.0000
21:32514811:CAGC:C	acceptor_loss	1.0000
21:32514812:A:AG	acceptor_gain	1.0000
21:32514812:A:AT	acceptor_loss	1.0000
21:32514813:G:A	acceptor_loss	1.0000
21:32514813:G:GT	acceptor_gain	1.0000
21:32514813:GC:G	acceptor_gain	1.0000
21:32514813:GCC:G	acceptor_gain	1.0000
21:32514813:GCCC:G	acceptor_gain	1.0000
21:32514813:GCCCA:G	acceptor_gain	1.0000
21:32582247:T:TA	donor_gain	1.0000
21:32584159:A:AC	donor_gain	1.0000
21:32584160:C:CC	donor_gain	1.0000
21:32503917:A:AG	acceptor_gain	0.9900
21:32503917:AT:A	acceptor_gain	0.9900
21:32503918:T:G	acceptor_gain	0.9900
21:32503921:AACAG:A	acceptor_loss	0.9900
21:32503922:ACAGG:A	acceptor_loss	0.9900
21:32503923:CA:C	acceptor_loss	0.9900
21:32503925:G:C	acceptor_loss	0.9900
21:32503925:GGT:G	acceptor_gain	0.9900
21:32504011:TAGAG:T	donor_loss	0.9900
21:32504012:AGAGG:A	donor_loss	0.9900
21:32504013:GAG:G	donor_gain	0.9900
21:32504014:AGGTA:A	donor_loss	0.9900
21:32504015:GGTA:G	donor_loss	0.9900
21:32504016:G:A	donor_loss	0.9900

AlphaMissense

1384 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:32582356:C:A	W68C	0.913
21:32582356:C:G	W68C	0.913
21:32582358:A:G	W68R	0.894
21:32582358:A:T	W68R	0.894
21:32582336:A:G	L75P	0.879
21:32582294:A:G	L89P	0.857
21:32582390:A:G	L57P	0.846
21:32582315:A:G	L82S	0.797
21:32582357:C:G	W68S	0.774
21:32582336:A:T	L75H	0.761
21:32582282:A:G	L93P	0.747
21:32582378:A:G	L61P	0.747
21:32582319:C:G	A81P	0.735
21:32582399:A:G	I54T	0.735
21:32578814:A:C	F126L	0.732
21:32578814:A:T	F126L	0.732
21:32578816:A:G	F126L	0.732
21:32582303:T:A	N86I	0.716
21:32582306:T:G	Q85P	0.716
21:32582355:C:G	A69P	0.698
21:32582291:C:G	R90P	0.697
21:32582333:C:G	R76P	0.692
21:32582369:T:G	Q64P	0.678
21:32582399:A:C	I54S	0.674
21:32582358:A:C	W68G	0.668
21:32582302:G:C	N86K	0.662
21:32582302:G:T	N86K	0.662
21:32582315:A:C	L82W	0.651
21:32582336:A:C	L75R	0.634
21:32582304:T:A	N86Y	0.630

dbSNP variants (sampled 300 via entrez): RS1000044419 (21:32578895 T>A,C), RS1000120043 (21:32583355 C>G,T), RS1000395532 (21:32579150 G>A,C), RS1000431677 (21:32577818 C>T), RS1000986531 (21:32583025 T>C), RS1001001137 (21:32577544 G>A), RS1001676828 (21:32580409 G>T), RS1002483732 (21:32576090 A>T), RS1002516273 (21:32575802 G>A), RS1002628773 (21:32581664 A>C,G), RS1003395717 (21:32581343 A>G), RS1003472128 (21:32575817 G>A,T), RS1003524700 (21:32575654 G>T), RS1003525059 (21:32577065 C>T), RS1004054595 (21:32583654 C>T)

Disease associations

OMIM: gene MIM:608365 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
propionaldehyde	decreases expression	1
terbufos	increases methylation	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
K 7174	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Aldehydes	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1
Fonofos	increases methylation	1
Formaldehyde	decreases expression	1
Lead	increases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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