TCFL5

Summary

TCFL5 (transcription factor like 5, HGNC:11646) is a protein-coding gene on chromosome 20q13.33, encoding Transcription factor-like 5 protein (Q9UL49). Putative transcription factor.

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including negative regulation of transcription by RNA polymerase II; regulation of cell population proliferation; and spermatogenesis. Located in nucleus.

Source: NCBI Gene 10732 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_006602

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11646
Approved symbol	TCFL5
Name	transcription factor like 5
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	Figlb, E2BP-1, CHA, bHLHe82
Ensembl gene	ENSG00000101190
Ensembl biotype	protein_coding
OMIM	604745
Entrez	10732

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000217162, ENST00000335351, ENST00000895007, ENST00000895008, ENST00000949323

RefSeq mRNA: 2 — MANE Select: NM_006602 NM_001301726, NM_006602

CCDS: CCDS13506

Canonical transcript exons

ENST00000335351 — 6 exons

Exon	Start	End
ENSE00000663333	62854016	62854157
ENSE00000663334	62857395	62857638
ENSE00000663335	62859364	62859526
ENSE00000663336	62860125	62860308
ENSE00000856515	62841005	62842097
ENSE00003895964	62861024	62861822

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 97.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.9070 / max 163.6229, expressed in 1757 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188305	11.7210	1755
188306	0.1860	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.53	gold quality
adult organism	UBERON:0007023	97.18	gold quality
male germ cell	CL:0000015	96.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.65	gold quality
spinal cord	UBERON:0002240	94.76	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.66	gold quality
inferior olivary complex	UBERON:0002127	94.39	gold quality
lateral globus pallidus	UBERON:0002476	93.41	gold quality
left testis	UBERON:0004533	93.41	gold quality
right testis	UBERON:0004534	93.33	gold quality
cranial nerve II	UBERON:0000941	93.03	gold quality
middle frontal gyrus	UBERON:0002702	92.64	gold quality
substantia nigra	UBERON:0002038	92.42	gold quality
testis	UBERON:0000473	92.37	gold quality
midbrain	UBERON:0001891	91.61	gold quality
inferior vagus X ganglion	UBERON:0005363	90.96	gold quality
substantia nigra pars reticulata	UBERON:0001966	90.91	gold quality
globus pallidus	UBERON:0001875	90.67	gold quality
amygdala	UBERON:0001876	90.44	gold quality
hypothalamus	UBERON:0001898	90.23	gold quality
putamen	UBERON:0001874	90.03	gold quality
medial globus pallidus	UBERON:0002477	89.77	gold quality
corpus callosum	UBERON:0002336	89.57	gold quality
Ammon’s horn	UBERON:0001954	89.34	gold quality
pons	UBERON:0000988	89.25	gold quality
subthalamic nucleus	UBERON:0001906	89.19	gold quality
substantia nigra pars compacta	UBERON:0001965	88.93	gold quality
medulla oblongata	UBERON:0001896	88.12	gold quality
Brodmann (1909) area 10	UBERON:0013541	87.89	gold quality
endometrium epithelium	UBERON:0004811	87.75	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.59
E-GEOD-124858	no	79.78

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CD2	Repression
CLGN	Unknown
SLC10A2

JASPAR motifs

Motif	Name	Family
MA0632.2	TCFL5	PAS domain factors
MA0632.3	TCFL5	PAS domain factors

JASPAR matrix evidence (PMIDs): PMID:15585666

Upstream regulators (CollecTRI, top): NOTCH1

miRNA regulators (miRDB)

78 targeting TCFL5, 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-4455	100.00	65.48	1587
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-144-3P	99.94	73.98	2698
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-10395-5P	99.86	67.35	676
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548AI	99.69	69.24	1494

Literature-anchored findings (GeneRIF, showing 6)

• Cha is a new bHLH transcription factor that negatively regulates upstream transcription factor-dependent transcription (PMID:12923186)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• HPVs16 and 18 commonly are present in normal oral mucosa and emphasize the importance of distinguishing clinical (PMID:24588599)
• Report differential expression of TCFL5 in normal human spermatogenesis, testicular mixed germ cell-sex cord stromal tumor, spermatocytic tumor, and seminoma. (PMID:30067948)
• Isoform-specific effects of transcription factor TCFL5 on the pluripotency-related genes SOX2 and KLF4 in colorectal cancer development. (PMID:34623757)
• TCFL5 knockdown sensitizes DLBCL to doxorubicin treatment via regulation of GPX4. (PMID:37516394)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tcfl5	ENSMUSG00000038932
rattus_norvegicus	Tcfl5	ENSRNOG00000061199

Protein

Protein identifiers

Transcription factor-like 5 protein — Q9UL49 (reviewed: Q9UL49)

Alternative names: Cha transcription factor, HPV-16 E2-binding protein 1

All UniProt accessions (2): Q9UL49, F8W9A4

UniProt curated annotations — full annotation on UniProt →

Function. Putative transcription factor. Isoform 3 may play a role in early spermatogenesis.

Subunit / interactions. Efficient DNA binding requires dimerization with another bHLH protein.

Subcellular location. Nucleus.

Tissue specificity. Isoform 3 is testis specific. Isoform 2 is pancreas specific.

Miscellaneous. Antibodies against TCFL5 are present in sera from patients with Chagas disease (also called American Trypanosomiasis), a disease caused by Trypanosoma cruzi. Two different epitopes that mimic Trypanosoma cruzi antigens have been identified: R1 and R3 epitopes, which are recognized by T- and B-cells, respectively.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UL49-3	3	yes
Q9UL49-1	1
Q9UL49-2	2

RefSeq proteins (2): NP_001288655, NP_006593* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR039583	TCFL5/SOLH1/2	Family

Pfam: PF00010

UniProt features (15 total): region of interest 5, compositionally biased region 3, splice variant 2, sequence variant 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL49-F1	54.93	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 130 (showing top): PEREZ_TP63_TARGETS, GOBP_MALE_GAMETE_GENERATION, GNF2_CCNA1, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, AFFAR_YY1_TARGETS_UP, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, DOUGLAS_BMI1_TARGETS_UP, ACEVEDO_LIVER_CANCER_UP, YAMAZAKI_TCEB3_TARGETS_DN, CHANG_IMMORTALIZED_BY_HPV31_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_UP, WANG_HCP_PROSTATE_CANCER, GOCC_GERM_CELL_NUCLEUS, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GEORGES_TARGETS_OF_MIR192_AND_MIR215

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), transcription by RNA polymerase II (GO:0006366), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), regulation of cell population proliferation (GO:0042127), regulation of cell differentiation (GO:0045595)

GO Molecular Function (7): 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), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein dimerization activity (GO:0046983), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (3): chromatin (GO:0000785), male germ cell nucleus (GO:0001673), nucleus (GO:0005634)

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
DNA-templated transcription	2
regulation of cellular process	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
cell population proliferation	1
cell differentiation	1
regulation of developmental process	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
nucleic acid binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
protein binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
chromosome	1
cellular anatomical structure	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCFL5	PPFIBP2	Q8ND30	574
TCFL5	RBM28	Q9NW13	504
TCFL5	ALB	P02768	478
TCFL5	MORN3	Q6PF18	450
TCFL5	CHGA	P10645	417
TCFL5	ZFX	P17010	404
TCFL5	CFH	P08603	384
TCFL5	NRF1	Q16656	383
TCFL5	NOMO2	Q5JPE7	378
TCFL5	NOMO3	P69849	374
TCFL5	BRICD5	Q6PL45	372
TCFL5	CUX2	O14529	371
TCFL5	NOMO1	P78421	368
TCFL5	DHRSX	Q8N5I4	363
TCFL5	PUDP	Q08623	363
TCFL5	KLHL4	Q9C0H6	363

IntAct

0 interactions, top by confidence:

BioGRID (6): TCFL5 (Affinity Capture-RNA), TCFL5 (Negative Genetic), TCFL5 (Positive Genetic), TCFL5 (Affinity Capture-Western), TCFL5 (Reconstituted Complex), USF1 (Reconstituted Complex)

ESM2 similar proteins: A0A2Z4LIS9, A2CE44, A6NFI3, E9PZZ1, O95201, P09066, P15863, P19622, P22091, P46099, P49640, P70338, P82976, P97503, P98168, P98169, Q05917, Q07120, Q13351, Q14549, Q14V87, Q15270, Q19A40, Q2QGD7, Q3SY56, Q3U133, Q58DK7, Q5DWN0, Q6IQX8, Q6NUN9, Q8C8V1, Q8NCA9, Q8TD94, Q8WUU4, Q924A2, Q92618, Q96RK0, Q99684, Q9BV97, Q9BYN7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
NOTCH1	“up-regulates quantity by expression”	TCFL5	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1353 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62854011:CTAA:C	donor_loss	1.0000
20:62854012:TAAC:T	donor_loss	1.0000
20:62854014:ACCTT:A	donor_loss	1.0000
20:62854015:C:T	donor_loss	1.0000
20:62854041:T:A	donor_gain	1.0000
20:62857442:T:A	donor_gain	1.0000
20:62857641:T:C	acceptor_gain	1.0000
20:62857641:T:TC	acceptor_gain	1.0000
20:62857644:C:CT	acceptor_gain	1.0000
20:62859415:A:C	donor_gain	1.0000
20:62860309:C:CC	acceptor_gain	1.0000
20:62842095:TTC:T	acceptor_gain	0.9900
20:62842096:TCCTG:T	acceptor_loss	0.9900
20:62842098:C:CC	acceptor_gain	0.9900
20:62842098:CTG:C	acceptor_loss	0.9900
20:62842099:T:A	acceptor_loss	0.9900
20:62857433:TTGAG:T	donor_gain	0.9900
20:62857471:C:CA	donor_gain	0.9900
20:62857472:C:A	donor_gain	0.9900
20:62857639:C:CC	acceptor_gain	0.9900
20:62857640:T:C	acceptor_gain	0.9900
20:62860121:CTA:C	donor_loss	0.9900
20:62860123:ACCTG:A	donor_loss	0.9900
20:62860124:CCTGT:C	donor_loss	0.9900
20:62860304:CCAAA:C	acceptor_gain	0.9900
20:62860305:CAAA:C	acceptor_gain	0.9900
20:62860305:CAAAC:C	acceptor_gain	0.9900
20:62861022:A:AC	donor_gain	0.9900
20:62861023:C:CC	donor_gain	0.9900
20:62842093:AATTC:A	acceptor_gain	0.9800

AlphaMissense

3215 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62842092:A:C	F462L	1.000
20:62842092:A:T	F462L	1.000
20:62842093:A:G	F462S	1.000
20:62842094:A:G	F462L	1.000
20:62854056:A:G	L447P	1.000
20:62854058:G:C	F446L	1.000
20:62854058:G:T	F446L	1.000
20:62854059:A:G	F446S	1.000
20:62854060:A:G	F446L	1.000
20:62854070:C:A	W442C	1.000
20:62854070:C:G	W442C	1.000
20:62854072:A:G	W442R	1.000
20:62854072:A:T	W442R	1.000
20:62854077:A:G	L440P	1.000
20:62854077:A:T	L440Q	1.000
20:62854088:C:A	K436N	1.000
20:62854088:C:G	K436N	1.000
20:62854092:T:A	D435V	1.000
20:62854093:C:G	D435H	1.000
20:62854106:G:C	C430W	1.000
20:62854107:C:T	C430Y	1.000
20:62854128:A:G	L423S	1.000
20:62854149:A:G	I416T	1.000
20:62854157:C:A	R413S	1.000
20:62854157:C:G	R413S	1.000
20:62857395:C:A	R413M	1.000
20:62857395:C:G	R413T	1.000
20:62857397:T:A	R412S	1.000
20:62857397:T:G	R412S	1.000
20:62857398:C:G	R412T	1.000

dbSNP variants (sampled 300 via entrez): RS1000049472 (20:62855061 T>A,C), RS1000081918 (20:62855307 G>A), RS1000201449 (20:62844707 T>C), RS1000254894 (20:62858811 C>T), RS1000275890 (20:62849642 T>A,C), RS1000309056 (20:62860035 GA>G,GAA), RS1000444034 (20:62845294 G>A,T), RS1000481588 (20:62844985 T>C), RS1000535541 (20:62845891 C>T), RS1000644710 (20:62851095 T>C), RS1000709368 (20:62849987 TA>T,TAA), RS1000717848 (20:62841310 CCA>C), RS1000818601 (20:62846138 A>G), RS1000839918 (20:62843605 T>C), RS1001040850 (20:62853301 G>C)

Disease associations

OMIM: gene MIM:604745 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): oligoasthenoteratozoospermia (MONDO:0850098)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001762_809	Obesity-related traits	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression	3
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression	2
TL8-506	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
beta-methylcholine	affects expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
picoxystrobin	increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Etoposide	affects response to substance	1
Methotrexate	decreases expression	1
Poly I-C	affects cotreatment, increases expression	1
Sarin	decreases expression	1
Thiram	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Phenol	increases expression	1
tert-Butylhydroperoxide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07579858	PHASE3	COMPLETED	PRP Improves Blastocyst Formation in ICSI Cycles
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT02752555	Not specified	UNKNOWN	Severe Male Factor Infertility Management
NCT06088693	Not specified	COMPLETED	The Role of Electroacupuncture With Standard Therapy on Sperm Analysis and SOD Levels in Oligozoospermia.
NCT07286279	Not specified	COMPLETED	Identifying Candidates for Limited Dissection at Microdissection TESE.
NCT07345455	Not specified	RECRUITING	Probiotics on Sperm Quality in Male Infertility Patients