TCEAL1

Summary

TCEAL1 (transcription elongation factor A like 1, HGNC:11616) is a protein-coding gene on chromosome Xq22.2, encoding Transcription elongation factor A protein-like 1 (Q15170). May be involved in transcriptional regulation.

This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. The encoded protein is similar to transcription elongation factor A/transcription factor SII and contains a zinc finger-like motif as well as a sequence related to the transcription factor SII Pol II-binding region. It may exert its effects via protein-protein interactions with other transcriptional regulators rather than via direct binding of DNA. Multiple family members are located on the X chromosome. Alternative splicing results in multiple transcript variants encoding a single isoform.

Source: NCBI Gene 9338 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked (Strong, GenCC)
• Clinical variants (ClinVar): 41 total — 2 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 26
• MANE Select transcript: NM_004780

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11616
Approved symbol	TCEAL1
Name	transcription elongation factor A like 1
Location	Xq22.2
Locus type	gene with protein product
Status	Approved
Aliases	p21, pp21, SIIR, P21, WEX9
Ensembl gene	ENSG00000172465
Ensembl biotype	protein_coding
OMIM	300237
Entrez	9338

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000372624, ENST00000372625, ENST00000372626, ENST00000469820, ENST00000868027, ENST00000868028, ENST00000868029, ENST00000868030, ENST00000868031, ENST00000868032, ENST00000868033, ENST00000868034, ENST00000868035, ENST00000964759

RefSeq mRNA: 3 — MANE Select: NM_004780 NM_001006639, NM_001006640, NM_004780

CCDS: CCDS35358

Canonical transcript exons

ENST00000372625 — 3 exons

Exon	Start	End
ENSE00001458247	103629885	103630953
ENSE00001458248	103629494	103629573
ENSE00001458249	103628975	103629025

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3881 / max 217.0966, expressed in 1679 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197038	6.9750	1553
197035	2.4130	1208

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right ovary	UBERON:0002118	98.69	gold quality
left ovary	UBERON:0002119	98.57	gold quality
left uterine tube	UBERON:0001303	98.19	gold quality
body of uterus	UBERON:0009853	98.14	gold quality
mucosa of stomach	UBERON:0001199	98.05	gold quality
right coronary artery	UBERON:0001625	97.68	gold quality
endocervix	UBERON:0000458	97.64	gold quality
thoracic aorta	UBERON:0001515	97.33	gold quality
descending thoracic aorta	UBERON:0002345	97.33	gold quality
ascending aorta	UBERON:0001496	97.25	gold quality
left coronary artery	UBERON:0001626	97.15	gold quality
aorta	UBERON:0000947	97.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.03	gold quality
popliteal artery	UBERON:0002250	96.96	gold quality
tibial artery	UBERON:0007610	96.96	gold quality
myometrium	UBERON:0001296	96.88	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.68	gold quality
lower esophagus	UBERON:0013473	96.65	gold quality
coronary artery	UBERON:0001621	96.58	gold quality
seminal vesicle	UBERON:0000998	96.32	gold quality
right adrenal gland cortex	UBERON:0035827	96.18	gold quality
right adrenal gland	UBERON:0001233	95.88	gold quality
urethra	UBERON:0000057	95.81	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.59	gold quality
left adrenal gland cortex	UBERON:0035825	95.42	gold quality
left adrenal gland	UBERON:0001234	95.34	gold quality
ectocervix	UBERON:0012249	95.16	gold quality
prefrontal cortex	UBERON:0000451	95.15	gold quality
adrenal cortex	UBERON:0001235	95.12	gold quality
cerebellar cortex	UBERON:0002129	95.00	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	47.22
E-GEOD-134144	yes	31.31
E-HCAD-11	yes	7.83
E-GEOD-36552	no	31.27
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, TP53

miRNA regulators (miRDB)

50 targeting TCEAL1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-153-3P	98.96	72.51	1644

Literature-anchored findings (GeneRIF, showing 5)

• There was a marked decrease in the levels of the transcriptional elongation factor A gene in squamous cell cancer compared to normal samples. Reduced expression of the TCEAL1 gene may be important in esophageal squamous cell carcinogenesis. (PMID:15773840)
• Treatment with active matabolite of vitamin D (1alpha,25-dihydroxyvitamin D3) up-regulates mRNA expression of p21. (PMID:19475409)
• In vivo CRISPR/Cas9 knockout screen: TCEAL1 silencing enhances docetaxel efficacy in prostate cancer. (PMID:33033111)
• TCEAL1 loss-of-function results in an X-linked dominant neurodevelopmental syndrome and drives the neurological disease trait in Xq22.2 deletions. (PMID:36368327)
• Confirmation and expansion of the phenotype of the TCEAL1-related neurodevelopmental disorder. (PMID:38200082)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tceal1	ENSMUSG00000049536
rattus_norvegicus	Tceal1	ENSRNOG00000002387

Paralogs (8): TCEAL4 (ENSG00000133142), TCEAL8 (ENSG00000180964), TCEAL7 (ENSG00000182916), TCEAL2 (ENSG00000184905), TCEAL9 (ENSG00000185222), TCEAL3 (ENSG00000196507), TCEAL5 (ENSG00000204065), TCEAL6 (ENSG00000204071)

Protein

Protein identifiers

Transcription elongation factor A protein-like 1 — Q15170 (reviewed: Q15170)

Alternative names: Nuclear phosphoprotein p21/SIIR, Transcription elongation factor S-II protein-like 1

All UniProt accessions (1): Q15170

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in transcriptional regulation. Modulates various viral and cellular promoters in a promoter context-dependent manner. For example, transcription from the FOS promoter is increased, while Rous sarcoma virus (RSV) long terminal repeat (LTR) promoter activity is repressed. Does not bind DNA directly.

Subcellular location. Nucleus.

Tissue specificity. Expressed in all tissues examined. Highly expressed in heart, ovary, prostate and skeletal muscle. Moderately expressed in brain, placenta, testis and small intestine. Weakly expressed in lung, liver and spleen. Expressed in several cancer cell lines.

Post-translational modifications. Phosphorylation of Ser-38 and Ser-39 is critical for transcriptional repression.

Disease relevance. Hijazi-Reis syndrome (HIJRS) [MIM:301094] A neurodevelopmental disorder characterized by hypotonia, abnormal gait, developmental delay, intellectual disability especially affecting expressive language, and autistic behavior. Additional features include facial dysmorphism,ocular anomalies, and gastrointestinal issues. Rare patients have seizures. Disease severity is variable. Males tend to be more severely affected than females. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TFS-II family. TFA subfamily.

RefSeq proteins (3): NP_001006640, NP_001006641, NP_004771* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021156	TF_A-like/BEX	Family

Pfam: PF04538

UniProt features (25 total): sequence conflict 7, modified residue 6, sequence variant 5, compositionally biased region 3, mutagenesis site 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15170-F1	67.38	0.18

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 (6): 44, 28, 33, 38, 39, 43

Mutagenesis-validated functional residues (2):

Position	Phenotype
38–39	loss of transcriptional repression.
43–44	no effect on transcriptional repression.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 218 (showing top): WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, BENPORATH_ES_WITH_H3K27ME3, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, EFC_Q6, CEBP_Q2, NKX62_Q2, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, OCT1_06, WINTER_HYPOXIA_METAGENE, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, STREICHER_LSM1_TARGETS_UP, OCT1_B, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (0):

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

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TCEAL1	TCEAL7	Q9BRU2	948
TCEAL1	BEX3	Q00994	852
TCEAL1	TCEA1	P23193	714
TCEAL1	HEBP2	Q9Y5Z4	713
TCEAL1	TCEAL3	Q969E4	607
TCEAL1	TCEAL4	Q96EI5	603
TCEAL1	RAB9B	Q9NP90	591
TCEAL1	ENDOU	P21128	582
TCEAL1	SRSF2	Q01130	550
TCEAL1	TCEAL5	Q5H9L2	537
TCEAL1	LGALS13	Q9UHV8	505
TCEAL1	ZNF598	Q86UK7	489
TCEAL1	STMN1	P16949	472
TCEAL1	ATF7IP2	Q5U623	451
TCEAL1	TPK1	Q9H3S4	445

IntAct

47 interactions, top by confidence:

A	B	Type	Score
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.790
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
CCNDBP1	TCEAL1	psi-mi:“MI:0915”(physical association)	0.560
TCEAL1	CHEK1	psi-mi:“MI:0914”(association)	0.530
SCNM1	SNX3	psi-mi:“MI:0914”(association)	0.530
Mgu	GCLM	psi-mi:“MI:0914”(association)	0.530
GPSM3	ATE1	psi-mi:“MI:0914”(association)	0.530
RAB20	CHM	psi-mi:“MI:0914”(association)	0.530
HOXB6	TCEAL1	psi-mi:“MI:0915”(physical association)	0.370
USP11	CNOT8	psi-mi:“MI:0914”(association)	0.350
MAPK6		psi-mi:“MI:0914”(association)	0.350
WDR4	PBX2	psi-mi:“MI:0914”(association)	0.350
PHF7	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
HAUS7	GOLIM4	psi-mi:“MI:0914”(association)	0.350
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.350
TRUB1	USP11	psi-mi:“MI:0914”(association)	0.350
USP11	PRRC2B	psi-mi:“MI:0914”(association)	0.350
TCEAL1	PDCD5	psi-mi:“MI:0914”(association)	0.350
SETD4	PMM2	psi-mi:“MI:0914”(association)	0.350
NKX2-5		psi-mi:“MI:0914”(association)	0.350
UBL3	RCCD1	psi-mi:“MI:0914”(association)	0.350
ARL2BP	GNPAT	psi-mi:“MI:0914”(association)	0.350
CITED1	RAD21	psi-mi:“MI:0914”(association)	0.350

BioGRID (137): TCEAL1 (Affinity Capture-MS), TCEAL1 (Affinity Capture-MS), TCEAL1 (Affinity Capture-MS), TCEAL1 (Affinity Capture-MS), TCEAL1 (Affinity Capture-MS), USP11 (Affinity Capture-MS), USP4 (Affinity Capture-MS), EYA3 (Affinity Capture-MS), KDM3A (Affinity Capture-MS), HOXB9 (Affinity Capture-MS), MCMBP (Affinity Capture-MS), USP7 (Affinity Capture-MS), POGK (Affinity Capture-MS), TRIM25 (Affinity Capture-MS), ZNF703 (Affinity Capture-MS)

ESM2 similar proteins: A0JP43, A1YEW9, A2D4U8, A2D5N1, A2D671, A2T6K9, A8T6P4, B8AE37, F6QRE9, G3V9A7, O60238, P48785, P79149, Q0IIJ3, Q0P6D6, Q15170, Q15361, Q15390, Q2KIJ9, Q3T013, Q3ULM0, Q3ZBJ9, Q4V7L5, Q5H9J7, Q5NVG8, Q5PPP3, Q5PR69, Q5RFN3, Q5W0A0, Q66HD8, Q67XL4, Q6K678, Q86X53, Q8BP27, Q8BPM6, Q8C627, Q8N4S0, Q8R5H6, Q91W45, Q921P9

Diamond homologs: A1YEW9, A2D4U8, A2D5N1, A2D671, A2T6K9, Q15170, Q2KIJ9, Q3T020, Q5PPP3, Q6I7R5, Q8IYN2, Q921P9, Q9CZY2, Q9DD24, Q9UHQ7, A3KGA4, D3ZT37, Q9BRU2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	13
Uncertain significance	17
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
3175047	NM_004780.3(TCEAL1):c.196G>T (p.Glu66Ter)	Pathogenic
564877	GRCh37/hg19 Xq22.2(chrX:102718261-103490112)x2	Pathogenic
1700029	NM_004780.3(TCEAL1):c.447G>A (p.Trp149Ter)	Likely pathogenic
1700030	NM_004780.3(TCEAL1):c.299_302del (p.Gly100fs)	Likely pathogenic
1700031	NM_004780.3(TCEAL1):c.259C>T (p.Gln87Ter)	Likely pathogenic
1700032	NM_004780.3(TCEAL1):c.269G>A (p.Cys90Tyr)	Likely pathogenic
1700033	Single allele	Likely pathogenic
1700034	Single allele	Likely pathogenic
1700035	NM_004780.3(TCEAL1):c.169del (p.Leu57fs)	Likely pathogenic
2673275	NM_004780.3(TCEAL1):c.61G>T (p.Glu21Ter)	Likely pathogenic
2673276	NM_004780.3(TCEAL1):c.151G>T (p.Glu51Ter)	Likely pathogenic
2673277	NM_004780.3(TCEAL1):c.324_333del (p.Ser109fs)	Likely pathogenic
2673278	NM_004780.3(TCEAL1):c.311_314del (p.Glu104fs)	Likely pathogenic
3376876	NM_004780.3(TCEAL1):c.427_430del (p.Asn142_Lys143insTer)	Likely pathogenic
4293896	NM_004780.3(TCEAL1):c.211G>T (p.Glu71Ter)	Likely pathogenic

SpliceAI

285 predictions. Top by Δscore:

Variant	Effect	Δscore
X:103629874:T:A	acceptor_gain	1.0000
X:103629882:A:AG	acceptor_gain	1.0000
X:103629883:A:C	acceptor_loss	1.0000
X:103629883:A:G	acceptor_gain	1.0000
X:103629884:G:GC	acceptor_gain	1.0000
X:103629884:GA:G	acceptor_gain	1.0000
X:103629884:GAAT:G	acceptor_gain	1.0000
X:103629884:GAATA:G	acceptor_gain	1.0000
X:103628789:GAGAG:G	donor_gain	0.9900
X:103628791:GAG:G	donor_gain	0.9900
X:103628792:AGGTG:A	donor_loss	0.9900
X:103628794:G:GA	donor_loss	0.9900
X:103628795:T:A	donor_loss	0.9900
X:103629552:A:T	donor_gain	0.9900
X:103629568:G:T	donor_gain	0.9900
X:103629884:GAA:G	acceptor_gain	0.9900
X:103629887:T:G	acceptor_gain	0.9900
X:103629888:A:AG	acceptor_gain	0.9800
X:103628796:GAGT:G	donor_loss	0.9700
X:103629571:GGG:G	donor_gain	0.9700
X:103629572:GGG:G	donor_gain	0.9700
X:103628794:G:GG	donor_gain	0.9600
X:103629886:A:AG	acceptor_gain	0.9600
X:103629888:AACT:A	acceptor_gain	0.9600
X:103629889:A:G	acceptor_gain	0.9600
X:103628779:C:T	donor_gain	0.9500
X:103629879:CCTAA:C	acceptor_gain	0.9500
X:103629880:CTAAG:C	acceptor_gain	0.9500
X:103629881:TAAGA:T	acceptor_gain	0.9500
X:103629882:AAGA:A	acceptor_gain	0.9500

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000381677 (X:103629003 G>A), RS1001168590 (X:103628633 G>C), RS1002096700 (X:103629430 TGTCA>T,TGTCAGTCA), RS1004502622 (X:103630818 AT>A), RS1004787430 (X:103628216 A>G), RS1004858272 (X:103629589 G>A), RS1004946374 (X:103627748 G>A,T), RS1005245292 (X:103628570 G>C), RS1006962350 (X:103627226 C>T), RS1013410518 (X:103629417 G>T), RS1013546117 (X:103631093 G>C), RS1013941904 (X:103629149 C>G), RS1013993206 (X:103628705 G>C), RS1014316490 (X:103627472 A>T), RS1014836469 (X:103626806 T>C)

Disease associations

OMIM: gene MIM:300237 | disease phenotypes: MIM:301094

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked	Strong	X-linked

Mondo (1): neurodevelopmental disorder with gait disturbance, dysmorphic facies, and behavioral abnormalities, X-linked (MONDO:0859085)

Orphanet (0):

HPO phenotypes

26 total (26 of 26 shown, HPO-id order):

HPO	Term
HP:0000337	Broad forehead
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000540	Hypermetropia
HP:0000612	Iris coloboma
HP:0000639	Nystagmus
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001423	X-linked dominant inheritance
HP:0002020	Gastroesophageal reflux
HP:0002061	Lower limb spasticity
HP:0002205	Recurrent respiratory infections
HP:0002376	Developmental regression
HP:0002904	Hyperbilirubinemia
HP:0003593	Infantile onset
HP:0008897	Postnatal growth retardation
HP:0011448	Ankle clonus
HP:0011471	Gastrostomy tube feeding in infancy
HP:0012450	Chronic constipation
HP:0410018	Recurrent ear infections

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

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Valproic Acid	decreases expression	2
aristolochic acid I	increases expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
geraniol	increases expression	1
terbufos	increases methylation	1
afimoxifene	decreases expression, decreases reaction	1
potassium chromate(VI)	decreases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
seocalcitol	increases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1
Bortezomib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases abundance, affects cotreatment, decreases expression	1
Azathioprine	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Calcitriol	increases expression	1
Cisplatin	increases expression	1
Dietary Carbohydrates	decreases expression	1
Doxorubicin	affects expression	1
Fonofos	increases methylation	1
Estrogens	decreases expression, decreases reaction	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Parathion	increases methylation	1
Potassium Dichromate	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	decreases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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