TEDC1

Summary

TEDC1 (tubulin epsilon and delta complex 1, HGNC:20127) is a protein-coding gene on chromosome 14q32.33, encoding Tubulin epsilon and delta complex protein 1 (Q86SX3). Acts as a positive regulator of ciliary hedgehog signaling. It is a selective cancer dependency (DepMap: 36.3% of cell lines).

Predicted to be involved in positive regulation of smoothened signaling pathway. Predicted to be located in centriole and cilium.

Source: NCBI Gene 283643 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 20 total
• Cancer dependency (DepMap): dependent in 36.3% of screened cell lines
• MANE Select transcript: NM_001367178

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20127
Approved symbol	TEDC1
Name	tubulin epsilon and delta complex 1
Location	14q32.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185347
Ensembl biotype	protein_coding
Entrez	283643

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000329886, ENST00000354560, ENST00000392522, ENST00000392523, ENST00000392527, ENST00000421892, ENST00000427614, ENST00000432805, ENST00000443229, ENST00000450383, ENST00000451719, ENST00000455454, ENST00000460959, ENST00000463869, ENST00000546492, ENST00000546536, ENST00000548920, ENST00000551054, ENST00000551538, ENST00000854956, ENST00000854957, ENST00000854958

RefSeq mRNA: 5 — MANE Select: NM_001367178 NM_001134875, NM_001134876, NM_001134877, NM_001198983, NM_001367178

CCDS: CCDS45180, CCDS45181, CCDS45182, CCDS55955, CCDS91958

Canonical transcript exons

ENST00000392523 — 9 exons

Exon	Start	End
ENSE00001332728	105495880	105496086
ENSE00001425611	105491246	105491522
ENSE00002382013	105498617	105499248
ENSE00003490378	105491622	105491700
ENSE00003529049	105492107	105492309
ENSE00003589738	105493835	105493933
ENSE00003642374	105492579	105492734
ENSE00003650338	105497798	105497977
ENSE00003785044	105497357	105497443

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 92.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.6298 / max 127.2513, expressed in 1522 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
141943	6.6298	1522

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	92.19	silver quality
granulocyte	CL:0000094	87.73	gold quality
mucosa of transverse colon	UBERON:0004991	86.86	gold quality
anterior cingulate cortex	UBERON:0009835	85.10	gold quality
putamen	UBERON:0001874	84.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.16	gold quality
sural nerve	UBERON:0015488	83.75	gold quality
right frontal lobe	UBERON:0002810	83.71	gold quality
caudate nucleus	UBERON:0001873	83.48	gold quality
prefrontal cortex	UBERON:0000451	83.21	gold quality
nucleus accumbens	UBERON:0001882	83.17	gold quality
amygdala	UBERON:0001876	82.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.07	gold quality
right uterine tube	UBERON:0001302	81.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.20	gold quality
right lobe of liver	UBERON:0001114	81.17	gold quality
skin of abdomen	UBERON:0001416	80.83	gold quality
ventricular zone	UBERON:0003053	80.81	gold quality
neocortex	UBERON:0001950	80.72	gold quality
right coronary artery	UBERON:0001625	80.37	gold quality
hypothalamus	UBERON:0001898	80.31	gold quality
frontal cortex	UBERON:0001870	80.11	gold quality
tibial artery	UBERON:0007610	80.04	gold quality
popliteal artery	UBERON:0002250	80.01	gold quality
spinal cord	UBERON:0002240	79.99	gold quality
ganglionic eminence	UBERON:0004023	79.96	gold quality
skin of leg	UBERON:0001511	79.84	gold quality
lower esophagus mucosa	UBERON:0035834	79.59	gold quality
apex of heart	UBERON:0002098	79.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

3 targeting TEDC1, 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-187-5P	99.74	70.26	1404
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-767-3P	98.61	67.69	1192

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 36.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Second report of TEDC1-related microcephaly caused by a novel biallelic mutation in an Iranian consanguineous family. (PMID:38252227)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tedc1	ENSMUSG00000037466
rattus_norvegicus	Tedc1	ENSRNOG00000070355

Protein

Protein identifiers

Tubulin epsilon and delta complex protein 1 — Q86SX3 (reviewed: Q86SX3)

All UniProt accessions (8): C9IYA4, C9J1F2, C9J317, C9J6B2, C9JZ80, C9K0G6, Q86SX3, F8VP51

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a positive regulator of ciliary hedgehog signaling. Required for centriole stability. May play a role in counteracting perturbation of actin filaments, such as after treatment with the actin depolymerizing microbial metabolite Chivosazole F.

Subunit / interactions. Interacts with TEDC2. Found in a complex with TEDC1, TEDC2, TUBE1 and TUBD1.

Subcellular location. Cell projection. Cilium. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole.

Isoforms (6)

UniProt ID	Names	Canonical?
Q86SX3-1	1	yes
Q86SX3-2	2
Q86SX3-3	3
Q86SX3-4	4
Q86SX3-5	5
Q86SX3-6	6

RefSeq proteins (5): NP_001128347, NP_001128348, NP_001128349, NP_001185912, NP_001354107* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027996	TEDC1_dom	Domain
IPR043535	TEDC1	Family

Pfam: PF14970

UniProt features (11 total): splice variant 6, coiled-coil region 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SX3-F1	63.08	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_SMOOTHENED_SIGNALING_PATHWAY, FISCHER_DREAM_TARGETS, GOBP_POSITIVE_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, chr14q32, TGGAAA_NFAT_Q4_01, GOCC_CENTRIOLE, NUYTTEN_EZH2_TARGETS_DN, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOCC_CILIUM, WHITFIELD_CELL_CYCLE_G2, MARTENS_TRETINOIN_RESPONSE_DN

GO Biological Process (1): positive regulation of smoothened signaling pathway (GO:0045880)

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

GO Cellular Component (5): centriole (GO:0005814), cilium (GO:0005929), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	2
cellular anatomical structure	2
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
positive regulation of signal transduction	1
binding	1
microtubule organizing center	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

312 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TEDC1	TEDC2	Q7L2K0	610
TEDC1	C22orf31	O95567	541
TEDC1	TMEM121	Q9BTD3	515
TEDC1	CEP44	Q9C0F1	511
TEDC1	C19orf25	Q9UFG5	479
TEDC1	TUBD1	Q9UJT1	448
TEDC1	TUBE1	Q9UJT0	418
TEDC1	RTTN	Q86VV8	399
TEDC1	MAP10	Q9P2G4	392
TEDC1	CEP295	Q9C0D2	353
TEDC1	SPICE1	Q8N0Z3	348
TEDC1	CEP120	Q8N960	348
TEDC1	HYLS1	Q96M11	336
TEDC1	ZNF133	P52736	324
TEDC1	SASS6	Q6UVJ0	322

IntAct

49 interactions, top by confidence:

A	B	Type	Score
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
DDIT3	TEDC1	psi-mi:“MI:0915”(physical association)	0.660
ENPP6	SCAMP1	psi-mi:“MI:0914”(association)	0.640
DDIT3	DDIT3	psi-mi:“MI:0914”(association)	0.590
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
C6orf118	FANCA	psi-mi:“MI:0914”(association)	0.530
ALOX5	DDHD2	psi-mi:“MI:0914”(association)	0.530
TUBE1	TEDC2	psi-mi:“MI:0914”(association)	0.530
TEDC2	TEDC1	psi-mi:“MI:0915”(physical association)	0.500
TEDC2	TEDC1	psi-mi:“MI:0914”(association)	0.500
DDIT3	TEDC1	psi-mi:“MI:0915”(physical association)	0.370
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
TNIP2	TMEM178B	psi-mi:“MI:0914”(association)	0.350
KRT2	IFT56	psi-mi:“MI:0914”(association)	0.350
CDC16	IFT56	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
EFNA4	NBAS	psi-mi:“MI:0914”(association)	0.350
CFAP184	TARS3	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350
TRIM52	MEIOC	psi-mi:“MI:0914”(association)	0.350
C6orf141	KRBA1	psi-mi:“MI:0914”(association)	0.350
KRT38	KRBA1	psi-mi:“MI:0914”(association)	0.350
GPR182	METTL15	psi-mi:“MI:0914”(association)	0.350
CEBPG	CCDC85C	psi-mi:“MI:0914”(association)	0.350

BioGRID (84): C14orf80 (Two-hybrid), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS), C14orf80 (Affinity Capture-MS)

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: Q3UK37, Q86SX3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 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.

GO biological processes:

GO term	Partners	Fold	FDR
cilium assembly	7	8.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1767 predictions. Top by Δscore:

Variant	Effect	Δscore
14:105491517:G:GT	donor_gain	1.0000
14:105491537:G:GT	donor_gain	1.0000
14:105492577:A:AG	acceptor_gain	1.0000
14:105492578:G:GG	acceptor_gain	1.0000
14:105492578:GT:G	acceptor_gain	1.0000
14:105497449:G:GT	donor_gain	1.0000
14:105491451:T:G	donor_gain	0.9900
14:105491504:G:GG	donor_gain	0.9900
14:105491525:G:GT	donor_gain	0.9900
14:105491536:G:GT	donor_gain	0.9900
14:105491540:G:GT	donor_gain	0.9900
14:105491541:G:T	donor_gain	0.9900
14:105491620:A:AG	acceptor_gain	0.9900
14:105491621:G:GG	acceptor_gain	0.9900
14:105491697:CTGGG:C	donor_loss	0.9900
14:105491699:GG:G	donor_gain	0.9900
14:105491699:GGGT:G	donor_loss	0.9900
14:105491700:GG:G	donor_gain	0.9900
14:105491700:GGTA:G	donor_loss	0.9900
14:105491701:G:A	donor_loss	0.9900
14:105491701:G:GG	donor_gain	0.9900
14:105491702:TAA:T	donor_loss	0.9900
14:105492105:A:AG	acceptor_gain	0.9900
14:105492106:G:GG	acceptor_gain	0.9900
14:105492473:G:GT	donor_gain	0.9900
14:105492578:GTGT:G	acceptor_gain	0.9900
14:105493833:A:AG	acceptor_gain	0.9900
14:105493834:G:GG	acceptor_gain	0.9900
14:105493929:AGCAG:A	donor_loss	0.9900
14:105493930:GCAG:G	donor_gain	0.9900

AlphaMissense

3098 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:105491505:T:C	F44L	0.987
14:105491507:C:A	F44L	0.987
14:105491507:C:G	F44L	0.987
14:105491491:T:C	F39S	0.982
14:105492226:T:A	W116R	0.982
14:105492226:T:C	W116R	0.982
14:105497438:T:A	W325R	0.981
14:105497438:T:C	W325R	0.981
14:105497429:T:C	F322L	0.979
14:105497431:C:A	F322L	0.979
14:105497431:C:G	F322L	0.979
14:105491490:T:C	F39L	0.974
14:105491492:C:A	F39L	0.974
14:105491492:C:G	F39L	0.974
14:105492684:T:A	W179R	0.974
14:105492684:T:C	W179R	0.974
14:105492129:G:C	K83N	0.972
14:105492129:G:T	K83N	0.972
14:105492151:T:G	Y91D	0.972
14:105492661:T:C	L171P	0.972
14:105492673:T:C	L175P	0.972
14:105491634:T:A	W54R	0.970
14:105491634:T:C	W54R	0.970
14:105497440:G:C	W325C	0.970
14:105497440:G:T	W325C	0.970
14:105493836:T:C	I196T	0.968
14:105491504:G:C	K43N	0.964
14:105491504:G:T	K43N	0.964
14:105492230:T:C	L117P	0.963
14:105491491:T:G	F39C	0.962

dbSNP variants (sampled 300 via entrez): RS1000295542 (14:105488052 C>A,G,T), RS1000385504 (14:105496941 A>G), RS1000667177 (14:105487883 C>T), RS1000698837 (14:105495770 C>T), RS1000740184 (14:105491550 C>A,T), RS1000756570 (14:105496776 T>C), RS1000854513 (14:105499246 C>G,T), RS1001132182 (14:105495991 G>A,C,T), RS1001592981 (14:105492135 A>G), RS1001869498 (14:105495482 G>A), RS1001924691 (14:105490992 G>C,T), RS1001934330 (14:105496489 G>A), RS1001954313 (14:105491172 C>A,T), RS1002012294 (14:105499234 G>A), RS1002490354 (14:105495188 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly	Limited	Autosomal recessive
autosomal recessive primary microcephaly	Limited	Autosomal recessive

Mondo (2): microcephaly (MONDO:0001149), autosomal recessive primary microcephaly (MONDO:0016660)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008572_3	Composite immunoglobulin trait (IgA/IgG)	5.000000e-06

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
C579935	Autosomal Recessive Primary Microcephaly (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression, affects cotreatment	3
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Smoke	decreases expression, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
FR900359	decreases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
glycidyl methacrylate	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
chromium hexavalent ion	decreases expression, increases abundance	1
obeticholic acid	decreases expression	1
ICG 001	increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Coumestrol	increases expression	1
Diazinon	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.