TTC23

Summary

TTC23 (tetratricopeptide repeat domain 23, HGNC:25730) is a protein-coding gene on chromosome 15q26.3, encoding Tetratricopeptide repeat protein 23 (Q5W5X9). Participates positively in the ciliary Hedgehog (Hh) signaling.

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

Source: NCBI Gene 64927 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_001288615

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25730
Approved symbol	TTC23
Name	tetratricopeptide repeat domain 23
Location	15q26.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12572, HCC-8
Ensembl gene	ENSG00000103852
Ensembl biotype	protein_coding
Entrez	64927

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 34 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000262074, ENST00000394129, ENST00000394132, ENST00000394135, ENST00000434594, ENST00000459771, ENST00000468436, ENST00000480371, ENST00000490671, ENST00000490688, ENST00000494567, ENST00000558078, ENST00000558438, ENST00000558663, ENST00000560235, ENST00000560279, ENST00000560772, ENST00000560860, ENST00000561365, ENST00000875679, ENST00000875680, ENST00000875681, ENST00000875682, ENST00000875683, ENST00000875684, ENST00000875685, ENST00000875686, ENST00000875687, ENST00000875688, ENST00000875689, ENST00000875690, ENST00000875691, ENST00000924087, ENST00000924088, ENST00000924089, ENST00000924090, ENST00000961241, ENST00000961242, ENST00000961243, ENST00000961244, ENST00000961245

RefSeq mRNA: 3 — MANE Select: NM_001288615 NM_001288615, NM_001288616, NM_001353869

CCDS: CCDS10379

Canonical transcript exons

ENST00000394132 — 14 exons

Exon	Start	End
ENSE00001014615	99241365	99241559
ENSE00001179711	99218588	99218713
ENSE00001517576	99249171	99249581
ENSE00002507753	99234988	99235080
ENSE00002526611	99245389	99245510
ENSE00002610908	99228533	99228732
ENSE00003503956	99199919	99200096
ENSE00003512603	99156148	99156297
ENSE00003530031	99139317	99139399
ENSE00003597916	99175050	99175155
ENSE00003601041	99221741	99221864
ENSE00003669565	99161740	99161867
ENSE00003694736	99136323	99138127
ENSE00003784331	99218898	99219048

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 95.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8463 / max 162.6621, expressed in 1720 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151761	5.4608	1486
151763	2.9759	1182
151762	0.3780	189
151759	0.0315	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus muscularis layer	UBERON:0035833	95.01	gold quality
lower esophagus	UBERON:0013473	94.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.26	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.20	gold quality
mucosa of stomach	UBERON:0001199	90.76	gold quality
muscle of leg	UBERON:0001383	89.30	gold quality
esophagus	UBERON:0001043	89.10	gold quality
gastrocnemius	UBERON:0001388	89.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.99	gold quality
lower esophagus mucosa	UBERON:0035834	88.75	gold quality
ventricular zone	UBERON:0003053	88.60	gold quality
popliteal artery	UBERON:0002250	88.42	gold quality
tibial artery	UBERON:0007610	88.41	gold quality
right coronary artery	UBERON:0001625	88.17	gold quality
aorta	UBERON:0000947	87.25	gold quality
descending thoracic aorta	UBERON:0002345	87.01	gold quality
right atrium auricular region	UBERON:0006631	86.89	gold quality
calcaneal tendon	UBERON:0003701	86.85	gold quality
adrenal tissue	UBERON:0018303	86.56	gold quality
apex of heart	UBERON:0002098	86.35	gold quality
thoracic aorta	UBERON:0001515	86.14	gold quality
ascending aorta	UBERON:0001496	86.09	gold quality
transverse colon	UBERON:0001157	86.02	gold quality
body of uterus	UBERON:0009853	86.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.95	gold quality
left uterine tube	UBERON:0001303	85.83	gold quality
gall bladder	UBERON:0002110	85.83	gold quality
left adrenal gland	UBERON:0001234	85.68	gold quality
left adrenal gland cortex	UBERON:0035825	85.55	gold quality
left ovary	UBERON:0002119	85.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.89
E-MTAB-7303	no	295.14

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• TTC23 is a functional target gene of the BACH1 transcription factor according to ChIP-seq and knockdown analysis in HEK 293 cells. (PMID:21555518)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc23	ENSDARG00000022160
mus_musculus	Ttc23	ENSMUSG00000030555
rattus_norvegicus	Ttc23	ENSRNOG00000013877

Paralogs (1): TTC23L (ENSG00000205838)

Protein

Protein identifiers

Tetratricopeptide repeat protein 23 — Q5W5X9 (reviewed: Q5W5X9)

Alternative names: Cervical cancer proto-oncogene 8 protein

All UniProt accessions (9): Q5W5X9, H0YET0, H0YKN9, H0YM10, H0YMN1, H0YN45, H0YNH7, H0YNV8, H7BZG4

UniProt curated annotations — full annotation on UniProt →

Function. Participates positively in the ciliary Hedgehog (Hh) signaling.

Subunit / interactions. Found Associated with the EvC complex composed of EFCAB7, IQCE, EVC2 and EVC.

Subcellular location. Cell projection. Cilium.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5W5X9-1	1	yes
Q5W5X9-2	2
Q5W5X9-3	3

RefSeq proteins (3): NP_001275544, NP_001275545, NP_001340798 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR042621	TTC23/TTC23L	Family

Pfam: PF13424

UniProt features (8 total): repeat 4, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5W5X9-F1	85.44	0.74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, NIKOLSKY_BREAST_CANCER_15Q26_AMPLICON, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, AACTTT_UNKNOWN, GOBP_SMOOTHENED_SIGNALING_PATHWAY, RGAGGAARY_PU1_Q6, GOBP_POSITIVE_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOCC_CILIUM, SCGGAAGY_ELK1_02, chr15q26, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, BRUINS_UVC_RESPONSE_MIDDLE, TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_UP, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D

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

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

GO Cellular Component (2): cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC23	PGPEP1L	A6NFU8	555
TTC23	RAP1GDS1	P52306	533
TTC23	TXNDC15	Q96J42	517
TTC23	CIBAR1	A1XBS5	514
TTC23	IQCE	Q6IPM2	507
TTC23	PPP4R3B	Q5MIZ7	475
TTC23	EFCAB7	A8K855	454
TTC23	CCDC172	P0C7W6	447
TTC23	INTS10	Q9NVR2	443
TTC23	SLC25A48	Q6ZT89	422
TTC23	SNAPC1	Q16533	392
TTC23	TMEM229B	Q8NBD8	392
TTC23	ARMC9	Q7Z3E5	390
TTC23	SMPDL3A	Q92484	387
TTC23	DPH1	Q9BZG8	386

IntAct

69 interactions, top by confidence:

A	B	Type	Score
LDOC1	TTC23	psi-mi:“MI:0915”(physical association)	0.670
TRIM10	TTC23	psi-mi:“MI:0915”(physical association)	0.670
TTC23	TRIM10	psi-mi:“MI:0915”(physical association)	0.670
TTC23	LDOC1	psi-mi:“MI:0915”(physical association)	0.670
BHLHE40	TTC23	psi-mi:“MI:0915”(physical association)	0.560
TTC23	TADA2A	psi-mi:“MI:0915”(physical association)	0.560
CCNDBP1	TTC23	psi-mi:“MI:0915”(physical association)	0.560
ALAS1	TTC23	psi-mi:“MI:0915”(physical association)	0.560
TTC23	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
TTC23	KRT31	psi-mi:“MI:0915”(physical association)	0.560
KRT40	TTC23	psi-mi:“MI:0915”(physical association)	0.560
CNTROB	TTC23	psi-mi:“MI:0915”(physical association)	0.560
TTC23	PNMA5	psi-mi:“MI:0915”(physical association)	0.560
SPAG5	TTC23	psi-mi:“MI:0915”(physical association)	0.560
TTC23	MDFI	psi-mi:“MI:0915”(physical association)	0.560
TTC23	LZTS2	psi-mi:“MI:0915”(physical association)	0.560
TRIM54	TTC23	psi-mi:“MI:0915”(physical association)	0.560
CREBZF	TTC23	psi-mi:“MI:0915”(physical association)	0.560
TTC23	SSX2IP	psi-mi:“MI:0915”(physical association)	0.560
TTC23	MAGED1	psi-mi:“MI:0915”(physical association)	0.560
TTC23		psi-mi:“MI:0915”(physical association)	0.560
TTC23	BHLHE40	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (112): TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), TTC23 (Two-hybrid), LZTS2 (Two-hybrid), PNMA5 (Two-hybrid)

ESM2 similar proteins: A0AVF1, A1L1K3, A4III8, A5PLI4, A6H6E9, A8JA42, E9Q6P5, P09913, Q06AN9, Q14DN9, Q2KHY7, Q2TBM9, Q32NR4, Q3U213, Q3V172, Q4R3N2, Q4R6M4, Q4R7Z9, Q4V7F0, Q569C2, Q57ZL2, Q5PR66, Q5RE52, Q5TEA6, Q5U2N8, Q5W5X9, Q5XI05, Q5ZKK3, Q60462, Q64112, Q64282, Q66GN3, Q6AYP3, Q6IND7, Q80VM3, Q80YE7, Q86TV6, Q86TZ1, Q8BGB2, Q8BS45

Diamond homologs: A6H6E9, A6H7D1, Q2KHY7, Q4V7F0, Q5W5X9, Q6PF05, Q8CHY7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2632 predictions. Top by Δscore:

Variant	Effect	Δscore
15:99156142:CTTTA:C	donor_loss	1.0000
15:99156143:TTTAC:T	donor_loss	1.0000
15:99156144:TTACC:T	donor_loss	1.0000
15:99156145:TA:T	donor_loss	1.0000
15:99156147:C:CT	donor_loss	1.0000
15:99156147:CCTT:C	donor_gain	1.0000
15:99156293:GCTCT:G	acceptor_gain	1.0000
15:99156294:CTCT:C	acceptor_gain	1.0000
15:99156294:CTCTC:C	acceptor_gain	1.0000
15:99156295:TCT:T	acceptor_gain	1.0000
15:99156295:TCTCT:T	acceptor_gain	1.0000
15:99156296:CT:C	acceptor_gain	1.0000
15:99156296:CTC:C	acceptor_gain	1.0000
15:99156296:CTCTG:C	acceptor_loss	1.0000
15:99156297:TC:T	acceptor_loss	1.0000
15:99156297:TCT:T	acceptor_gain	1.0000
15:99156298:C:CA	acceptor_loss	1.0000
15:99156298:C:CC	acceptor_gain	1.0000
15:99156300:G:C	acceptor_gain	1.0000
15:99175163:C:CT	acceptor_gain	1.0000
15:99200095:CC:C	acceptor_gain	1.0000
15:99200096:CC:C	acceptor_gain	1.0000
15:99221735:GCTTA:G	donor_loss	1.0000
15:99221736:CTTA:C	donor_loss	1.0000
15:99221737:TTACC:T	donor_loss	1.0000
15:99221738:TACC:T	donor_loss	1.0000
15:99221739:A:AC	donor_gain	1.0000
15:99221740:C:CC	donor_gain	1.0000
15:99221740:CCTTT:C	donor_gain	1.0000
15:99221860:TTGTA:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000007585 (15:99178743 C>T), RS1000021121 (15:99250649 C>T), RS1000038590 (15:99231469 A>T), RS1000042908 (15:99147655 T>C), RS1000105733 (15:99225556 A>G), RS1000121658 (15:99184243 G>C), RS1000125444 (15:99221160 T>C), RS1000191061 (15:99216338 G>A,T), RS1000191389 (15:99207063 A>G), RS1000229905 (15:99172259 C>A), RS1000257381 (15:99214942 G>A), RS1000260420 (15:99158601 A>T), RS1000341794 (15:99186139 C>T), RS1000347072 (15:99219830 G>T), RS1000366305 (15:99177837 T>C,G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:311200

GenCC curated gene-disease

Mondo (1): orofaciodigital syndrome (MONDO:0015375)

Orphanet (1): Orofaciodigital syndrome (Orphanet:140997)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011354_62	Bell’s palsy	7.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009958	Orofaciodigital Syndromes	C05.116.099.370.652; C05.660.207.700; C16.131.077.676; C16.131.260.830.670; C16.131.621.207.700; C16.320.180.830.670; C16.320.714

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 cotreatment, decreases expression, affects expression	7
Aflatoxin B1	affects methylation, increases methylation	2
pirinixic acid	decreases expression, increases activity, affects binding	1
bisphenol A	decreases expression	1
trichostatin A	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01962129	Not specified	UNKNOWN	Clinical and Molecular Characterisation of Orofaciodigital Syndromes and Other Clinical Phenotypes Secondary to Mutations in the OFD1 Gene