TTC9

Summary

TTC9 (tetratricopeptide repeat domain 9, HGNC:20267) is a protein-coding gene on chromosome 14q24.2, encoding Tetratricopeptide repeat protein 9A (Q92623).

This gene encodes a protein that contains three tetratricopeptide repeats. The gene has been shown to be hormonally regulated in breast cancer cells and may play a role in cancer cell invasion and metastasis.

Source: NCBI Gene 23508 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_015351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20267
Approved symbol	TTC9
Name	tetratricopeptide repeat domain 9
Location	14q24.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0227, TTC9A
Ensembl gene	ENSG00000133985
Ensembl biotype	protein_coding
OMIM	610488
Entrez	23508

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000256367, ENST00000928641

RefSeq mRNA: 1 — MANE Select: NM_015351 NM_015351

CCDS: CCDS45132

Canonical transcript exons

ENST00000256367 — 3 exons

Exon	Start	End
ENSE00000940946	70667564	70667746
ENSE00001167125	70641916	70642535
ENSE00001332325	70671076	70675366

Expression profiles

Bgee: expression breadth ubiquitous, 231 present calls, max score 97.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4675 / max 84.5050, expressed in 941 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140406	2.3015	745
140405	0.7514	441
140403	0.4842	159
140404	0.3451	173
140409	0.2399	119
140407	0.2138	98
140402	0.0731	32
140408	0.0584	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
amniotic fluid	UBERON:0000173	97.81	gold quality
lower esophagus mucosa	UBERON:0035834	97.79	gold quality
buccal mucosa cell	CL:0002336	96.15	gold quality
esophagus squamous epithelium	UBERON:0006920	94.53	gold quality
epithelium of esophagus	UBERON:0001976	94.10	gold quality
esophagus mucosa	UBERON:0002469	92.46	gold quality
cortical plate	UBERON:0005343	90.94	gold quality
tendon of biceps brachii	UBERON:0008188	89.88	gold quality
squamous epithelium	UBERON:0006914	88.82	gold quality
palpebral conjunctiva	UBERON:0001812	88.20	gold quality
cervix squamous epithelium	UBERON:0006922	88.14	silver quality
endothelial cell	CL:0000115	87.54	gold quality
nasal cavity epithelium	UBERON:0005384	87.02	gold quality
ventricular zone	UBERON:0003053	86.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.06	gold quality
oral cavity	UBERON:0000167	85.90	gold quality
ganglionic eminence	UBERON:0004023	84.41	gold quality
prefrontal cortex	UBERON:0000451	83.94	gold quality
epithelium of nasopharynx	UBERON:0001951	83.88	gold quality
nasopharynx	UBERON:0001728	83.87	gold quality
pharyngeal mucosa	UBERON:0000355	83.57	gold quality
eye	UBERON:0000970	83.23	gold quality
olfactory bulb	UBERON:0002264	82.90	gold quality
middle temporal gyrus	UBERON:0002771	82.81	silver quality
Brodmann (1909) area 23	UBERON:0013554	82.53	gold quality
tongue squamous epithelium	UBERON:0006919	82.25	silver quality
dorsolateral prefrontal cortex	UBERON:0009834	81.98	gold quality
CA1 field of hippocampus	UBERON:0003881	81.65	silver quality
oviduct epithelium	UBERON:0004804	81.41	gold quality
epithelium of bronchus	UBERON:0002031	81.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-114	yes	47.26
E-ANND-3	yes	7.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

197 targeting TTC9, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6780B-5P	99.96	69.60	2562

Literature-anchored findings (GeneRIF, showing 4)

• TTC9A acts as a chaperone protein to facilitate the function of tropomyosins (including Tm5NM-1) in stabilizing microfilament and it may play a role in cancer cell invasion and metastasis (PMID:18699990)
• It is plausible therefore that TTC9A negatively regulates ERalpha activity through interacting with co-chaperone proteins such as FKBP38 and FKBP51. (PMID:25798063)
• In this study, we propose a molecular mechanism whereby TTC9 mutations function to generate ichthyosiform hyperkeratosis of the skin, either directly or indirectly through altered myofibroblasts and altered hormone regulation. (PMID:30325323)
• [A pan-cancer analysis of TTC9A expression level and its correlation with prognosis and immune microenvironment]. (PMID:38293978)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	TTC9	ENSDARG00000074363
mus_musculus	Ttc9	ENSMUSG00000042734
rattus_norvegicus	Ttc9	ENSRNOG00000007254
caenorhabditis_elegans		WBGENE00001429
caenorhabditis_elegans	fkb-5	WBGENE00001430

Paralogs (18): FKBP4 (ENSG00000004478), FKBP6 (ENSG00000077800), FKBP7 (ENSG00000079150), FKBP1A (ENSG00000088832), FKBP5 (ENSG00000096060), FKBP3 (ENSG00000100442), FKBP8 (ENSG00000105701), FKBP14 (ENSG00000106080), FKBP15 (ENSG00000119321), FKBP1B (ENSG00000119782), FKBP9 (ENSG00000122642), FKBP11 (ENSG00000134285), FKBP10 (ENSG00000141756), TTC9C (ENSG00000162222), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Tetratricopeptide repeat protein 9A — Q92623 (reviewed: Q92623)

All UniProt accessions (1): Q92623

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the TTC9 family.

RefSeq proteins (1): NP_056166* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013105	TPR_2	Repeat
IPR019734	TPR_rpt	Repeat
IPR050754	FKBP4/5/8-like	Family

Pfam: PF07719

UniProt features (8 total): repeat 3, region of interest 2, chain 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92623-F1	81.09	0.65

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 (1): 105

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): BROWNE_HCMV_INFECTION_6HR_DN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOZGIT_ESR1_TARGETS_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_BONE_DEVELOPMENT, chr14q24, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, MORF_EPHA7

GO Biological Process (1): bone development (GO:0060348)

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
skeletal system development	1
animal organ development	1
binding	1

Protein interactions and networks

STRING

1502 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC9	PGR	P06401	634
TTC9	C6orf132	Q5T0Z8	566
TTC9	INSYN2B	A6NMK8	491
TTC9	ADM5	C9JUS6	478
TTC9	OR13C8	Q8NGS7	473
TTC9	GRAMD1C	Q8IYS0	458
TTC9	MAPK14	Q16539	446
TTC9	TMEM191B	P0C7N4	445
TTC9	TMEM205	Q6UW68	440
TTC9	TMEM236	Q5W0B7	437
TTC9	LRRC14B	A6NHZ5	433
TTC9	MSLNL	Q96KJ4	432
TTC9	WDR17	Q8IZU2	428
TTC9	RASEF	Q8IZ41	420
TTC9	FAM47B	Q8NA70	412

IntAct

5 interactions, top by confidence:

A	B	Type	Score
TTC9	NUP98	psi-mi:“MI:0915”(physical association)	0.400
PRIMA1	TTC9	psi-mi:“MI:0915”(physical association)	0.400
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): TTC9 (Proximity Label-MS), TTC9 (Affinity Capture-MS), MBNL1 (Co-fractionation), TTC9 (Affinity Capture-MS), TTC9 (Affinity Capture-MS)

ESM2 similar proteins: A2AWP8, A6QNS9, A7YY62, A7Z026, B2RYF1, D3ZVU9, D4ABL6, E9PV86, M0R7T9, O08838, O09112, O43189, O54951, O60347, O70141, O75864, O94827, P23726, P98201, Q13202, Q29RM4, Q3U2I3, Q3V038, Q5R448, Q5R5M3, Q5R8V2, Q5RD33, Q5TAQ9, Q5U2M6, Q5XI70, Q66T02, Q6A039, Q6DN14, Q6IR34, Q6P5H6, Q6ZN54, Q7Z6G3, Q8BKR5, Q8N612, Q8N7N5

Diamond homologs: A4IFF3, A4IHU6, O35450, O35465, P26882, P53691, Q08752, Q14318, Q3B7U9, Q3V038, Q5RAP0, Q6DGG0, Q6MG81, Q6P5P3, Q7DMA9, Q810A3, Q8N5M4, Q8N6N2, Q92623, Q9BGT1, Q9CR16, Q9D6E4, Q9H3U1, Q38931, Q43207, Q9LDC0, Q9VDE4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

350 predictions. Top by Δscore:

Variant	Effect	Δscore
14:70642534:AGGTG:A	donor_loss	1.0000
14:70642536:GTGAG:G	donor_loss	1.0000
14:70642537:T:A	donor_loss	1.0000
14:70666675:C:G	acceptor_gain	1.0000
14:70667560:A:AG	acceptor_gain	1.0000
14:70667561:T:G	acceptor_gain	1.0000
14:70667562:A:AG	acceptor_gain	1.0000
14:70667562:AGCCT:A	acceptor_gain	1.0000
14:70667563:G:GC	acceptor_gain	1.0000
14:70667563:GC:G	acceptor_gain	1.0000
14:70667563:GCC:G	acceptor_gain	1.0000
14:70667563:GCCT:G	acceptor_gain	1.0000
14:70667563:GCCTG:G	acceptor_gain	1.0000
14:70667742:AACAG:A	donor_gain	1.0000
14:70667743:ACAG:A	donor_gain	1.0000
14:70667744:CAG:C	donor_gain	1.0000
14:70667744:CAGG:C	donor_loss	1.0000
14:70667745:AG:A	donor_gain	1.0000
14:70667746:GG:G	donor_gain	1.0000
14:70667746:GGTA:G	donor_loss	1.0000
14:70667747:G:GG	donor_gain	1.0000
14:70671074:A:AG	acceptor_gain	1.0000
14:70671075:G:GG	acceptor_gain	1.0000
14:70671160:G:GT	donor_gain	1.0000
14:70642533:C:T	donor_gain	0.9900
14:70666674:A:AG	acceptor_gain	0.9900
14:70667558:CCATA:C	acceptor_gain	0.9900
14:70667559:CATA:C	acceptor_gain	0.9900
14:70667560:ATAG:A	acceptor_gain	0.9900
14:70667561:TAG:T	acceptor_gain	0.9900

AlphaMissense

1412 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:70642319:G:T	G64W	1.000
14:70642370:C:G	H81D	1.000
14:70667570:T:C	L138P	1.000
14:70667616:C:G	C153W	1.000
14:70667659:T:G	Y168D	1.000
14:70667669:G:A	G171D	1.000
14:70667675:C:A	A173D	1.000
14:70667717:T:C	L187P	1.000
14:70671103:T:C	L206P	1.000
14:70642320:G:A	G64E	0.999
14:70642362:G:A	G78D	0.999
14:70642370:C:A	H81N	0.999
14:70642372:C:A	H81Q	0.999
14:70642372:C:G	H81Q	0.999
14:70642374:G:C	R82P	0.999
14:70642517:T:C	C130R	0.999
14:70642519:T:G	C130W	0.999
14:70642530:T:C	L134P	0.999
14:70667566:T:C	C137R	0.999
14:70667568:C:G	C137W	0.999
14:70667573:T:C	L139P	0.999
14:70667603:T:A	V149D	0.999
14:70667614:T:C	C153R	0.999
14:70667615:G:A	C153Y	0.999
14:70667652:G:C	K165N	0.999
14:70667652:G:T	K165N	0.999
14:70667662:C:G	R169G	0.999
14:70667663:G:C	R169P	0.999
14:70667668:G:C	G171R	0.999
14:70667680:T:G	Y175D	0.999

dbSNP variants (sampled 300 via entrez): RS1000048408 (14:70657701 C>G), RS1000205643 (14:70668887 T>G), RS1000231769 (14:70654125 C>A), RS1000246974 (14:70658075 C>G,T), RS1000281620 (14:70661287 T>G), RS1000409137 (14:70644004 T>C), RS1000485243 (14:70667026 T>C), RS1000500466 (14:70673311 C>T), RS1000516739 (14:70664050 T>C), RS1000531536 (14:70654418 C>G,T), RS1000587047 (14:70651332 A>T), RS1000669112 (14:70674951 T>G), RS1000814859 (14:70666676 G>A,C), RS1000892439 (14:70668883 G>A), RS1000949391 (14:70648842 TA>T,TAA)

Disease associations

OMIM: gene MIM:610488 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002606_19	Prostate cancer	1.000000e-08
GCST002606_38	Prostate cancer	3.000000e-07
GCST009150_12	Low density lipoprotein cholesterol levels	5.000000e-22
GCST012489_21	Heel bone mineral density x serum urate levels interaction	8.000000e-11
GCST90026416_7	Mild age-related type 2 diabetes	1.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004531	urate measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Valproic Acid	increases expression	2
Cadmium Chloride	increases expression	2
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
kojic acid	increases expression	1
sodium arsenite	increases expression	1
corosolic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
incobotulinumtoxinA	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Zoledronic Acid	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lead	affects expression	1
Malathion	decreases expression	1
Nickel	increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1

Clinical trials (associated diseases)

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