TTC9C

Summary

TTC9C (tetratricopeptide repeat domain 9C, HGNC:28432) is a protein-coding gene on chromosome 11q12.3, encoding Tetratricopeptide repeat protein 9C (Q8N5M4).

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_173810

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28432
Approved symbol	TTC9C
Name	tetratricopeptide repeat domain 9C
Location	11q12.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC29649
Ensembl gene	ENSG00000162222
Ensembl biotype	protein_coding
Entrez	283237

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000294161, ENST00000316461, ENST00000530625, ENST00000532276, ENST00000532583, ENST00000601045, ENST00000851206, ENST00000851207, ENST00000851208, ENST00000851209, ENST00000939223, ENST00000939224, ENST00000939225, ENST00000947257

RefSeq mRNA: 6 — MANE Select: NM_173810 NM_001318812, NM_001318813, NM_001318814, NM_001318815, NM_001318816, NM_173810

CCDS: CCDS8033

Canonical transcript exons

ENST00000316461 — 3 exons

Exon	Start	End
ENSE00001275345	62728486	62729086
ENSE00001299033	62738288	62738636
ENSE00003785738	62735382	62735564

Expression profiles

Bgee: expression breadth ubiquitous, 235 present calls, max score 92.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.1942 / max 237.4867, expressed in 1815 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114735	29.7622	1809
114737	4.1285	1387
114734	2.5931	1053
114736	1.1728	942
114733	0.7728	445
114738	0.7279	209
114739	0.0368	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.27	gold quality
stromal cell of endometrium	CL:0002255	91.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.64	gold quality
mucosa of transverse colon	UBERON:0004991	91.55	gold quality
cerebellar hemisphere	UBERON:0002245	91.41	gold quality
leukocyte	CL:0000738	91.25	gold quality
cerebellar cortex	UBERON:0002129	91.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.17	gold quality
monocyte	CL:0000576	91.11	gold quality
right coronary artery	UBERON:0001625	91.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.66	gold quality
endocervix	UBERON:0000458	90.62	gold quality
descending thoracic aorta	UBERON:0002345	90.61	gold quality
anterior cingulate cortex	UBERON:0009835	90.52	gold quality
calcaneal tendon	UBERON:0003701	90.49	gold quality
islet of Langerhans	UBERON:0000006	90.44	gold quality
spleen	UBERON:0002106	90.43	gold quality
right ovary	UBERON:0002118	90.28	gold quality
left ovary	UBERON:0002119	90.20	gold quality
skin of leg	UBERON:0001511	90.02	gold quality
prefrontal cortex	UBERON:0000451	89.91	gold quality
right frontal lobe	UBERON:0002810	89.91	gold quality
lower esophagus mucosa	UBERON:0035834	89.91	gold quality
granulocyte	CL:0000094	89.84	gold quality
cerebellum	UBERON:0002037	89.84	gold quality
body of uterus	UBERON:0009853	89.80	gold quality
popliteal artery	UBERON:0002250	89.74	gold quality
tibial artery	UBERON:0007610	89.74	gold quality
vermiform appendix	UBERON:0001154	89.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	no	2.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting TTC9C, 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-3134	100.00	66.43	777
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-6073	99.60	70.36	793
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-2276-3P	98.76	67.75	1384
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-4494	97.86	64.93	850
HSA-MIR-3920	97.75	69.02	1168
HSA-MIR-2467-5P	97.36	67.71	991

Literature-anchored findings (GeneRIF, showing 1)

• Using shotgun mass spectrometry, we found this protein differentially expressed in the dorsolateral prefrontal cortex from patients with schizophrenia. (PMID:19165527)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc9c	ENSDARG00000007025
mus_musculus	Ttc9c	ENSMUSG00000071660
rattus_norvegicus	Ttc9c	ENSRNOG00000019464
drosophila_melanogaster	Fkbp39	FBGN0013269
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), TTC9 (ENSG00000133985), FKBP11 (ENSG00000134285), FKBP10 (ENSG00000141756), FKBP2 (ENSG00000173486), TTC9B (ENSG00000174521), FKBP1C (ENSG00000198225), FKBPL (ENSG00000204315)

Protein

Protein identifiers

Tetratricopeptide repeat protein 9C — Q8N5M4 (reviewed: Q8N5M4)

All UniProt accessions (4): E7EST3, E9PKV8, Q8N5M4, H0YDR3

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the TTC9 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N5M4-1	1	yes
Q8N5M4-2	2

RefSeq proteins (6): NP_001305741, NP_001305742, NP_001305743, NP_001305744, NP_001305745, NP_776171* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR039663	AIP/AIPL1/TTC9	Family

Pfam: PF14559

UniProt features (6 total): repeat 3, splice variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5M4-F1	93.06	0.82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 131 (showing top): CCAWYNNGAAR_UNKNOWN, LFA1_Q6, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GGCNKCCATNK_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, NKX22_01, NKX25_01, ZHANG_BREAST_CANCER_PROGENITORS_UP, EGR1_01, PITX2_Q2, AP4_01, YGCGYRCGC_UNKNOWN, AHR_Q5, NUYTTEN_NIPP1_TARGETS_DN, YGCANTGCR_UNKNOWN

GO Biological Process (0):

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
binding	1

Protein interactions and networks

STRING

2117 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC9C	DNAJC7	Q99615	663
TTC9C	TTC4	O95801	573
TTC9C	VWDE	Q8N2E2	561
TTC9C	ODAD4	Q96NG3	551
TTC9C	SMPDL3A	Q92484	530
TTC9C	HSP90AA1	P07900	513
TTC9C	HSP90AB1	P08238	513
TTC9C	TTC39C	Q8N584	510
TTC9C	DNAAF3	Q8N9W5	505
TTC9C	DNALI1	O14645	498
TTC9C	IFT56	A0AVF1	497
TTC9C	ZMYND10	O75800	486
TTC9C	DNAAF4	Q8WXU2	483
TTC9C	DNAI2	Q9GZS0	477
TTC9C	CCDC39	Q9UFE4	474

IntAct

130 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
TTC9C	SKP1	psi-mi:“MI:0915”(physical association)	0.870
SKP1	TTC9C	psi-mi:“MI:0915”(physical association)	0.870
SKP1	TTC9C	psi-mi:“MI:0914”(association)	0.870
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HSP90AA1	CHUK	psi-mi:“MI:0914”(association)	0.670
ATP6V1C2	ATP6V1G1	psi-mi:“MI:0914”(association)	0.640
DNAJC8	SF3B1	psi-mi:“MI:0914”(association)	0.640
SKP1	MYCBP2	psi-mi:“MI:0914”(association)	0.640
TTC9C	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
TADA2A	TTC9C	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	TTC9C	psi-mi:“MI:0915”(physical association)	0.560
PNMA1	TTC9C	psi-mi:“MI:0915”(physical association)	0.560
TTC9C	TADA2A	psi-mi:“MI:0915”(physical association)	0.560
TTC9C	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
TTC9C	PNMA1	psi-mi:“MI:0915”(physical association)	0.560
TOLLIP	TTC9C	psi-mi:“MI:0915”(physical association)	0.560
TTC9C	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	TTC9C	psi-mi:“MI:0915”(physical association)	0.560
TTC9C	USHBP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (193): TTC9C (Two-hybrid), TTC9C (Two-hybrid), TTC9C (Two-hybrid), TTC9C (Two-hybrid), TTC9C (Two-hybrid), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS), TTC9C (Affinity Capture-MS)

ESM2 similar proteins: A2VE45, A4IFF3, A4IHU6, A6H739, A6QQ71, A6QR40, A8E7I5, D3ZQF4, E9Q6P5, F6PHZ6, O75344, O95801, Q0HA38, Q0P5H9, Q1JQC5, Q32KL4, Q499U2, Q4G069, Q5BK48, Q5EA11, Q5R8E4, Q60864, Q66H45, Q66HA5, Q68G30, Q6P1N0, Q6P5E6, Q6P5P3, Q7Z4L5, Q7ZU45, Q810A3, Q86VI3, Q86WT1, Q8BYZ7, Q8K1A6, Q8N0Z6, Q8N4P2, Q8N5M4, Q8R0H9, Q8R307

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, F1RBN2, H9IWW7, K7TQE3, O08915, O97628, P15705, Q02790, Q07617, Q28IV3, Q32PZ3, Q5FWY5, Q5U2X2, Q68FQ7, Q6NU95, Q75Q39, Q7YRC1, Q80ZX8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 110 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Attenuation phase	5	27.6×	7e-04
HSF1-dependent transactivation	5	21.4×	1e-03
Fatty acid metabolism	5	8.9×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process	5	19.9×	5e-03
epithelial cell differentiation	6	11.2×	6e-03
protein folding	7	7.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

592 predictions. Top by Δscore:

Variant	Effect	Δscore
11:62728914:G:T	donor_gain	1.0000
11:62735368:A:AG	acceptor_gain	1.0000
11:62735368:ATTT:A	acceptor_gain	1.0000
11:62735368:ATTTG:A	acceptor_gain	1.0000
11:62735369:T:G	acceptor_gain	1.0000
11:62735371:T:A	acceptor_gain	1.0000
11:62735380:A:AG	acceptor_gain	1.0000
11:62735380:AGCTT:A	acceptor_gain	1.0000
11:62735381:G:GA	acceptor_gain	1.0000
11:62735381:GC:G	acceptor_gain	1.0000
11:62735381:GCT:G	acceptor_gain	1.0000
11:62735381:GCTT:G	acceptor_gain	1.0000
11:62735381:GCTTG:G	acceptor_gain	1.0000
11:62735560:TAAAG:T	donor_gain	1.0000
11:62735561:AAAGG:A	donor_gain	1.0000
11:62735562:AAGG:A	donor_gain	1.0000
11:62735563:AGGT:A	donor_gain	1.0000
11:62735564:GGT:G	donor_gain	1.0000
11:62735565:G:GG	donor_gain	1.0000
11:62735565:GT:G	donor_gain	1.0000
11:62735566:T:A	donor_gain	1.0000
11:62738263:A:AG	acceptor_gain	1.0000
11:62738263:AATT:A	acceptor_gain	1.0000
11:62738275:A:AG	acceptor_gain	1.0000
11:62738278:A:AG	acceptor_gain	1.0000
11:62738279:T:G	acceptor_gain	1.0000
11:62738285:A:AG	acceptor_gain	1.0000
11:62738286:A:AG	acceptor_gain	1.0000
11:62738287:G:GG	acceptor_gain	1.0000
11:62728914:G:GT	donor_gain	0.9900

AlphaMissense

1096 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:62728884:G:C	K12N	0.998
11:62728884:G:T	K12N	0.998
11:62728891:G:T	G15W	0.998
11:62728891:G:A	G15R	0.997
11:62728891:G:C	G15R	0.997
11:62728892:G:A	G15E	0.997
11:62729070:C:G	C74W	0.997
11:62729081:T:C	L78P	0.997
11:62735386:T:G	C81W	0.997
11:62735470:G:C	K109N	0.997
11:62735470:G:T	K109N	0.997
11:62735487:G:A	G115E	0.997
11:62729068:T:C	C74R	0.996
11:62735432:A:C	S97R	0.996
11:62735434:T:A	S97R	0.996
11:62735434:T:G	S97R	0.996
11:62735481:G:C	R113P	0.996
11:62735486:G:A	G115R	0.996
11:62735486:G:C	G115R	0.996
11:62728892:G:T	G15V	0.995
11:62728942:C:G	H32D	0.995
11:62735384:T:C	C81R	0.995
11:62735385:G:A	C81Y	0.995
11:62735493:C:A	A117D	0.995
11:62735522:G:C	A127P	0.995
11:62735535:T:C	L131P	0.995
11:62728928:C:A	A27D	0.993
11:62728948:G:C	A34P	0.993
11:62728952:T:C	L35P	0.993
11:62729069:G:A	C74Y	0.993

dbSNP variants (sampled 300 via entrez): RS1000010504 (11:62736362 C>T), RS1000519479 (11:62733000 T>G), RS1000553131 (11:62732287 G>A), RS1000707265 (11:62727479 C>G,T), RS1000826593 (11:62727383 A>C,T), RS1000928647 (11:62732487 G>A), RS1000985293 (11:62737828 C>G), RS1001000852 (11:62728456 G>GA,GT), RS1001239413 (11:62728951 C>T), RS1001312609 (11:62731551 T>G), RS1001343898 (11:62731348 A>G), RS1001377735 (11:62734340 C>G), RS1001471332 (11:62728357 CAAAT>C), RS1001890832 (11:62727678 C>G,T), RS1002259946 (11:62727828 C>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005956_2	Waist-to-hip ratio adjusted for BMI	1.000000e-08
GCST005962_37	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-07
GCST005962_51	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
beta-methylcholine	affects expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
Leflunomide	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Demecolcine	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Vincristine	increases expression, decreases expression	1
Zinc	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	decreases expression	1
Genistein	decreases expression, increases reaction	1

Clinical trials (associated diseases)

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