TTC39C

Summary

TTC39C (tetratricopeptide repeat domain 39C, HGNC:26595) is a protein-coding gene on chromosome 18q11.2, encoding Tetratricopeptide repeat protein 39C (Q8N584).

Predicted to be involved in cilium assembly and otolith morphogenesis.

Source: NCBI Gene 125488 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_001135993

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26595
Approved symbol	TTC39C
Name	tetratricopeptide repeat domain 39C
Location	18q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33761, HsT2697
Ensembl gene	ENSG00000168234
Ensembl biotype	protein_coding
Entrez	125488

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 13 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000304621, ENST00000317571, ENST00000540918, ENST00000577185, ENST00000578150, ENST00000579214, ENST00000581394, ENST00000584095, ENST00000584250, ENST00000584424, ENST00000905385, ENST00000905386, ENST00000905387, ENST00000905388, ENST00000919099, ENST00000919100, ENST00000919101

RefSeq mRNA: 4 — MANE Select: NM_001135993 NM_001135993, NM_001243425, NM_001292030, NM_153211

CCDS: CCDS32804, CCDS45839, CCDS58616, CCDS77165

Canonical transcript exons

ENST00000317571 — 14 exons

Exon	Start	End
ENSE00001013771	24123834	24123943
ENSE00001136280	24080585	24080939
ENSE00001136286	24069157	24069271
ENSE00001178870	24082913	24083081
ENSE00002714749	24014754	24015038
ENSE00002726662	24132485	24135600
ENSE00003504942	24131882	24131920
ENSE00003533596	24114554	24114647
ENSE00003570408	24130313	24130417
ENSE00003651798	24064140	24064188
ENSE00003654065	24125427	24125550
ENSE00003655004	24128886	24128983
ENSE00003664312	24066012	24066140
ENSE00003678652	24118125	24118232

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 96.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3232 / max 370.4643, expressed in 1691 samples.

FANTOM5 promoters (16 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169722	12.4364	1663
169718	1.4251	893
169719	1.1723	358
169720	1.1215	401
169721	0.7855	347
169726	0.3874	23
169715	0.2110	55
169713	0.2043	56
169716	0.1412	50
169727	0.1082	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.74	gold quality
liver	UBERON:0002107	96.12	gold quality
oviduct epithelium	UBERON:0004804	94.89	gold quality
skin of abdomen	UBERON:0001416	94.20	gold quality
skin of leg	UBERON:0001511	93.68	gold quality
zone of skin	UBERON:0000014	92.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.92	gold quality
upper arm skin	UBERON:0004263	92.75	gold quality
left testis	UBERON:0004533	91.21	gold quality
right testis	UBERON:0004534	90.93	gold quality
granulocyte	CL:0000094	90.76	gold quality
left adrenal gland cortex	UBERON:0035825	90.74	gold quality
right adrenal gland	UBERON:0001233	90.70	gold quality
left adrenal gland	UBERON:0001234	90.23	gold quality
right uterine tube	UBERON:0001302	90.17	gold quality
right adrenal gland cortex	UBERON:0035827	90.13	gold quality
gall bladder	UBERON:0002110	90.10	gold quality
adrenal cortex	UBERON:0001235	89.95	gold quality
testis	UBERON:0000473	89.60	gold quality
adrenal gland	UBERON:0002369	89.41	gold quality
minor salivary gland	UBERON:0001830	89.02	gold quality
leukocyte	CL:0000738	88.62	gold quality
pigmented layer of retina	UBERON:0001782	88.58	gold quality
retina	UBERON:0000966	88.56	gold quality
nasal cavity mucosa	UBERON:0001826	88.34	gold quality
monocyte	CL:0000576	88.30	gold quality
vagina	UBERON:0000996	87.73	gold quality
blood	UBERON:0000178	87.71	gold quality
endocervix	UBERON:0000458	87.69	gold quality
tonsil	UBERON:0002372	87.64	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	45.67
E-CURD-122	yes	27.68
E-CURD-46	yes	16.44
E-ENAD-27	yes	10.19
E-MTAB-7303	no	709.28
E-MTAB-7606	no	264.09
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

145 targeting TTC39C, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118

Literature-anchored findings (GeneRIF, showing 2)

• Single Nucleotide Polymorphism in the TTC39C gene is associated with diabetic maculopathy with decreased visual acuity. (PMID:31264924)
• Ttc39c is a potential target for the treatment of lung cancer. (PMID:36303158)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc39c	ENSDARG00000102308
mus_musculus	Ttc39c	ENSMUSG00000024424
rattus_norvegicus	Ttc39c	ENSRNOG00000050949
caenorhabditis_elegans		WBGENE00016314

Paralogs (2): TTC39A (ENSG00000085831), TTC39B (ENSG00000155158)

Protein

Protein identifiers

Tetratricopeptide repeat protein 39C — Q8N584 (reviewed: Q8N584)

All UniProt accessions (4): Q8N584, G3V1P2, J3QKX7, J3QLL8

UniProt curated annotations — full annotation on UniProt →

Similarity. Belongs to the TTC39 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N584-1	1	yes
Q8N584-2	2
Q8N584-3	3

RefSeq proteins (4): NP_001129465, NP_001230354, NP_001278959, NP_694943 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019412	IML2/TPR_39	Family

Pfam: PF10300

UniProt features (10 total): repeat 3, splice variant 3, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N584-F1	85.75	0.62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EAR_DEVELOPMENT, GOBP_EMBRYONIC_ORGAN_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, TGACATY_UNKNOWN, GOBP_EAR_MORPHOGENESIS, GOBP_EMBRYO_DEVELOPMENT, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_SENSORY_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_ORGAN_DEVELOPMENT

GO Biological Process (2): otolith morphogenesis (GO:0032474), cilium assembly (GO:0060271)

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
inner ear morphogenesis	1
embryonic morphogenesis	1
otolith development	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
plasma membrane bounded cell projection assembly	1
ciliary transition zone assembly	1
binding	1

Protein interactions and networks

STRING

466 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC39C	TTC9C	Q8N5M4	510
TTC39C	HAUS4	Q9H6D7	502
TTC39C	TTC5	Q8N0Z6	483
TTC39C	RMP24	Q32NC0	432
TTC39C	IFT56	A0AVF1	406
TTC39C	TTC4	O95801	402
TTC39C	RAB30	Q15771	388
TTC39C	ODAD4	Q96NG3	380
TTC39C	TMEM19	Q96HH6	365
TTC39C	ANKRD13A	Q8IZ07	352
TTC39C	LMNTD2	Q8IXW0	349
TTC39C	KIAA1328	Q86T90	348
TTC39C	TMEM37	Q8WXS4	340
TTC39C	PCCA	P05165	339
TTC39C	C2orf69	Q8N8R5	334
TTC39C	ANKRD13C	Q8N6S4	334

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TTC39C	TMEM43	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	TTC39C	psi-mi:“MI:0915”(physical association)	0.370
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (12): TTC39C (Affinity Capture-RNA), TTC39C (Affinity Capture-RNA), TTC39C (Affinity Capture-RNA), TTC39C (Two-hybrid), TMEM43 (Affinity Capture-MS), TTC39C (Affinity Capture-MS), TTC39C (Affinity Capture-MS), TTC39C (Cross-Linking-MS (XL-MS)), TTC39C (Cross-Linking-MS (XL-MS)), TTC39C (Affinity Capture-MS), TTC39C (Co-fractionation), TTC39C (Co-fractionation)

ESM2 similar proteins: A1A5Y5, A1Z6M6, A2ACP1, A7E727, A7SUU7, A8NY27, A8X419, D3ZC96, O13693, O42897, O61820, O94699, P34560, P40515, Q03560, Q09266, Q0VGK2, Q1LXE6, Q20255, Q28D40, Q28DB0, Q2TBN6, Q5AFF7, Q5FWP8, Q5JVF3, Q5SRH9, Q5U3P0, Q5VTQ0, Q5XHH9, Q60YJ7, Q61LA1, Q6BLG8, Q6CU37, Q6FIQ1, Q6INC1, Q7RXQ1, Q7SI58, Q8BFV2, Q8BYY4, Q8C0S4

Diamond homologs: Q0VGK2, Q1LXE6, Q8N584, Q8VE09

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3047 predictions. Top by Δscore:

Variant	Effect	Δscore
18:24066006:T:TA	acceptor_gain	1.0000
18:24066007:G:A	acceptor_gain	1.0000
18:24066008:GAAG:G	acceptor_loss	1.0000
18:24066009:AAGA:A	acceptor_loss	1.0000
18:24066010:A:AG	acceptor_gain	1.0000
18:24066010:AG:A	acceptor_loss	1.0000
18:24066010:AGAAT:A	acceptor_gain	1.0000
18:24066011:G:GA	acceptor_gain	1.0000
18:24066011:GA:G	acceptor_gain	1.0000
18:24066011:GAA:G	acceptor_gain	1.0000
18:24066011:GAAT:G	acceptor_gain	1.0000
18:24066011:GAATG:G	acceptor_gain	1.0000
18:24066014:T:TA	acceptor_gain	1.0000
18:24066136:AGAAC:A	donor_gain	1.0000
18:24066137:GAAC:G	donor_gain	1.0000
18:24066137:GAACG:G	donor_gain	1.0000
18:24066138:AAC:A	donor_gain	1.0000
18:24066139:AC:A	donor_gain	1.0000
18:24066139:ACGTA:A	donor_loss	1.0000
18:24066141:G:GG	donor_gain	1.0000
18:24066141:GTAA:G	donor_loss	1.0000
18:24066142:T:A	donor_loss	1.0000
18:24066145:G:GG	donor_gain	1.0000
18:24069268:TCAG:T	donor_loss	1.0000
18:24069269:CAG:C	donor_loss	1.0000
18:24069270:AGG:A	donor_loss	1.0000
18:24069271:GG:G	donor_loss	1.0000
18:24069272:G:A	donor_loss	1.0000
18:24069273:T:A	donor_loss	1.0000
18:24080583:A:AG	acceptor_gain	1.0000

AlphaMissense

3840 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:24014977:G:C	G36R	1.000
18:24014978:G:A	G36D	1.000
18:24014993:T:C	L41P	1.000
18:24015014:C:G	S48W	1.000
18:24064165:G:A	G65R	1.000
18:24064165:G:C	G65R	1.000
18:24064166:G:A	G65E	1.000
18:24064171:A:C	S67R	1.000
18:24064173:C:A	S67R	1.000
18:24064173:C:G	S67R	1.000
18:24066015:G:C	A74P	1.000
18:24069218:C:A	A136D	1.000
18:24080600:G:A	G159E	1.000
18:24080609:T:C	L162P	1.000
18:24080612:G:C	R163T	1.000
18:24080612:G:T	R163M	1.000
18:24080780:T:A	V219D	1.000
18:24080788:G:A	G222R	1.000
18:24080788:G:C	G222R	1.000
18:24080789:G:A	G222E	1.000
18:24080794:G:C	G224R	1.000
18:24080795:G:A	G224D	1.000
18:24080795:G:T	G224V	1.000
18:24080807:T:C	L228P	1.000
18:24080815:T:C	S231P	1.000
18:24080861:T:C	F246S	1.000
18:24080881:G:A	G253R	1.000
18:24080881:G:C	G253R	1.000
18:24080881:G:T	G253W	1.000
18:24080882:G:A	G253E	1.000

dbSNP variants (sampled 300 via entrez): RS1000009355 (18:24044987 G>T), RS1000021272 (18:24087110 A>G), RS1000027592 (18:24004327 C>T), RS1000035421 (18:24091820 T>TG), RS1000086494 (18:24088603 G>A), RS1000132237 (18:24003564 A>G), RS1000147310 (18:24026625 C>G,T), RS1000174971 (18:24006796 C>G,T), RS1000196324 (18:24117701 CA>C,CAA), RS1000198967 (18:24072330 G>C), RS1000227473 (18:24056943 G>A), RS1000228873 (18:24039013 T>G), RS1000246433 (18:24124340 A>G), RS1000262401 (18:24026248 A>G), RS1000280001 (18:24056750 G>T)

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

7 associations (top):

Study	Trait	p-value
GCST007022_5	Type 2 diabetes nephropathy including microalbuminuria	6.000000e-07
GCST008545_1	Diabetic maculopathy with decreased visual acuity in type 2 diabetes	7.000000e-08
GCST009391_1961	Metabolite levels	7.000000e-06
GCST90002394_421	Monocyte percentage of white cells	3.000000e-14
GCST90002398_318	Neutrophil count	2.000000e-18
GCST90002398_319	Neutrophil count	3.000000e-10
GCST90002407_158	White blood cell count	5.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008385	visual acuity measurement
EFO:0010133	diabetic maculopathy
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	5
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression	4
Estradiol	increases expression, affects cotreatment, decreases expression	3
Tetrachlorodibenzodioxin	increases expression	3
Valproic Acid	affects cotreatment, increases expression, decreases methylation	3
Aflatoxin B1	affects expression, decreases expression, decreases methylation	3
bisphenol A	increases abundance, decreases expression, decreases methylation, decreases reaction	2
Acetaminophen	decreases expression	2
Tretinoin	decreases expression	2
Cyclosporine	decreases expression	2
ginger extract	decreases expression, decreases reaction, increases abundance	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
mercuric bromide	affects cotreatment, increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	increases expression	1
Dexamethasone	increases expression	1
Dimethyl Sulfoxide	increases expression	1

Clinical trials (associated diseases)

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