TTC16

Summary

TTC16 (tetratricopeptide repeat domain 16, HGNC:26536) is a protein-coding gene on chromosome 9q34.11, encoding Tetratricopeptide repeat protein 16 (Q8NEE8).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 176 total
• MANE Select transcript: NM_144965

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26536
Approved symbol	TTC16
Name	tetratricopeptide repeat domain 16
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32780
Ensembl gene	ENSG00000167094
Ensembl biotype	protein_coding
Entrez	158248

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000373289, ENST00000488285, ENST00000489226, ENST00000862124, ENST00000956085

RefSeq mRNA: 2 — MANE Select: NM_144965 NM_001317037, NM_144965

CCDS: CCDS6875

Canonical transcript exons

ENST00000373289 — 14 exons

Exon	Start	End
ENSE00001109575	127724756	127724897
ENSE00001673279	127730636	127731590
ENSE00001737324	127716844	127717016
ENSE00002714302	127716079	127716163
ENSE00003463413	127729581	127729668
ENSE00003502894	127717629	127717772
ENSE00003534673	127727270	127727465
ENSE00003548233	127726239	127726404
ENSE00003558488	127726970	127727112
ENSE00003567393	127720266	127720395
ENSE00003595460	127723119	127723333
ENSE00003648701	127717334	127717424
ENSE00003661665	127724120	127724364
ENSE00003668598	127720078	127720178

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 91.69.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6464 / max 74.0859, expressed in 86 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98654	0.3837	57
98653	0.1792	48
98650	0.0562	8
98651	0.0236	7
98652	0.0037	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	91.69	gold quality
bronchial epithelial cell	CL:0002328	89.22	gold quality
granulocyte	CL:0000094	88.83	gold quality
bronchus	UBERON:0002185	87.84	gold quality
right testis	UBERON:0004534	83.31	gold quality
left testis	UBERON:0004533	83.28	gold quality
testis	UBERON:0000473	80.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	78.59	gold quality
kidney epithelium	UBERON:0004819	78.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	75.55	gold quality
nasal cavity epithelium	UBERON:0005384	74.74	gold quality
sperm	CL:0000019	73.36	gold quality
blood	UBERON:0000178	70.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	70.59	gold quality
left ventricle myocardium	UBERON:0006566	69.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.12	gold quality
epithelium of nasopharynx	UBERON:0001951	68.85	silver quality
epithelial cell of pancreas	CL:0000083	68.14	gold quality
myocardium	UBERON:0002349	67.45	gold quality
vastus lateralis	UBERON:0001379	65.75	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	65.58	gold quality
quadriceps femoris	UBERON:0001377	65.23	gold quality
nasal cavity mucosa	UBERON:0001826	64.70	gold quality
adult organism	UBERON:0007023	64.53	gold quality
fallopian tube	UBERON:0003889	64.41	gold quality
parotid gland	UBERON:0001831	64.32	gold quality
gingival epithelium	UBERON:0001949	64.15	gold quality
upper arm skin	UBERON:0004263	63.76	gold quality
lymph node	UBERON:0000029	63.04	gold quality
secondary oocyte	CL:0000655	62.97	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting TTC16, 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-10401-5P	99.99	65.79	948
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-1909-5P	98.94	64.01	484
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-635	96.00	65.54	687
HSA-MIR-6774-5P	95.94	65.18	722
HSA-MIR-2861	95.24	65.47	1056

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc16	ENSDARG00000104035
		ENSDARG00000110648
mus_musculus	Ttc16	ENSMUSG00000039021
rattus_norvegicus	Ttc16	ENSRNOG00000050650

Paralogs (14): IFT88 (ENSG00000032742), TTC7A (ENSG00000068724), TMTC4 (ENSG00000125247), TMTC1 (ENSG00000133687), TMTC3 (ENSG00000139324), TTC6 (ENSG00000139865), BBS4 (ENSG00000140463), TTC13 (ENSG00000143643), OGT (ENSG00000147162), CFAP70 (ENSG00000156042), TTC8 (ENSG00000165533), TTC7B (ENSG00000165914), TMTC2 (ENSG00000179104), TTC34 (ENSG00000215912)

Protein

Protein identifiers

Tetratricopeptide repeat protein 16 — Q8NEE8 (reviewed: Q8NEE8)

All UniProt accessions (1): Q8NEE8

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NEE8-1	1	yes
Q8NEE8-2	2

RefSeq proteins (2): NP_001303966, NP_659402* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat

Pfam: PF00515, PF13432

UniProt features (29 total): compositionally biased region 10, repeat 8, sequence variant 4, region of interest 3, splice variant 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEE8-F1	65.70	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, EFC_Q6, ZIC1_01, CYTAGCAAY_UNKNOWN, ATF_01, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, RFX1_01, MYB_Q6, TCANNTGAY_SREBP1_01, DODD_NASOPHARYNGEAL_CARCINOMA_DN, SREBP_Q3, chr9q34, ASH1L_TARGET_GENES, CIITA_TARGET_GENES, ELF2_TARGET_GENES

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

1198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC16	MDH1B	Q5I0G3	574
TTC16	TEX261	Q6UWH6	537
TTC16	OR4K5	Q8NGD3	529
TTC16	STON2	Q8WXE9	505
TTC16	SLC25A36	Q96CQ1	497
TTC16	SAP18	O00422	471
TTC16	FOXN3	O00409	458
TTC16	ZNF716	A6NP11	448
TTC16	BPIFB3	P59826	446
TTC16	TM4SF20	Q53R12	444
TTC16	YME1L1	Q96TA2	443
TTC16	OR12D2	P58182	424
TTC16	GPR108	Q9NPR9	417
TTC16	AMZ1	Q400G9	393
TTC16	SLC6A18	Q96N87	392

IntAct

7 interactions, top by confidence:

A	B	Type	Score
TTC16	MYH9	psi-mi:“MI:0915”(physical association)	0.400
TTC16	C1QBP	psi-mi:“MI:0915”(physical association)	0.400
GSK3A	TTC16	psi-mi:“MI:0915”(physical association)	0.370
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
TTC16	UBE2O	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): TTC16 (Proximity Label-MS), TTC16 (Affinity Capture-MS), TTC16 (Two-hybrid), TTC16 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), TTC16 (Cross-Linking-MS (XL-MS)), TTC16 (Affinity Capture-MS)

ESM2 similar proteins: A0A0J9YX94, A0A0J9YXQ4, A0A0J9YY54, A0A494C1R9, A1L443, A5D7L8, A6NDY0, A6NKD2, E9PGG2, F6SZT2, O19110, O75807, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0CW24, P0DV79, P17564, P59644, P78358, Q01534, Q0P5N2, Q15735, Q2KI51, Q587J8, Q5R5G8, Q5R6R8, Q5RFC2, Q5SV97, Q60465, Q6P752, Q86V59, Q8BSI6, Q8N9W4, Q8NAG6, Q8NEE8, Q8VD63, Q95LS7

Diamond homologs: Q8C1F5, Q8NEE8, Q95LZ5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	146
Likely benign	20
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3165 predictions. Top by Δscore:

Variant	Effect	Δscore
9:127717421:GCTG:G	donor_gain	1.0000
9:127717768:TACAG:T	donor_loss	1.0000
9:127717769:ACAG:A	donor_loss	1.0000
9:127717770:CAG:C	donor_loss	1.0000
9:127717771:AGGTG:A	donor_loss	1.0000
9:127717772:GG:G	donor_loss	1.0000
9:127717773:G:T	donor_loss	1.0000
9:127717774:T:G	donor_loss	1.0000
9:127720076:AG:A	acceptor_gain	1.0000
9:127720077:GG:G	acceptor_gain	1.0000
9:127720264:A:AG	acceptor_gain	1.0000
9:127720264:AGCAT:A	acceptor_gain	1.0000
9:127720265:G:GG	acceptor_gain	1.0000
9:127720265:GC:G	acceptor_gain	1.0000
9:127720265:GCAT:G	acceptor_gain	1.0000
9:127720265:GCATG:G	acceptor_gain	1.0000
9:127720280:T:TA	acceptor_gain	1.0000
9:127720289:A:G	acceptor_gain	1.0000
9:127720392:GAAG:G	donor_gain	1.0000
9:127720393:A:T	donor_gain	1.0000
9:127720396:GTAC:G	donor_loss	1.0000
9:127723345:G:GT	donor_gain	1.0000
9:127723345:G:T	donor_gain	1.0000
9:127723346:A:T	donor_gain	1.0000
9:127724105:C:CA	acceptor_gain	1.0000
9:127724105:C:G	acceptor_gain	1.0000
9:127724114:C:CA	acceptor_gain	1.0000
9:127724118:A:AG	acceptor_gain	1.0000
9:127724118:AG:A	acceptor_gain	1.0000
9:127724119:G:GT	acceptor_gain	1.0000

AlphaMissense

5728 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:127724359:G:C	R371P	0.996
9:127717650:G:C	A102P	0.994
9:127717699:T:C	L118P	0.994
9:127724789:C:A	A384D	0.994
9:127717687:C:A	A114D	0.993
9:127724260:C:A	A338D	0.993
9:127724362:G:A	G372D	0.993
9:127717648:G:C	R101P	0.990
9:127717675:A:G	D110G	0.990
9:127717686:G:C	A114P	0.990
9:127720275:T:G	C179W	0.990
9:127720078:G:A	G143R	0.989
9:127720078:G:C	G143R	0.989
9:127723141:T:C	L227P	0.989
9:127724308:T:C	L354P	0.989
9:127724361:G:C	G372R	0.989
9:127724758:T:C	C374R	0.989
9:127726328:G:C	R450P	0.989
9:127717697:C:A	N117K	0.988
9:127717697:C:G	N117K	0.988
9:127724121:G:C	G292R	0.988
9:127724134:G:C	R296P	0.988
9:127726318:G:C	A447P	0.988
9:127726363:G:C	D462H	0.988
9:127717380:G:C	A80P	0.987
9:127717656:G:C	A104P	0.987
9:127720273:T:C	C179R	0.987
9:127723233:G:C	A258P	0.987
9:127724122:G:A	G292D	0.987
9:127724362:G:T	G372V	0.987

dbSNP variants (sampled 300 via entrez): RS1000281861 (9:127716006 C>A,G,T), RS1000393803 (9:127718348 A>C), RS1000883430 (9:127722181 G>A), RS1000933978 (9:127730062 G>A), RS1001210299 (9:127726785 C>T), RS1001261246 (9:127726501 C>T), RS1001281095 (9:127730325 C>T), RS1001493059 (9:127717933 G>A), RS1001606731 (9:127714940 G>A,T), RS1002200321 (9:127718761 T>G), RS1002207872 (9:127725119 T>A,G), RS1002328335 (9:127729972 G>A), RS1002891588 (9:127719027 A>G), RS1003005628 (9:127721277 C>A), RS1003013694 (9:127727371 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): premature menopause (MONDO:0001119)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005024_4	Pursuit maintenance gain	4.000000e-07
GCST005024_44	Pursuit maintenance gain	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008594	Menopause, Premature	C12.050.351.500.056.630.250; C12.100.250.056.630.250; G08.686.157.500.500; G08.686.841.249.500.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
Diazinon	increases methylation	1
Paraoxon	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists