TTC6

Summary

TTC6 (tetratricopeptide repeat domain 6, HGNC:19739) is a protein-coding gene on chromosome 14q21.1, encoding Tetratricopeptide repeat protein 6 (Q86TZ1).

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_001310135

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19739
Approved symbol	TTC6
Name	tetratricopeptide repeat domain 6
Location	14q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000139865
Ensembl biotype	protein_coding
OMIM	620954
Entrez	319089

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000267368, ENST00000382320, ENST00000476979, ENST00000478811, ENST00000533625, ENST00000553443, ENST00000553887, ENST00000554555, ENST00000555921

RefSeq mRNA: 2 — MANE Select: NM_001310135 NM_001310135, NM_001368142

CCDS: CCDS91870, CCDS91871

Canonical transcript exons

ENST00000553443 — 33 exons

Exon	Start	End
ENSE00000940524	37827196	37827366
ENSE00001092424	37817578	37817651
ENSE00001092425	37826195	37826347
ENSE00001092426	37823747	37823957
ENSE00001294209	37812314	37812433
ENSE00001321617	37808733	37808846
ENSE00001337477	37804680	37804814
ENSE00001491737	37807320	37807460
ENSE00001491740	37806361	37806510
ENSE00001823872	37787468	37787637
ENSE00001833733	37753099	37753235
ENSE00001835782	37790717	37790837
ENSE00001910865	37842155	37842717
ENSE00001914200	37792264	37792414
ENSE00002215586	37682758	37682964
ENSE00002245012	37680151	37680261
ENSE00002300392	37622050	37623003
ENSE00002468189	37748939	37749401
ENSE00002488109	37606663	37606742
ENSE00002492601	37749714	37749843
ENSE00002499192	37595629	37596008
ENSE00002523216	37751053	37751225
ENSE00002526357	37696717	37696835
ENSE00003500896	37735921	37736010
ENSE00003532160	37796787	37796947
ENSE00003535797	37795270	37795352
ENSE00003548308	37841445	37841670
ENSE00003549828	37796294	37796370
ENSE00003586562	37714655	37714796
ENSE00003594966	37701332	37701526
ENSE00003668592	37737660	37737734
ENSE00003671658	37738776	37739155
ENSE00003693847	37724898	37725002

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 87.00.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0437 / max 34.3263, expressed in 241 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139322	0.5216	198
139323	0.4159	105
139324	0.0921	34
139325	0.0141	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	87.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.52	gold quality
sperm	CL:0000019	85.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.47	gold quality
prostate gland	UBERON:0002367	82.16	gold quality
right lobe of liver	UBERON:0001114	81.13	gold quality
cerebellar vermis	UBERON:0004720	80.85	silver quality
cardia of stomach	UBERON:0001162	79.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	78.90	gold quality
oocyte	CL:0000023	77.99	gold quality
bronchial epithelial cell	CL:0002328	74.85	gold quality
bronchus	UBERON:0002185	74.72	gold quality
nasal cavity mucosa	UBERON:0001826	74.11	gold quality
left testis	UBERON:0004533	73.66	gold quality
right testis	UBERON:0004534	73.19	gold quality
superior surface of tongue	UBERON:0007371	72.75	gold quality
testis	UBERON:0000473	72.65	gold quality
liver	UBERON:0002107	72.39	gold quality
nipple	UBERON:0002030	72.24	gold quality
saphenous vein	UBERON:0007318	72.12	gold quality
trachea	UBERON:0003126	71.95	gold quality
pericardium	UBERON:0002407	71.68	silver quality
minor salivary gland	UBERON:0001830	71.62	gold quality
ventral tegmental area	UBERON:0002691	71.47	silver quality
stomach	UBERON:0000945	71.29	gold quality
body of stomach	UBERON:0001161	71.03	gold quality
dorsal root ganglion	UBERON:0000044	70.94	silver quality
superior vestibular nucleus	UBERON:0007227	70.54	gold quality
subthalamic nucleus	UBERON:0001906	70.44	silver quality
inferior vagus X ganglion	UBERON:0005363	70.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	1821.78
E-HCAD-25	yes	8.50
E-ANND-3	yes	6.95
E-CURD-10	no	15.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting TTC6, 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-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-606	98.72	67.34	960
HSA-MIR-4277	98.34	67.17	1323
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-6813-3P	95.78	63.78	540
HSA-MIR-1468-5P	94.18	69.04	176

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc6	ENSDARG00000104125
mus_musculus	Ttc6	ENSMUSG00000046782
rattus_norvegicus	Ttc6	ENSRNOG00000022791

Paralogs (14): IFT88 (ENSG00000032742), TTC7A (ENSG00000068724), TMTC4 (ENSG00000125247), TMTC1 (ENSG00000133687), TMTC3 (ENSG00000139324), BBS4 (ENSG00000140463), TTC13 (ENSG00000143643), OGT (ENSG00000147162), CFAP70 (ENSG00000156042), TTC8 (ENSG00000165533), TTC7B (ENSG00000165914), TTC16 (ENSG00000167094), TMTC2 (ENSG00000179104), TTC34 (ENSG00000215912)

Protein

Protein identifiers

Tetratricopeptide repeat protein 6 — Q86TZ1 (reviewed: Q86TZ1)

All UniProt accessions (6): Q86TZ1, G3V3A5, G3V435, G5E9W5, H0YJ01, Q3SY87

Isoforms (2)

UniProt ID	Names	Canonical?
Q86TZ1-1	1	yes
Q86TZ1-2	2

RefSeq proteins (2): NP_001297064, NP_001355071 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR050498	Ycf3	Family

Pfam: PF00515, PF13181, PF13432

UniProt features (22 total): repeat 13, splice variant 4, sequence variant 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86TZ1-F1	91.96	0.78

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_DN, DODD_NASOPHARYNGEAL_CARCINOMA_DN, KUMAR_PATHOGEN_LOAD_BY_MACROPHAGES, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, IGLV5_37_TARGET_GENES, NFKBIA_TARGET_GENES, SNAI1_TARGET_GENES, SRSF9_TARGET_GENES, MIR5688, MIR495_3P, MIR3529_3P, MIR4666A_3P

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

0 interactions, top by confidence (×1000):

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TTC6	HERC1	psi-mi:“MI:0914”(association)	0.350

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: Q13217, Q27968, Q86TZ1, Q91YW3, Q9R0T3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

6655 predictions. Top by Δscore:

Variant	Effect	Δscore
14:37623001:G:GT	donor_gain	1.0000
14:37623001:G:T	donor_gain	1.0000
14:37623004:G:GG	donor_gain	1.0000
14:37696794:A:T	donor_gain	1.0000
14:37696836:G:GG	donor_gain	1.0000
14:37701324:T:A	acceptor_gain	1.0000
14:37701329:CAGA:C	acceptor_gain	1.0000
14:37701330:A:AG	acceptor_gain	1.0000
14:37701330:AGAA:A	acceptor_gain	1.0000
14:37701331:G:GG	acceptor_gain	1.0000
14:37701331:GA:G	acceptor_gain	1.0000
14:37701331:GAA:G	acceptor_gain	1.0000
14:37701331:GAAT:G	acceptor_gain	1.0000
14:37701331:GAATT:G	acceptor_gain	1.0000
14:37701522:GATAG:G	donor_gain	1.0000
14:37701523:A:G	donor_gain	1.0000
14:37701524:TAGG:T	donor_loss	1.0000
14:37701525:AG:A	donor_loss	1.0000
14:37701526:GGTA:G	donor_loss	1.0000
14:37701527:G:C	donor_loss	1.0000
14:37701527:G:GG	donor_gain	1.0000
14:37714793:GGAA:G	donor_gain	1.0000
14:37714794:G:GT	donor_gain	1.0000
14:37714794:G:T	donor_gain	1.0000
14:37714797:G:GG	donor_gain	1.0000
14:37724895:A:G	acceptor_gain	1.0000
14:37735920:GA:G	acceptor_gain	1.0000
14:37736617:GA:G	donor_gain	1.0000
14:37737734:GGTAT:G	donor_gain	1.0000
14:37749398:GAGA:G	donor_gain	1.0000

AlphaMissense

12480 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:37826282:G:C	A322P	0.995
14:37812387:G:C	R182P	0.994
14:37827227:G:C	R354P	0.994
14:37827286:G:C	A374P	0.993
14:37827229:G:T	G355W	0.992
14:37823830:G:C	R250P	0.991
14:37826281:A:C	R321S	0.990
14:37826281:A:T	R321S	0.990
14:37827230:G:A	G355E	0.990
14:37827328:G:C	A388P	0.987
14:37827332:G:A	G389E	0.987
14:37826216:G:C	A300P	0.986
14:37827229:G:A	G355R	0.986
14:37827229:G:C	G355R	0.986
14:37808811:G:C	A146P	0.985
14:37841445:G:C	A401P	0.985
14:37808810:A:C	R145S	0.984
14:37808810:A:T	R145S	0.984
14:37817636:C:A	A217D	0.984
14:37823766:G:C	A229P	0.984
14:37826295:T:C	L326P	0.984
14:37808812:C:A	A146E	0.983
14:37826280:G:C	R321T	0.983
14:37827265:G:C	A367P	0.983
14:37812386:C:A	R182S	0.982
14:37826318:G:C	A334P	0.982
14:37826283:C:A	A322D	0.981
14:37826319:C:A	A334E	0.979
14:37827331:G:A	G389R	0.978
14:37827331:G:C	G389R	0.978

dbSNP variants (sampled 300 via entrez): RS1000047670 (14:37825856 G>T), RS1000049253 (14:37708964 A>AT), RS1000059489 (14:37784546 G>A), RS1000086410 (14:37628964 A>G), RS1000091498 (14:37802727 T>C), RS1000093063 (14:37685700 T>G), RS1000095284 (14:37751298 A>C), RS1000103445 (14:37668043 G>A), RS1000131030 (14:37606166 A>G,T), RS1000137301 (14:37810161 T>C), RS1000150350 (14:37775998 A>C), RS1000166305 (14:37811824 T>C), RS1000170244 (14:37773169 C>A), RS1000183359 (14:37694993 A>T), RS1000185258 (14:37638484 A>C)

Disease associations

OMIM: gene MIM:620954 | disease phenotypes: MIM:249000

GenCC curated gene-disease

Mondo (1): Meckel syndrome (MONDO:0018921)

Orphanet (1): Meckel syndrome (Orphanet:564)

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002083_9	Self-reported allergy	5.000000e-08
GCST003262_606	Post bronchodilator FEV1	1.000000e-06
GCST003805_7	Diastolic blood pressure response to hydrochlorothiazide in hypertension	6.000000e-06
GCST003990_17	Allergy	4.000000e-10
GCST004781_22	Sulfasalazine-induced agranulocytosis	5.000000e-07
GCST005038_85	Allergic disease (asthma, hay fever or eczema)	8.000000e-09
GCST006409_26	Allergic rhinitis	6.000000e-09
GCST011464_2	Café-au-lait macule number in neurofibromatosis type1	8.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004314	forced expiratory volume
EFO:0006945	diastolic blood pressure change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs177852	TTC6		0.00	0

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Leflunomide	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Methapyrilene	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01401998	Not specified	RECRUITING	ARPKD Database Study