TTC39B

Summary

TTC39B (tetratricopeptide repeat domain 39B, HGNC:23704) is a protein-coding gene on chromosome 9p22.3, encoding Tetratricopeptide repeat protein 39B (Q5VTQ0). Regulates high density lipoprotein (HDL) cholesterol metabolism by promoting the ubiquitination and degradation of the oxysterols receptors LXR (NR1H2 and NR1H3).

Predicted to be involved in several processes, including cholesterol homeostasis; negative regulation of cholesterol storage; and regulation of cholesterol efflux.

Source: NCBI Gene 158219 — RefSeq curated summary.

At a glance

• GWAS associations: 37
• Clinical variants (ClinVar): 168 total
• MANE Select transcript: NM_152574

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23704
Approved symbol	TTC39B
Name	tetratricopeptide repeat domain 39B
Location	9p22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ33868
Ensembl gene	ENSG00000155158
Ensembl biotype	protein_coding
OMIM	613574
Entrez	158219

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297615, ENST00000380850, ENST00000380853, ENST00000505732, ENST00000506891, ENST00000507285, ENST00000507993, ENST00000512701, ENST00000582994, ENST00000866788, ENST00000911740

RefSeq mRNA: 5 — MANE Select: NM_152574 NM_001168339, NM_001168340, NM_001168341, NM_001168342, NM_152574

CCDS: CCDS55294, CCDS55295, CCDS55296, CCDS6477

Canonical transcript exons

ENST00000512701 — 20 exons

Exon	Start	End
ENSE00001222424	15185280	15185406
ENSE00001222486	15163622	15172109
ENSE00003473076	15225917	15226012
ENSE00003473967	15203823	15203890
ENSE00003476338	15182307	15182415
ENSE00003555570	15192590	15192695
ENSE00003557952	15175019	15175135
ENSE00003568531	15211266	15211397
ENSE00003582495	15191190	15191255
ENSE00003582758	15189725	15189792
ENSE00003588723	15186944	15187035
ENSE00003594197	15214139	15214249
ENSE00003598900	15267914	15267948
ENSE00003602069	15199861	15199925
ENSE00003603832	15187971	15188132
ENSE00003609859	15190554	15190662
ENSE00003647045	15189574	15189633
ENSE00003684623	15177697	15177814
ENSE00003693398	15210088	15210164
ENSE00003963366	15307084	15307216

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 90.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.7134 / max 225.1090, expressed in 1642 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100070	7.4173	1624
100066	0.9429	130
100069	0.9053	455
205433	0.2295	107
100064	0.1698	60
100065	0.0485	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	90.83	gold quality
buccal mucosa cell	CL:0002336	88.79	gold quality
gingival epithelium	UBERON:0001949	85.11	silver quality
skin of leg	UBERON:0001511	84.96	gold quality
skin of abdomen	UBERON:0001416	84.93	gold quality
upper arm skin	UBERON:0004263	84.73	gold quality
oviduct epithelium	UBERON:0004804	84.71	gold quality
zone of skin	UBERON:0000014	84.58	gold quality
esophagus squamous epithelium	UBERON:0006920	84.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.25	gold quality
islet of Langerhans	UBERON:0000006	83.77	gold quality
upper leg skin	UBERON:0004262	83.50	gold quality
calcaneal tendon	UBERON:0003701	83.20	gold quality
pancreatic ductal cell	CL:0002079	83.09	gold quality
gall bladder	UBERON:0002110	83.02	gold quality
sperm	CL:0000019	82.97	silver quality
rectum	UBERON:0001052	82.66	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.56	gold quality
granulocyte	CL:0000094	82.52	gold quality
cerebellar vermis	UBERON:0004720	81.96	gold quality
epithelium of nasopharynx	UBERON:0001951	80.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.79	gold quality
esophagus mucosa	UBERON:0002469	80.62	gold quality
gingiva	UBERON:0001828	80.55	silver quality
endothelial cell	CL:0000115	80.20	silver quality
monocyte	CL:0000576	80.10	gold quality
leukocyte	CL:0000738	80.08	gold quality
primary visual cortex	UBERON:0002436	80.08	gold quality
lower esophagus mucosa	UBERON:0035834	80.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting TTC39B, 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-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-374A-5P	99.90	71.34	2923

Literature-anchored findings (GeneRIF, showing 2)

• Two new polymorphisms associated with gall bladder disease and obesity in women have been identified, GCKR rs1260326, and TTC39B rs686030. (PMID:25920552)
• association of rs519664[T] in TTC39B on 9p22 with endometriosis, is reported. (PMID:27453397)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ttc39b	ENSDARG00000100962
mus_musculus	Ttc39b	ENSMUSG00000038172
rattus_norvegicus	Ttc39b	ENSRNOG00000042603
caenorhabditis_elegans		WBGENE00016314

Paralogs (2): TTC39A (ENSG00000085831), TTC39C (ENSG00000168234)

Protein

Protein identifiers

Tetratricopeptide repeat protein 39B — Q5VTQ0 (reviewed: Q5VTQ0)

All UniProt accessions (5): Q5VTQ0, A0A8V8N5K5, A0A8V8NCV2, A0A8V8PNE1, H0YAJ6

UniProt curated annotations — full annotation on UniProt →

Function. Regulates high density lipoprotein (HDL) cholesterol metabolism by promoting the ubiquitination and degradation of the oxysterols receptors LXR (NR1H2 and NR1H3).

Similarity. Belongs to the TTC39 family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q5VTQ0-1	1	yes
Q5VTQ0-2	2
Q5VTQ0-3	3
Q5VTQ0-4	4
Q5VTQ0-5	5
Q5VTQ0-6	6
Q5VTQ0-7	7

RefSeq proteins (5): NP_001161811, NP_001161812, NP_001161813, NP_001161814, NP_689787* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019412	IML2/TPR_39	Family
IPR019734	TPR_rpt	Repeat

Pfam: PF10300, PF13181

UniProt features (17 total): splice variant 7, sequence conflict 5, repeat 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VTQ0-F1	81.88	0.67

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 232 (showing top): GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_STEROL_HOMEOSTASIS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_REGULATION_OF_CHOLESTEROL_EFFLUX, AREB6_01, GOLDRATH_ANTIGEN_RESPONSE, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, TERAMOTO_OPN_TARGETS_CLUSTER_4, GOBP_LIPID_HOMEOSTASIS, GOBP_CHOLESTEROL_EFFLUX, CEBP_Q2, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (5): lipid metabolic process (GO:0006629), regulation of cholesterol efflux (GO:0010874), negative regulation of cholesterol storage (GO:0010887), cholesterol homeostasis (GO:0042632), regulation of cholesterol metabolic process (GO:0090181)

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
primary metabolic process	1
regulation of cholesterol transport	1
cholesterol efflux	1
cholesterol storage	1
regulation of cholesterol storage	1
negative regulation of lipid storage	1
sterol homeostasis	1
cholesterol metabolic process	1
regulation of steroid metabolic process	1
regulation of small molecule metabolic process	1
binding	1

Protein interactions and networks

STRING

563 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TTC39B	GALNT2	Q10471	583
TTC39B	PPP1R3B	Q86XI6	547
TTC39B	CCDC171	Q6TFL3	516
TTC39B	VEZT	Q9HBM0	458
TTC39B	GNG5	P30670	453
TTC39B	SLC35G5	Q96KT7	445
TTC39B	LIPG	Q9Y5X9	430
TTC39B	SNAPC3	Q92966	424
TTC39B	CETP	P11597	420
TTC39B	ABCG8	Q9H221	416
TTC39B	PLTP	P55058	390
TTC39B	CLEC19A	Q6UXS0	377
TTC39B	LCAT	P04180	376
TTC39B	MMAB	Q96EY8	376
TTC39B	XKR6	Q5GH73	370

IntAct

16 interactions, top by confidence:

A	B	Type	Score
VAPB	TTC39B	psi-mi:“MI:0915”(physical association)	0.740
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
VAPA	FAM83G	psi-mi:“MI:0914”(association)	0.640
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
	AGPS	psi-mi:“MI:0914”(association)	0.350
STX17	A2ML1	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
TTC39B	HSPD1	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
	MYO1C	psi-mi:“MI:0914”(association)	0.350
VAPB	TTC39B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): TTC39B (Two-hybrid), HSPD1 (Affinity Capture-MS), MTIF2 (Affinity Capture-MS), PREPL (Affinity Capture-MS), FDXR (Affinity Capture-MS), TTC39B (Affinity Capture-MS), TTC39B (Affinity Capture-MS), TTC39B (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), FDXR (Affinity Capture-MS), TTC39B (Affinity Capture-MS), TTC39B (Two-hybrid), TTC39B (Affinity Capture-MS), TTC39B (Affinity Capture-RNA), FDXR (Affinity Capture-MS)

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: A1A5Y5, A2ACP1, D3ZC96, Q09266, Q28D40, Q28DB0, Q5SRH9, Q5VTQ0, Q5XHH9, Q8BYY4, Q95LT8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	126
Likely benign	12
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

4582 predictions. Top by Δscore:

Variant	Effect	Δscore
9:15172004:T:TA	donor_gain	1.0000
9:15175014:CTTA:C	donor_loss	1.0000
9:15175016:TA:T	donor_loss	1.0000
9:15175017:A:AC	donor_gain	1.0000
9:15175017:AC:A	donor_gain	1.0000
9:15175018:C:CT	donor_gain	1.0000
9:15175018:CC:C	donor_gain	1.0000
9:15175018:CCTT:C	donor_gain	1.0000
9:15175018:CCTTG:C	donor_gain	1.0000
9:15175131:TTTCA:T	acceptor_gain	1.0000
9:15175132:TTCA:T	acceptor_gain	1.0000
9:15175132:TTCAC:T	acceptor_gain	1.0000
9:15175133:TCA:T	acceptor_gain	1.0000
9:15175133:TCACT:T	acceptor_gain	1.0000
9:15175134:CA:C	acceptor_gain	1.0000
9:15175134:CAC:C	acceptor_gain	1.0000
9:15175136:C:CC	acceptor_gain	1.0000
9:15175136:CTGAA:C	acceptor_loss	1.0000
9:15175137:T:C	acceptor_loss	1.0000
9:15175145:C:CT	acceptor_gain	1.0000
9:15175146:A:T	acceptor_gain	1.0000
9:15177691:TCTTA:T	donor_loss	1.0000
9:15177692:CTTAC:C	donor_loss	1.0000
9:15177693:TTACC:T	donor_loss	1.0000
9:15177694:TACC:T	donor_loss	1.0000
9:15177813:AT:A	acceptor_gain	1.0000
9:15177815:C:CC	acceptor_gain	1.0000
9:15177816:T:C	acceptor_gain	1.0000
9:15177816:T:TC	acceptor_gain	1.0000
9:15177822:C:CT	acceptor_gain	1.0000

AlphaMissense

4466 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:15203854:A:G	L243P	1.000
9:15210158:C:A	R207S	1.000
9:15210158:C:G	R207S	1.000
9:15172074:A:G	L665P	0.999
9:15177728:C:G	A604P	0.999
9:15177754:A:G	L595P	0.999
9:15177763:C:T	G592E	0.999
9:15185347:G:T	A516D	0.999
9:15185374:C:T	G507E	0.999
9:15187979:A:G	W463R	0.999
9:15187979:A:T	W463R	0.999
9:15191203:A:G	F328S	0.999
9:15191206:C:T	G327E	0.999
9:15191239:G:A	P316L	0.999
9:15191239:G:C	P316R	0.999
9:15191239:G:T	P316Q	0.999
9:15199875:A:C	S270R	0.999
9:15199875:A:T	S270R	0.999
9:15199877:T:G	S270R	0.999
9:15199903:A:T	I261N	0.999
9:15203836:A:G	L249P	0.999
9:15203843:C:G	A247P	0.999
9:15203851:A:G	L244P	0.999
9:15203863:G:T	A240D	0.999
9:15203864:C:G	A240P	0.999
9:15203868:A:C	C238W	0.999
9:15203878:G:T	A235D	0.999
9:15203879:C:G	A235P	0.999
9:15210159:C:A	R207M	0.999
9:15210159:C:G	R207T	0.999

dbSNP variants (sampled 300 via entrez): RS1000013287 (9:15211046 TC>T,TCC), RS1000018578 (9:15216672 A>C,G), RS1000030042 (9:15216437 G>A), RS1000044345 (9:15284457 T>A,C), RS1000061952 (9:15199936 T>A,C,G), RS1000067448 (9:15214509 C>A,T), RS1000146415 (9:15214716 T>C), RS1000150541 (9:15196659 A>G), RS1000160485 (9:15196975 C>G), RS1000164805 (9:15274584 T>C), RS1000180188 (9:15266185 C>T), RS1000197475 (9:15229973 T>A,C), RS1000209963 (9:15236300 C>G), RS1000231715 (9:15303133 A>C,G), RS1000243795 (9:15244630 T>C)

Disease associations

OMIM: gene MIM:613574 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

37 associations (top):

Study	Trait	p-value
GCST000290_7	HDL cholesterol	3.000000e-10
GCST000755_42	HDL cholesterol	1.000000e-13
GCST000760_4	Cholesterol, total	3.000000e-09
GCST000769_4	Calcium levels	6.000000e-06
GCST000805_9	HDL cholesterol	7.000000e-09
GCST001647_6	Bipolar disorder	2.000000e-06
GCST002221_23	Cholesterol, total	1.000000e-13
GCST002223_60	HDL cholesterol	1.000000e-19
GCST002899_27	HDL cholesterol	5.000000e-10
GCST003523_12	Coenzyme Q10 levels	1.000000e-06
GCST004232_49	HDL cholesterol levels	1.000000e-16
GCST004235_33	Total cholesterol levels	2.000000e-12
GCST004860_145	Alcoholic chronic pancreatitis	4.000000e-06
GCST005196_165	Coronary artery disease	3.000000e-06
GCST006611_72	HDL cholesterol	1.000000e-27
GCST007209_26	Gallstone disease	2.000000e-20
GCST008070_19	HDL cholesterol levels	9.000000e-12
GCST008070_78	HDL cholesterol levels	7.000000e-11
GCST008075_15	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-38
GCST008075_150	HDL cholesterol levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-41
GCST008083_103	Triglyceride levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-06
GCST008084_234	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	8.000000e-38
GCST008084_29	HDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	2.000000e-37
GCST008085_131	HDL cholesterol levels in current drinkers	1.000000e-18
GCST008085_57	HDL cholesterol levels in current drinkers	6.000000e-21
GCST008162_94	Hip circumference	5.000000e-07
GCST009367_84	HDL cholesterol levels x short total sleep time interaction (2df test)	3.000000e-11
GCST010241_152	Apolipoprotein A1 levels	8.000000e-89
GCST010242_508	HDL cholesterol levels	1.000000e-73
GCST010243_115	Apolipoprotein B levels	7.000000e-12

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004838	calcium measurement
EFO:0007836	coenzyme Q10 measurement
EFO:0004329	alcohol drinking
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0007874	gut microbiome measurement
EFO:1002009	macular telangiectasia type 2
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression	4
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
Cyclosporine	increases expression	3
sodium arsenite	increases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, decreases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
perfluoro-n-nonanoic 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
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Benzoates	increases expression	1
Cadmium	increases abundance, increases expression	1
Coumestrol	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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