THEM6

Summary

THEM6 (thioesterase superfamily member 6, HGNC:29656) is a protein-coding gene on chromosome 8q24.3, encoding Protein THEM6 (Q8WUY1).

Predicted to be located in extracellular region.

Source: NCBI Gene 51337 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 34 total
• Druggable target: yes
• MANE Select transcript: NM_016647

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29656
Approved symbol	THEM6
Name	thioesterase superfamily member 6
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	DSCD75
Ensembl gene	ENSG00000130193
Ensembl biotype	protein_coding
Entrez	51337

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000336138, ENST00000518798, ENST00000520217, ENST00000866704, ENST00000866705, ENST00000866706

RefSeq mRNA: 2 — MANE Select: NM_016647 NM_001363000, NM_016647

CCDS: CCDS6386

Canonical transcript exons

ENST00000336138 — 2 exons

Exon	Start	End
ENSE00001355879	142735326	142736927
ENSE00001355886	142727223	142727859

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 90.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.6223 / max 243.1974, expressed in 1738 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
91364	15.4222	1670
91363	6.2001	1457

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	90.66	gold quality
mucosa of transverse colon	UBERON:0004991	90.40	gold quality
apex of heart	UBERON:0002098	87.37	gold quality
lower esophagus mucosa	UBERON:0035834	86.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.95	gold quality
right adrenal gland cortex	UBERON:0035827	85.88	gold quality
right frontal lobe	UBERON:0002810	85.71	gold quality
right adrenal gland	UBERON:0001233	85.36	gold quality
body of pancreas	UBERON:0001150	85.32	gold quality
left adrenal gland cortex	UBERON:0035825	85.13	gold quality
metanephros cortex	UBERON:0010533	85.10	gold quality
left adrenal gland	UBERON:0001234	84.90	gold quality
esophagus mucosa	UBERON:0002469	84.48	gold quality
prefrontal cortex	UBERON:0000451	84.28	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.70	gold quality
adrenal cortex	UBERON:0001235	83.64	gold quality
body of stomach	UBERON:0001161	83.35	gold quality
right uterine tube	UBERON:0001302	83.20	gold quality
adult mammalian kidney	UBERON:0000082	83.13	gold quality
heart left ventricle	UBERON:0002084	83.04	gold quality
anterior cingulate cortex	UBERON:0009835	82.98	gold quality
cingulate cortex	UBERON:0003027	82.90	gold quality
skin of leg	UBERON:0001511	82.80	gold quality
minor salivary gland	UBERON:0001830	82.56	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.50	gold quality
transverse colon	UBERON:0001157	82.37	gold quality
liver	UBERON:0002107	82.33	gold quality
cardiac ventricle	UBERON:0002082	82.27	gold quality
right lobe of thyroid gland	UBERON:0001119	82.16	gold quality
adrenal gland	UBERON:0002369	82.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting THEM6, 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-4650-5P	99.98	64.69	999
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-1301-3P	98.64	68.27	1071
HSA-MIR-5047	98.64	68.62	1035
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-4632-5P	97.82	65.38	1470
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-4286	97.20	64.37	1587
HSA-MIR-3616-3P	96.96	65.45	983

Literature-anchored findings (GeneRIF, showing 1)

• THEM6 is a prognostic biomarker for breast cancer and is associated with immune infiltration. (PMID:38081884)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	them6	ENSDARG00000100260
danio_rerio	THEM6	ENSDARG00000103914
mus_musculus	Them6	ENSMUSG00000056665
rattus_norvegicus	Them6	ENSRNOG00000005929
drosophila_melanogaster	CG4666	FBGN0029838
drosophila_melanogaster	CG4660	FBGN0029839

Protein

Protein identifiers

Protein THEM6 — Q8WUY1 (reviewed: Q8WUY1)

Alternative names: Mesenchymal stem cell protein DSCD75, Thioesterase superfamily member 6

All UniProt accessions (3): Q8WUY1, B4DWJ7, H0YAR9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the THEM6 family.

RefSeq proteins (2): NP_001349929, NP_057731* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029069	HotDog_dom_sf	Homologous_superfamily
IPR051490	THEM6_lcsJ_thioesterase	Family

Pfam: PF13279

UniProt features (5 total): signal peptide 1, chain 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WUY1-F1	94.92	0.96

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 199

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 61 (showing top): MARTORIATI_MDM4_TARGETS_FETAL_LIVER_UP, GRADE_COLON_AND_RECTAL_CANCER_UP, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON, GEORGES_TARGETS_OF_MIR192_AND_MIR215, chr8q24, ERBB2_UP.V1_UP, MEK_UP.V1_UP, PTEN_DN.V2_DN, RPS14_DN.V1_DN, STK33_NOMO_DN, FEV_TARGET_GENES, FOXD2_TARGET_GENES, PCGF1_TARGET_GENES, PHF21A_TARGET_GENES, SKIL_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	1

Protein interactions and networks

STRING

388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THEM6	FLYWCH2	Q96CP2	471
THEM6	TMEM200A	Q86VY9	459
THEM6	SYNGR4	O95473	454
THEM6	PROSER2	Q86WR7	436
THEM6	TMEM220	Q6QAJ8	430
THEM6	JRK	O75564	425
THEM6	SLC4A7	Q9Y6M7	403
THEM6	LYNX1	P0DP58	389
THEM6	ANKRD29	Q8N6D5	358
THEM6	NCKAP5L	Q9HCH0	348
THEM6	PLEKHG1	Q9ULL1	336
THEM6	UBXN2B	Q14CS0	323
THEM6	LETM1	O95202	320
THEM6	SEPTIN5	Q99719	315
THEM6	MID1IP1	Q9NPA3	314

IntAct

123 interactions, top by confidence:

A	B	Type	Score
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
P2RX4	FAM20B	psi-mi:“MI:0914”(association)	0.640
TEX28	TMCC2	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
TBC1D15	UBXN8	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
EVA1C	STK25	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
TMEM63A	AP3D1	psi-mi:“MI:0914”(association)	0.530
CHRNA4	FZD6	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
SLC6A8	ILVBL	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
ERBB2	NDUFA4	psi-mi:“MI:0914”(association)	0.530
ESR1		psi-mi:“MI:0914”(association)	0.460
FLT4	ILVBL	psi-mi:“MI:0914”(association)	0.420
Them6		psi-mi:“MI:0915”(physical association)	0.400
CFTR	SNHG32	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350

BioGRID (180): THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), THEM6 (Proximity Label-MS), THEM6 (Proximity Label-MS), THEM6 (Proximity Label-MS), THEM6 (Proximity Label-MS), THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS), THEM6 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L8, A1A4Q9, A1L134, A2BDX3, A5YM72, A6H707, B0BLZ5, B0JZP3, G3MZR2, O43292, O60831, O89109, P70295, Q11130, Q2TBP5, Q2V8X7, Q32NY4, Q3UPE3, Q4R4E4, Q4R4I9, Q5XIE1, Q5ZIW1, Q66HR0, Q6IQX7, Q6NRK8, Q6P2H8, Q7L1V2, Q80ZW2, Q86VU5, Q8IZ52, Q8N3Y3, Q8NE01, Q8NF37, Q8NI29, Q8TAC2, Q8TCD5, Q8TD43, Q8WUY1, Q92839, Q96DE0

Diamond homologs: A6H707, B0BLZ5, B0JZP3, Q5XIE1, Q6NRK8, Q80ZW2, Q8WUY1, Q9W440

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 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
Synthesis of PC	5	18.4×	9e-04
R-HSA-425393	10	11.7×	3e-06
SLC-mediated transmembrane transport	13	6.9×	8e-06

GO biological processes:

GO term	Partners	Fold	FDR
phosphatidylcholine biosynthetic process	5	28.1×	4e-04
cell volume homeostasis	5	21.0×	9e-04
amino acid transport	6	13.1×	1e-03
transmembrane transport	11	13.0×	8e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

459 predictions. Top by Δscore:

Variant	Effect	Δscore
8:142727858:GG:G	donor_gain	1.0000
8:142727859:GG:G	donor_gain	1.0000
8:142735314:T:TA	acceptor_gain	1.0000
8:142735323:CA:C	acceptor_loss	1.0000
8:142735324:A:AG	acceptor_gain	1.0000
8:142735324:AGGT:A	acceptor_gain	1.0000
8:142735324:AGGTG:A	acceptor_gain	1.0000
8:142735325:G:GT	acceptor_gain	1.0000
8:142735325:GGT:G	acceptor_gain	1.0000
8:142735325:GGTG:G	acceptor_gain	1.0000
8:142735325:GGTGG:G	acceptor_gain	1.0000
8:142727855:GCAGG:G	donor_gain	0.9900
8:142727856:CAGGG:C	donor_loss	0.9900
8:142727859:GGTGA:G	donor_loss	0.9900
8:142727860:G:C	donor_loss	0.9900
8:142727860:G:GG	donor_gain	0.9900
8:142727861:T:A	donor_loss	0.9900
8:142735321:T:TA	acceptor_gain	0.9900
8:142735324:AG:A	acceptor_gain	0.9900
8:142735325:GG:G	acceptor_gain	0.9900
8:142727862:GAGCG:G	donor_loss	0.9800
8:142734386:G:GT	donor_gain	0.9800
8:142734324:GC:G	donor_gain	0.9000
8:142728654:A:T	donor_gain	0.8900
8:142734357:G:T	donor_gain	0.8800
8:142727860:G:T	donor_gain	0.8600
8:142727863:AGCGG:A	donor_loss	0.8600
8:142727857:AGG:A	donor_gain	0.8500
8:142727858:GGG:G	donor_gain	0.8500
8:142729102:C:G	donor_gain	0.8500

AlphaMissense

1303 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:142727756:T:C	F137S	0.988
8:142727543:A:T	N66I	0.984
8:142735383:A:C	S191R	0.979
8:142735385:C:A	S191R	0.979
8:142735385:C:G	S191R	0.979
8:142727695:T:C	F117L	0.977
8:142727697:C:A	F117L	0.977
8:142727697:C:G	F117L	0.977
8:142727755:T:C	F137L	0.977
8:142727757:T:A	F137L	0.977
8:142727757:T:G	F137L	0.977
8:142727544:C:A	N66K	0.976
8:142727544:C:G	N66K	0.976
8:142727724:G:C	W126C	0.976
8:142727724:G:T	W126C	0.976
8:142735362:T:A	W184R	0.976
8:142735362:T:C	W184R	0.976
8:142727722:T:A	W126R	0.975
8:142727722:T:C	W126R	0.975
8:142727542:A:T	N66Y	0.967
8:142735364:G:C	W184C	0.967
8:142735364:G:T	W184C	0.967
8:142727547:C:A	N67K	0.963
8:142727547:C:G	N67K	0.963
8:142727776:T:C	F144L	0.960
8:142727778:C:A	F144L	0.960
8:142727778:C:G	F144L	0.960
8:142727560:C:A	R72S	0.959
8:142727519:A:T	D58V	0.958
8:142727726:A:T	D127V	0.958

dbSNP variants (sampled 300 via entrez): RS1000052565 (8:142735498 A>T), RS1000972215 (8:142726722 C>A,T), RS1001456886 (8:142734490 G>A), RS1001690054 (8:142728264 T>A), RS1001886653 (8:142734863 G>A,T), RS1002180336 (8:142734548 C>A,T), RS1002246538 (8:142727189 C>A,G,T), RS1002637905 (8:142734205 C>T), RS1002961370 (8:142729229 T>G), RS1003160011 (8:142733428 T>C), RS1003188701 (8:142735565 C>T), RS1003593859 (8:142735782 G>A), RS1003705318 (8:142728007 C>A,G,T), RS1004379049 (8:142732573 T>C), RS1004569023 (8:142734458 A>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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066289 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.21	Kd	62.14	nM	CHEMBL5653589
7.21	ED50	62.14	nM	CHEMBL5653589
5.77	Kd	1696	nM	CHEMBL3752910
5.77	ED50	1696	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149581: Binding affinity to human THEM6 incubated for 45 mins by Kinobead based pull down assay	kd	0.0621	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149581: Binding affinity to human THEM6 incubated for 45 mins by Kinobead based pull down assay	kd	1.6959	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	3
bisphenol A	affects expression, increases expression	2
Copper	affects binding, increases expression, decreases expression	2
Estradiol	affects cotreatment, decreases expression, affects binding, increases reaction	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
bisphenol F	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ferrous chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Bortezomib	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Coumestrol	increases expression, affects cotreatment	1
Demecolcine	decreases expression	1
Disulfiram	affects binding, increases expression	1
Formaldehyde	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652623	Binding	Binding affinity to human THEM6 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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