THEM4

Summary

THEM4 (thioesterase superfamily member 4, HGNC:17947) is a protein-coding gene on chromosome 1q21.3, encoding Acyl-coenzyme A thioesterase THEM4 (Q5T1C6). Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays a role in mitochondrial fatty acid metabolism.

Protein kinase B (PKB) is a major downstream target of receptor tyrosine kinases that signal via phosphatidylinositol 3-kinase. Upon cell stimulation, PKB is translocated to the plasma membrane, where it is phosphorylated in the C-terminal regulatory domain. The protein encoded by this gene negatively regulates PKB activity by inhibiting phosphorylation. Transcription of this gene is commonly downregulated in glioblastomas.

Source: NCBI Gene 117145 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_053055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17947
Approved symbol	THEM4
Name	thioesterase superfamily member 4
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	CTMP
Ensembl gene	ENSG00000159445
Ensembl biotype	protein_coding
OMIM	606388
Entrez	117145

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000368814, ENST00000471464, ENST00000477437, ENST00000483207, ENST00000489410, ENST00000865233

RefSeq mRNA: 1 — MANE Select: NM_053055 NM_053055

CCDS: CCDS1006

Canonical transcript exons

ENST00000368814 — 6 exons

Exon	Start	End
ENSE00001072430	151895008	151895194
ENSE00001380288	151870866	151874928
ENSE00001870114	151909360	151909511
ENSE00003510898	151888273	151888383
ENSE00003539807	151889214	151889373
ENSE00003645293	151877001	151877125

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 92.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1958 / max 219.0301, expressed in 1774 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14477	6.7705	1670
14475	3.5124	1524
14476	2.6367	1306
14478	1.0979	680
14474	1.0170	711
14473	0.6108	384
14479	0.5506	299

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	92.76	gold quality
pancreatic ductal cell	CL:0002079	91.78	gold quality
epithelial cell of pancreas	CL:0000083	90.73	gold quality
right adrenal gland	UBERON:0001233	90.61	gold quality
right adrenal gland cortex	UBERON:0035827	90.48	gold quality
metanephros cortex	UBERON:0010533	90.29	gold quality
left adrenal gland	UBERON:0001234	89.79	gold quality
left adrenal gland cortex	UBERON:0035825	89.77	gold quality
left ventricle myocardium	UBERON:0006566	89.76	silver quality
adrenal cortex	UBERON:0001235	89.64	gold quality
cardiac muscle of right atrium	UBERON:0003379	89.60	silver quality
body of pancreas	UBERON:0001150	89.41	gold quality
buccal mucosa cell	CL:0002336	88.99	gold quality
gastrocnemius	UBERON:0001388	88.94	gold quality
adrenal gland	UBERON:0002369	88.80	gold quality
muscle of leg	UBERON:0001383	88.61	gold quality
cerebellar hemisphere	UBERON:0002245	88.35	gold quality
right lobe of thyroid gland	UBERON:0001119	88.29	gold quality
cerebellar cortex	UBERON:0002129	88.26	gold quality
right lobe of liver	UBERON:0001114	88.19	gold quality
apex of heart	UBERON:0002098	88.19	gold quality
adult mammalian kidney	UBERON:0000082	88.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.12	gold quality
pituitary gland	UBERON:0000007	88.01	gold quality
right atrium auricular region	UBERON:0006631	87.86	gold quality
cardiac atrium	UBERON:0002081	87.85	gold quality
endometrium	UBERON:0001295	87.51	gold quality
adenohypophysis	UBERON:0002196	87.47	gold quality
heart left ventricle	UBERON:0002084	87.43	gold quality
thyroid gland	UBERON:0002046	87.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

113 targeting THEM4, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-12124	99.68	69.17	2700
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-7150	99.62	66.80	1322

Literature-anchored findings (GeneRIF, showing 10)

• CTMP induces translocation of Akt to the membrane and thereby increases the level of Akt phosphorylation. As a result, CTMP enhances various cellular activities that are principally mediated by the PI3-kinase/Akt pathway. (PMID:17615157)
• Proper maturation of CTMP is essential for its pro-apoptotic function. CTMP delays PKB phosphorylation following cell death induction, suggesting that CTMP regulates apoptosis via inhibition of PKB. (PMID:19168129)
• Phosphorylation on Ser37/Ser38 of CTMP is important for the prevention of mitochondrial localization of CTMP, eventually leading to cell death by binding to heat shock protein 70. (PMID:19604401)
• Data show low or moderate methylation was found in seven selected genes BAD, BBC3, CAV1, CDK2AP1, NPM1, PRKCDBP and THEM4. (PMID:19679565)
• Suggest that CTMP may therefore play a critical role in mitochondrial-mediated apoptosis in lung cancer cells. (PMID:22200884)
• Results find that head and neck squamous cell carcinoma (HNSCC) tumor tissues and cell lines had high levels of CTMP expression. These data suggest that CTMP functions as a positive regulator of Akt and facilitates HNSCC invasion such as LN metastasis by regulating EMT in a Snail-dependent manner indicating the oncogenic activity of CTMP in HNSCC, and its expression is an independent predictor of clinical prognosis. (PMID:27328758)
• CTMP expression may be considered as a prognostic biomarker in HER2-enriched breast cancer and high expression may indicate a utility for AKT-inhibition in these patients. (PMID:27447863)
• Enolase-phosphatase 1 acts as an oncogenic driver in glioma. (PMID:32654229)
• Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer. (PMID:36400965)
• Overview of carboxyl-terminal modulator protein 1 and its importance in various metabolic regulations (Review). (PMID:38994770)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	them4	ENSDARG00000061621
mus_musculus	Them4	ENSMUSG00000028145
rattus_norvegicus	Them4	ENSRNOG00000020829

Paralogs (1): THEM5 (ENSG00000196407)

Protein

Protein identifiers

Acyl-coenzyme A thioesterase THEM4 — Q5T1C6 (reviewed: Q5T1C6)

Alternative names: Carboxyl-terminal modulator protein, Thioesterase superfamily member 4

All UniProt accessions (3): Q5T1C6, E9PLJ7, F6XC58

UniProt curated annotations — full annotation on UniProt →

Function. Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays a role in mitochondrial fatty acid metabolism. Plays a role in the apoptotic process, possibly via its regulation of AKT1 activity. According to PubMed:11598301, inhibits AKT1 phosphorylation and activity. According to PubMed:17615157, enhances AKT1 activity by favoring its phosphorylation and translocation to plasma membrane.

Subunit / interactions. Homodimer and homotetramer. Interacts with AKT1 in the cytosol.

Subcellular location. Cell membrane. Cell projection. Ruffle membrane. Cytoplasm. Mitochondrion. Mitochondrion inner membrane. Mitochondrion intermembrane space.

Tissue specificity. Expressed predominantly in skeletal muscle, testis, uterus, brain and kidney. Down-regulated in glioblastoma or glioma compared to non-neoplastic brain due to promoter hypermethylation.

Post-translational modifications. Phosphorylated.

Similarity. Belongs to the THEM4/THEM5 thioesterase family.

RefSeq proteins (1): NP_444283* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006683	Thioestr_dom	Domain
IPR029069	HotDog_dom_sf	Homologous_superfamily
IPR052365	THEM4/THEM5_acyl-CoA_thioest	Family

Pfam: PF03061

Enzyme classification (BRENDA):

• EC 3.1.2.20 — acyl-CoA hydrolase (BRENDA: 47 organisms, 273 substrates, 173 inhibitors, 271 Km, 184 kcat entries)

Substrate kinetics (BRENDA)

77 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
HEXADECANOYL-COA	—	25
PALMITOYL-COA	0.0024–33	14
MYRISTOYL-COA	0.0025–0.0228	13
3-HYDROXYPHENYLACETYL-COA	0.0037–0.9	11
OLEOYL-COA	0.0014–0.0274	10
ARACHIDONOYL-COA	0.0004–0.02	9
DODECANOYL-COA	0.0018–0.325	9
LAUROYL-COA	0.0035–0.0275	9
PALMITOLEOYL-COA	0.0014–0.058	9
2,3-DIHYDROXYBENZOYL-COA	0.0375–1.42	7
ACETYL-COA	0.0047–0.29	7
SALICYLYL-COA	0.162–0.729	7
DECANOYL-COA	0.0027–19.78	6
LINOLEOYL-COA	0.0014–0.31	6
STEAROYL-COA	0.0015–0.0279	6

Catalyzed reactions (Rhea), 7 shown:

• hexadecanoyl-CoA + H2O = hexadecanoate + CoA + H(+) (RHEA:16645)
• dodecanoyl-CoA + H2O = dodecanoate + CoA + H(+) (RHEA:30135)
• octanoyl-CoA + H2O = octanoate + CoA + H(+) (RHEA:30143)
• decanoyl-CoA + H2O = decanoate + CoA + H(+) (RHEA:40059)
• tetradecanoyl-CoA + H2O = tetradecanoate + CoA + H(+) (RHEA:40119)
• (9Z)-octadecenoyl-CoA + H2O = (9Z)-octadecenoate + CoA + H(+) (RHEA:40139)
• (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + CoA + H(+) (RHEA:40151)

UniProt features (40 total): mutagenesis site 8, strand 8, modified residue 7, helix 5, turn 4, binding site 3, sequence variant 2, transit peptide 1, chain 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4AE8	X-RAY DIFFRACTION	1.59
4GAH	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T1C6-F1	84.09	0.67

Functional residue map

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

Catalytic / active sites (1): 161 (proton donor/acceptor)

Ligand- & substrate-binding residues (3): 183; 185; 206–207

Post-translational modifications (7): 74, 98, 207, 37, 38, 55, 66

Mutagenesis-validated functional residues (8):

Position	Phenotype
37–38	abolishes import into the mitochondria.
37	abolishes cleavage of mitochondrial transit peptide.
152	strongly reduced enzyme activity.
161	nearly abolishes enzyme activity. strongly reduced affinity for myristoyl-coa.
177	strongly reduced enzyme activity.
183	no effect on enzyme activity.
206	reduces enzyme activity.
207	slightly reduced enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

25 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-165158	Activation of AKT2
R-HSA-199418	Negative regulation of the PI3K/AKT network
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-5218920	VEGFR2 mediated vascular permeability
R-HSA-77289	Mitochondrial Fatty Acid Beta-Oxidation
R-HSA-109704	PI3K Cascade
R-HSA-112399	IRS-mediated signalling
R-HSA-1280218	Adaptive Immune System
R-HSA-1430728	Metabolism
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-2404192	Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-2428924	IGF1R signaling cascade
R-HSA-2428928	IRS-related events triggered by IGF1R
R-HSA-388841	Regulation of T cell activation by CD28 family
R-HSA-389356	Co-stimulation by CD28
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-556833	Metabolism of lipids
R-HSA-74751	Insulin receptor signalling cascade
R-HSA-74752	Signaling by Insulin receptor
R-HSA-8978868	Fatty acid metabolism
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 134 (showing top): REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_RUFFLE, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, REACTOME_CO_STIMULATION_BY_CD28, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOCC_MITOCHONDRIAL_ENVELOPE, LIAO_METASTASIS, REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING, GOBP_LIPID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, REACTOME_MITOCHONDRIAL_FATTY_ACID_BETA_OXIDATION

GO Biological Process (6): fatty acid metabolic process (GO:0006631), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), regulation of mitochondrial membrane permeability involved in apoptotic process (GO:1902108), lipid metabolic process (GO:0006629), apoptotic process (GO:0006915), small molecule metabolic process (GO:0044281)

GO Molecular Function (3): long-chain fatty acyl-CoA hydrolase activity (GO:0052816), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (10): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), plasma membrane (GO:0005886), ruffle membrane (GO:0032587), cytoplasm (GO:0005737), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	2
Intracellular signaling by second messengers	1
PI3K Cascade	1
PIP3 activates AKT signaling	1
Co-stimulation by CD28	1
VEGFA-VEGFR2 Pathway	1
Fatty acid metabolism	1
IRS-mediated signalling	1
IRS-related events triggered by IGF1R	1
Insulin receptor signalling cascade	1
Immune System	1
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)	1
IGF1R signaling cascade	1
Adaptive Immune System	1
Regulation of T cell activation by CD28 family	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
lipid metabolic process	1
monocarboxylic acid metabolic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
apoptotic process	1
apoptotic mitochondrial changes	1
regulation of mitochondrial membrane permeability	1
primary metabolic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
metabolic process	1
fatty acyl-CoA hydrolase activity	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle envelope lumen	1
mitochondrion	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
ruffle	1
cell projection membrane	1
leading edge membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
THEM4	AKT1	P31749	692
THEM4	MAPKAP1	Q9BPZ7	533
THEM4	PTEN	P60484	506
THEM4	RICTOR	Q6R327	504
THEM4	ACOT13	Q9NPJ3	473
THEM4	GSK3B	P49841	454
THEM4	AKT2	P31751	439
THEM4	PDPK1	O15530	425
THEM4	NOPCHAP1	Q8N5I9	425
THEM4	PAK4	O96013	423
THEM4	RAB14	P35287	423
THEM4	ECH1	Q13011	402
THEM4	ACOT11	Q8WXI4	400
THEM4	PIK3CG	P48736	398
THEM4	LETM1	O95202	396

IntAct

46 interactions, top by confidence:

A	B	Type	Score
THEM4	AKT1	psi-mi:“MI:0915”(physical association)	0.730
AKT1	THEM4	psi-mi:“MI:0914”(association)	0.730
AKT1	THEM4	psi-mi:“MI:0915”(physical association)	0.730
FGFR3	THEM4	psi-mi:“MI:0915”(physical association)	0.560
THEM4	HRAS	psi-mi:“MI:0915”(physical association)	0.560
THEM4	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
VIM	THEM4	psi-mi:“MI:0915”(physical association)	0.560
	THEM4	psi-mi:“MI:0915”(physical association)	0.560
SPRED1	THEM4	psi-mi:“MI:0915”(physical association)	0.560
ENOPH1	THEM4	psi-mi:“MI:0914”(association)	0.530
ULBP1	IGLL5	psi-mi:“MI:0914”(association)	0.530
POMC	AMD1	psi-mi:“MI:0914”(association)	0.530
THEM4	KIAA0391	psi-mi:“MI:0914”(association)	0.350
CLDN18	ACTBL2	psi-mi:“MI:0914”(association)	0.350
THEM5	PRORP	psi-mi:“MI:0914”(association)	0.350
MRPL49	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): GPT2 (Affinity Capture-MS), GSTT2 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), ALAS1 (Affinity Capture-MS), PDSS2 (Affinity Capture-MS), DBT (Affinity Capture-MS), THEM4 (Affinity Capture-MS), FPGS (Affinity Capture-MS), SIRT5 (Affinity Capture-MS), KIAA0391 (Affinity Capture-MS), CARD9 (Affinity Capture-MS), THEM4 (Affinity Capture-MS), KLC2 (Affinity Capture-MS), TOP3A (Affinity Capture-MS), THEM4 (Affinity Capture-RNA)

ESM2 similar proteins: A2AIG8, A6NKP2, E9PTA2, O00764, O14734, O15315, O35331, O35719, O43502, O54783, O55229, O94759, P33124, P58137, Q3SWX2, Q3U129, Q4PS77, Q5I0K3, Q5RE34, Q5RJZ1, Q5T1C6, Q5ZM83, Q6AYT9, Q6DC64, Q6GV29, Q6NUN0, Q8BGA8, Q8CIW5, Q8IZ69, Q8K183, Q8K297, Q8N0X4, Q8R2J9, Q8R4N0, Q8TCT0, Q8VCE6, Q8VHK0, Q8VHQ9, Q8WXI4, Q91WC3

Diamond homologs: A1A4L1, Q3UUI3, Q566R0, Q5T1C6, Q6GLK2, Q8N1Q8, Q9CQJ0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
THEM4	down-regulates	AKT1	binding
THEM4	down-regulates	AKT	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

825 predictions. Top by Δscore:

Variant	Effect	Δscore
1:151876999:A:AC	donor_gain	1.0000
1:151877000:C:CC	donor_gain	1.0000
1:151889212:A:AC	donor_gain	1.0000
1:151889212:AC:A	donor_gain	1.0000
1:151889213:C:CC	donor_gain	1.0000
1:151889213:CC:C	donor_gain	1.0000
1:151889374:C:CC	acceptor_gain	1.0000
1:151877000:CTTGT:C	donor_gain	0.9900
1:151877121:TAGGT:T	acceptor_gain	0.9900
1:151877126:C:CC	acceptor_gain	0.9900
1:151889208:TCTTA:T	donor_loss	0.9900
1:151889209:CTTA:C	donor_loss	0.9900
1:151889210:TTA:T	donor_loss	0.9900
1:151889211:TA:T	donor_loss	0.9900
1:151889212:ACCCA:A	donor_loss	0.9900
1:151889213:C:CT	donor_loss	0.9900
1:151889226:T:TA	donor_gain	0.9900
1:151889369:TGGGT:T	acceptor_gain	0.9900
1:151889370:GGGT:G	acceptor_gain	0.9900
1:151889372:GT:G	acceptor_gain	0.9900
1:151889373:TC:T	acceptor_loss	0.9900
1:151889374:CTAT:C	acceptor_loss	0.9900
1:151889375:T:C	acceptor_loss	0.9900
1:151889376:A:C	acceptor_gain	0.9900
1:151894958:G:C	donor_gain	0.9900
1:151895193:CT:C	acceptor_gain	0.9900
1:151895195:C:CC	acceptor_gain	0.9900
1:151909354:ACTC:A	donor_loss	0.9900
1:151909355:CT:C	donor_loss	0.9900
1:151909356:TCA:T	donor_loss	0.9900

AlphaMissense

1588 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151877089:G:C	S198R	0.973
1:151877089:G:T	S198R	0.973
1:151877091:T:G	S198R	0.973
1:151889282:G:C	F126L	0.972
1:151889282:G:T	F126L	0.972
1:151889284:A:G	F126L	0.972
1:151889297:A:C	F121L	0.967
1:151889297:A:T	F121L	0.967
1:151889299:A:G	F121L	0.967
1:151877007:C:G	A226P	0.965
1:151874927:G:C	S228R	0.964
1:151874927:G:T	S228R	0.964
1:151877001:T:G	S228R	0.964
1:151895137:A:G	W53R	0.959
1:151895137:A:T	W53R	0.959
1:151888291:A:G	L180P	0.958
1:151895077:A:G	W73R	0.958
1:151895077:A:T	W73R	0.958
1:151877042:A:T	V214D	0.944
1:151889283:A:G	F126S	0.942
1:151889254:A:G	C136R	0.939
1:151889224:C:G	G146R	0.934
1:151889224:C:T	G146R	0.934
1:151888360:G:T	A157E	0.933
1:151888347:A:C	D161E	0.931
1:151888347:A:T	D161E	0.931
1:151889252:G:C	C136W	0.929
1:151889298:A:G	F121S	0.928
1:151895135:C:A	W53C	0.928
1:151895135:C:G	W53C	0.928

dbSNP variants (sampled 300 via entrez): RS1000015132 (1:151903138 T>A,C), RS1000027438 (1:151896362 G>A), RS1000082836 (1:151908099 T>C,G), RS1000199996 (1:151909882 T>C), RS1000203750 (1:151876298 G>A,C), RS1000231115 (1:151883136 G>A), RS1000348261 (1:151879454 T>C), RS1000371944 (1:151873038 G>A), RS1000590339 (1:151905336 C>T), RS1000625455 (1:151897955 A>C), RS1000664629 (1:151891419 C>T), RS1000707350 (1:151874410 T>C), RS1000712721 (1:151883548 T>C), RS1000782022 (1:151874135 C>A), RS1000991450 (1:151871527 A>G)

Disease associations

OMIM: gene MIM:606388 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002388_10	Serum metabolite levels	3.000000e-13
GCST004751_22	Serum uric acid levels in response to allopurinol in gout	2.000000e-06
GCST005648_34	Serum metabolite concentrations in chronic kidney disease	4.000000e-09
GCST005649_5	Urinary metabolite ratios in chronic kidney disease	1.000000e-12
GCST006448_1	Eye movement in schizophrenia (horizontal position gain)	7.000000e-09
GCST006457_1	Eye movement (horizontal position gain)	7.000000e-09
GCST008916_82	Asthma	5.000000e-27
GCST008916_88	Asthma	1.000000e-25
GCST012020_237	Serum metabolite levels	1.000000e-11
GCST012020_238	Serum metabolite levels	1.000000e-15
GCST012020_239	Serum metabolite levels	1.000000e-30
GCST012020_35	Serum metabolite levels	3.000000e-14
GCST012020_557	Serum metabolite levels	2.000000e-16
GCST012021_30	Serum metabolite levels	2.000000e-16

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004761	uric acid measurement
EFO:0005116	urinary metabolite measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
monomethylarsonous acid	decreases expression, increases methylation, affects acetylation, affects methylation	3
sodium arsenite	affects acetylation, affects methylation, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
methylmercuric chloride	decreases expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	decreases expression, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
Irinotecan	decreases expression	1
Sunitinib	decreases expression	1
Vorinostat	affects cotreatment, increases expression	1
Glyphosate	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases methylation, decreases expression	1
Carbamazepine	affects expression	1
Chelating Agents	affects binding, decreases expression	1
Copper	affects binding, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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