TRPC4AP

Summary

TRPC4AP (transient receptor potential cation channel subfamily C member 4 associated protein, HGNC:16181) is a protein-coding gene on chromosome 20q11.22, encoding Short transient receptor potential channel 4-associated protein (Q8TEL6). Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control.

Enables phosphatase binding activity and ubiquitin-like ligase-substrate adaptor activity. Involved in protein ubiquitination and ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in cytosol. Part of Cul4A-RING E3 ubiquitin ligase complex. Is active in Cul4-RING E3 ubiquitin ligase complex.

Source: NCBI Gene 26133 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypothyroidism (Limited, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 108 total
• MANE Select transcript: NM_015638

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16181
Approved symbol	TRPC4AP
Name	transient receptor potential cation channel subfamily C member 4 associated protein
Location	20q11.22
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP727M231, DKFZp586C1223, dJ756N5.2, TRRP4AP, PPP1R158
Ensembl gene	ENSG00000100991
Ensembl biotype	protein_coding
OMIM	608430
Entrez	26133

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 36 protein_coding

ENST00000252015, ENST00000451813, ENST00000888645, ENST00000888646, ENST00000888647, ENST00000888648, ENST00000888649, ENST00000888650, ENST00000888651, ENST00000888652, ENST00000888653, ENST00000888654, ENST00000888655, ENST00000888656, ENST00000888657, ENST00000937639, ENST00000937640, ENST00000937641, ENST00000937642, ENST00000937643, ENST00000937644, ENST00000937645, ENST00000937646, ENST00000937647, ENST00000937648, ENST00000937649, ENST00000937650, ENST00000970988, ENST00000970989, ENST00000970990, ENST00000970991, ENST00000970992, ENST00000970993, ENST00000970994, ENST00000970995, ENST00000970996

RefSeq mRNA: 2 — MANE Select: NM_015638 NM_015638, NM_199368

CCDS: CCDS13246, CCDS46591

Canonical transcript exons

ENST00000252015 — 19 exons

Exon	Start	End
ENSE00000661537	35003410	35003616
ENSE00000661538	35004458	35004570
ENSE00000661540	35006435	35006575
ENSE00000661541	35007550	35007640
ENSE00000661542	35008664	35008747
ENSE00000661544	35016008	35016139
ENSE00000860172	35005695	35005803
ENSE00000860173	35010187	35010288
ENSE00000860174	35013008	35013066
ENSE00000860175	35021190	35021356
ENSE00001615365	35044505	35044712
ENSE00001628826	35035123	35035308
ENSE00001634131	35078046	35078174
ENSE00001649831	35049866	35049994
ENSE00001680428	35057514	35057571
ENSE00001730198	35054976	35055031
ENSE00001776753	35069296	35069412
ENSE00001817074	35002404	35003283
ENSE00002254384	35092614	35092807

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 96.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 89.3182 / max 1665.9787, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187016	86.7356	1828
187017	1.4327	965
187018	0.5811	331
209091	0.5688	323

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.07	gold quality
right adrenal gland cortex	UBERON:0035827	95.94	gold quality
adenohypophysis	UBERON:0002196	95.86	gold quality
right adrenal gland	UBERON:0001233	95.79	gold quality
mucosa of stomach	UBERON:0001199	95.78	gold quality
body of pancreas	UBERON:0001150	95.76	gold quality
left adrenal gland	UBERON:0001234	95.60	gold quality
stromal cell of endometrium	CL:0002255	95.59	gold quality
left adrenal gland cortex	UBERON:0035825	95.49	gold quality
gastrocnemius	UBERON:0001388	95.30	gold quality
upper lobe of left lung	UBERON:0008952	95.26	gold quality
body of stomach	UBERON:0001161	95.22	gold quality
right lung	UBERON:0002167	95.22	gold quality
right lobe of thyroid gland	UBERON:0001119	95.19	gold quality
pituitary gland	UBERON:0000007	94.96	gold quality
adrenal cortex	UBERON:0001235	94.96	gold quality
left lobe of thyroid gland	UBERON:0001120	94.76	gold quality
muscle of leg	UBERON:0001383	94.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.65	gold quality
endocervix	UBERON:0000458	94.59	gold quality
skin of leg	UBERON:0001511	94.57	gold quality
apex of heart	UBERON:0002098	94.56	gold quality
upper lobe of lung	UBERON:0008948	94.54	gold quality
minor salivary gland	UBERON:0001830	94.52	gold quality
metanephros cortex	UBERON:0010533	94.51	gold quality
nerve	UBERON:0001021	94.46	gold quality
tibial nerve	UBERON:0001323	94.46	gold quality
adrenal gland	UBERON:0002369	94.35	gold quality
ectocervix	UBERON:0012249	94.31	gold quality
omental fat pad	UBERON:0010414	94.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

53 targeting TRPC4AP, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-3199	99.17	65.19	696
HSA-MIR-8052	99.17	65.01	719
HSA-MIR-4742-5P	98.89	68.41	1542

Literature-anchored findings (GeneRIF, showing 7)

• results suggest that TRPC4AP is involved with the disease in these late-onset Alzheimer’s families (PMID:18449908)
• The latent classification method of analysis showed that the TRPC4AP H1 haplotype was characteristic of Alzheimer’s patients, with ages-of-onset between 66 and 80 years. (PMID:19059308)
• These findings suggest that TNF-R1, TRUSS, and TRPC4 augment Ca(2+) loading of endoplasmic reticulum Ca(2+) stores in the context of m1AchR stimulation (PMID:20458742)
• TRPC4AP/TRUSS binds specifically to the Myc C terminus and promotes its ubiquitination and destruction through the recognition of evolutionarily conserved domains in the Myc N terminus (PMID:20551172)
• TRUSS is a novel substrate of E3 ligase Skp2. (PMID:26038816)
• Hepatocyte TRUSS promotes pathological stimuli-induced non alcoholic fatty liver disease and metabolic disorders, through activation of NF-kappaB by promoting ubiquitination and degradation of IkappaBalpha (PMID:29704259)
• Identification of Transient Receptor Potential Channel 4-Associated Protein as a Novel Candidate Gene Causing Congenital Primary Hypothyroidism. (PMID:32428920)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	trpc4apa	ENSDARG00000018840
danio_rerio	trpc4apb	ENSDARG00000020647
mus_musculus	Trpc4ap	ENSMUSG00000038324
rattus_norvegicus	Trpc4ap	ENSRNOG00000019152

Protein

Protein identifiers

Short transient receptor potential channel 4-associated protein — Q8TEL6 (reviewed: Q8TEL6)

Alternative names: Protein TAP1, TNF-receptor ubiquitous scaffolding/signaling protein

All UniProt accessions (2): Q8TEL6, B4E0Q1

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control. The DCX(TRPC4AP) complex specifically mediates the polyubiquitination and subsequent degradation of MYC as part of the DesCEND (destruction via C-end degrons) pathway. The DesCEND (destruction via C-end degrons) pathway recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The DCX(TRPC4AP) complex specifically recognizes proteins with an arginine at the minus 3 position (R-3 motif) at the C-terminus, such as MYC, leading to their ubiquitination and degradation. Also participates in the activation of NFKB1 in response to ligation of TNFRSF1A, possibly by linking TNFRSF1A to the IKK signalosome. Involved in JNK activation via its interaction with TRAF2. Also involved in elevation of endoplasmic reticulum Ca(2+) storage reduction in response to CHRM1.

Subunit / interactions. Component of the DCX(TRPC4AP) E3 ubiquitin ligase complex, at least composed of CUL4A, DDB1, TRPC4AP/TRUSS and RBX1. Interacts with MYC. Constitutively associated with TNFRSF1A. Directly interacts with TRADD, TRAF2, CHUK, IKBKB and IKBKG. Interacts with TRPC1, TRPC4 and TRPC5. (Microbial infection) Interacts with Hepatitis B virus (HBV) protein X; leading to prevent ubiquitination of TRPC4AP by SKP2.

Subcellular location. Cytoplasm. Perinuclear region.

Post-translational modifications. Phosphorylated by GSK3B; phosphorylation is required for ubiquitination. Ubiquitinated by a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase containing SKP2, leading to its degradation. Phosphorylation by GSK3B is required for ubiquitination.

Pathway. Protein modification; protein ubiquitination.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TEL6-1	1	yes
Q8TEL6-2	2
Q8TEL6-3	3

RefSeq proteins (2): NP_056453, NP_955400 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016024	ARM-type_fold	Homologous_superfamily
IPR022162	TRPC4AP	Family

Pfam: PF12463

UniProt features (6 total): splice variant 2, initiator methionine 1, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TEL6-F1	82.81	0.59

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): 2

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3295583	TRP channels

MSigDB gene sets: 202 (showing top): MODULE_52, GOBP_EPITHELIUM_DEVELOPMENT, NIKOLSKY_BREAST_CANCER_20Q11_AMPLICON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AATGGAG_MIR136, GOBP_MONOATOMIC_CATION_TRANSPORT, MODULE_66, GOBP_ANATOMICAL_STRUCTURE_MATURATION, TGACATY_UNKNOWN, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_MOLTING_CYCLE, HIF1_Q3, GOBP_EPIDERMIS_DEVELOPMENT, MODULE_88, RYTTCCTG_ETS2_B

GO Biological Process (5): ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), hair follicle maturation (GO:0048820), calcium ion transmembrane transport (GO:0070588), ubiquitin-dependent protein catabolic process via the C-end degron rule pathway (GO:0140627)

GO Molecular Function (4): calcium channel activity (GO:0005262), phosphatase binding (GO:0019902), ubiquitin-like ligase-substrate adaptor activity (GO:1990756), protein binding (GO:0005515)

GO Cellular Component (6): cytosol (GO:0005829), plasma membrane (GO:0005886), Cul4A-RING E3 ubiquitin ligase complex (GO:0031464), perinuclear region of cytoplasm (GO:0048471), Cul4-RING E3 ubiquitin ligase complex (GO:0080008), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Stimuli-sensing channels	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
hair follicle development	1
hair cycle process	1
anatomical structure maturation	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
enzyme binding	1
enzyme-substrate adaptor activity	1
binding	1
membrane	1
cell periphery	1
Cul4-RING E3 ubiquitin ligase complex	1
cullin-RING ubiquitin ligase complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1082 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRPC4AP	DDB1	Q16531	856
TRPC4AP	TNFRSF1A	P19438	686
TRPC4AP	CUL4A	Q13619	575
TRPC4AP	EDEM2	Q9BV94	575
TRPC4AP	MYCN	P04198	553
TRPC4AP	MYH7B	A7E2Y1	533
TRPC4AP	CUL4B	Q13620	497
TRPC4AP	FBXO28	Q9NVF7	474
TRPC4AP	ERGIC3	Q9Y282	471
TRPC4AP	TRADD	Q15628	449
TRPC4AP	SLA2	Q9H6Q3	420
TRPC4AP	SERINC3	Q13530	407
TRPC4AP	CAPRIN2	Q6IMN6	397
TRPC4AP	RNF169	Q8NCN4	393
TRPC4AP	NDRG3	Q9UGV2	388

IntAct

67 interactions, top by confidence:

A	B	Type	Score
CUL4B	COPS2	psi-mi:“MI:0914”(association)	0.790
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
TRPC4AP	CUL4A	psi-mi:“MI:0914”(association)	0.730
CUL4A	COPS2	psi-mi:“MI:0914”(association)	0.640
TRPC4AP	PPP1CA	psi-mi:“MI:0915”(physical association)	0.540
PPP1CA	TRPC4AP	psi-mi:“MI:0407”(direct interaction)	0.540
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
ODAPH	TCAF2	psi-mi:“MI:0914”(association)	0.530
TRPC4AP	SMCHD1	psi-mi:“MI:0914”(association)	0.530
GPS1	PXDNL	psi-mi:“MI:0914”(association)	0.530
IGFBP6	TCAF2	psi-mi:“MI:0914”(association)	0.530
NPPA	VGF	psi-mi:“MI:0914”(association)	0.530
EPB41L5	SETD1A	psi-mi:“MI:0914”(association)	0.530
CCDC6	LZTS3	psi-mi:“MI:0914”(association)	0.530
TRIM32	TRPC4AP	psi-mi:“MI:0914”(association)	0.510
Ddb1	PHGDH	psi-mi:“MI:0915”(physical association)	0.400
SDR9C7	TRPC4AP	psi-mi:“MI:0915”(physical association)	0.400
IRX1	TRPC4AP	psi-mi:“MI:0915”(physical association)	0.400
TRAF2	TRPC4AP	psi-mi:“MI:0915”(physical association)	0.400
M	TRPC4AP	psi-mi:“MI:0915”(physical association)	0.370
TRPC4AP	CHMP4C	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (158): TRPC4AP (Affinity Capture-MS), SKP2 (Affinity Capture-Western), TRPC4AP (Affinity Capture-Western), MYC (Affinity Capture-Western), DDB1 (Affinity Capture-Western), TRPC4AP (Affinity Capture-MS), TRPC4AP (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), CUL4B (Affinity Capture-MS), CUL4A (Affinity Capture-MS), NCOA1 (Affinity Capture-MS), DDB1 (Affinity Capture-MS), TRPC4AP (Affinity Capture-MS), HERC1 (Affinity Capture-MS)

ESM2 similar proteins: A1A535, A2AIV2, A2RRP1, A8XSV3, D3YVL2, F1QJX5, F1QN74, Q09263, Q0KK59, Q14D04, Q19317, Q3UHQ6, Q3URV1, Q3V129, Q571H0, Q5JWR5, Q5PQS3, Q5RHR6, Q5SPP5, Q5TYW4, Q5U430, Q5WNI9, Q5ZLS8, Q61QK6, Q620W3, Q642P2, Q69YN4, Q69ZR2, Q6GN08, Q6TNU3, Q6ZQ18, Q6ZT12, Q7Z3E5, Q86VV8, Q8BL99, Q8GY23, Q8H0T4, Q8IGJ0, Q8K2A7, Q8R4Y8

Diamond homologs: Q8TEL6, Q9JLV2

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TRPC4AP	“down-regulates quantity by destabilization”	MYC	binding
TRPC4AP	“up-regulates activity”	Cullin4-RBX1-DDB1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
DNA Damage Recognition in GG-NER	7	38.4×	2e-07
Formation of TC-NER Pre-Incision Complex	7	28.5×	8e-07
Neddylation	8	7.3×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
nuclear membrane reassembly	5	71.8×	8e-07
late endosome to lysosome transport	5	71.8×	8e-07
viral budding via host ESCRT complex	5	58.1×	2e-06
multivesicular body sorting pathway	5	58.1×	2e-06
midbody abscission	5	53.1×	2e-06
regulation of mitotic spindle assembly	5	53.1×	2e-06
plasma membrane repair	5	42.1×	7e-06
nucleus organization	5	40.7×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

6301 predictions. Top by Δscore:

Variant	Effect	Δscore
20:34995332:CCA:C	acceptor_loss	1.0000
20:34995333:CA:C	acceptor_loss	1.0000
20:34995334:A:AG	acceptor_gain	1.0000
20:34995334:AG:A	acceptor_gain	1.0000
20:34995335:G:GG	acceptor_gain	1.0000
20:34995335:GG:G	acceptor_gain	1.0000
20:34995335:GGA:G	acceptor_gain	1.0000
20:34995335:GGAGC:G	acceptor_gain	1.0000
20:34995576:AAGGT:A	donor_loss	1.0000
20:34995577:AGGT:A	donor_loss	1.0000
20:34995578:GG:G	donor_loss	1.0000
20:34995579:G:GG	donor_loss	1.0000
20:34996519:GGAC:G	donor_gain	1.0000
20:34996520:GAC:G	donor_gain	1.0000
20:34996520:GACG:G	donor_gain	1.0000
20:34996523:G:GG	donor_gain	1.0000
20:34996608:T:A	acceptor_gain	1.0000
20:34996608:TGCA:T	acceptor_loss	1.0000
20:34996609:GCA:G	acceptor_loss	1.0000
20:34996610:CA:C	acceptor_loss	1.0000
20:34996611:A:AG	acceptor_gain	1.0000
20:34996611:AGCT:A	acceptor_gain	1.0000
20:34996611:AGCTG:A	acceptor_gain	1.0000
20:34996612:G:A	acceptor_loss	1.0000
20:34996612:G:GT	acceptor_gain	1.0000
20:34996612:GC:G	acceptor_gain	1.0000
20:34996612:GCT:G	acceptor_gain	1.0000
20:34996612:GCTG:G	acceptor_gain	1.0000
20:34996612:GCTGG:G	acceptor_gain	1.0000
20:34996755:AGAA:A	donor_gain	1.0000

AlphaMissense

5256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:35003257:C:A	W761C	1.000
20:35003257:C:G	W761C	1.000
20:35003259:A:G	W761R	1.000
20:35003259:A:T	W761R	1.000
20:35003266:G:C	F758L	1.000
20:35003266:G:T	F758L	1.000
20:35003268:A:G	F758L	1.000
20:35003417:A:G	L750P	1.000
20:35003417:A:T	L750Q	1.000
20:35003430:C:G	D746H	1.000
20:35003448:A:G	Y740H	1.000
20:35003451:G:C	H739D	1.000
20:35003458:C:A	W736C	1.000
20:35003458:C:G	W736C	1.000
20:35003460:A:G	W736R	1.000
20:35003460:A:T	W736R	1.000
20:35003461:G:C	F735L	1.000
20:35003461:G:T	F735L	1.000
20:35003462:A:G	F735S	1.000
20:35003463:A:G	F735L	1.000
20:35003468:A:G	L733P	1.000
20:35003471:A:G	L732P	1.000
20:35003588:A:G	L693P	1.000
20:35003590:G:C	S692R	1.000
20:35003590:G:T	S692R	1.000
20:35003592:T:G	S692R	1.000
20:35003594:G:A	T691I	1.000
20:35003596:G:C	N690K	1.000
20:35003596:G:T	N690K	1.000
20:35003600:A:G	L689P	1.000

dbSNP variants (sampled 300 via entrez): RS1000009485 (20:35026360 G>A), RS1000096363 (20:35017145 G>A), RS1000101864 (20:35074893 G>A,C), RS1000117125 (20:35078958 C>G,T), RS1000121826 (20:35033039 T>C), RS1000133228 (20:35075147 G>A,C), RS1000164941 (20:35063201 T>C), RS1000271808 (20:35072077 C>T), RS1000284947 (20:35022769 C>T), RS1000310558 (20:35041905 T>A), RS1000311202 (20:35062806 T>C), RS1000321760 (20:35007258 G>A), RS1000340559 (20:35062412 A>G), RS1000340640 (20:35022982 G>A), RS1000382208 (20:35066007 A>G)

Disease associations

OMIM: gene MIM:608430 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hypothyroidism	Limited	Autosomal dominant

Mondo (1): hypothyroidism (MONDO:0005420)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001573_2	Prothrombin time	5.000000e-13
GCST005956_31	Waist-to-hip ratio adjusted for BMI	8.000000e-08
GCST005958_16	Waist-to-hip ratio adjusted for BMI (age >50)	6.000000e-06
GCST005962_40	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	3.000000e-08
GCST006979_540	Heel bone mineral density	2.000000e-09
GCST010142_10	Fish- and plant-related diet	8.000000e-12
GCST010242_24	HDL cholesterol levels	1.000000e-18
GCST90013410_67	Basal cell carcinoma	1.000000e-33
GCST90020028_1519	Hip circumference adjusted for BMI	4.000000e-08
GCST90020028_1520	Hip circumference adjusted for BMI	3.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0008390	prothrombin time measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density
EFO:0008111	diet measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007037	Hypothyroidism	C19.874.482

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, affects expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	affects methylation	1
Sodium Selenite	increases expression	1

Cellosaurus cell lines

18 cell lines: 18 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0179	BT-474	Cancer cell line	Female
CVCL_4V65	BT474-5FU[r]	Cancer cell line	Female
CVCL_4Y08	BT-474/CMV-Luc	Cancer cell line	Female
CVCL_A2GH	LR-BT474	Cancer cell line	Female
CVCL_A4AK	BT-474 Tam2	Cancer cell line	Female
CVCL_A4CL	BT-474 Ecadherin EmGFP	Cancer cell line	Female
CVCL_AQ07	BT-474 Clone 5	Cancer cell line	Female
CVCL_AR86	BT-474 Tam1	Cancer cell line	Female
CVCL_AR96	BT-474 EEI	Cancer cell line	Female
CVCL_C9CU	BT-474-Luc2	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001730	PHASE4	COMPLETED	Study of Radioiodine (131-I) Uptake Following Administration of Thyrogen and Hypothyroid States During Thyroid Hormone Withdrawal.
NCT00111735	PHASE4	UNKNOWN	Thyroxine Titration Study
NCT00206375	PHASE4	TERMINATED	Growth Hormone and GnRH Agonist in Adolescents With Acquired Hypothyroidism
NCT00565864	PHASE4	COMPLETED	Neurocognitive and Metabolic Effects of Mild Hypothyroidism
NCT01379170	PHASE4	UNKNOWN	Thyroid Study Type 2 Diabetes Mellitus (T2DM)
NCT01536678	PHASE4	COMPLETED	Bioequivalence of Two Levothyroxine Tablet Formulations in Healthy Indian Volunteers
NCT01647750	PHASE4	COMPLETED	Study of Optimal Replacement of Thyroxine in the Elderly
NCT01769157	PHASE4	COMPLETED	Effects of L-carnitine on Hypothyroidism
NCT01831869	PHASE4	UNKNOWN	Effect of L-Thyroxine on Lipid Profiles and Atherosclerosis in Subclinical Hypothyroidism
NCT01848171	PHASE4	UNKNOWN	Effects of L-thyroxine Replacement on Serum Lipid and Atherosclerosis in Hypothyroidism
NCT01921452	PHASE4	COMPLETED	Study to Verify Clinical Utility of Point-of-Care (POC) Thyroid Stimulating Hormone (TSH) Test Kits as Compared to Third Generation TSH Test Kit
NCT02280330	PHASE4	COMPLETED	Iodine Status of Preschoolers Given Micronutrient Powder for 6 Months
NCT02512978	PHASE4	UNKNOWN	Thyroid Hormone Replacement for Hypothyroidism and Acute Myocardial Infarction(ThyroHeart-AMI)
NCT02577367	PHASE4	WITHDRAWN	Mean Percentage of Levothyroxine Dosage Increase in Patients With Hypothyroidism Started on Enteral Feeding
NCT02917863	PHASE4	UNKNOWN	Randomized Crossover Trial for the Evaluation of the Possible Effects in the Intestine of Two Different Pharmaceutical Forms of L - Thyroxine in Patients With Primary Acquired Hypothyroidism
NCT03342001	PHASE4	COMPLETED	Hypothyroidism Treated With Calcitonin
NCT03631771	PHASE4	WITHDRAWN	Pediatric Risk of Hypothyroidism With Iodinated Contrast Media
NCT03779906	PHASE4	TERMINATED	Thyroid Function of Pediatric Subjects Following Isovue® Administration
NCT04747275	PHASE4	TERMINATED	Use of Liquid Stable Levothyroxine in Trisomy 21 Pediatric Patients
NCT04878614	PHASE4	TERMINATED	Comparison of Levothyroxine Formulation in Hypothyroid Patients With Enteral Feeding
NCT05247476	PHASE4	UNKNOWN	Type 2 Deiodinase Gene Polymorphism and the Treatment of Hypothyroidism Caused by Thyroidectomy in Thyroid Cancer Patients.
NCT06073665	PHASE4	RECRUITING	Dosing of LT4 in Older Individuals
NCT06096454	PHASE4	UNKNOWN	Effect of Life Style Modification and Metformin on Hypothyroidism With Insulin Resistance
NCT01204359	PHASE3	UNKNOWN	The Prospective Study of Standard Treatment of Graves Disease Iodine 131 and Prevention of Adverse Reactions
NCT01800617	PHASE2	COMPLETED	A Study of T3 Therapy in Patients With Hypothyroidism
NCT01916304	PHASE2	COMPLETED	Study of Dose Adjustment From Levothyroxine to a New Levothyroxine Sodium Test Formulation
NCT03627611	PHASE2	COMPLETED	Identification of Non-responders to Levothyroxine Therapy
NCT04124705	PHASE2	COMPLETED	A Study of Armour® Thyroid Compared to Synthetic T4 (Levothyroxine) in Previously Hypothyroid Participants
NCT04782856	PHASE2	COMPLETED	Energy Metabolism in Thyroidectomized Patients
NCT05412979	PHASE2	COMPLETED	A Study Evaluating the Safety and Efficacy of Hormone Replacement Therapy With ST-1891 Compared to Levothyroxine in Patients With Primary Hypothyroidism
NCT05712421	PHASE2	COMPLETED	A Study Evaluation the Safety and Efficacy of Hormone Replacement Therapy With North Star Compared to Levothyroxine in Patients With Primary Hypothyroidism
NCT05733078	PHASE2	UNKNOWN	Effect of Vitamin C Supplementation in Patients With Primary Hypothyroidism
NCT05804149	PHASE2	COMPLETED	Effect of Acupuncture and Low Caloric Diet on Primary Hypothyroidism and Irregular Menstruation in Infertile Women
NCT05823012	PHASE2	COMPLETED	Study of XP-8121 For the Treatment of Adult Subjects With Hypothyroidism
NCT02548715	PHASE2/PHASE3	WITHDRAWN	Levothyroxine Treatment for Subclinical Hypothyroidism After Head and Neck Surgery
NCT03053115	PHASE2/PHASE3	COMPLETED	Combined Replacement Therapy With Levothyroxine and Liothyronine in Thyroidectomized Patients
NCT06345339	PHASE2/PHASE3	RECRUITING	A Study to Assess the Safety and Efficacy of Oral Armour Thyroid Compared to Synthetic T4 for the Treatment of Primary Hypothyroidism in Adult Participants
NCT06731764	PHASE2/PHASE3	RECRUITING	Novel Approaches to the Treatment of Hypothyroidism
NCT06826248	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Clinical Efficacy of Darqeen Capsule for the Management of Hypothyroidism Associated with Female Reproductive Hormonal Imbalance
NCT00001159	Not specified	RECRUITING	Natural History of Thyroid Function Disorders