SYNE4

Summary

SYNE4 (spectrin repeat containing nuclear envelope family member 4, HGNC:26703) is a protein-coding gene on chromosome 19q13.12, encoding Nesprin-4 (Q8N205). As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton.

This gene is a member of the nesprin family of genes, that encode KASH (Klarsicht, Anc-1, Syne Homology) domain-containing proteins. In addition to the KASH domain, this protein also contains a coiled-coil and leucine zipper region, a spectrin repeat, and a kinesin-1 binding region. This protein localizes to the outer nuclear membrane, and is part of the linker of nucleoskeleton and cytoskeleton (LINC) complex in the nuclear envelope. LINC complexes are formed by SUN (Sad1, UNC-84)-KASH pairs, and are thought to mechanically couple nuclear components to the cytoskeleton. Mutations in this gene have been associated with progressive high-frequency hearing loss. The absence of this protein in mice also caused hearing loss, and changes in hair cell morphology in the ears. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 163183 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive nonsyndromic hearing loss 76 (Strong, GenCC) — +2 more curated relationships
• Clinical variants (ClinVar): 365 total — 20 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 5
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001039876

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26703
Approved symbol	SYNE4
Name	spectrin repeat containing nuclear envelope family member 4
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36445, Nesprin-4, Nesp4
Ensembl gene	ENSG00000181392
Ensembl biotype	protein_coding
OMIM	615535
Entrez	163183

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 33 protein_coding, 2 retained_intron

ENST00000324444, ENST00000340477, ENST00000397428, ENST00000465425, ENST00000490730, ENST00000503121, ENST00000505054, ENST00000871995, ENST00000871996, ENST00000871997, ENST00000871998, ENST00000871999, ENST00000872000, ENST00000872001, ENST00000872002, ENST00000872003, ENST00000872004, ENST00000872005, ENST00000872006, ENST00000872007, ENST00000872008, ENST00000872009, ENST00000872010, ENST00000872011, ENST00000921831, ENST00000921832, ENST00000921833, ENST00000921834, ENST00000921835, ENST00000921836, ENST00000921837, ENST00000921838, ENST00000921839, ENST00000921840, ENST00000952118

RefSeq mRNA: 2 — MANE Select: NM_001039876 NM_001039876, NM_001297735

CCDS: CCDS42553, CCDS77285

Canonical transcript exons

ENST00000324444 — 8 exons

Exon	Start	End
ENSE00002185346	36006423	36006671
ENSE00003540250	36005333	36005437
ENSE00003541947	36003613	36003671
ENSE00003599757	36007125	36007268
ENSE00003605385	36008217	36008367
ENSE00003685888	36006750	36006944
ENSE00003817486	36003307	36003520
ENSE00003843809	36008554	36008813

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 89.09.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8073 / max 51.9652, expressed in 393 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180614	2.8073	393

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	89.09	silver quality
cerebellar cortex	UBERON:0002129	87.63	gold quality
cerebellar hemisphere	UBERON:0002245	87.62	gold quality
pituitary gland	UBERON:0000007	87.39	gold quality
cerebellum	UBERON:0002037	87.10	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.75	gold quality
adenohypophysis	UBERON:0002196	86.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.24	gold quality
right lobe of liver	UBERON:0001114	84.70	gold quality
left lobe of thyroid gland	UBERON:0001120	83.90	gold quality
right lobe of thyroid gland	UBERON:0001119	83.76	gold quality
thyroid gland	UBERON:0002046	83.21	gold quality
parotid gland	UBERON:0001831	82.93	gold quality
cerebellar vermis	UBERON:0004720	82.53	gold quality
nasal cavity epithelium	UBERON:0005384	81.64	gold quality
kidney epithelium	UBERON:0004819	81.58	gold quality
prostate gland	UBERON:0002367	81.34	gold quality
right uterine tube	UBERON:0001302	81.03	gold quality
metanephros cortex	UBERON:0010533	79.54	gold quality
saliva-secreting gland	UBERON:0001044	78.81	gold quality
minor salivary gland	UBERON:0001830	78.06	gold quality
liver	UBERON:0002107	77.94	gold quality
tibialis anterior	UBERON:0001385	77.90	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	77.80	gold quality
islet of Langerhans	UBERON:0000006	77.73	gold quality
ileal mucosa	UBERON:0000331	77.45	gold quality
oviduct epithelium	UBERON:0004804	77.41	gold quality
adult mammalian kidney	UBERON:0000082	77.39	gold quality
body of pancreas	UBERON:0001150	76.68	gold quality
pancreas	UBERON:0001264	76.55	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.46
E-GEOD-110499	no	12.71

Regulation

Is transcription factor: no

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 1)

• progressive high-frequency hearing loss in 2 families of Iraqi Jewish ancestry was due to homozygosity for mutation SYNE4 c.228delAT. SYNE4, a gene not previously associated with hearing loss, encodes nesprin-4, a protein expressed in outer hair cells. (PMID:23348741)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Syne4	ENSMUSG00000019737
rattus_norvegicus	Syne4	ENSRNOG00000049277

Protein

Protein identifiers

Nesprin-4 — Q8N205 (reviewed: Q8N205)

Alternative names: KASH domain-containing protein 4, Nuclear envelope spectrin repeat protein 4

All UniProt accessions (4): D6RAE3, Q8N205, H0Y9Z1, H9KVA3

UniProt curated annotations — full annotation on UniProt →

Function. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Behaves as a kinesin cargo, providing a functional binding site for kinesin-1 at the nuclear envelope. Hence may contribute to the establishment of secretory epithelial morphology by promoting kinesin-dependent apical migration of the centrosome and Golgi apparatus and basal localization of the nucleus.

Subunit / interactions. Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents can give rise to specific assemblies. Probably part of a SUN1-containing LINC complex. Interacts with kinesins KIF5B and KLC1.

Subcellular location. Nucleus outer membrane.

Post-translational modifications. The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces.

Disease relevance. Deafness, autosomal recessive, 76 (DFNB76) [MIM:615540] A form of non-syndromic sensorineural deafness, a disorder resulting from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNB76 affected individuals have onset of progressive high frequency hearing impairment between birth and 6 years of age. The hearing loss is severe at high frequencies by adulthood. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The KASH domain, which contains a transmembrane domain, mediates the nuclear envelope targeting and is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.

Similarity. Belongs to the nesprin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N205-1	1	yes
Q8N205-2	2

RefSeq proteins (2): NP_001034965, NP_001284664 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012315	KASH	Domain
IPR030268	SYNE4	Family

Pfam: PF10541

UniProt features (15 total): topological domain 2, disulfide bond 2, sequence variant 2, region of interest 2, compositionally biased region 2, chain 1, splice variant 1, strand 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6WMD	X-RAY DIFFRACTION	1.5
6R16	X-RAY DIFFRACTION	2.75

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N205-F1	57.88	0.14

Functional residue map

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

Disulfide bonds (2): 381, 381

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_MONOPOLAR_CELL_POLARITY, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_ESTABLISHMENT_OF_EPITHELIAL_CELL_POLARITY, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_POLARIZED_EPITHELIAL_CELL_DIFFERENTIATION, HNF1_C, GOBP_MORPHOGENESIS_OF_A_POLARIZED_EPITHELIUM, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_BIPOLAR_CELL_POLARITY, GOBP_TISSUE_MORPHOGENESIS, GOCC_NUCLEAR_ENVELOPE, GOCC_NUCLEAR_OUTER_MEMBRANE, CHARAFE_BREAST_CANCER_LUMINAL_VS_MESENCHYMAL_UP

GO Biological Process (1): establishment of epithelial cell apical/basal polarity (GO:0045198)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): nuclear outer membrane (GO:0005640), meiotic nuclear membrane microtubule tethering complex (GO:0034993), nucleus (GO:0005634), nuclear envelope (GO:0005635), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
polarized epithelial cell differentiation	1
establishment of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
establishment of epithelial cell polarity	1
binding	1
nuclear membrane	1
organelle outer membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
microtubule organizing center attachment site	1
nuclear membrane microtubule tethering complex	1
intracellular membrane-bounded organelle	1
nucleus	1
endomembrane system	1
organelle envelope	1
cellular anatomical structure	1

Protein interactions and networks

STRING

446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYNE4	SYNE3	Q6ZMZ3	916
SYNE4	KIF5B	P33176	894
SYNE4	KASH5	Q8N6L0	878
SYNE4	SYNE1	Q8NF91	869
SYNE4	SUN1	O94901	855
SYNE4	SUN2	Q9UH99	846
SYNE4	PLEC	Q15149	837
SYNE4	SYNE2	Q8WXH0	668
SYNE4	EMD	P50402	643
SYNE4	SUN3	Q8TAQ9	624
SYNE4	IRAG2	Q12912	624
SYNE4	SPAG4	Q9NPE6	587
SYNE4	SUN5	Q8TC36	583
SYNE4	KLC2	Q9H0B6	582
SYNE4	KLC3	Q6P597	574

IntAct

170 interactions, top by confidence:

A	B	Type	Score
SUN2	SYNE4	psi-mi:“MI:0407”(direct interaction)	0.710
OCLN	SYNE4	psi-mi:“MI:0915”(physical association)	0.670
SYNE4	CLEC7A	psi-mi:“MI:0915”(physical association)	0.670
SYNE4	CSGALNACT2	psi-mi:“MI:0915”(physical association)	0.670
KLC4	SYNE4	psi-mi:“MI:0915”(physical association)	0.670
SYNE4	VTI1B	psi-mi:“MI:0915”(physical association)	0.670
CLEC7A	SYNE4	psi-mi:“MI:0915”(physical association)	0.670
SYNE4	OCLN	psi-mi:“MI:0915”(physical association)	0.670
SUN1	SYNE4	psi-mi:“MI:0407”(direct interaction)	0.650

BioGRID (175): SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid), SYNE4 (Two-hybrid)

ESM2 similar proteins: A0A096LP49, A0A8V8TNH8, A0A8V8TPE2, A1L443, A2IDD5, A5D7L8, A6NDY2, A6NIJ5, A6NNJ1, A6NNL0, A7E346, A8K0R7, A8MXJ8, A8MXZ1, B1AL46, B1ASB6, C9JSJ3, E9PGG2, O08574, P0C7V4, P0C7W8, P0C7X0, P0CG20, P0DV73, P0DV75, P0DV76, Q0VG99, Q0ZCJ7, Q149B8, Q2M3G4, Q3TQ03, Q3V0C3, Q4KLY2, Q5JXC2, Q5RCJ6, Q5SV97, Q5SW24, Q5VT03, Q5VZR2, Q6ZMY3

Diamond homologs: Q5M844, Q8CII8, Q8N205

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SYNE4	“form complex”	“LINC complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	14
Uncertain significance	104
Likely benign	167
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2445666	NM_001039876.3(SYNE4):c.336C>A (p.Cys112Ter)	Pathogenic
2694675	NM_001039876.3(SYNE4):c.89del (p.Gly30fs)	Pathogenic
2732773	NM_001039876.3(SYNE4):c.707G>A (p.Trp236Ter)	Pathogenic
2736873	NM_001039876.3(SYNE4):c.129-1G>T	Pathogenic
2753737	NM_001039876.3(SYNE4):c.400C>T (p.Gln134Ter)	Pathogenic
2762575	NM_001039876.3(SYNE4):c.249C>G (p.Tyr83Ter)	Pathogenic
2773052	NM_001039876.3(SYNE4):c.155_209del (p.Gln52fs)	Pathogenic
2799588	NM_001039876.3(SYNE4):c.493del (p.Ala165fs)	Pathogenic
2808646	NM_001039876.3(SYNE4):c.828_829del (p.Cys276fs)	Pathogenic
2825620	NM_001039876.3(SYNE4):c.249del (p.Ser82_Tyr83insTer)	Pathogenic
2834024	NM_001039876.3(SYNE4):c.361C>T (p.Gln121Ter)	Pathogenic
2855771	NM_001297735.3(SYNE4):c.280-273del	Pathogenic
2878825	NM_001039876.3(SYNE4):c.46del (p.Leu16fs)	Pathogenic
2899915	NM_001039876.3(SYNE4):c.832C>T (p.Gln278Ter)	Pathogenic
2982109	NM_001039876.3(SYNE4):c.853G>T (p.Gly285Ter)	Pathogenic
2989159	NM_001039876.3(SYNE4):c.889C>T (p.Arg297Ter)	Pathogenic
3012557	NM_001039876.3(SYNE4):c.678G>A (p.Trp226Ter)	Pathogenic
4536658	NM_001039876.3(SYNE4):c.742del (p.Glu248fs)	Pathogenic
4731729	NM_001039876.3(SYNE4):c.415del (p.Gln139fs)	Pathogenic
504047	NM_001039876.3(SYNE4):c.511_526del (p.Arg171fs)	Pathogenic
1723402	NM_001039876.3(SYNE4):c.377del (p.Gly126fs)	Likely pathogenic
228292	NM_001039876.1(SYNE4):c.(?1)(1215_?)del	Likely pathogenic
2445877	NM_001039876.3(SYNE4):c.653T>A (p.Leu218Ter)	Likely pathogenic
2501099	NM_001039876.3(SYNE4):c.973-2A>T	Likely pathogenic
2775787	NM_001039876.3(SYNE4):c.618+1G>A	Likely pathogenic
2834704	NM_001039876.3(SYNE4):c.868-2A>G	Likely pathogenic
3010424	NM_001039876.3(SYNE4):c.972+2T>A	Likely pathogenic
3020134	NM_001039876.3(SYNE4):c.618+2T>A	Likely pathogenic
3583760	NM_001039876.3(SYNE4):c.972+2T>G	Likely pathogenic
3583761	NM_001039876.3(SYNE4):c.742dup (p.Glu248fs)	Likely pathogenic

SpliceAI

1120 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36005328:CTCA:C	donor_loss	1.0000
19:36005330:CA:C	donor_loss	1.0000
19:36005331:ACCTG:A	donor_loss	1.0000
19:36005332:C:CT	donor_loss	1.0000
19:36005438:C:CC	acceptor_gain	1.0000
19:36005439:T:C	acceptor_loss	1.0000
19:36005447:C:CT	acceptor_gain	1.0000
19:36005448:A:T	acceptor_gain	1.0000
19:36005451:A:T	acceptor_gain	1.0000
19:36006606:T:TA	donor_gain	1.0000
19:36006625:C:CA	donor_gain	1.0000
19:36006744:CCCTA:C	donor_loss	1.0000
19:36006746:CTACC:C	donor_loss	1.0000
19:36006747:TACCA:T	donor_loss	1.0000
19:36006748:A:AC	donor_gain	1.0000
19:36006748:A:T	donor_loss	1.0000
19:36006749:C:CC	donor_gain	1.0000
19:36006749:CCAGG:C	donor_gain	1.0000
19:36006759:G:C	donor_gain	1.0000
19:36007120:CCTA:C	donor_loss	1.0000
19:36007121:CTA:C	donor_loss	1.0000
19:36007122:TACCT:T	donor_loss	1.0000
19:36007264:GGGTG:G	acceptor_gain	1.0000
19:36007265:GGTG:G	acceptor_gain	1.0000
19:36007266:GTGC:G	acceptor_loss	1.0000
19:36007267:TG:T	acceptor_gain	1.0000
19:36007268:GC:G	acceptor_loss	1.0000
19:36007269:C:CC	acceptor_gain	1.0000
19:36007269:CTGGG:C	acceptor_loss	1.0000
19:36007364:T:TA	donor_gain	1.0000

AlphaMissense

2560 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:36006543:C:A	W249C	0.970
19:36006543:C:G	W249C	0.970
19:36006545:A:G	W249R	0.959
19:36006545:A:T	W249R	0.959
19:36006888:A:C	F160L	0.941
19:36006888:A:T	F160L	0.941
19:36006890:A:G	F160L	0.941
19:36006928:A:G	L147P	0.876
19:36006778:A:G	L197P	0.859
19:36006795:G:C	F191L	0.852
19:36006795:G:T	F191L	0.852
19:36006797:A:G	F191L	0.852
19:36006544:C:A	W249L	0.844
19:36006544:C:G	W249S	0.843
19:36006787:A:G	L194P	0.835
19:36006541:T:C	D250G	0.829
19:36006917:C:G	A151P	0.818
19:36006766:A:G	L201P	0.798
19:36007210:A:G	L113P	0.794
19:36006540:A:C	D250E	0.791
19:36006540:A:T	D250E	0.791
19:36006541:T:G	D250A	0.783
19:36006666:G:C	F208L	0.776
19:36006666:G:T	F208L	0.776
19:36006668:A:G	F208L	0.776
19:36006783:C:A	W195C	0.770
19:36006783:C:G	W195C	0.770
19:36006889:A:C	F160C	0.763
19:36006898:A:G	L157P	0.763
19:36006542:C:G	D250H	0.753

dbSNP variants (sampled 300 via entrez): RS1000037235 (19:36003199 T>C), RS1000461148 (19:36007761 C>A,T), RS1000743169 (19:36008034 G>A), RS1001819024 (19:36005293 A>G), RS1002151520 (19:36009655 A>C,G), RS1002221880 (19:36009405 G>A), RS1002471963 (19:36005059 G>A), RS1002753584 (19:36005330 C>T), RS1003735788 (19:36002840 A>C), RS1004037479 (19:36009959 G>A), RS1004936195 (19:36005751 G>C), RS1005008642 (19:36005510 T>A), RS1005063018 (19:36005227 T>G), RS1005108943 (19:36005030 G>A), RS1005360949 (19:36010294 T>A,C)

Disease associations

OMIM: gene MIM:615535 | disease phenotypes: MIM:615540

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive nonsyndromic hearing loss 76	Strong	Autosomal recessive
nonsyndromic genetic hearing loss	Moderate	Autosomal recessive
hearing loss, autosomal recessive	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Moderate	AR

Mondo (3): autosomal recessive nonsyndromic hearing loss 76 (MONDO:0014237), nonsyndromic genetic hearing loss (MONDO:0019497), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (3): Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare non-syndromic genetic deafness (Orphanet:87884), Rare genetic deafness (Orphanet:96210)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000408	Progressive sensorineural hearing impairment
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0011463	Childhood onset

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564609	Deafness, Autosomal Recessive (supp.)
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
sodium arsenate	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
K 7174	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Carbamazepine	affects expression	1
Cisplatin	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Quercetin	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Urethane	decreases expression	1
Gold Compounds	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations