SPAG17

Summary

SPAG17 (sperm associated antigen 17, HGNC:26620) is a protein-coding gene on chromosome 1p12, encoding Sperm-associated antigen 17 (Q6Q759). Component of the central pair apparatus of ciliary axonemes.

This gene encodes a central pair protein present in the axonemes of cells with a “9 + 2” organization of microtubules. The encoded protein is required for the proper function of the axoneme. Mutations in the orthologous gene in mice lead to primary ciliary dyskinesia characterized by immotile nasal and tracheal cilia, reduced clearance of nasal mucus, profound respiratory distress, hydrocephalus, and neonatal lethality within twelve hours of birth due to impaired airway mucociliary clearance. Single-nucleotide polymorphisms in this gene are associated with human height and targeted mutations lead to skeletal malformations affecting the limbs in mice, suggesting a role for this gene in skeletal development.

Source: NCBI Gene 200162 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 56
• Clinical variants (ClinVar): 414 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_206996

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26620
Approved symbol	SPAG17
Name	sperm associated antigen 17
Location	1p12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ34497, PF6, RP4-776P7.2, CT143
Ensembl gene	ENSG00000155761
Ensembl biotype	protein_coding
OMIM	616554
Entrez	200162

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 11 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000336338, ENST00000437255, ENST00000463628, ENST00000465053, ENST00000466857, ENST00000469128, ENST00000470550, ENST00000473472, ENST00000477444, ENST00000478697, ENST00000483383, ENST00000486589, ENST00000492438

RefSeq mRNA: 1 — MANE Select: NM_206996 NM_206996

CCDS: CCDS899

Canonical transcript exons

ENST00000336338 — 49 exons

Exon	Start	End
ENSE00000785144	117971863	117972047
ENSE00001022589	118081415	118081642
ENSE00001022590	118097670	118097851
ENSE00001022591	118086871	118087008
ENSE00001022592	118101740	118101926
ENSE00001022593	118099606	118099800
ENSE00001022594	118085922	118086072
ENSE00001022596	118093156	118093317
ENSE00001022597	118115310	118115441
ENSE00001022616	118150543	118150629
ENSE00001072878	118091606	118091718
ENSE00001157549	118066745	118066899
ENSE00001249619	118091930	118092002
ENSE00001249674	117970056	117970116
ENSE00001249937	118054002	118054093
ENSE00001359462	118073854	118073967
ENSE00001401624	118025238	118025416
ENSE00001404545	118036770	118036883
ENSE00001407220	118041803	118042042
ENSE00001407754	118040730	118040841
ENSE00001410239	117988105	117988204
ENSE00001410841	117987834	117987881
ENSE00001417098	118008044	118008198
ENSE00001417712	118015965	118016182
ENSE00001418917	118012228	118012372
ENSE00001418968	118023304	118023463
ENSE00001422364	117966609	117966753
ENSE00001428432	117990861	117990906
ENSE00001430298	117994406	117994530
ENSE00001431433	117992466	117992648
ENSE00001432029	117991415	117991528
ENSE00001432632	117996370	117996500
ENSE00001433217	118005414	118005602
ENSE00001434431	117996598	117996743
ENSE00003467921	118151229	118151369
ENSE00003474059	118039292	118039444
ENSE00003483133	118028274	118028394
ENSE00003512810	117981270	117981401
ENSE00003520201	117984683	117984782
ENSE00003537944	118086671	118086784
ENSE00003551381	118185071	118185228
ENSE00003569049	118081101	118081319
ENSE00003580607	118055733	118055914
ENSE00003599979	117983811	117983913
ENSE00003642614	117963799	117963938
ENSE00003658463	117973425	117973561
ENSE00003674790	118031692	118031867
ENSE00003680882	118074539	118074600
ENSE00003891612	117953590	117954049

Expression profiles

Bgee: expression breadth ubiquitous, 173 present calls, max score 98.89.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7777 / max 125.5792, expressed in 241 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14044	0.7267	228
14045	0.0510	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.89	gold quality
bronchial epithelial cell	CL:0002328	97.40	gold quality
sperm	CL:0000019	96.73	gold quality
bronchus	UBERON:0002185	95.91	gold quality
right testis	UBERON:0004534	94.49	gold quality
left testis	UBERON:0004533	94.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.46	gold quality
testis	UBERON:0000473	90.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.92	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.74	gold quality
lower esophagus mucosa	UBERON:0035834	87.56	gold quality
esophagus mucosa	UBERON:0002469	86.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.66	gold quality
adenohypophysis	UBERON:0002196	84.82	gold quality
oviduct epithelium	UBERON:0004804	83.21	gold quality
pituitary gland	UBERON:0000007	81.77	gold quality
fallopian tube	UBERON:0003889	80.73	gold quality
caput epididymis	UBERON:0004358	79.63	gold quality
esophagus squamous epithelium	UBERON:0006920	79.01	gold quality
metanephros cortex	UBERON:0010533	78.87	gold quality
epithelium of nasopharynx	UBERON:0001951	77.70	gold quality
right lung	UBERON:0002167	77.48	gold quality
vagina	UBERON:0000996	75.51	gold quality
hypothalamus	UBERON:0001898	74.17	gold quality
esophagus	UBERON:0001043	73.48	gold quality
cortex of kidney	UBERON:0001225	72.12	gold quality
ventricular zone	UBERON:0003053	72.12	gold quality
caudate nucleus	UBERON:0001873	71.93	gold quality
left uterine tube	UBERON:0001303	71.85	gold quality
left lobe of thyroid gland	UBERON:0001120	69.98	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1773.40
E-GEOD-100618	yes	195.15
E-MTAB-10287	yes	26.61
E-GEOD-130148	yes	14.58
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting SPAG17, 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-4534	99.99	66.58	1907
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-20B-3P	99.29	67.05	784
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-1843	98.97	66.07	838
HSA-MIR-4802-5P	98.97	66.26	833
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6868-3P	98.63	69.64	2259
HSA-MIR-5187-5P	98.54	67.94	952
HSA-MIR-6838-3P	98.40	65.88	559
HSA-MIR-3929	98.32	65.58	1026
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-4443	98.02	66.25	1928

Literature-anchored findings (GeneRIF, showing 4)

• In silico analysis revealed that R1448Q is a potential pathogenic mutation. Immunostaining and western blot assays showed that the R1448Q mutation may exert a negative effect on the steady-state of the SPAG17 protein. Therefore, SPAG17 may be a new pathogenic gene causing Asthenozoospermia (AZS) . (PMID:28548327)
• Homozygous missense mutation in SPAG17 gene is associated with multiple congenital anomalies, including brain malformations and skeletal dysplasia suggestive of cranioectodermal dysplasia ciliopathy. (PMID:29174089)
• Alterations of the Primary Cilia Gene SPAG17 and SOX9 Locus Noncoding RNAs Identified by RNA-Sequencing Analysis in Patients With Systemic Sclerosis. (PMID:35762854)
• Reduced SPAG17 Expression in Systemic Sclerosis Triggers Myofibroblast Transition and Drives Fibrosis. (PMID:36116512)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	spag17	ENSDARG00000058280
mus_musculus	Spag17	ENSMUSG00000027867
rattus_norvegicus	Spag17	ENSRNOG00000037196

Protein

Protein identifiers

Sperm-associated antigen 17 — Q6Q759 (reviewed: Q6Q759)

Alternative names: Projection protein PF6 homolog

All UniProt accessions (2): Q6Q759, Q5TDG6

UniProt curated annotations — full annotation on UniProt →

Function. Component of the central pair apparatus of ciliary axonemes. Plays a critical role in the function and structure of motile cilia. May play a role in endochondral bone formation, most likely because of a function in primary cilia of chondrocytes and osteoblasts. Essential for normal spermatogenesis and male fertility. Required for normal manchette structure, transport of proteins along the manchette microtubules and formation of the sperm head and flagellum. Essential for sperm flagellum development and proper assembly of the respiratory motile cilia central pair apparatus, but not the brain ependymal cilia.

Subunit / interactions. Interacts (via the C-terminus) with SPAG6; the interaction probably occurs on polymerized microtubules.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Golgi apparatus.

Tissue specificity. Highly expressed in testis. Expressed in organs that contain cilia-bearing cells including brain, oviduct, lung, and uterus.

Disease relevance. Spermatogenic failure 55 (SPGF55) [MIM:619380] An autosomal recessive male infertility disorder characterized by asthenozoospermia. Semen analysis shows severely reduced sperm motility. The disease may be caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_996879* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026173	SPAG17	Family

Pfam: PF14874

UniProt features (31 total): region of interest 9, compositionally biased region 7, sequence variant 6, sequence conflict 5, coiled-coil region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6Q759-F1	64.20	0.13

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_SECRETORY_GRANULE, GOBP_MALE_GAMETE_GENERATION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, WTGAAAT_UNKNOWN, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_MICROTUBULE_BUNDLE_FORMATION, chr1p12, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY

GO Biological Process (9): epithelial cilium movement involved in extracellular fluid movement (GO:0003351), spermatogenesis (GO:0007283), motile cilium assembly (GO:0044458), axonemal central apparatus assembly (GO:1904158), manchette assembly (GO:1905198), intramanchette transport (GO:1990953), cell projection organization (GO:0030030), cell differentiation (GO:0030154), establishment of localization in cell (GO:0051649)

GO Molecular Function (0):

GO Cellular Component (12): acrosomal vesicle (GO:0001669), manchette (GO:0002177), extracellular region (GO:0005576), Golgi apparatus (GO:0005794), microtubule (GO:0005874), axonemal central apparatus (GO:1990716), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cytoplasmic vesicle (GO:0031410), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cellular component assembly	2
spermatid development	2
microtubule cytoskeleton	2
cytoplasm	2
cilium movement	1
extracellular transport	1
microtubule-based transport	1
developmental process involved in reproduction	1
male gamete generation	1
cilium assembly	1
axoneme assembly	1
manchette	1
protein-containing complex localization	1
protein transport along microtubule	1
cellular component organization	1
cellular developmental process	1
establishment of localization	1
cellular localization	1
secretory granule	1
endomembrane system	1
intracellular membrane-bounded organelle	1
polymeric cytoskeletal fiber	1
axoneme	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
intracellular vesicle	1
cilium	1

Protein interactions and networks

STRING

1776 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPAG17	SPAG6	O75602	886
SPAG17	SPAG16	Q8N0X2	673
SPAG17	SPAG8	Q99932	654
SPAG17	SPEF2	Q9C093	632
SPAG17	CFAP221	Q4G0U5	583
SPAG17	FBXO39	Q8N4B4	540
SPAG17	CFAP263	Q9H0I3	535
SPAG17	WDR3	Q9UNX4	535
SPAG17	HYDIN	Q4G0P3	523
SPAG17	CFAP92	Q9ULG3	520
SPAG17	SPAG1	Q07617	514
SPAG17	ASCC3	Q8N3C0	500
SPAG17	NEK4	P51957	499
SPAG17	C1D	Q13901	485
SPAG17	TEX9	Q8N6V9	479

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PRKCSH	SPAG17	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
N		psi-mi:“MI:0914”(association)	0.350

BioGRID (21): SPAG17 (Affinity Capture-RNA), SPAG17 (Proximity Label-MS), SPAG17 (Proximity Label-MS), SPAG17 (Affinity Capture-MS), SPAG17 (Affinity Capture-MS), SPAG17 (Affinity Capture-MS), SPAG17 (Affinity Capture-MS), SPAG17 (Affinity Capture-MS), SPAG17 (Cross-Linking-MS (XL-MS)), SPAG17 (Cross-Linking-MS (XL-MS)), SPAG17 (Cross-Linking-MS (XL-MS)), SPAG17 (Cross-Linking-MS (XL-MS)), SPAG17 (Cross-Linking-MS (XL-MS)), SPAG17 (Cross-Linking-MS (XL-MS)), SPAG17 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GVH7, A6PVS8, A8DZJ1, A9Q751, D3ZSP7, D4AEC2, Q08AD1, Q08CX2, Q14DL3, Q2T9P0, Q2TA00, Q32KQ1, Q3UZ57, Q3V0J4, Q4G0U5, Q4R7B1, Q4R7Z7, Q5S003, Q5SUV2, Q5T1B0, Q5ZLS8, Q63164, Q66HC0, Q69CM7, Q6AXP3, Q6AYL8, Q6IRN6, Q6NXP0, Q6Q759, Q80X60, Q86WZ0, Q8C1B1, Q8C4J0, Q8C636, Q8CDN1, Q8CDU5, Q8IWF9, Q8N7B9, Q8N7U6, Q8ND61

Diamond homologs: Q5S003, Q6Q759

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	308
Likely benign	49
Benign	25

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1172754	NM_206996.4(SPAG17):c.4343G>A (p.Arg1448Gln)	Pathogenic
437866	NM_206996.4(SPAG17):c.1069G>C (p.Asp357His)	Likely pathogenic

SpliceAI

8801 predictions. Top by Δscore:

Variant	Effect	Δscore
1:117954003:GTA:G	acceptor_loss	1.0000
1:117954004:TAG:T	acceptor_loss	1.0000
1:117954005:A:AC	acceptor_loss	1.0000
1:117954005:A:AG	acceptor_gain	1.0000
1:117954006:G:GT	acceptor_gain	1.0000
1:117954111:GTACA:G	donor_gain	1.0000
1:117954116:G:GG	donor_gain	1.0000
1:117954628:G:GG	donor_gain	1.0000
1:117957067:GT:G	acceptor_gain	1.0000
1:117957280:GAT:G	donor_gain	1.0000
1:117959405:G:GT	donor_gain	1.0000
1:117959420:G:GT	donor_gain	1.0000
1:117970054:A:AC	donor_gain	1.0000
1:117970055:C:CC	donor_gain	1.0000
1:117970055:CAGGT:C	donor_gain	1.0000
1:117973460:G:C	donor_gain	1.0000
1:117973478:TC:T	donor_gain	1.0000
1:117973562:C:CC	acceptor_gain	1.0000
1:117983808:TACC:T	donor_loss	1.0000
1:117983809:ACC:A	donor_loss	1.0000
1:117983810:C:G	donor_loss	1.0000
1:117983909:TTATA:T	acceptor_gain	1.0000
1:117983910:TATA:T	acceptor_gain	1.0000
1:117983911:ATA:A	acceptor_gain	1.0000
1:117983912:TA:T	acceptor_gain	1.0000
1:117983912:TACTG:T	acceptor_loss	1.0000
1:117983914:C:CC	acceptor_gain	1.0000
1:117983914:CTGA:C	acceptor_loss	1.0000
1:117983915:T:C	acceptor_loss	1.0000
1:117984796:CCA:C	acceptor_gain	1.0000

AlphaMissense

14761 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:118081499:A:G	W636R	0.998
1:118081499:A:T	W636R	0.998
1:117991431:A:G	L1820P	0.997
1:117991422:A:G	L1823P	0.996
1:117992470:A:G	L1786P	0.996
1:118036808:A:G	L1132P	0.996
1:118036833:C:G	A1124P	0.996
1:117992530:C:G	R1766P	0.995
1:118025269:A:T	V1293D	0.995
1:118085942:A:G	L581P	0.995
1:118005577:A:G	L1538P	0.994
1:118008049:A:C	Y1528D	0.994
1:118036832:G:T	A1124D	0.994
1:118039399:A:G	F1071S	0.994
1:118073895:A:G	W782R	0.994
1:118073895:A:T	W782R	0.994
1:118115374:A:G	L128P	0.994
1:117992482:A:G	L1782P	0.993
1:118025371:C:G	R1259P	0.993
1:118036798:A:C	S1135R	0.993
1:118036798:A:T	S1135R	0.993
1:118036800:T:G	S1135R	0.993
1:118073909:C:G	R777P	0.993
1:118081477:G:T	A643D	0.993
1:117991428:A:G	L1821P	0.992
1:117991463:T:A	R1809S	0.992
1:117991463:T:G	R1809S	0.992
1:117991509:A:G	L1794P	0.992
1:118185106:A:G	W18R	0.992
1:118185106:A:T	W18R	0.992

dbSNP variants (sampled 300 via entrez): RS1000006082 (1:118158604 G>A), RS1000016918 (1:118070518 C>A), RS1000036945 (1:118030303 C>T), RS1000041510 (1:118007405 T>A,C), RS1000047276 (1:118090050 G>A), RS1000047767 (1:117987182 C>T), RS1000067134 (1:118118472 G>A), RS1000069325 (1:118070177 C>A,T), RS1000070655 (1:118162394 C>T), RS1000086712 (1:118169791 T>A), RS1000088756 (1:118030514 G>A), RS1000090234 (1:118186413 C>A), RS1000101136 (1:118146917 T>A), RS1000101848 (1:118096756 A>C), RS1000114740 (1:117984528 G>A)

Disease associations

OMIM: gene MIM:616554 | disease phenotypes: MIM:619380, MIM:156000, MIM:613610

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	Autosomal recessive
non-syndromic male infertility due to sperm motility disorder	Supportive	Autosomal recessive
spermatogenic failure 55	Limited	Unknown

Mondo (5): spermatogenic failure 55 (MONDO:0030307), Meniere disease (MONDO:0007972), cranioectodermal dysplasia 2 (MONDO:0013323), (MONDO:0017173), (MONDO:0018393)

Orphanet (2): Cranioectodermal dysplasia (Orphanet:1515), NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000837	Increased circulating gonadotropin level
HP:0003251	Male infertility
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia
HP:0011962	Obstructive azoospermia
HP:0012207	Reduced sperm motility

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST000174_8	Height	4.000000e-11
GCST000817_112	Height	6.000000e-23
GCST001762_396	Obesity-related traits	2.000000e-06
GCST001956_45	Height	2.000000e-16
GCST002036_1	Congenital heart malformation	8.000000e-10
GCST002646_1	Infant length	1.000000e-10
GCST002647_88	Height	3.000000e-36
GCST002702_16	Height	2.000000e-32
GCST002782_278	Waist-to-hip ratio adjusted for body mass index	1.000000e-07
GCST002782_279	Waist-to-hip ratio adjusted for body mass index	5.000000e-07
GCST003263_119	Post bronchodilator FEV1 in COPD	5.000000e-06
GCST003983_15	Male-pattern baldness	9.000000e-14
GCST003985_12	Breast size	4.000000e-09
GCST004063_17	Waist circumference adjusted for body mass index	1.000000e-15
GCST004063_48	Waist circumference adjusted for body mass index	2.000000e-07
GCST004063_85	Waist circumference adjusted for body mass index	4.000000e-12
GCST004184_10	Lung function (FVC)	8.000000e-14
GCST004500_111	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	2.000000e-15
GCST004500_39	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	5.000000e-10
GCST004500_64	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-08
GCST004501_64	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	7.000000e-17
GCST004501_65	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-10
GCST004501_66	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-08
GCST004504_101	Waist circumference adjusted for BMI in non-smokers	3.000000e-07
GCST004504_102	Waist circumference adjusted for BMI in non-smokers	6.000000e-14
GCST004504_103	Waist circumference adjusted for BMI in non-smokers	4.000000e-09
GCST004505_108	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	8.000000e-07
GCST004562_119	Waist circumference adjusted for body mass index	6.000000e-16
GCST004562_161	Waist circumference adjusted for body mass index	5.000000e-10
GCST004562_190	Waist circumference adjusted for body mass index	6.000000e-07

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004730	hormone measurement
EFO:0006785	infant body height
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004314	forced expiratory volume
EFO:0007789	BMI-adjusted waist circumference
EFO:0004312	vital capacity
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009718	peak expiratory flow
EFO:0009819	comparative body size at age 10, self-reported
EFO:0008343	sex interaction measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008575	Meniere Disease	C09.218.568.217.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
2,3-pentanedione	decreases expression	1
sodium arsenite	increases expression	1
bisphenol S	increases methylation	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Diacetyl	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Nickel	decreases expression	1
Smoke	increases expression, increases abundance	1
Valproic Acid	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT04674735	PHASE1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT04218123	PHASE2/PHASE3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	PHASE1/PHASE2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	EARLY_PHASE1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	RECRUITING	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?
NCT04935970	Not specified	UNKNOWN	Metabolic Disorders and Vertigo
NCT05322538	Not specified	NOT_YET_RECRUITING	Menier’s Disease - Bone Density Study
NCT05328895	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT05424302	Not specified	RECRUITING	Effect of Peripheral Vestibular Disease Location on Outcomes Following Home-based Virtual Reality Vestibular Therapy
NCT05582148	Not specified	UNKNOWN	Meniere Disease and Hearing Aids
NCT05844657	Not specified	COMPLETED	Comprehensive Evaluation in Patients With Meniere’s Disease
NCT05960786	Not specified	COMPLETED	Treating the Symptoms of Vertigo in a Real-world Setting Using the OtoBand
NCT06278129	Not specified	UNKNOWN	Evaluation of the Diagnostic and Prognostic Efficacy of MRI in Acute Sensorineural Hearing Loss and Ménière’s Disease
NCT06544590	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT07272473	Not specified	RECRUITING	Effects of Cervical Mobilization on Dizziness, Balance, and Joint Position Sense in Patients With Meniere’s Disease