DNAH10

Summary

DNAH10 (dynein axonemal heavy chain 10, HGNC:2941) is a protein-coding gene on chromosome 12q24.31, encoding Dynein axonemal heavy chain 10 (Q8IVF4). Force generating protein of respiratory cilia.

Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH10 is an inner arm dynein heavy chain (Maiti et al., 2000 [PubMed 11175280]).

Source: NCBI Gene 196385 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 56 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 146
• Clinical variants (ClinVar): 923 total — 3 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 16
• MANE Select transcript: NM_001372106

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2941
Approved symbol	DNAH10
Name	dynein axonemal heavy chain 10
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ43808
Ensembl gene	ENSG00000197653
Ensembl biotype	protein_coding
OMIM	605884
Entrez	196385

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay

ENST00000409039, ENST00000447853, ENST00000467219, ENST00000492261, ENST00000497783, ENST00000538983, ENST00000540041, ENST00000545078, ENST00000638045, ENST00000673944

RefSeq mRNA: 2 — MANE Select: NM_001372106 NM_001372106, NM_207437

CCDS: CCDS91767, CCDS9255

Canonical transcript exons

ENST00000631855 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.32.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4486 / max 59.3647, expressed in 167 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128609	0.2071	108
128603	0.1913	46
128604	0.0502	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	96.32	gold quality
cortical plate	UBERON:0005343	87.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.65	gold quality
right testis	UBERON:0004534	79.38	gold quality
left testis	UBERON:0004533	79.17	gold quality
testis	UBERON:0000473	79.10	gold quality
sural nerve	UBERON:0015488	78.92	gold quality
ganglionic eminence	UBERON:0004023	77.95	gold quality
cerebellar hemisphere	UBERON:0002245	77.72	gold quality
cerebellar cortex	UBERON:0002129	77.68	gold quality
right hemisphere of cerebellum	UBERON:0014890	77.59	gold quality
cerebellum	UBERON:0002037	77.58	gold quality
bone marrow	UBERON:0002371	77.28	gold quality
fallopian tube	UBERON:0003889	77.08	gold quality
bone marrow cell	CL:0002092	76.11	gold quality
corpus callosum	UBERON:0002336	75.27	gold quality
ventricular zone	UBERON:0003053	75.17	gold quality
right lung	UBERON:0002167	75.14	gold quality
nucleus accumbens	UBERON:0001882	74.10	gold quality
superior frontal gyrus	UBERON:0002661	73.13	gold quality
caudate nucleus	UBERON:0001873	73.03	gold quality
primary visual cortex	UBERON:0002436	72.55	gold quality
stromal cell of endometrium	CL:0002255	72.51	gold quality
Ammon’s horn	UBERON:0001954	72.48	gold quality
frontal cortex	UBERON:0001870	72.43	gold quality
prefrontal cortex	UBERON:0000451	72.39	gold quality
right frontal lobe	UBERON:0002810	72.36	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.09	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.22

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TGFB1, TNF

Literature-anchored findings (GeneRIF, showing 8)

• Mutations in the genes glucokinase regulatory protein (GCKR), RNase L (RNASEL), leukocyte immunoglobulin-like receptor 3 (LILRA3), and dynein axonemal heavy chain 10 (DNAH10) segregated with elevated HDLc levels in families, while no mutations associated with low HDLc. (PMID:24891332)
• This is the first time a haplotype on chromosome 12 containing sequence variants in the genes DCTN2, DNAH10, LRIG3, and MYO1A has been linked to an inherited neuropathy in humans. (PMID:26517670)
• Mutation in DNAH10 gene is associated with insulin-resistant cardiometabolic disease. (PMID:27841877)
• Discovery of increased epidermal DNAH10 expression after regeneration of dermis in a randomized with-in person trial - reflections on psoriatic inflammation. (PMID:31836722)
• DNAH10 mutation correlates with cisplatin sensitivity and tumor mutation burden in small-cell lung cancer. (PMID:31959735)
• Bi-allelic mutations of DNAH10 cause primary male infertility with asthenoteratozoospermia in humans and mice. (PMID:34237282)
• Bi-allelic variants in DNAH10 cause asthenoteratozoospermia and male infertility. (PMID:34657236)
• Dynein axonemal heavy chain 10 deficiency causes primary ciliary dyskinesia in humans and mice. (PMID:37314648)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnah10	ENSDARG00000061486
mus_musculus	Dnah10	ENSMUSG00000038011
rattus_norvegicus	Dnah10	ENSRNOG00000052704
drosophila_melanogaster	Dhc98D	FBGN0013813

Paralogs (15): DNAH9 (ENSG00000007174), DNAH5 (ENSG00000039139), DNAH11 (ENSG00000105877), DNAH1 (ENSG00000114841), DNAH6 (ENSG00000115423), DNAH7 (ENSG00000118997), DNAH8 (ENSG00000124721), DNAH3 (ENSG00000158486), DNAH12 (ENSG00000174844), DNHD1 (ENSG00000179532), DNAH2 (ENSG00000183914), DNAH14 (ENSG00000185842), DYNC2H1 (ENSG00000187240), DNAH17 (ENSG00000187775), DYNC1H1 (ENSG00000197102)

Protein

Protein identifiers

Dynein axonemal heavy chain 10 — Q8IVF4 (reviewed: Q8IVF4)

Alternative names: Axonemal beta dynein heavy chain 10, Ciliary dynein heavy chain 10

All UniProt accessions (6): A0A096LNK1, A0A1C7CYW8, A0A669KB38, F5H515, Q8IVF4, H0YGZ2

UniProt curated annotations — full annotation on UniProt →

Function. Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly. Probable inner arm dynein heavy chain.

Subunit / interactions. Consists of at least two heavy chains and a number of intermediate and light chains.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme.

Tissue specificity. Expressed primarily in trachea and testis, 2 tissues containing axonemal structures. Also expressed in brain but not in adult heart.

Disease relevance. Spermatogenic failure 56 (SPGF56) [MIM:619515] An autosomal recessive male infertility disorder characterized by severely reduced sperm motility, due to multiple morphologic abnormalities of the flagella. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function.

Similarity. Belongs to the dynein heavy chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IVF4-1	1	yes
Q8IVF4-2	2

RefSeq proteins (2): NP_001359035, NP_997320 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR004273	Dhc_D6_P-loop	Domain
IPR013594	Dynein_heavy_tail	Domain
IPR013602	Dhc_linker	Domain
IPR024317	Dhc_D4	Domain
IPR024743	Dynein_HC_stalk	Domain
IPR026983	DHC	Family
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR035699	Dhc_AAA	Domain
IPR035706	AAA_9	Domain
IPR041228	Dhc_C	Domain
IPR041466	Dhc_AAA5_ext	Domain
IPR041589	DNAH3_AAA_lid_1	Domain
IPR041658	AAA_lid_11	Domain
IPR042219	AAA_lid_11_sf	Homologous_superfamily
IPR042222	Dynein_2_N	Homologous_superfamily
IPR042228	Dynein_linker_3	Homologous_superfamily
IPR043157	Dynein_AAA1S	Homologous_superfamily
IPR043160	Dynein_C_barrel	Homologous_superfamily

Pfam: PF03028, PF08385, PF08393, PF12774, PF12775, PF12777, PF12780, PF12781, PF17852, PF17857, PF18198, PF18199

UniProt features (48 total): sequence variant 12, region of interest 9, coiled-coil region 9, repeat 5, binding site 4, sequence conflict 3, short sequence motif 2, splice variant 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q8IVF4 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Ligand- & substrate-binding residues (4): 1832–1839; 2113–2120; 2455–2462; 2803–2810

Glycosylation sites (1): 1074

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): WHITEHURST_PACLITAXEL_SENSITIVITY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_DYNEIN_COMPLEX, GOCC_CILIUM, GOCC_AXONEMAL_DYNEIN_COMPLEX, chr12q24, GOMF_CYTOSKELETAL_PROTEIN_BINDING, GOMF_MICROTUBULE_MOTOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (3): cilium movement involved in cell motility (GO:0060294), microtubule-based process (GO:0007017), microtubule-based movement (GO:0007018)

GO Molecular Function (8): ATP binding (GO:0005524), microtubule binding (GO:0008017), minus-end-directed microtubule motor activity (GO:0008569), dynein intermediate chain binding (GO:0045505), dynein light intermediate chain binding (GO:0051959), nucleotide binding (GO:0000166), microtubule motor activity (GO:0003777), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (10): axonemal dynein complex (GO:0005858), microtubule (GO:0005874), dynein complex (GO:0030286), 9+2 motile cilium (GO:0097729), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), axoneme (GO:0005930), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
protein binding	2
ATP-dependent activity	2
cilium movement	1
cell motility	1
cilium-dependent cell motility	1
cellular process	1
microtubule-based process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
tubulin binding	1
microtubule motor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ribonucleoside triphosphate phosphatase activity	1
axoneme	1
dynein complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
microtubule associated complex	1
catalytic complex	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1
axonemal doublet microtubule	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
microtubule	1
ciliary plasm	1

Protein interactions and networks

STRING

1432 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAH10	CCDC92	Q53HC0	787
DNAH10	ZNF664	Q8N3J9	702
DNAH10	DNAI4	Q5VTH9	480
DNAH10	DNAH12	Q6ZR08	479
DNAH10	DNAL4	O96015	478
DNAH10	CFAP45	Q9UL16	477
DNAH10	DNAI3	Q8IWG1	454
DNAH10	TTC21A	Q8NDW8	447
DNAH10	DNAI2	Q9GZS0	439
DNAH10	CFAP44	Q96MT7	434
DNAH10	CFAP70	Q5T0N1	433
DNAH10	DNALI1	O14645	423
DNAH10	DRC7	Q8IY82	421
DNAH10	DNAI1	Q9UI46	421
DNAH10	CFAP184	Q2M329	420

IntAct

14 interactions, top by confidence:

A	B	Type	Score
DNAH10	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
DNAH10	H3-4	psi-mi:“MI:0915”(physical association)	0.400
DNAH10	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
GATA4	PCCA	psi-mi:“MI:0914”(association)	0.350
NKX2-5		psi-mi:“MI:0914”(association)	0.350
EPHA1	MYO1B	psi-mi:“MI:0914”(association)	0.350
EPHB2	BANF1	psi-mi:“MI:0914”(association)	0.350
IGF1R	HAX1	psi-mi:“MI:0914”(association)	0.350
CANX	NACA	psi-mi:“MI:2364”(proximity)	0.270
EPHA1	PIK3R2	psi-mi:“MI:2364”(proximity)	0.270
MST1R	SHTN1	psi-mi:“MI:2364”(proximity)	0.270
DISC1	DNAH10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): DNAH10 (Affinity Capture-MS), DNAH10 (Proximity Label-MS), DNAH10 (Protein-RNA), DNAH10 (Affinity Capture-MS), DNAH10 (Synthetic Lethality), DNAH10 (Affinity Capture-MS), DNAH10 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), DNAH10 (Proximity Label-MS), DNAH10 (Affinity Capture-MS), DNAH10 (Affinity Capture-MS), DNAH10 (Proximity Label-MS), DNAH10 (Proximity Label-MS), DNAH10 (Proximity Label-MS), DNAH10 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVH7, A2RRP1, D3YVL2, E9Q8T7, O55007, O88480, P0C6F1, P37276, P38650, Q0KK59, Q14204, Q3UHQ6, Q3UMB5, Q3V0Q1, Q4R7B1, Q5R414, Q5SQX6, Q5T0N1, Q5ZLS8, Q63164, Q63170, Q642P2, Q69Z23, Q6GYP7, Q6GYQ0, Q6ZR08, Q7L576, Q7TMB8, Q8BW94, Q8IVF4, Q8K2A7, Q8TD57, Q8TDY2, Q8TEV9, Q8WVF1, Q8WXX0, Q91XQ0, Q923J6, Q95LN2, Q96F07

Diamond homologs: E9Q8T7, F1SC07, M0R8U1, P0C6F1, P23098, P39057, Q39565, Q39575, Q39610, Q3V0Q1, Q63164, Q63170, Q69Z23, Q6ZR08, Q8BW94, Q8IVF4, Q8TD57, Q8TE73, Q8VHE6, Q8WXX0, Q91XQ0, Q923J6, Q96DT5, Q96JB1, Q9C0G6, Q9MBF8, Q9NYC9, Q9P225, Q9P2D7, Q9SMH3, Q9UFH2, P84753, O75369, P80197, P87061, Q2R2W1, Q5Z8K3, Q67UX0, Q7M3S9, Q80X90

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
DNAH10	up-regulates	Proliferation
TNF	“down-regulates quantity by repression”	DNAH10	“transcriptional regulation”
TGFB1	“down-regulates quantity by repression”	DNAH10	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	4
Uncertain significance	679
Likely benign	106
Benign	82

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1217308	NM_001372106.1(DNAH10):c.12589del (p.Ser4197fs)	Pathogenic
1217309	NM_001372106.1(DNAH10):c.7614dup (p.Glu2539fs)	Pathogenic
3239654	NM_001372106.1(DNAH10):c.3904C>T (p.Arg1302Ter)	Pathogenic
1217310	NM_001372106.1(DNAH10):c.13192G>A (p.Gly4398Arg)	Likely pathogenic
3779261	NM_001372106.1(DNAH10):c.7699C>T (p.Gln2567Ter)	Likely pathogenic
3893099	NM_001372106.1(DNAH10):c.7698del (p.Lys2566fs)	Likely pathogenic
4845748	NM_207437.3(DNAH10):c.10369delG	Likely pathogenic

SpliceAI

12711 predictions. Top by Δscore:

Variant	Effect	Δscore
12:123762532:G:GT	donor_gain	1.0000
12:123771580:AAACT:A	acceptor_gain	1.0000
12:123771584:T:A	acceptor_gain	1.0000
12:123771600:GCTAA:G	acceptor_gain	1.0000
12:123771695:CAAA:C	donor_gain	1.0000
12:123771695:CAAAG:C	donor_loss	1.0000
12:123771696:AAAG:A	donor_loss	1.0000
12:123771697:AA:A	donor_gain	1.0000
12:123771697:AAG:A	donor_loss	1.0000
12:123771698:AGT:A	donor_loss	1.0000
12:123771699:G:C	donor_loss	1.0000
12:123771699:G:GG	donor_gain	1.0000
12:123771700:TAAG:T	donor_loss	1.0000
12:123772825:A:AG	acceptor_gain	1.0000
12:123772825:AT:A	acceptor_gain	1.0000
12:123772826:T:G	acceptor_gain	1.0000
12:123772826:T:TA	acceptor_gain	1.0000
12:123772830:TCA:T	acceptor_loss	1.0000
12:123772831:CA:C	acceptor_loss	1.0000
12:123772832:A:AG	acceptor_gain	1.0000
12:123772832:A:AT	acceptor_loss	1.0000
12:123772833:G:GA	acceptor_gain	1.0000
12:123772833:GA:G	acceptor_gain	1.0000
12:123772833:GAGA:G	acceptor_gain	1.0000
12:123772833:GAGAA:G	acceptor_gain	1.0000
12:123772917:G:GA	donor_gain	1.0000
12:123772940:AAGGT:A	donor_loss	1.0000
12:123772941:AGGTA:A	donor_loss	1.0000
12:123772942:GGT:G	donor_loss	1.0000
12:123772943:G:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000018549 (12:123857912 C>T), RS1000033966 (12:123768683 C>T), RS1000067878 (12:123778193 A>G), RS1000102890 (12:123780794 C>T), RS1000107061 (12:123777861 G>A), RS1000120939 (12:123805271 G>A), RS1000128349 (12:123854738 A>G,T), RS1000133691 (12:123815541 C>T), RS1000147423 (12:123866368 C>A,G,T), RS1000166185 (12:123918444 C>A,T), RS1000166704 (12:123895707 G>A), RS1000183059 (12:123850492 T>C), RS1000187466 (12:123795519 C>T), RS1000196203 (12:123816152 G>C), RS1000199021 (12:123905119 A>G)

Disease associations

OMIM: gene MIM:605884 | disease phenotypes: MIM:619515

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 56	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
spermatogenic failure 56	Moderate	AR
primary ciliary dyskinesia	Limited	AR

Mondo (3): spermatogenic failure 56 (MONDO:0030430), oligospermia (MONDO:0001913), male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000798	Oligozoospermia
HP:0000837	Increased circulating gonadotropin level
HP:0003251	Male infertility
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011961	Non-obstructive azoospermia
HP:0011962	Obstructive azoospermia
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0033393	Irregularly shaped sperm tail
HP:0034011	Reduced progressive sperm motility

GWAS associations

146 associations (top):

Study	Trait	p-value
GCST001465_13	Adiponectin levels	3.000000e-10
GCST001523_24	Visceral adipose tissue adjusted for BMI	5.000000e-06
GCST001524_30	Visceral adipose tissue/subcutaneous adipose tissue ratio	9.000000e-07
GCST001524_33	Visceral adipose tissue/subcutaneous adipose tissue ratio	1.000000e-07
GCST002155_2	Osteoarthritis (hip)	2.000000e-06
GCST004063_64	Waist circumference adjusted for body mass index	6.000000e-09
GCST004063_75	Waist circumference adjusted for body mass index	1.000000e-13
GCST004500_130	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	4.000000e-09
GCST004500_69	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-17
GCST004501_18	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	8.000000e-18
GCST004501_19	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-09
GCST004504_37	Waist circumference adjusted for BMI in non-smokers	1.000000e-09
GCST004504_38	Waist circumference adjusted for BMI in non-smokers	1.000000e-16
GCST004562_147	Waist circumference adjusted for body mass index	7.000000e-11
GCST004562_246	Waist circumference adjusted for body mass index	2.000000e-13
GCST004562_43	Waist circumference adjusted for body mass index	9.000000e-09
GCST004563_24	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-11
GCST004564_77	Waist circumference adjusted for BMI in active individuals	2.000000e-12
GCST004567_12	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	3.000000e-18
GCST004567_31	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-18
GCST004576_12	Waist-to-hip ratio adjusted for body mass index	1.000000e-19
GCST004576_13	Waist-to-hip ratio adjusted for body mass index	8.000000e-21
GCST004578_140	Waist-to-hip ratio adjusted for BMI in active individuals	6.000000e-19
GCST004622_124	Reticulocyte count	6.000000e-09
GCST004627_146	Lymphocyte count	4.000000e-09
GCST005196_71	Coronary artery disease	2.000000e-08
GCST005956_10	Waist-to-hip ratio adjusted for BMI	6.000000e-08
GCST005958_11	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-07
GCST005962_22	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST006061_216	Atrial fibrillation	2.000000e-09

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004502	adiponectin measurement
EFO:0004340	body mass index
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430
D009845	Oligospermia	C12.100.500.430.508; C12.100.750.700.508; C12.200.294.430.508

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases reaction, increases abundance	2
sodium arsenite	increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Aflatoxin B1	increases expression, affects methylation	2
ginger extract	decreases expression, decreases reaction, increases abundance	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
terbufos	increases methylation	1
butyraldehyde	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Fonofos	increases methylation	1
Folic Acid	decreases expression	1
Methapyrilene	decreases methylation	1
Oils, Volatile	decreases expression, decreases reaction, increases abundance	1
Parathion	increases methylation	1
Phthalic Acids	decreases methylation	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02307994	PHASE4	UNKNOWN	Clinical Research on Effectiveness and Safety of Treatment of Severe Oligospermia or Azoospermia With uFSH
NCT05320536	PHASE4	UNKNOWN	A Clinical Study of Gulingji Capsule in the Treatment of Idiopathic Oligospermia, Asthenia, and Teratozoospermia
NCT06260007	PHASE4	RECRUITING	Efficacy and Safety Study of Products Based on Tribulus Terrestris, L. in Men With Oligospermia
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00440180	PHASE3	TERMINATED	Aromatase Inhibitors in the Treatment of Male Infertility
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01409837	PHASE2	COMPLETED	The Effect and Safety of Lisinopril in Non-hypertensive Men With Infertility From Low Sperm Count
NCT02234206	PHASE2	COMPLETED	A Clinical Trial to Study the Safety and Efficacy of Chandrakanthi Choornam in Patients With Low Sperm Count
NCT07481370	PHASE2	ENROLLING_BY_INVITATION	Isotretinoin vs hCG for Male Infertility Due to Low or Absent Sperm
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT05158114	PHASE1	WITHDRAWN	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for Testicular Injury and Oligospermia
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT02063256	PHASE2/PHASE3	UNKNOWN	7 NUTS Study. Diet Modification and Male Fertility.
NCT06869863	PHASE1/PHASE2	RECRUITING	Study of Tolerability, Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of the Medicinal Product MediReg®
NCT00479960	EARLY_PHASE1	UNKNOWN	A Preliminary Study on Effect of Omega-3 on Human Sperm
NCT06342856	EARLY_PHASE1	UNKNOWN	Evaluation of Treatment With Coenzyme Q10 and L-Carnitine on Semen Parameters in Infertile Men With Idiopathic Oligoasthenoteratospermia
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT01239186	Not specified	COMPLETED	Identification and Characterization of the Methylation Abnormalities on Whole Genome Among Infertile Men
NCT01509482	Not specified	COMPLETED	Insulin Resistance in Idiopathic Oligospermia and Azoospermia
NCT01520584	Not specified	UNKNOWN	Supplement Intake in Infertile Men;the Effect on Sperm Parameters,Fertilization Rate and Embryo Quality
NCT01828710	Not specified	COMPLETED	Myo-inositol on Human Semen Parameters
NCT01856361	Not specified	TERMINATED	Ramipril for the Treatment of Oligospermia
NCT02155179	Not specified	COMPLETED	Sperm Pathology Samples and Morphokinetics
NCT03898752	Not specified	COMPLETED	Is Oxidative Stress in Semen Reduced by Lifestyle Intervention
NCT04349345	Not specified	COMPLETED	Seminal Fluid’s Changes Over 20 Years