DNAH17

Summary

DNAH17 (dynein axonemal heavy chain 17, HGNC:2946) is a protein-coding gene on chromosome 17q25.3, encoding Dynein axonemal heavy chain 17 (Q9UFH2). Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum.

Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).

Source: NCBI Gene 8632 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 39 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 1,558 total — 7 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 9
• MANE Select transcript: NM_173628

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2946
Approved symbol	DNAH17
Name	dynein axonemal heavy chain 17
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	DNEL2, FLJ40457
Ensembl gene	ENSG00000187775
Ensembl biotype	protein_coding
OMIM	610063
Entrez	8632

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding_CDS_not_defined, 4 retained_intron, 1 protein_coding, 1 nonsense_mediated_decay

ENST00000389840, ENST00000586052, ENST00000586850, ENST00000587177, ENST00000589793, ENST00000590227, ENST00000591369, ENST00000591647, ENST00000592152, ENST00000592192

RefSeq mRNA: 1 — MANE Select: NM_173628 NM_173628

CCDS: CCDS11757

Canonical transcript exons

ENST00000389840 — 81 exons

Exon	Start	End
ENSE00001111608	78458565	78458680
ENSE00001547460	78577295	78577396
ENSE00001550535	78574713	78575082
ENSE00001552045	78501742	78501873
ENSE00001557842	78539737	78539880
ENSE00001594346	78510384	78510506
ENSE00001595807	78491443	78491570
ENSE00001611363	78543857	78543997
ENSE00001619603	78480684	78480786
ENSE00001620086	78475669	78475833
ENSE00001628573	78484868	78485033
ENSE00001628622	78492633	78492765
ENSE00001631213	78494593	78494820
ENSE00001641991	78476572	78476733
ENSE00001644428	78526880	78526996
ENSE00001659842	78501184	78501344
ENSE00001673738	78572701	78572894
ENSE00001675445	78479025	78479116
ENSE00001693050	78529472	78529694
ENSE00001701197	78532482	78532736
ENSE00001714185	78530343	78530512
ENSE00001714436	78495875	78496032
ENSE00001718970	78494036	78494173
ENSE00001735428	78571590	78571782
ENSE00001766646	78571279	78571378
ENSE00001772275	78494959	78495097
ENSE00001793835	78514774	78515022
ENSE00001798045	78537299	78537481
ENSE00002332261	78500305	78500461
ENSE00002398154	78499008	78499112
ENSE00002751654	78526651	78526737
ENSE00002822692	78502591	78502698
ENSE00002855243	78525009	78525161
ENSE00003460328	78566614	78566730
ENSE00003462885	78570247	78570372
ENSE00003467185	78454470	78454705
ENSE00003486116	78453343	78453465
ENSE00003497601	78461544	78461708
ENSE00003499668	78462844	78463077
ENSE00003500432	78505293	78505445
ENSE00003500798	78502886	78503011
ENSE00003502813	78570948	78571033
ENSE00003505174	78507458	78507805
ENSE00003505521	78551535	78551638
ENSE00003507558	78434029	78434220
ENSE00003508059	78460162	78460257
ENSE00003517793	78479485	78479632
ENSE00003518832	78449414	78449584
ENSE00003518922	78450254	78450394
ENSE00003528436	78475278	78475469
ENSE00003533101	78455644	78455836
ENSE00003536536	78426926	78427108
ENSE00003540137	78552697	78552805
ENSE00003557700	78451469	78451673
ENSE00003562466	78445558	78445680
ENSE00003573362	78485550	78485757
ENSE00003582471	78560740	78560935
ENSE00003592485	78490699	78490847
ENSE00003603791	78468617	78468883
ENSE00003611025	78466655	78466816
ENSE00003614518	78561715	78561980
ENSE00003615665	78459784	78460001
ENSE00003625990	78459001	78459208
ENSE00003632124	78441051	78441199
ENSE00003643026	78569166	78569252
ENSE00003643741	78558108	78558254
ENSE00003648133	78423697	78424153
ENSE00003648940	78439090	78439217
ENSE00003650526	78444604	78444797
ENSE00003650822	78450682	78450846
ENSE00003660089	78485960	78486133
ENSE00003662749	78426457	78426600
ENSE00003662897	78566999	78567166
ENSE00003671320	78437641	78437868
ENSE00003673026	78506720	78506846
ENSE00003673694	78428525	78428707
ENSE00003678554	78425346	78425571
ENSE00003679841	78486224	78486506
ENSE00003681718	78569375	78569527
ENSE00003684828	78507278	78507369
ENSE00003691661	78429121	78429300

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 93.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.9017 / max 162.8225, expressed in 83 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168417	0.5283	73
168418	0.1466	46
168416	0.1219	44
168435	0.0621	3
168411	0.0332	23
168422	0.0060	2
168436	0.0034	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	93.97	gold quality
spinal cord	UBERON:0002240	91.64	gold quality
left testis	UBERON:0004533	88.28	gold quality
right testis	UBERON:0004534	87.48	gold quality
testis	UBERON:0000473	85.52	gold quality
inferior olivary complex	UBERON:0002127	85.44	gold quality
corpus callosum	UBERON:0002336	84.52	gold quality
cranial nerve II	UBERON:0000941	83.54	gold quality
substantia nigra	UBERON:0002038	82.33	gold quality
sperm	CL:0000019	81.45	silver quality
midbrain	UBERON:0001891	80.82	gold quality
blood	UBERON:0000178	80.81	gold quality
male germ cell	CL:0000015	80.19	silver quality
upper lobe of left lung	UBERON:0008952	80.11	gold quality
spleen	UBERON:0002106	80.03	gold quality
right lung	UBERON:0002167	79.97	gold quality
substantia nigra pars reticulata	UBERON:0001966	79.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.56	gold quality
upper lobe of lung	UBERON:0008948	77.44	gold quality
inferior vagus X ganglion	UBERON:0005363	77.15	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.15	gold quality
metanephros cortex	UBERON:0010533	76.01	gold quality
cerebellar hemisphere	UBERON:0002245	75.63	gold quality
cerebellar cortex	UBERON:0002129	75.40	gold quality
prefrontal cortex	UBERON:0000451	74.32	gold quality
Ammon’s horn	UBERON:0001954	74.29	gold quality
omental fat pad	UBERON:0010414	74.20	gold quality
peritoneum	UBERON:0002358	74.15	gold quality
skin of abdomen	UBERON:0001416	74.01	gold quality
medial globus pallidus	UBERON:0002477	73.99	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.26
E-CURD-119	no	32243.41
E-GEOD-131882	no	13252.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting DNAH17, 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-186-5P	99.99	70.83	3707
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-4675	97.69	64.82	774
HSA-MIR-4741	97.69	64.14	883
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-3622B-3P	96.82	66.36	988
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-764	94.16	64.85	656

Literature-anchored findings (GeneRIF, showing 8)

• We found that overexpression of DNAH17 by down-regulation of methylation levels might contribute to hepatocellular carcinoma (HCC) initiation and progression. In addition, the hypomethylation status of the DNAH17 gene, both in tumor tissue and adjacent non-cancerous tissue, could be a promising biomarker for tumor thrombosis in HCC. (PMID:30575322)
• Mutations in DNAH17 Cause Isolated Male Infertility Due to Asthenozoospermia. (PMID:31178125)
• A DNAH17 missense variant causes flagella destabilization and asthenozoospermia. (PMID:31658987)
• DNAH17 is associated with asthenozoospermia and multiple morphological abnormalities of sperm flagella. (PMID:31841227)
• Novel loss-of-function variants in DNAH17 cause multiple morphological abnormalities of the sperm flagella in humans and mice. (PMID:33070343)
• Novel compound heterozygous variants in dynein axonemal heavy chain 17 cause asthenoteratospermia with sperm flagellar defects. (PMID:33423959)
• Novel compound heterozygous variants of DNAH17 in a Chinese infertile man with multiple morphological abnormalities of sperm flagella. (PMID:35932098)
• Novel mutations in DNAH17 cause sperm flagellum defects and their influence on ICSI outcome. (PMID:37574497)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dnah17	ENSMUSG00000033987
rattus_norvegicus	Dnah17	ENSRNOG00000003028

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), DYNC1H1 (ENSG00000197102), DNAH10 (ENSG00000197653)

Protein

Protein identifiers

Dynein axonemal heavy chain 17 — Q9UFH2 (reviewed: Q9UFH2)

Alternative names: Axonemal beta dynein heavy chain 17, Axonemal dynein heavy chain-like protein 1, Ciliary dynein heavy chain 17, Ciliary dynein heavy chain-like protein 1, Dynein axonemal light chain 2

All UniProt accessions (2): Q9UFH2, K7ELN3

UniProt curated annotations — full annotation on UniProt →

Function. Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum. Produces force towards the minus ends of microtubules. Key component of dynein, a family of motor proteins essential for movement along microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required for structural and functional integrity of cilia. Plays a major role in sperm motility, implicated in sperm flagellar assembly and beating.

Subunit / interactions. Part of the ciliary outer dynein arms (ODAs), at least consisting of dynein axonemal heavy chains, light chains and intermediate chains. The ODAs interact with DNAAF9; this interaction inactivates the dyneins.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme. Cell projection. Cilium. Flagellum.

Tissue specificity. Expressed in testis. Expressed in spermatozoa (at protein level). Not detected in airway epithelial cells (at protein level).

Disease relevance. Spermatogenic failure 39 (SPGF39) [MIM:618643] An autosomal recessive infertility disorder characterized by asthenoteratozoospermia. Spermatozoa exhibit multiple morphologic anomalies including short, absent, irregularly shaped and coiled flagella, and abnormalities of the head and midpiece. 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.

Miscellaneous. Gene prediction based on partial mRNA data.

Similarity. Belongs to the dynein heavy chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UFH2-1	1	yes
Q9UFH2-4	4

RefSeq proteins (1): NP_775899* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
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 (46 total): sequence conflict 16, sequence variant 9, region of interest 8, binding site 4, repeat 3, splice variant 3, coiled-coil region 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9UFH2 — 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): 1847–1854; 2128–2135; 2455–2462; 2801–2808

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): AREB6_03, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOMF_CYTOSKELETAL_MOTOR_ACTIVITY, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_OUTER_DYNEIN_ARM_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_CELL_PROJECTION_ORGANIZATION, GATA4_Q3, MARIADASON_REGULATED_BY_HISTONE_ACETYLATION_UP, GOBP_AXONEME_ASSEMBLY, RICKMAN_HEAD_AND_NECK_CANCER_C, FOXO4_02

GO Biological Process (5): outer dynein arm assembly (GO:0036158), cilium-dependent cell motility (GO:0060285), cilium movement involved in cell motility (GO:0060294), microtubule-based process (GO:0007017), microtubule-based movement (GO:0007018)

GO Molecular Function (6): microtubule motor activity (GO:0003777), ATP binding (GO:0005524), 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)

GO Cellular Component (12): axonemal dynein complex (GO:0005858), microtubule (GO:0005874), axoneme (GO:0005930), dynein complex (GO:0030286), sperm flagellum (GO:0036126), outer dynein arm (GO:0036157), 9+2 motile cilium (GO:0097729), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium movement	2
protein binding	2
axonemal dynein complex assembly	1
cilium or flagellum-dependent cell motility	1
cell motility	1
cilium-dependent cell motility	1
cellular process	1
microtubule-based process	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
ATP-dependent activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
microtubule motor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
axoneme	1
dynein complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
microtubule associated complex	1
catalytic complex	1
9+2 motile cilium	1
axonemal dynein 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
cilium	1

Protein interactions and networks

STRING

1593 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAH17	TTC29	Q8NA56	611
DNAH17	CFAP43	Q8NDM7	595
DNAH17	QRICH2	Q9H0J4	591
DNAH17	CFAP69	A5D8W1	584
DNAH17	CFAP44	Q96MT7	582
DNAH17	AK7	Q96M32	574
DNAH17	ARMC2	Q8NEN0	572
DNAH17	CFAP70	Q5T0N1	558
DNAH17	TTC21A	Q8NDW8	553
DNAH17	CFAP251	Q8TBY9	535
DNAH17	SPACDR	Q8IZ16	530
DNAH17	FSIP2	Q5CZC0	518
DNAH17	SPATA16	Q9BXB7	516
DNAH17	DNAJB13	P59910	495
DNAH17	DNAH8	Q96JB1	490

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DNAH17	PLRG1	psi-mi:“MI:0915”(physical association)	0.400
DNAH17	H1-5	psi-mi:“MI:0915”(physical association)	0.400
CXCR2	PSMD11	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
DNAH17	IGHA2	psi-mi:“MI:0914”(association)	0.350

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

1 interactions.

A	Effect	B	Mechanism
DNAH17	up-regulates	Cilium_movement

Disease & clinical

Clinical variants and AI predictions

ClinVar

1558 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	15
Uncertain significance	947
Likely benign	170
Benign	349

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1696866	NM_173628.4(DNAH17):c.5408G>A (p.Cys1803Tyr)	Pathogenic
1698434	NM_173628.4(DNAH17):c.5707C>T (p.Arg1903Cys)	Pathogenic
3388882	NM_173628.4(DNAH17):c.1076_1077dup (p.Lys360Ter)	Pathogenic
4534367	NM_173628.4(DNAH17):c.3577C>T (p.Gln1193Ter)	Pathogenic
692266	NM_173628.4(DNAH17):c.5486G>A (p.Cys1829Tyr)	Pathogenic
692267	NM_173628.4(DNAH17):c.1293_1294del (p.Tyr431_Lys432delinsTer)	Pathogenic
692268	NM_173628.4(DNAH17):c.7994_8012del (p.Gly2665fs)	Pathogenic
2441656	NM_173628.4(DNAH17):c.2869G>T (p.Glu957Ter)	Likely pathogenic
2630219	NM_173628.4(DNAH17):c.11753del (p.Ala3918fs)	Likely pathogenic
2630533	NM_173628.4(DNAH17):c.5562_5563del (p.Glu1855fs)	Likely pathogenic
2634755	NM_173628.4(DNAH17):c.12390dup (p.Asn4131fs)	Likely pathogenic
3032922	NM_173628.4(DNAH17):c.6818+1G>A	Likely pathogenic
3037103	NM_173628.4(DNAH17):c.10571del (p.Lys3524fs)	Likely pathogenic
3075982	NM_173628.4(DNAH17):c.7020dup (p.Asp2341fs)	Likely pathogenic
3382358	NM_173628.4(DNAH17):c.8821C>T (p.Arg2941Ter)	Likely pathogenic
3779262	NM_173628.4(DNAH17):c.11793G>A (p.Trp3931Ter)	Likely pathogenic
3779263	NM_173628.4(DNAH17):c.2314C>T (p.Arg772Ter)	Likely pathogenic
3779266	NM_173628.4(DNAH17):c.4502_4503dup (p.Ile1502fs)	Likely pathogenic
3779267	NM_173628.4(DNAH17):c.2182_2183del (p.Lys728fs)	Likely pathogenic
4540404	NM_173628.4(DNAH17):c.7900+1G>T	Likely pathogenic
599507	NM_173628.4(DNAH17):c.3766G>A (p.Gly1256Arg)	Likely pathogenic
599509	NM_173628.4(DNAH17):c.6563G>A (p.Arg2188Gln)	Likely pathogenic

SpliceAI

12279 predictions. Top by Δscore:

Variant	Effect	Δscore
17:78424151:CCC:C	acceptor_gain	1.0000
17:78424152:CC:C	acceptor_gain	1.0000
17:78424152:CCC:C	acceptor_gain	1.0000
17:78424153:CC:C	acceptor_gain	1.0000
17:78424153:CCTGC:C	acceptor_loss	1.0000
17:78424154:C:CA	acceptor_loss	1.0000
17:78424154:C:CC	acceptor_gain	1.0000
17:78424155:T:A	acceptor_loss	1.0000
17:78425342:TTA:T	donor_loss	1.0000
17:78425343:TA:T	donor_loss	1.0000
17:78425344:A:AC	donor_gain	1.0000
17:78425344:ACCTT:A	donor_gain	1.0000
17:78425345:C:CC	donor_gain	1.0000
17:78425345:CCTT:C	donor_gain	1.0000
17:78425345:CCTTC:C	donor_gain	1.0000
17:78425592:C:CC	acceptor_gain	1.0000
17:78426452:CTTA:C	donor_loss	1.0000
17:78426454:TAC:T	donor_loss	1.0000
17:78426455:A:AC	donor_gain	1.0000
17:78426455:AC:A	donor_gain	1.0000
17:78426455:ACC:A	donor_gain	1.0000
17:78426456:C:CC	donor_gain	1.0000
17:78426456:CC:C	donor_gain	1.0000
17:78426456:CCC:C	donor_gain	1.0000
17:78426597:CTCC:C	acceptor_gain	1.0000
17:78426598:TCCC:T	acceptor_loss	1.0000
17:78426599:CCCT:C	acceptor_loss	1.0000
17:78426601:C:CC	acceptor_gain	1.0000
17:78426602:T:A	acceptor_loss	1.0000
17:78426925:C:CT	donor_loss	1.0000

AlphaMissense

29604 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:78425476:C:A	Q4337H	1.000
17:78425476:C:G	Q4337H	1.000
17:78466717:A:G	W2960R	1.000
17:78466717:A:T	W2960R	1.000
17:78475372:C:T	G2806D	1.000
17:78475461:A:C	F2776L	1.000
17:78475461:A:T	F2776L	1.000
17:78475463:A:G	F2776L	1.000
17:78423944:A:G	W4451R	0.999
17:78423944:A:T	W4451R	0.999
17:78423985:A:T	V4437D	0.999
17:78424023:A:C	C4424W	0.999
17:78424025:A:G	C4424R	0.999
17:78424145:A:G	W4384R	0.999
17:78424145:A:T	W4384R	0.999
17:78425376:C:G	G4371R	0.999
17:78425447:A:G	L4347P	0.999
17:78425447:A:T	L4347Q	0.999
17:78425468:G:T	A4340D	0.999
17:78425486:G:T	A4334D	0.999
17:78425559:A:G	W4310R	0.999
17:78425559:A:T	W4310R	0.999
17:78427008:A:T	V4230D	0.999
17:78429227:C:G	R4100P	0.999
17:78429230:T:A	D4099V	0.999
17:78429231:C:G	D4099H	0.999
17:78434112:A:G	W4048R	0.999
17:78434112:A:T	W4048R	0.999
17:78434125:G:C	F4043L	0.999
17:78434125:G:T	F4043L	0.999

dbSNP variants (sampled 300 via entrez): RS1000012054 (17:78539673 A>C,G), RS1000017190 (17:78451554 T>C), RS1000045523 (17:78468101 C>A), RS1000073350 (17:78521291 A>G), RS1000079553 (17:78482028 A>C,T), RS1000091443 (17:78554987 T>C), RS1000107046 (17:78508006 T>A,C,G), RS1000113367 (17:78457967 G>T), RS1000144336 (17:78457805 C>G,T), RS1000164166 (17:78423199 G>C), RS1000208306 (17:78531684 G>C), RS1000242217 (17:78451808 C>T), RS1000244209 (17:78478404 T>G), RS1000244538 (17:78503454 G>C), RS1000254843 (17:78543491 C>T)

Disease associations

OMIM: gene MIM:610063 | disease phenotypes: MIM:618643

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 39	Strong	Autosomal recessive
non-syndromic male infertility due to sperm motility disorder	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
spermatogenic failure 39	Definitive	AR

Mondo (3): spermatogenic failure 39 (MONDO:0032845), male infertility (MONDO:0005372), (MONDO:0017173)

Orphanet (1): Male infertility with spermatogenesis disorder (Orphanet:399775)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000798	Oligozoospermia
HP:0003251	Male infertility
HP:0011462	Young adult onset
HP:0012207	Reduced sperm motility
HP:0032558	Absent sperm flagella
HP:0032559	Short sperm flagella
HP:0032560	Coiled sperm flagella
HP:0032562	Tapered sperm head

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002468_7	Triglycerides	7.000000e-09
GCST005588_11	Idiopathic dilated cardiomyopathy	6.000000e-06
GCST005648_31	Serum metabolite concentrations in chronic kidney disease	4.000000e-08
GCST008161_54	Waist circumference adjusted for body mass index	5.000000e-06
GCST009325_60	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	3.000000e-09
GCST90002388_511	Lymphocyte count	2.000000e-09
GCST90002405_557	Reticulocyte count	1.000000e-09
GCST90002406_504	Reticulocyte fraction of red cells	2.000000e-09

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0007789	BMI-adjusted waist circumference
EFO:0004587	lymphocyte count
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression, decreases reaction, increases abundance	3
Cadmium Chloride	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
OTX015	decreases expression	1
FR900359	decreases phosphorylation	1
mivebresib	decreases expression	1
ginger extract	decreases reaction, increases abundance, increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
ferrous chloride	increases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	increases methylation	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
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
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
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
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia