DNAH8

Summary

DNAH8 (dynein axonemal heavy chain 8, HGNC:2952) is a protein-coding gene on chromosome 6p21.2, encoding Dynein axonemal heavy chain 8 (Q96JB1). Force generating protein component of the outer dynein arms (ODAs) in the sperm flagellum.

The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules.

Source: NCBI Gene 1769 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 46 (Strong, ClinGen) — +2 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 2,742 total — 118 pathogenic, 40 likely-pathogenic
• Phenotypes (HPO): 8
• MANE Select transcript: NM_001206927

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2952
Approved symbol	DNAH8
Name	dynein axonemal heavy chain 8
Location	6p21.2
Locus type	gene with protein product
Status	Approved
Aliases	hdhc9
Ensembl gene	ENSG00000124721
Ensembl biotype	protein_coding
OMIM	603337
Entrez	1769

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000327475, ENST00000359357, ENST00000373278, ENST00000394393, ENST00000449981

RefSeq mRNA: 2 — MANE Select: NM_001206927 NM_001206927, NM_001371

CCDS: CCDS4838, CCDS75447

Canonical transcript exons

ENST00000327475 — 93 exons

Exon	Start	End
ENSE00000750425	39026546	39026667
ENSE00000929579	38860457	38860629
ENSE00000929639	38921369	38921506
ENSE00000929641	38923058	38923185
ENSE00000929643	38923991	38924162
ENSE00000929645	38926055	38926210
ENSE00000929646	38929511	38929666
ENSE00000929649	38931811	38931993
ENSE00000929650	38935592	38935697
ENSE00000929652	38937974	38938226
ENSE00000929654	38938798	38938988
ENSE00000929656	38945467	38945588
ENSE00000929658	38951318	38951520
ENSE00000929660	38973661	38973813
ENSE00000929661	38974374	38974529
ENSE00000929662	38982346	38982462
ENSE00000929663	38984206	38984307
ENSE00000929664	38990012	38990172
ENSE00000929665	39008814	39008970
ENSE00000929667	39012448	39012637
ENSE00000974010	38737067	38737256
ENSE00000974011	38737809	38737972
ENSE00000974012	38741711	38741887
ENSE00000974013	38750476	38750589
ENSE00000974014	38755972	38756079
ENSE00000974015	38761702	38761803
ENSE00000974016	38770413	38770559
ENSE00000974017	38775754	38775951
ENSE00000974018	38778388	38778464
ENSE00000974019	38779966	38780065
ENSE00000974020	38781254	38781373
ENSE00000974021	38783004	38783139
ENSE00000974022	38786765	38786952
ENSE00000974023	38789803	38789883
ENSE00000974024	38790289	38790405
ENSE00000974025	38791555	38791674
ENSE00000974026	38803179	38803311
ENSE00000974027	38805481	38805596
ENSE00000974029	38807610	38807716
ENSE00000974030	38814054	38814129
ENSE00000974031	38815468	38815657
ENSE00000974032	38822838	38823034
ENSE00000974033	38823562	38823688
ENSE00000974034	38826156	38826391
ENSE00000974036	38828184	38828288
ENSE00000974037	38832322	38832435
ENSE00000974038	38834579	38834641
ENSE00000974039	38837942	38838042
ENSE00000974040	38842368	38842505
ENSE00000974041	38842663	38842903
ENSE00000974042	38845574	38845773
ENSE00000974043	38848648	38848801
ENSE00000974044	38850251	38850414
ENSE00000974045	38851572	38851674
ENSE00000974046	38852694	38852798
ENSE00000974047	38853186	38853347
ENSE00000974048	38857518	38857742
ENSE00000974052	38863873	38864060
ENSE00000974056	38866769	38866876
ENSE00000974073	38949452	38949570
ENSE00000974074	38971592	38971665
ENSE00001085900	38915201	38915377
ENSE00001085903	38909518	38909744
ENSE00001085906	38896033	38896225
ENSE00001085909	38890652	38890761
ENSE00001085913	38913849	38913952
ENSE00001085915	38868062	38868196
ENSE00001085916	38899776	38899906
ENSE00001085919	38873236	38873376
ENSE00001085923	38886791	38887004
ENSE00001085925	38894701	38894864
ENSE00001085929	38906254	38906407
ENSE00001085932	38875591	38875828
ENSE00001085935	38907956	38908120
ENSE00001085936	38883322	38883456
ENSE00001085938	38872536	38872782
ENSE00001085944	38917239	38917406
ENSE00001085945	38917925	38918140
ENSE00001085946	38911468	38911586
ENSE00001085947	38872906	38873147
ENSE00001085964	38898258	38898380
ENSE00001122907	38882910	38883052
ENSE00001278580	38866591	38866677
ENSE00001279019	39012215	39012367
ENSE00001326528	38729902	38729986
ENSE00001518390	38870401	38870562
ENSE00001643346	38883876	38883998
ENSE00001681064	39030105	39030792
ENSE00001734713	38862280	38862458
ENSE00001878919	38722776	38723199
ENSE00002561608	38715311	38715415
ENSE00003467142	38734474	38734625
ENSE00003562532	38723337	38723471

Expression profiles

Bgee: expression breadth broad, 68 present calls, max score 89.09.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1771 / max 50.9726, expressed in 45 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67678	0.1334	45
67676	0.0395	3
67677	0.0042	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	89.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.77	gold quality
adult organism	UBERON:0007023	75.16	gold quality
testis	UBERON:0000473	69.05	gold quality
upper arm skin	UBERON:0004263	68.01	gold quality
left testis	UBERON:0004533	67.91	gold quality
right testis	UBERON:0004534	67.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	66.66	gold quality
epithelial cell of pancreas	CL:0000083	62.05	gold quality
bone marrow cell	CL:0002092	57.54	gold quality
upper leg skin	UBERON:0004262	57.41	silver quality
spleen	UBERON:0002106	56.40	gold quality
epithelium of nasopharynx	UBERON:0001951	55.60	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
gingival epithelium	UBERON:0001949	54.04	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
vermiform appendix	UBERON:0001154	53.71	gold quality
lymph node	UBERON:0000029	53.27	gold quality
endothelial cell	CL:0000115	52.35	gold quality
skin of leg	UBERON:0001511	50.93	gold quality
tonsil	UBERON:0002372	50.82	gold quality
caecum	UBERON:0001153	50.68	gold quality
myocardium	UBERON:0002349	50.25	gold quality
deltoid	UBERON:0001476	49.98	gold quality
gingiva	UBERON:0001828	49.94	gold quality
ventricular zone	UBERON:0003053	49.89	gold quality
zone of skin	UBERON:0000014	49.77	gold quality
oocyte	CL:0000023	49.73	gold quality
skin of abdomen	UBERON:0001416	49.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.50

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SMARCA1, SMARCA5, TBP

miRNA regulators (miRDB)

58 targeting DNAH8, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 6)

• SNP genotyping of an affected proband with primary ciliary dyskinesia reveals homozygous nonsense variant in DNAH8 gene which can be a candidate for disease susceptibility. (PMID:24307375)
• DNAH8 has a role in androgen receptor activity and prostate cancer progression (PMID:27363033)
• Loss-of-function mutation in DNAH8 induces asthenoteratospermia associated with multiple morphological abnormalities of the sperm flagella. (PMID:32681648)
• A novel splicing variant in DNAH8 causes asthenozoospermia. (PMID:33611675)
• Mutations in DNAH8 contribute to multiple morphological abnormalities of sperm flagella and male infertility. (PMID:33704367)
• ‘Rotor free-wheeling’ in impaired F1FO-ATPase induces congenital hypermetabolism. (PMID:36526552)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnah5l	ENSDARG00000056888
mus_musculus	Dnah8	ENSMUSG00000033826
rattus_norvegicus	Dnah8	ENSRNOG00000000542
drosophila_melanogaster	Dhc1	FBGN0287844

Paralogs (15): DNAH9 (ENSG00000007174), DNAH5 (ENSG00000039139), DNAH11 (ENSG00000105877), DNAH1 (ENSG00000114841), DNAH6 (ENSG00000115423), DNAH7 (ENSG00000118997), DNAH3 (ENSG00000158486), DNAH12 (ENSG00000174844), DNHD1 (ENSG00000179532), DNAH2 (ENSG00000183914), DNAH14 (ENSG00000185842), DYNC2H1 (ENSG00000187240), DNAH17 (ENSG00000187775), DYNC1H1 (ENSG00000197102), DNAH10 (ENSG00000197653)

Protein

Protein identifiers

Dynein axonemal heavy chain 8 — Q96JB1 (reviewed: Q96JB1)

Alternative names: Axonemal beta dynein heavy chain 8, Ciliary dynein heavy chain 8

All UniProt accessions (5): A0A075B6F3, Q96JB1, H0Y7V4, H3BLZ4, Q8IU65

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. Involved in sperm motility; implicated in sperm flagellar assembly.

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.

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

Disease relevance. Spermatogenic failure 46 (SPGF46) [MIM:619095] An autosomal recessive infertility disorder caused by spermatogenesis defects resulting in asthenoteratozoospermia. SPGF46 is characterized by multiple morphologic abnormalities of sperm flagella with disorganization of axonemal and periaxonemal structures. Flagella are absent, short, coiled, angulated, and/or of irregular caliber. 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 (4)

UniProt ID	Names	Canonical?
Q96JB1-1	1	yes
Q96JB1-2	2
Q96JB1-3	3
Q96JB1-4	4

RefSeq proteins (2): NP_001193856, NP_001362 (=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
IPR056759	DYH2-5-8_CC	Domain

Pfam: PF03028, PF08385, PF08393, PF12774, PF12775, PF12777, PF12780, PF12781, PF17852, PF17857, PF18198, PF18199, PF25007

UniProt features (34 total): sequence variant 15, region of interest 7, sequence conflict 4, coiled-coil region 3, binding site 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q96JB1 — 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 (2): 1846–1853; 2128–2135

Post-translational modifications (1): 674

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 154 (showing top): GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, BRN2_01, 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, WANG_TARGETS_OF_MLL_CBP_FUSION_UP, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY, LEE_AGING_NEOCORTEX_UP, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM

GO Biological Process (4): outer dynein arm assembly (GO:0036158), cilium-dependent cell motility (GO:0060285), cilium movement involved in cell motility (GO:0060294), microtubule-based movement (GO:0007018)

GO Molecular Function (7): 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), ATP hydrolysis activity (GO:0016887)

GO Cellular Component (14): axonemal dynein complex (GO:0005858), microtubule (GO:0005874), axoneme (GO:0005930), sperm flagellum (GO:0036126), outer dynein arm (GO:0036157), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), dynein complex (GO:0030286), motile cilium (GO:0031514), cell projection (GO:0042995), 9+2 motile cilium (GO:0097729)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cilium movement	2
ATP-dependent activity	2
protein binding	2
sperm flagellum	2
axonemal dynein complex assembly	1
cilium or flagellum-dependent cell motility	1
cell motility	1
cilium-dependent cell motility	1
microtubule-based process	1
cytoskeletal motor activity	1
polypeptide conformation or assembly isomerase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
microtubule motor activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
ribonucleoside triphosphate phosphatase activity	1
axoneme	1
dynein complex	1
microtubule cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
9+2 motile cilium	1
axonemal dynein complex	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
microtubule associated complex	1
catalytic complex	1
cilium	1
radial spoke	1
motile cilium	1
inner dynein arm	1
outer dynein arm	1
axonemal central pair	1

Protein interactions and networks

STRING

1606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAH8	SAYSD1	Q9NPB0	648
DNAH8	TTC29	Q8NA56	614
DNAH8	DNAAF11	Q86X45	604
DNAH8	DNAI2	Q9GZS0	598
DNAH8	ZMYND10	O75800	545
DNAH8	RSPH1	Q8WYR4	545
DNAH8	DNAAF5	Q86Y56	541
DNAH8	DNAI1	Q9UI46	539
DNAH8	RSPH4A	Q5TD94	536
DNAH8	DNAAF19	Q8IW40	534
DNAH8	CFAP298	P57076	524
DNAH8	RSPH9	Q9H1X1	522
DNAH8	CCDC39	Q9UFE4	515
DNAH8	ODAD3	A5D8V7	512
DNAH8	ODAD2	Q5T2S8	511

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ITGB1	DNAH8	psi-mi:“MI:0915”(physical association)	0.400
RNF31	HNRNPCL2	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): DNAH8 (Affinity Capture-MS), DNAH8 (Affinity Capture-MS), DNAH8 (Affinity Capture-MS), DNAH8 (Co-fractionation), DNAH8 (Co-fractionation), DNAH8 (Co-fractionation), TOMM22 (Co-fractionation), VDAC3 (Co-fractionation), DNAH8 (Affinity Capture-MS), DNAH8 (Proximity Label-MS), DNAH8 (Affinity Capture-MS), HIST1H3A (Cross-Linking-MS (XL-MS)), ENO1 (Cross-Linking-MS (XL-MS)), RPL19 (Cross-Linking-MS (XL-MS)), EIF5A (Cross-Linking-MS (XL-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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2742 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	118
Likely pathogenic	40
Uncertain significance	1189
Likely benign	944
Benign	358

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070202	NC_000006.12:g.38973662dup	Pathogenic
1070746	NM_001206927.2(DNAH8):c.5635C>T (p.Gln1879Ter)	Pathogenic
1073246	NM_001206927.2(DNAH8):c.11087_11088insCTTTTTCC (p.Lys3697fs)	Pathogenic
1074619	NM_001206927.2(DNAH8):c.2084del (p.His695fs)	Pathogenic
1075071	NC_000006.11:g.(?38754521)(38759470_?)del	Pathogenic
1075526	NM_001206927.2(DNAH8):c.2919G>A (p.Trp973Ter)	Pathogenic
1075678	NM_001206927.2(DNAH8):c.9898A>T (p.Lys3300Ter)	Pathogenic
1384798	NM_001206927.2(DNAH8):c.5251C>T (p.Arg1751Ter)	Pathogenic
1409915	NM_001206927.2(DNAH8):c.9298_9305del (p.Lys3100fs)	Pathogenic
1453683	NM_001206927.2(DNAH8):c.5762G>A (p.Trp1921Ter)	Pathogenic
1455639	NM_001206927.2(DNAH8):c.2685del (p.Gly896fs)	Pathogenic
1455659	NM_001206927.2(DNAH8):c.6679C>T (p.Gln2227Ter)	Pathogenic
1455731	NM_001206927.2(DNAH8):c.7086_7089dup (p.Glu2364fs)	Pathogenic
1459612	NC_000006.11:g.(?38690586)(38697782_?)del	Pathogenic
1938267	NM_001206927.2(DNAH8):c.4198C>T (p.Gln1400Ter)	Pathogenic
1941964	NM_001206927.2(DNAH8):c.7362del (p.Ser2455fs)	Pathogenic
1999878	NM_001206927.2(DNAH8):c.9529del (p.Arg3177fs)	Pathogenic
2006154	NM_001206927.2(DNAH8):c.3139G>T (p.Glu1047Ter)	Pathogenic
2031122	NM_001206927.2(DNAH8):c.11286_11293del (p.Asp3763fs)	Pathogenic
2033017	NM_001206927.2(DNAH8):c.9812_9813insGGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGAGNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAACATTTATGC (p.Glu3272fs)	Pathogenic
2037549	NM_001206927.2(DNAH8):c.8635_8636del (p.Asp2879fs)	Pathogenic
2040014	NM_001206927.2(DNAH8):c.8375del (p.Pro2792fs)	Pathogenic
2062692	NM_001206927.2(DNAH8):c.5738_5741dup (p.Leu1915fs)	Pathogenic
2141653	NM_001206927.2(DNAH8):c.3031_3034del (p.Ser1011fs)	Pathogenic
2159717	NM_001206927.2(DNAH8):c.1124_1127del (p.Ile375fs)	Pathogenic
2160631	NM_001206927.2(DNAH8):c.549dup (p.Ala184fs)	Pathogenic
2423975	NC_000006.11:g.(?38939348)(38942325_?)del	Pathogenic
2696684	NM_001206927.2(DNAH8):c.5005G>T (p.Glu1669Ter)	Pathogenic
2706964	NM_001206927.2(DNAH8):c.8081_8085del (p.Val2694fs)	Pathogenic
2711299	NM_001206927.2(DNAH8):c.7396G>T (p.Glu2466Ter)	Pathogenic

SpliceAI

14090 predictions. Top by Δscore:

Variant	Effect	Δscore
6:38722773:TAG:T	acceptor_loss	1.0000
6:38723179:G:GT	donor_gain	1.0000
6:38734468:TTTCA:T	acceptor_loss	1.0000
6:38734469:TTCA:T	acceptor_loss	1.0000
6:38734470:TCAG:T	acceptor_loss	1.0000
6:38734471:CAG:C	acceptor_loss	1.0000
6:38734472:A:AG	acceptor_gain	1.0000
6:38734473:G:C	acceptor_loss	1.0000
6:38734473:G:GG	acceptor_gain	1.0000
6:38734473:GA:G	acceptor_gain	1.0000
6:38734473:GAA:G	acceptor_gain	1.0000
6:38734473:GAAT:G	acceptor_gain	1.0000
6:38734561:G:GT	donor_gain	1.0000
6:38737061:TTTCA:T	acceptor_loss	1.0000
6:38737063:TCAG:T	acceptor_loss	1.0000
6:38737065:A:G	acceptor_loss	1.0000
6:38737065:AG:A	acceptor_gain	1.0000
6:38737066:GG:G	acceptor_gain	1.0000
6:38737066:GGA:G	acceptor_gain	1.0000
6:38737066:GGAA:G	acceptor_gain	1.0000
6:38737253:GATG:G	donor_gain	1.0000
6:38737254:ATG:A	donor_gain	1.0000
6:38737254:ATGGT:A	donor_loss	1.0000
6:38737256:GGTA:G	donor_loss	1.0000
6:38737257:G:A	donor_loss	1.0000
6:38737258:TAAG:T	donor_loss	1.0000
6:38737804:TTTAG:T	acceptor_gain	1.0000
6:38737805:TTAG:T	acceptor_gain	1.0000
6:38737806:TAGG:T	acceptor_gain	1.0000
6:38737807:A:AG	acceptor_gain	1.0000

AlphaMissense

31206 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:38790328:T:A	W685R	1.000
6:38790328:T:C	W685R	1.000
6:38807659:T:C	L850P	1.000
6:38842450:T:A	W1300R	1.000
6:38842450:T:C	W1300R	1.000
6:38842793:T:A	W1362R	1.000
6:38842793:T:C	W1362R	1.000
6:38842795:G:C	W1362C	1.000
6:38842795:G:T	W1362C	1.000
6:38845589:G:C	A1404P	1.000
6:38845590:C:A	A1404D	1.000
6:38845597:G:C	K1406N	1.000
6:38845597:G:T	K1406N	1.000
6:38845620:T:C	L1414P	1.000
6:38845640:T:A	W1421R	1.000
6:38845640:T:C	W1421R	1.000
6:38848724:T:A	W1491R	1.000
6:38848724:T:C	W1491R	1.000
6:38848745:T:A	W1498R	1.000
6:38848745:T:C	W1498R	1.000
6:38848755:T:C	L1501P	1.000
6:38848766:T:C	F1505L	1.000
6:38848768:T:A	F1505L	1.000
6:38848768:T:G	F1505L	1.000
6:38848794:T:C	L1514P	1.000
6:38850263:T:C	F1521L	1.000
6:38850265:T:A	F1521L	1.000
6:38850265:T:G	F1521L	1.000
6:38850284:T:A	W1528R	1.000
6:38850284:T:C	W1528R	1.000

dbSNP variants (sampled 300 via entrez): RS1000005776 (6:38765996 A>T), RS1000047622 (6:38990201 G>A,T), RS1000052811 (6:38976126 A>G), RS1000061713 (6:38864112 T>C), RS1000062856 (6:38730098 A>G), RS1000064051 (6:38799409 G>T), RS1000073506 (6:38730598 G>A,T), RS1000084208 (6:39016348 G>A,T), RS1000103271 (6:38976254 C>T), RS1000105038 (6:38897767 T>C,G), RS1000105812 (6:38941039 G>A), RS1000106687 (6:38984364 T>C), RS1000111777 (6:38813287 T>G), RS1000123196 (6:38813533 G>A), RS1000125939 (6:38879012 C>G,T)

Disease associations

OMIM: gene MIM:603337 | disease phenotypes: MIM:244400, MIM:619095, MIM:209850, MIM:601665

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 46	Strong	Autosomal recessive
spermatogenic failure 5	Moderate	Autosomal recessive
primary ciliary dyskinesia	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
primary ciliary dyskinesia	Disputed	AR
spermatogenic failure 46	Strong	AR

Mondo (6): primary ciliary dyskinesia (MONDO:0016575), spermatogenic failure 46 (MONDO:0033673), prostate cancer (MONDO:0008315), autism (MONDO:0005260), inherited obesity (MONDO:0019182), spermatogenic failure 5 (MONDO:0009461)

Orphanet (3): Primary ciliary dyskinesia (Orphanet:244), Familial prostate cancer (Orphanet:1331), Genetic obesity (Orphanet:77828)

HPO phenotypes

8 total (9 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0003581	Adult onset
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:0000717	Autism

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007673_18	3-month functional outcome in ischaemic stroke (modified Rankin score)	5.000000e-06
GCST008667_13	Smoking status (heavy vs never)	3.000000e-08
GCST009532_23	Circulating leptin levels in high cardiovascular risk	6.000000e-06
GCST011354_56	Bell’s palsy	3.000000e-06
GCST012490_146	Femur bone mineral density x serum urate levels interaction	4.000000e-08
GCST012490_492	Femur bone mineral density x serum urate levels interaction	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement
EFO:0006527	smoking status measurement
EFO:0005000	leptin measurement
EFO:0004531	urate measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D002925	Ciliary Motility Disorders	C08.200; C09.150; C16.131.077.245.500; C16.320.184.500
D007619	Kartagener Syndrome	C08.127.384.500; C08.200.531; C08.695.501; C09.150.531; C14.240.400.280.500; C14.280.400.280.500; C16.131.077.245.500.531; C16.131.240.400.280.500; C16.131.740.501; C16.131.810.250.500; C16.320.184.500.531; C16.320.480
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C562903	Male Infertility with Large-Headed, Multiflagellar, Polyploid Spermatozoa (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases methylation	2
Benzo(a)pyrene	decreases methylation, increases methylation, increases mutagenesis	2
sodium arsenite	affects methylation	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
perfluorooctane sulfonic acid	decreases expression	1
Arsenic	affects methylation	1
Cocaine	affects response to substance	1
Methapyrilene	affects methylation	1
Oxygen	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer