DNAAF10

Summary

DNAAF10 (dynein axonemal assembly factor 10, HGNC:25176) is a protein-coding gene on chromosome 2p14, encoding Dynein axonemal assembly factor 10 (Q96MX6). Key assembly factor specifically required for the stability of axonemal dynein heavy chains in cytoplasm. It is a selective cancer dependency (DepMap: 86.8% of cell lines).

This gene encodes a protein with two WD40 repeat domains thought to be involved in an apoptosis via activation of caspase-3. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 116143 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 72 total
• Cancer dependency (DepMap): dependent in 86.8% of screened cell lines
• MANE Select transcript: NM_138458

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25176
Approved symbol	DNAAF10
Name	dynein axonemal assembly factor 10
Location	2p14
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31741, Monad
Ensembl gene	ENSG00000243667
Ensembl biotype	protein_coding
OMIM	610729
Entrez	116143

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000295121, ENST00000406245, ENST00000409164, ENST00000457114, ENST00000468984, ENST00000492039, ENST00000878382, ENST00000916820

RefSeq mRNA: 2 — MANE Select: NM_138458 NM_001256476, NM_138458

CCDS: CCDS1884, CCDS58712

Canonical transcript exons

ENST00000295121 — 8 exons

Exon	Start	End
ENSE00001604920	68129805	68131445
ENSE00001738493	68157261	68157527
ENSE00003496225	68138742	68138857
ENSE00003573259	68144585	68144715
ENSE00003601497	68134702	68134799
ENSE00003612565	68147467	68147567
ENSE00003616293	68137299	68137433
ENSE00003632961	68141694	68141795

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 85.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.3073 / max 114.8289, expressed in 1658 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28839	6.3073	1658

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.65	gold quality
right uterine tube	UBERON:0001302	84.95	gold quality
calcaneal tendon	UBERON:0003701	83.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.94	gold quality
endometrium	UBERON:0001295	82.03	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.42	gold quality
skeletal muscle tissue	UBERON:0001134	81.23	gold quality
fallopian tube	UBERON:0003889	81.14	gold quality
muscle tissue	UBERON:0002385	80.94	gold quality
smooth muscle tissue	UBERON:0001135	80.60	gold quality
lymph node	UBERON:0000029	80.54	gold quality
muscle of leg	UBERON:0001383	80.07	gold quality
rectum	UBERON:0001052	80.01	gold quality
gastrocnemius	UBERON:0001388	79.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.56	gold quality
apex of heart	UBERON:0002098	79.41	gold quality
corpus callosum	UBERON:0002336	79.17	gold quality
right adrenal gland cortex	UBERON:0035827	79.13	gold quality
ventricular zone	UBERON:0003053	79.02	gold quality
stromal cell of endometrium	CL:0002255	78.95	gold quality
right adrenal gland	UBERON:0001233	78.92	gold quality
cortical plate	UBERON:0005343	78.54	gold quality
left adrenal gland	UBERON:0001234	78.53	gold quality
left coronary artery	UBERON:0001626	78.45	gold quality
urinary bladder	UBERON:0001255	78.43	gold quality
testis	UBERON:0000473	78.36	gold quality
right coronary artery	UBERON:0001625	78.30	gold quality
left adrenal gland cortex	UBERON:0035825	78.29	gold quality
heart left ventricle	UBERON:0002084	78.23	gold quality
adrenal gland	UBERON:0002369	78.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting DNAAF10, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-3117-5P	99.04	67.93	618
HSA-MIR-198	98.70	67.32	920
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-211-3P	98.14	66.77	1052
HSA-MIR-6742-3P	97.95	64.50	1490

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 86.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 4)

• Monad could be involved in apoptosis induced by TNF-alpha (PMID:16487927)
• Monad may function as a novel modulator of apoptosis pathway. (PMID:16487927)
• Is part of an RNA polymerase II-associated complex with possible chaperone activity. (PMID:19450687)
• Exosome-bound WD repeat protein Monad inhibits breast cancer cell invasion by degrading amphiregulin mRNA. (PMID:23844004)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnaaf10	ENSDARG00000037334
mus_musculus	Dnaaf10	ENSMUSG00000078970
rattus_norvegicus	Dnaaf10	ENSRNOG00000085590
drosophila_melanogaster	Wdr92	FBGN0036771

Paralogs (2): RAE1 (ENSG00000101146), BUB3 (ENSG00000154473)

Protein

Protein identifiers

Dynein axonemal assembly factor 10 — Q96MX6 (reviewed: Q96MX6)

Alternative names: WD repeat-containing protein 92, WD repeat-containing protein Monad

All UniProt accessions (4): Q96MX6, A0A140VK67, H7C389, Q8ND98

UniProt curated annotations — full annotation on UniProt →

Function. Key assembly factor specifically required for the stability of axonemal dynein heavy chains in cytoplasm.

Subunit / interactions. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92. Interacts with PIH1D1; the interaction associates DNAAF10 with the R2TP complex. Interacts with several dynein axonemal assembly factors.

Subcellular location. Dynein axonemal particle.

Tissue specificity. Widely expressed with the highest expression in testis.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96MX6-1	1	yes
Q96MX6-2	2

RefSeq proteins (2): NP_001243405, NP_612467* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400

UniProt features (43 total): strand 30, repeat 6, turn 3, chain 1, helix 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3I2N	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96MX6-F1	96.66	0.95

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): chr2p14, GOBP_AXONEMAL_DYNEIN_COMPLEX_ASSEMBLY, MODULE_205, GOBP_CILIUM_ORGANIZATION, GOBP_PROTEIN_STABILIZATION, GOBP_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_MICROTUBULE_BUNDLE_FORMATION, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_AXONEME_ASSEMBLY, GOMF_UBIQUITIN_LIKE_PROTEIN_BINDING, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, LEE_BMP2_TARGETS_DN, GOMF_UBIQUITIN_BINDING, GSE13522_WT_VS_IFNG_KO_SKING_T_CRUZI_Y_STRAIN_INF_UP

GO Biological Process (3): apoptotic process (GO:0006915), protein stabilization (GO:0050821), axonemal dynein complex assembly (GO:0070286)

GO Molecular Function (2): ubiquitin binding (GO:0043130), protein binding (GO:0005515)

GO Cellular Component (3): dynein axonemal particle (GO:0120293), RPAP3/R2TP/prefoldin-like complex (GO:1990062), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
regulation of protein stability	1
axoneme assembly	1
protein-containing complex assembly	1
ubiquitin-like protein binding	1
binding	1
cytoplasm	1
intracellular membraneless organelle	1
protein-containing complex	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1835 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAAF10	PDRG1	Q9NUG6	984
DNAAF10	PFDN6	O15212	984
DNAAF10	POLR2E	P19388	984
DNAAF10	UXT	Q9UBK9	983
DNAAF10	PFDN2	Q9UHV9	982
DNAAF10	RPAP3	Q9H6T3	933
DNAAF10	PIH1D1	Q9NWS0	861
DNAAF10	RUVBL1	P82276	825
DNAAF10	RUVBL2	Q9Y230	804
DNAAF10	DNAAF6	Q9NQM4	721
DNAAF10	URI1	O94763	710
DNAAF10	SPAG1	Q07617	677
DNAAF10	DPCD	Q9BVM2	660
DNAAF10	ETAA1	Q9NY74	634
DNAAF10	DNAAF11	Q86X45	633

IntAct

107 interactions, top by confidence:

A	B	Type	Score
PARD6A	PRKCI	psi-mi:“MI:0914”(association)	0.950
NPHP1	NPHP4	psi-mi:“MI:2364”(proximity)	0.930
POLR2E	POLR3A	psi-mi:“MI:0914”(association)	0.870
DNAAF10	PPP1CC	psi-mi:“MI:0914”(association)	0.800
DNAAF2	UBE3D	psi-mi:“MI:0914”(association)	0.780
RPAP3	DNAAF10	psi-mi:“MI:0915”(physical association)	0.760
DNAAF10	RPAP3	psi-mi:“MI:0915”(physical association)	0.760
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
POLR2E	MED19	psi-mi:“MI:0914”(association)	0.730
POLR3E	POLR3A	psi-mi:“MI:0914”(association)	0.730
POLR2J	POLR2D	psi-mi:“MI:0914”(association)	0.730
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
RPRD1B	POLR2D	psi-mi:“MI:0914”(association)	0.730
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
PFDN2	POLR3A	psi-mi:“MI:0914”(association)	0.670
CCT2	PPP6C	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT7	TXNDC9	psi-mi:“MI:0914”(association)	0.640
POLR3K	POLR3A	psi-mi:“MI:0914”(association)	0.640

BioGRID (226): WDR92 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT3 (Affinity Capture-MS), PPP1CC (Affinity Capture-MS), PPP1CA (Affinity Capture-MS), PIH1D1 (Affinity Capture-Western), WDR92 (Affinity Capture-Western), WDR92 (Affinity Capture-MS), WDR92 (Co-fractionation), WDR92 (Co-fractionation), WDR92 (Affinity Capture-Western), WDR92 (Proximity Label-MS), WDR92 (Proximity Label-MS), WDR92 (Affinity Capture-MS), WDR92 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8EXB5, A4QNE6, A8WGF4, C1BK83, O35142, O43684, O55029, P35605, P35606, Q17QU5, Q1JP79, Q1JQB2, Q29RH4, Q29RZ9, Q3UGF1, Q4FZW5, Q4R4I8, Q561Y0, Q5I0B4, Q5M7F6, Q5MNZ6, Q5R664, Q5RB58, Q5U4Y8, Q5VQ78, Q6GNF1, Q6NWV3, Q6PA72, Q6TGU2, Q803V5, Q8AVT9, Q8BGF3, Q8IWZ6, Q8K2G4, Q8L828, Q8NEZ3, Q8VE80, Q92747, Q96J01, Q96MX6

Diamond homologs: A4QNE6, A8J3F6, Q29RZ9, Q561Y0, Q5M7F6, Q8BGF3, Q96MX6, Q9C827, Q9CAA0, B6HHJ8, F1DLK1, O43818, O60136, O74184, P29829, Q17QU5, Q3MKM6, Q75LV5, Q803V5, Q91WM3, Q99973, Q9BVC4, Q9DCJ1, Q9M0V4, Q9P7C0, Q9Z2K5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DNAAF10	“form complex”	“PAQosome co-chaperone complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FGFR2 mutant receptor activation	6	68.2×	8e-09
RNA Polymerase III Chain Elongation	7	66.3×	6e-10
Signaling by FGFR2 IIIa TM	6	53.8×	3e-08
RNA Polymerase III Transcription Termination	7	51.9×	2e-09
RNA Polymerase III Transcription Initiation From Type 2 Promoter	8	50.5×	4e-10
RNA Polymerase III Transcription Initiation From Type 1 Promoter	8	48.7×	4e-10
RNA Polymerase III Transcription Initiation From Type 3 Promoter	8	48.7×	4e-10
Abortive elongation of HIV-1 transcript in the absence of Tat	6	44.5×	9e-08

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of telomere maintenance via telomerase	5	43.6×	1e-05
protein dephosphorylation	6	15.8×	2e-04
protein stabilization	18	14.3×	1e-13
protein folding	10	12.3×	2e-06
transcription by RNA polymerase II	8	6.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1479 predictions. Top by Δscore:

Variant	Effect	Δscore
2:68134700:A:AC	donor_gain	1.0000
2:68134701:C:CC	donor_gain	1.0000
2:68134701:CTA:C	donor_gain	1.0000
2:68134706:T:TA	donor_gain	1.0000
2:68137431:CAC:C	acceptor_gain	1.0000
2:68137434:CTG:C	acceptor_loss	1.0000
2:68137435:T:C	acceptor_loss	1.0000
2:68138740:ACC:A	donor_gain	1.0000
2:68138741:CCC:C	donor_gain	1.0000
2:68138858:C:CC	acceptor_gain	1.0000
2:68147572:A:AC	acceptor_gain	1.0000
2:68147572:A:C	acceptor_gain	1.0000
2:68131446:C:CC	acceptor_gain	0.9900
2:68134652:TTAC:T	donor_gain	0.9900
2:68134701:CT:C	donor_gain	0.9900
2:68137294:TTTAC:T	donor_loss	0.9900
2:68137295:TTAC:T	donor_loss	0.9900
2:68137295:TTACC:T	donor_loss	0.9900
2:68137296:TA:T	donor_loss	0.9900
2:68137296:TAC:T	donor_loss	0.9900
2:68137297:A:C	donor_loss	0.9900
2:68137298:C:A	donor_loss	0.9900
2:68137429:CACAC:C	acceptor_gain	0.9900
2:68138735:A:AC	donor_gain	0.9900
2:68138735:ACTTT:A	donor_loss	0.9900
2:68138736:C:CC	donor_gain	0.9900
2:68138736:CTTT:C	donor_loss	0.9900
2:68138737:TTTA:T	donor_loss	0.9900
2:68138737:TTTAC:T	donor_loss	0.9900
2:68138738:TTA:T	donor_loss	0.9900

AlphaMissense

2353 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:68134781:A:G	W263R	1.000
2:68134781:A:T	W263R	1.000
2:68141709:A:G	W168R	1.000
2:68141709:A:T	W168R	1.000
2:68131327:A:G	W329R	0.999
2:68131327:A:T	W329R	0.999
2:68134779:C:A	W263C	0.999
2:68134779:C:G	W263C	0.999
2:68137428:A:C	C213W	0.999
2:68138743:C:T	G211E	0.999
2:68138806:C:A	G190V	0.999
2:68138806:C:T	G190E	0.999
2:68138807:C:A	G190W	0.999
2:68138818:C:T	G186D	0.999
2:68138819:C:G	G186R	0.999
2:68138821:G:T	A185D	0.999
2:68138827:A:T	V183D	0.999
2:68141707:C:A	W168C	0.999
2:68141707:C:G	W168C	0.999
2:68141710:A:C	C167W	0.999
2:68141753:A:T	V153D	0.999
2:68141781:A:G	W144R	0.999
2:68141781:A:T	W144R	0.999
2:68144592:G:C	S136R	0.999
2:68144592:G:T	S136R	0.999
2:68144594:T:G	S136R	0.999
2:68157368:A:G	W26R	0.999
2:68157368:A:T	W26R	0.999
2:68137372:A:G	L232P	0.998
2:68138744:C:A	G211W	0.998

dbSNP variants (sampled 300 via entrez): RS1000073957 (2:68129658 T>C), RS1000326171 (2:68140337 T>C), RS1000329472 (2:68148060 G>A), RS1000372833 (2:68157296 C>A,T), RS1000377423 (2:68133089 G>A), RS1000383294 (2:68147732 T>A,C), RS1000425157 (2:68129381 C>T), RS1000489934 (2:68154083 A>C), RS1000541710 (2:68146206 G>C), RS1000663193 (2:68149681 G>A), RS1000665745 (2:68133311 C>T), RS1000687752 (2:68136255 C>A), RS1000716563 (2:68149330 C>T), RS1000817367 (2:68135983 G>A,C), RS1000826629 (2:68131161 A>C,G,T)

Disease associations

OMIM: gene MIM:610729 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001538_14	Immune reponse to smallpox (secreted IFN-alpha)	2.000000e-18
GCST009646_1	Diastolic blood pressure response to thiazide and thiazide-like diuretics in hypertension	8.000000e-09
GCST90000025_750	Appendicular lean mass	2.000000e-26

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0006945	diastolic blood pressure change measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression, increases methylation	3
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Carbamazepine	affects expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	affects expression	1
Antirheumatic Agents	increases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

Clinical trials (associated diseases)

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