DND1

Summary

DND1 (DND microRNA-mediated repression inhibitor 1, HGNC:23799) is a protein-coding gene on chromosome 5q31.3, encoding Dead end protein homolog 1 (Q8IYX4). RNA-binding factor that positively regulates gene expression by prohibiting miRNA-mediated gene suppression.

This gene encodes a protein that binds to microRNA-targeting sequences of mRNAs, inhibiting microRNA-mediated repression. Reduced expression of this gene has been implicated in tongue squamous cell carcinoma. Two pseudogenes of this gene are located on the long arm of chromosome 17.

Source: NCBI Gene 373863 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_194249

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23799
Approved symbol	DND1
Name	DND microRNA-mediated repression inhibitor 1
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC34750, RBMS4
Ensembl gene	ENSG00000256453
Ensembl biotype	protein_coding
OMIM	609385
Entrez	373863

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000542735

RefSeq mRNA: 1 — MANE Select: NM_194249 NM_194249

CCDS: CCDS4236

Canonical transcript exons

ENST00000542735 — 4 exons

Exon	Start	End
ENSE00002320380	140670794	140671750
ENSE00002336746	140673519	140673576
ENSE00002359316	140672445	140672906
ENSE00002407444	140673271	140673388

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 89.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0211 / max 6.6528, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63827	0.0211	6

Top tissues by expression

132 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	89.19	gold quality
right testis	UBERON:0004534	78.36	gold quality
left testis	UBERON:0004533	77.44	gold quality
testis	UBERON:0000473	77.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.82	gold quality
granulocyte	CL:0000094	65.90	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.68	gold quality
cerebellum	UBERON:0002037	65.20	gold quality
cerebellar hemisphere	UBERON:0002245	65.08	gold quality
cerebellar cortex	UBERON:0002129	65.03	gold quality
apex of heart	UBERON:0002098	62.60	gold quality
mucosa of transverse colon	UBERON:0004991	59.32	gold quality
sural nerve	UBERON:0015488	57.72	silver quality
adenohypophysis	UBERON:0002196	56.49	gold quality
pituitary gland	UBERON:0000007	56.48	gold quality
stromal cell of endometrium	CL:0002255	55.37	gold quality
right lobe of liver	UBERON:0001114	55.21	gold quality
nucleus accumbens	UBERON:0001882	55.21	gold quality
gastrocnemius	UBERON:0001388	54.73	gold quality
spleen	UBERON:0002106	54.72	gold quality
ventricular zone	UBERON:0003053	54.46	gold quality
caudate nucleus	UBERON:0001873	53.81	gold quality
putamen	UBERON:0001874	53.65	gold quality
right frontal lobe	UBERON:0002810	53.13	gold quality
Brodmann (1909) area 9	UBERON:0013540	53.01	gold quality
brain	UBERON:0000955	52.88	gold quality
primary visual cortex	UBERON:0002436	52.44	gold quality
muscle of leg	UBERON:0001383	52.04	gold quality
temporal lobe	UBERON:0001871	51.85	gold quality
amygdala	UBERON:0001876	51.58	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting DND1, 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-1277-5P	100.00	73.95	5056
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-6887-5P	98.56	68.49	1295

Literature-anchored findings (GeneRIF, showing 17)

• Cloning of zebrafish dnd1 and identification of human DND1 by database analysis. (PMID:12932328)
• The variant, p. Glu86Ala, found in only one case of testiciular germ cell tumor, is within a known functional domain of DND1 and is highly conserved through evolution; mutations in DND1 make, at most, a very small contribution to TGCT susceptibility (PMID:18069663)
• Unravels a novel role of Dnd1 in protecting certain mRNAs from miRNA-mediated repression. (PMID:18155131)
• We conclude that germline DND1 mutations are unlikely to contribute significantly to human testicular germ cell tumor susceptibility (PMID:20411342)
• MiR-24 up-regulation reduced the expression of RNA-binding protein dead end 1 (DND1). Knockdown of miR-24 led to enhanced expression of DND1. (PMID:20816961)
• Results suggest that DND1 may impose another level of translational regulation to modulate expression of critical factors in ES cells. (PMID:21851623)
• The increased sensitivity of transformed keratinocytes to miR-21’s effects occurs in part through downregulation of the RNA-binding protein DND1 during the transformation process. (PMID:22614019)
• APOBEC3G inhibits DND1 function to regulate microRNA activity. (PMID:23890083)
• RBM38 and DND1 are repressed in primary acute myeloid leukemia, neutrophil differentiation is dependent on increased expression of both proteins, and they have a role in regulating p21(CIP1) expression during acute promyelocytic leukemia differentiation (PMID:26740055)
• Dnd1 facilitates apoptosis by increasing the expression of Bim via its competitive combining with miR-221 in Bim-3’UTR. (PMID:28191469)
• Mechanistically, Dnd1 could bind to 3’-UTR of LATS2, the key kinase of Hippo pathway, thus elevating LATS2 mRNA stability and its expression, subsequently leading to phosphorylation of YAP and its cytoplasmic retention. (PMID:28593479)
• MicroRNA-24 inhibits the proliferation, migration and invasion and enhances chemosensitivity of human gastric cancer by targeting DND1. (PMID:32521898)
• Human DND1-RRM2 forms a non-canonical domain swapped dimer. (PMID:33860980)
• High DND1 Level Indicates a Poor Prognostic Factor in Prostate Cancer. (PMID:34721738)
• A cooperative mechanism of target RNA selection via germ-cell-specific RNA-binding proteins NANOS2 and DND1. (PMID:35705038)
• Circular RNA circFCHO2(hsa_circ_0002490) promotes the proliferation of melanoma by directly binding to DND1. (PMID:38311675)
• RNA-binding protein DND1 participates in migration, invasion, and EMT of prostate cancer cells by degrading CLIC4. (PMID:38390782)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnd1	ENSDARG00000022813
mus_musculus	Dnd1	ENSMUSG00000044595
rattus_norvegicus	Dnd1	ENSRNOG00000016894

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), A1CF (ENSG00000148584), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), HNRNPDL (ENSG00000152795), MSI2 (ENSG00000153944), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBMXL2 (ENSG00000170748), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395)

Protein

Protein identifiers

Dead end protein homolog 1 — Q8IYX4 (reviewed: Q8IYX4)

Alternative names: RNA-binding motif, single-stranded-interacting protein 4

All UniProt accessions (1): Q8IYX4

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding factor that positively regulates gene expression by prohibiting miRNA-mediated gene suppression. Relieves miRNA repression in germline cells. Prohibits the function of several miRNAs by blocking the accessibility of target mRNAs. Sequence-specific RNA-binding factor that binds specifically to U-rich regions (URRs) in the 3’ untranslated region (3’-UTR) of several mRNAs. Does not bind to miRNAs. May play a role during primordial germ cell (PGC) survival. However, does not seem to be essential for PGC migration.

Subunit / interactions. Interacts with APOBEC3.

Subcellular location. Nucleus. Cytoplasm.

RefSeq proteins (1): NP_919225* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034414	DND1_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR044448	DND1_DSRM	Domain

Pfam: PF00076, PF14709

UniProt features (24 total): strand 13, helix 8, domain 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6LE1	X-RAY DIFFRACTION	2.3
7Q4L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IYX4-F1	80.42	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 93 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CAGCAGG_MIR370, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, FOXJ2_02, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, chr5q31, GOMF_MIRNA_BINDING, GOMF_MRNA_BINDING

GO Biological Process (5): germ cell development (GO:0007281), spermatogenesis (GO:0007283), mRNA stabilization (GO:0048255), negative regulation of miRNA-mediated gene silencing (GO:0060965), 3’-UTR-mediated mRNA destabilization (GO:0061158)

GO Molecular Function (5): mRNA binding (GO:0003729), mRNA 3’-UTR binding (GO:0003730), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), focal adhesion (GO:0005925)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
developmental process involved in reproduction	2
binding	2
gamete generation	1
cellular process involved in reproduction in multicellular organism	1
cell development	1
male gamete generation	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
miRNA-mediated post-transcriptional gene silencing	1
regulation of miRNA-mediated gene silencing	1
negative regulation of post-transcriptional gene silencing by regulatory ncRNA	1
mRNA destabilization	1
RNA binding	1
mRNA binding	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
cell-substrate junction	1

Protein interactions and networks

STRING

868 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DND1	NANOS3	P60323	807
DND1	TDRD7	Q8NHU6	782
DND1	NANOS2	P60321	767
DND1	NANOS1	Q8WY41	755
DND1	DAZL	Q92904	669
DND1	PRDM14	Q9GZV8	609
DND1	RALY	Q9UKM9	608
DND1	EIF2S2	P20042	598
DND1	CNOT1	A5YKK6	590
DND1	CDKN1B	P46527	588
DND1	DMRT1	Q9Y5R6	530
DND1	ELAVL1	Q15717	519
DND1	DDX4	Q9NQI0	502
DND1	PIWIL1	Q96J94	497
DND1	PUM1	Q14671	483

IntAct

12 interactions, top by confidence:

A	B	Type	Score
DND1	FLNA	psi-mi:“MI:0915”(physical association)	0.560
RBPMS2	DND1	psi-mi:“MI:0915”(physical association)	0.560
DND1	CNOT1	psi-mi:“MI:0914”(association)	0.460
CNOT1	DND1	psi-mi:“MI:0914”(association)	0.460
DND1	RPSA2	psi-mi:“MI:0914”(association)	0.350
DND1	ATXN3	psi-mi:“MI:0914”(association)	0.350
DND1	HNRNPCL1	psi-mi:“MI:0914”(association)	0.350
DND1	UBA6	psi-mi:“MI:0914”(association)	0.350
DND1	RBPMS2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (29): HSPA1L (Affinity Capture-MS), TRAP1 (Affinity Capture-MS), PAIP2B (Affinity Capture-MS), RALGAPB (Affinity Capture-MS), ATXN3 (Affinity Capture-MS), PAIP1 (Affinity Capture-MS), EMB (Affinity Capture-MS), VCPIP1 (Affinity Capture-MS), APOBEC1 (Reconstituted Complex), ATXN3 (Affinity Capture-MS), PAIP2B (Affinity Capture-MS), RALGAPB (Affinity Capture-MS), EMB (Affinity Capture-MS), VCPIP1 (Affinity Capture-MS), ACTR3C (Affinity Capture-MS)

ESM2 similar proteins: A0JNQ6, A6NC42, A6NGQ2, A6NGR9, A6QP75, A7E3N7, A9X185, E1BDF2, E9PGG2, F6SZT2, P0C7A0, P85965, Q06VW1, Q0ZFW8, Q14DK4, Q3UK37, Q3UV16, Q3ZBN4, Q400G9, Q4VXA5, Q587J8, Q5JSQ8, Q60953, Q60I26, Q60I27, Q6NUI2, Q6ZUX3, Q810I0, Q8BH06, Q8C0R7, Q8IWB1, Q8IWY9, Q8IYX4, Q8K4C2, Q8N6L0, Q8N7F7, Q8NCV1, Q8TE82, Q91WA6, Q95JV3

Diamond homologs: A0A8M1NHK4, A0AV96, A0JM51, A4FV72, A4QUF0, A8WLV5, O01671, O04425, O43040, O43390, O60506, P28659, P33240, P86049, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q14498, Q28HE9, Q2HJG2, Q2UK72, Q3UEB3, Q4QQT3, Q4R2Z0, Q4R535, Q5B630, Q5EA36, Q5R469, Q5R5P4, Q5R723, Q5R9H4, Q5RC41, Q5RC80, Q5RDA3, Q5SZQ8, Q5YD48, Q66H68, Q6DCB7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

653 predictions. Top by Δscore:

Variant	Effect	Δscore
5:140671670:CAAG:C	donor_gain	1.0000
5:140672439:GCCTA:G	donor_loss	1.0000
5:140672440:CCTAC:C	donor_loss	1.0000
5:140672441:CTAC:C	donor_loss	1.0000
5:140672442:TA:T	donor_loss	1.0000
5:140672443:A:AT	donor_loss	1.0000
5:140672903:CAGC:C	acceptor_gain	1.0000
5:140672905:GCC:G	acceptor_loss	1.0000
5:140672907:C:CA	acceptor_loss	1.0000
5:140672907:C:CC	acceptor_gain	1.0000
5:140672908:T:C	acceptor_loss	1.0000
5:140673292:T:TA	donor_gain	1.0000
5:140671746:CTGCC:C	acceptor_gain	0.9900
5:140672446:TTCC:T	donor_gain	0.9900
5:140672902:CCAGC:C	acceptor_gain	0.9900
5:140672903:CAGCC:C	acceptor_gain	0.9900
5:140672904:AGC:A	acceptor_gain	0.9900
5:140672905:GC:G	acceptor_gain	0.9900
5:140672906:CC:C	acceptor_gain	0.9900
5:140673386:CAG:C	acceptor_gain	0.9900
5:140673513:GCTTA:G	donor_loss	0.9900
5:140673514:CTTA:C	donor_loss	0.9900
5:140673515:TTA:T	donor_loss	0.9900
5:140673516:TAC:T	donor_loss	0.9900
5:140671749:CC:C	acceptor_gain	0.9800
5:140671750:CC:C	acceptor_gain	0.9800
5:140671750:CCTG:C	acceptor_loss	0.9800
5:140671751:C:CC	acceptor_gain	0.9800
5:140671751:CTGTA:C	acceptor_loss	0.9800
5:140671752:T:A	acceptor_loss	0.9800

AlphaMissense

2250 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:140672741:G:T	A103D	1.000
5:140672749:G:C	F100L	1.000
5:140672749:G:T	F100L	1.000
5:140672751:A:G	F100L	1.000
5:140673293:C:A	R40S	1.000
5:140673293:C:G	R40S	1.000
5:140673294:C:G	R40T	1.000
5:140672708:G:T	A114D	0.999
5:140672736:A:C	Y105D	0.999
5:140672747:G:T	A101D	0.999
5:140672750:A:G	F100S	0.999
5:140672757:G:T	R98S	0.999
5:140672770:G:C	F93L	0.999
5:140672770:G:T	F93L	0.999
5:140672772:A:G	F93L	0.999
5:140672779:C:A	M90I	0.999
5:140672779:C:G	M90I	0.999
5:140672779:C:T	M90I	0.999
5:140672780:A:G	M90T	0.999
5:140672783:A:G	L89P	0.999
5:140672789:A:G	F87S	0.999
5:140672828:A:T	L74H	0.999
5:140672864:A:T	I62N	0.999
5:140672866:G:C	F61L	0.999
5:140672866:G:T	F61L	0.999
5:140672868:A:G	F61L	0.999
5:140673294:C:A	R40M	0.999
5:140673300:C:T	G38E	0.999
5:140671710:C:A	W215C	0.998
5:140671710:C:G	W215C	0.998

dbSNP variants (sampled 300 via entrez): RS1000253074 (5:140674508 A>C), RS1000790608 (5:140674191 T>A,C), RS1000936811 (5:140673714 T>C,G), RS1001734155 (5:140674893 C>G,T), RS1002661556 (5:140670672 A>G,T), RS1003596439 (5:140671713 C>G,T), RS1004098770 (5:140674126 G>A,T), RS1005511793 (5:140675534 C>G), RS1006133992 (5:140670340 A>G), RS1007671378 (5:140673598 T>C,G), RS1007766268 (5:140673736 G>A), RS1008578743 (5:140672506 G>A,C,T), RS1008857828 (5:140672979 G>A,C), RS1010687306 (5:140675057 C>T), RS1010780707 (5:140675290 A>C,G)

Disease associations

OMIM: gene MIM:609385 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006803_54	Schizophrenia	8.000000e-07
GCST010146_22	Serum immune biomarker levels	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004872	inflammatory biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
MT19c compound	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Air Pollutants	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Valproic Acid	increases methylation	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1

Clinical trials (associated diseases)

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