DNASE2B

Summary

DNASE2B (deoxyribonuclease 2 beta, HGNC:28875) is a protein-coding gene on chromosome 1p31.1-p22.3, encoding Deoxyribonuclease-2-beta (Q8WZ79). Hydrolyzes DNA under acidic conditions.

The protein encoded by this gene shares considerable sequence similarity to, and is structurally related to DNase II. The latter is a well characterized endonuclease that catalyzes DNA hydrolysis in the absence of divalent cations at acidic pH. Unlike DNase II which is ubiquitously expressed, expression of this gene product is restricted to the salivary gland and lungs. The gene has been localized to chromosome 1p22.3 adjacent (and in opposite orientation) to the uricase pseudogene. Two transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 58511 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_021233

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28875
Approved symbol	DNASE2B
Name	deoxyribonuclease 2 beta
Location	1p31.1-p22.3
Locus type	gene with protein product
Status	Approved
Aliases	DLAD
Ensembl gene	ENSG00000137976
Ensembl biotype	protein_coding
OMIM	608057
Entrez	58511

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000370662, ENST00000370665

RefSeq mRNA: 2 — MANE Select: NM_021233 NM_021233, NM_058248

CCDS: CCDS44167, CCDS694

Canonical transcript exons

ENST00000370665 — 6 exons

Exon	Start	End
ENSE00001632362	84401901	84402078
ENSE00001725172	84408437	84408518
ENSE00001890136	84414528	84415018
ENSE00002307921	84398484	84398689
ENSE00003616455	84410838	84410999
ENSE00003677606	84412349	84412546

Expression profiles

Bgee: expression breadth ubiquitous, 116 present calls, max score 85.06.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.2175 / max 550.4932, expressed in 127 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3797	1.5777	109
3793	0.3970	63
3794	0.0990	44
3796	0.0796	37
3795	0.0642	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	85.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.71	gold quality
saliva-secreting gland	UBERON:0001044	70.84	gold quality
minor salivary gland	UBERON:0001830	65.29	gold quality
gastrocnemius	UBERON:0001388	62.14	gold quality
mouth mucosa	UBERON:0003729	62.02	gold quality
muscle of leg	UBERON:0001383	60.53	gold quality
right lung	UBERON:0002167	59.64	gold quality
mucosa of transverse colon	UBERON:0004991	59.00	gold quality
upper lobe of left lung	UBERON:0008952	57.73	gold quality
muscle organ	UBERON:0001630	57.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	56.69	gold quality
upper lobe of lung	UBERON:0008948	56.45	gold quality
prostate gland	UBERON:0002367	54.49	gold quality
nucleus accumbens	UBERON:0001882	53.92	gold quality
tonsil	UBERON:0002372	53.73	gold quality
rectum	UBERON:0001052	52.51	gold quality
lymph node	UBERON:0000029	52.39	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	52.34	gold quality
lung	UBERON:0002048	51.97	gold quality
ileal mucosa	UBERON:0000331	51.72	silver quality
deltoid	UBERON:0001476	50.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	50.60	gold quality
skeletal muscle tissue	UBERON:0001134	50.54	gold quality
muscle tissue	UBERON:0002385	50.24	gold quality
gall bladder	UBERON:0002110	50.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	49.95	gold quality
islet of Langerhans	UBERON:0000006	49.89	gold quality
prefrontal cortex	UBERON:0000451	49.73	gold quality
spinal cord	UBERON:0002240	49.70	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.41

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF4, TBX15

miRNA regulators (miRDB)

17 targeting DNASE2B, 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-340-5P	100.00	72.50	4437
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-657	99.48	66.02	848
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-4712-3P	98.52	65.39	822
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-3667-5P	97.16	64.87	591

Literature-anchored findings (GeneRIF, showing 3)

• gene lie head-to-head with the urate oxidase gene (PMID:11700027)
• These data identify DNase 2 as the predominant DNase on the mammalian skin surface and indicate that its activity is primarily targeted to exogenous DNA. (PMID:21390259)
• HSF4 exerts its function on lens differentiation via positive regulation of DLAD expression. (PMID:23507146)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnase2b	ENSDARG00000077918
mus_musculus	Dnase2b	ENSMUSG00000028185
rattus_norvegicus	Dnase2b	ENSRNOG00000016262
drosophila_melanogaster	DNaseII	FBGN0000477
caenorhabditis_elegans		WBGENE00000799
caenorhabditis_elegans		WBGENE00003828
caenorhabditis_elegans		WBGENE00007056

Paralogs (1): DNASE2 (ENSG00000105612)

Protein

Protein identifiers

Deoxyribonuclease-2-beta — Q8WZ79 (reviewed: Q8WZ79)

Alternative names: DNase II-like acid DNase, DNase2-like acid DNase, Deoxyribonuclease II beta, Endonuclease DLAD

All UniProt accessions (1): Q8WZ79

UniProt curated annotations — full annotation on UniProt →

Function. Hydrolyzes DNA under acidic conditions. Does not require divalent cations for activity. Participates in the degradation of nuclear DNA during lens cell differentiation.

Subcellular location. Lysosome.

Tissue specificity. Highly expressed in the eye lens and in salivary gland. Detected at lower levels in lung, prostate and lymph node. Isoform 2 is lung specific.

Similarity. Belongs to the DNase II family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WZ79-1	1	yes
Q8WZ79-2	2

RefSeq proteins (2): NP_067056, NP_490649 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004947	DNase_II	Family

Pfam: PF03265

Enzyme classification (BRENDA):

• EC 3.1.22.1 — deoxyribonuclease II (BRENDA: 30 organisms, 69 substrates, 60 inhibitors, 6 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SUPERCOILED PLASMID DNA	—	6

UniProt features (10 total): glycosylation site 4, sequence variant 3, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WZ79-F1	91.22	0.82

Functional residue map

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

Glycosylation sites (4): 81, 103, 119, 278

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): GOMF_ENDONUCLEASE_ACTIVITY, HNF3ALPHA_Q6, GOMF_NUCLEASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, KEGG_LYSOSOME, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_DNA_CATABOLIC_PROCESS, TGCTGAY_UNKNOWN, INGRAM_SHH_TARGETS_UP, RYTTCCTG_ETS2_B, YY1_01, AML1_01, GOBP_APOPTOTIC_DNA_FRAGMENTATION, GOBP_EXECUTION_PHASE_OF_APOPTOSIS, NKX3A_01

GO Biological Process (2): apoptotic DNA fragmentation (GO:0006309), DNA metabolic process (GO:0006259)

GO Molecular Function (5): deoxyribonuclease II activity (GO:0004531), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), DNA endonuclease activity (GO:0004520), hydrolase activity (GO:0016787)

GO Cellular Component (3): extracellular region (GO:0005576), lysosome (GO:0005764), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
DNA catabolic process	1
apoptotic nuclear changes	1
nucleic acid metabolic process	1
DNA endonuclease activity, producing 3’-phosphomonoesters	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
endonuclease activity	1
DNA nuclease activity	1
catalytic activity	1
lytic vacuole	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

574 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNASE2B	DNASE1L1	P49184	556
DNASE2B	BFSP1	Q12934	535
DNASE2B	SOWAHA	Q2M3V2	487
DNASE2B	CRYGS	P22914	485
DNASE2B	DNASE1L2	Q92874	484
DNASE2B	LGSN	Q5TDP6	456
DNASE2B	ENTREP1	Q15884	454
DNASE2B	HSF4	Q9ULV5	447
DNASE2B	BFSP2	Q13515	439
DNASE2B	RLN1	P04808	435
DNASE2B	CRYGA	P11844	434
DNASE2B	FOXE3	Q13461	431
DNASE2B	GNS	P15586	427
DNASE2B	TDRD7	Q8NHU6	418
DNASE2B	BLK	P51451	410

IntAct

5 interactions, top by confidence:

A	B	Type	Score
DNASE2B	ARSA	psi-mi:“MI:0914”(association)	0.530
DNASE2B		psi-mi:“MI:0914”(association)	0.350
DNASE2B	LRP5	psi-mi:“MI:0914”(association)	0.350
DNASE2B	HEXA	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): FAT1 (Affinity Capture-MS), GALNS (Affinity Capture-MS), TOR3A (Affinity Capture-MS), PC (Affinity Capture-MS), AMD1 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), FREM2 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), SPATA5 (Affinity Capture-MS), PASK (Affinity Capture-MS), TBL3 (Affinity Capture-MS), CAPN2 (Affinity Capture-MS), SUCO (Affinity Capture-MS), TCTN1 (Affinity Capture-MS)

ESM2 similar proteins: O00115, O08590, O15547, O46406, O62855, O70423, O95897, P10820, P14222, P34387, P35763, P36633, P56541, P56542, Q04912, Q16853, Q17778, Q24K15, Q29437, Q2KJC3, Q2T8B0, Q3JJK4, Q3V5L5, Q4R9E0, Q5R9I0, Q5SSH8, Q62190, Q63IT3, Q6AX53, Q6NUS6, Q6TMA8, Q71SY6, Q75WF2, Q765H6, Q812C9, Q8JZQ5, Q8R2Q6, Q8WZ79, Q91ZV7, Q93086

Diamond homologs: O00115, O62855, P34387, P34508, P56541, P56542, Q17778, Q75WF2, Q8WZ79, Q9QY48, Q9QZK8, Q9QZK9, Q2T8B0, Q3JJK4, Q63IT3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HSF4	“up-regulates quantity by expression”	DNASE2B	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

426 predictions. Top by Δscore:

Variant	Effect	Δscore
1:84410937:G:GT	donor_gain	1.0000
1:84410993:GCAA:G	donor_gain	1.0000
1:84408514:CAAAG:C	donor_loss	0.9900
1:84408515:AAAG:A	donor_loss	0.9900
1:84408519:G:C	donor_loss	0.9900
1:84408520:T:A	donor_loss	0.9900
1:84410977:G:GG	donor_gain	0.9900
1:84410986:G:GG	donor_gain	0.9900
1:84411011:GTAT:G	donor_gain	0.9900
1:84412334:T:A	acceptor_gain	0.9900
1:84412341:T:A	acceptor_gain	0.9900
1:84412502:G:T	donor_gain	0.9900
1:84414519:A:AG	acceptor_gain	0.9900
1:84414520:A:G	acceptor_gain	0.9900
1:84412344:TTCA:T	acceptor_loss	0.9800
1:84412346:CA:C	acceptor_loss	0.9800
1:84412347:A:AT	acceptor_loss	0.9800
1:84412543:GACGG:G	donor_loss	0.9800
1:84412545:CGGT:C	donor_loss	0.9800
1:84412546:GGT:G	donor_loss	0.9800
1:84412547:GT:G	donor_loss	0.9800
1:84412548:T:G	donor_loss	0.9800
1:84414526:A:AG	acceptor_gain	0.9800
1:84414527:G:GG	acceptor_gain	0.9800
1:84414527:GAC:G	acceptor_gain	0.9800
1:84410996:A:G	donor_gain	0.9700
1:84410996:ATAG:A	donor_gain	0.9700
1:84412341:T:TA	acceptor_loss	0.9700
1:84412345:TCAGA:T	acceptor_gain	0.9700
1:84412347:A:AG	acceptor_gain	0.9700

AlphaMissense

2363 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:84408516:A:T	K128I	0.991
1:84414704:T:A	W308R	0.983
1:84414704:T:C	W308R	0.983
1:84414762:G:C	R327P	0.983
1:84401916:G:C	K47N	0.981
1:84401916:G:T	K47N	0.981
1:84408517:A:C	K128N	0.978
1:84408517:A:T	K128N	0.978
1:84410894:T:C	F148L	0.975
1:84410896:T:A	F148L	0.975
1:84410896:T:G	F148L	0.975
1:84410965:C:G	C171W	0.974
1:84412527:G:C	K242N	0.974
1:84412527:G:T	K242N	0.974
1:84414802:T:G	C340W	0.974
1:84414745:T:G	C321W	0.972
1:84414706:G:C	W308C	0.969
1:84414706:G:T	W308C	0.969
1:84401902:T:C	F43L	0.968
1:84401904:T:A	F43L	0.968
1:84401904:T:G	F43L	0.968
1:84414586:G:C	W268C	0.968
1:84414586:G:T	W268C	0.968
1:84414692:G:C	D304H	0.968
1:84414743:T:C	C321R	0.968
1:84408518:G:C	G129R	0.967
1:84410963:T:A	C171S	0.967
1:84410963:T:C	C171R	0.967
1:84410964:G:C	C171S	0.967
1:84414743:T:A	C321S	0.967

dbSNP variants (sampled 300 via entrez): RS1000114087 (1:84401801 T>A,C,G), RS1000152231 (1:84411960 G>A), RS1000332895 (1:84405083 G>C), RS1000602753 (1:84398419 G>A), RS1000992925 (1:84402270 C>T), RS1001001786 (1:84408916 G>A,C), RS1001177699 (1:84397054 A>C), RS1001316155 (1:84401148 T>G), RS1001358667 (1:84403304 T>C), RS1001425527 (1:84401953 G>A), RS1001724802 (1:84403662 T>A,C), RS1001816886 (1:84397244 T>A), RS1001824166 (1:84413561 T>A,C), RS1001833909 (1:84413351 G>C), RS1002062582 (1:84406394 T>A,C)

Disease associations

OMIM: gene MIM:608057 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001325_9	Response to hepatitis C treatment	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	2
bisphenol A	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
theaflavin-3,3’-digallate	affects expression	1
Dihydrotestosterone	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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