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
• GTEx eGene: eQTL in 13 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.21 (unconstrained)
• 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: 3 — 3 protein_coding

MANE Select: ENST00000370665

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2

ENST00000370665, ENST00000370662, ENST00001145435

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.

Highest expression (Bgee): parotid gland, male germ line stem cell (sensu Vertebrata) in testis, saliva-secreting gland, minor salivary gland, gastrocnemius.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DNASE2B is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

15 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Prostate	eqtl	7.3e-30	-0.62	1:84403370:A:T
Stomach	eqtl	4.1e-26	-0.41	1:84420612:T:A
Spleen	eqtl	1.2e-08	+0.42	1:84408934:C:T
Minor Salivary Gland	eqtl	1.5e-08	-0.36	1:84403370:A:T
Brain Nucleus accumbens basal ganglia	eqtl	2.1e-08	+1.35	1:84402249:C:T
Pituitary	eqtl	7.6e-08	-0.39	1:84408152:A:G
Pancreas	eqtl	4.0e-06	-0.37	1:84403370:A:T
Testis	eqtl	2.5e-03	-0.82	1:84308650:GCTTT:G
Artery Aorta	eqtl	3.3e-03	-0.25	1:84415988:C:T
Breast Mammary Tissue	eqtl	8.2e-03	-0.24	1:84403985:T:C
Muscle Skeletal	eqtl	1.3e-02	-0.13	1:84458496:A:T
Testis	sqtl	1.7e-02	+1.62	1:84382544:A:G
Brain Caudate basal ganglia	eqtl	2.2e-02	-0.27	1:84810967:T:C
Muscle Skeletal	sqtl	2.2e-02	+1.13	1:83978493:T:A
Brain Cerebellum	eqtl	2.5e-02	+0.41	1:84479751:T:C

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

showing 100 of 253 tissues 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
quadriceps femoris	UBERON:0001377	49.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
body of stomach	UBERON:0001161	49.08	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
cerebellar vermis	UBERON:0004720	48.32	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
epithelial cell of pancreas	CL:0000083	48.22	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
thymus	UBERON:0002370	48.15	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
visceral pleura	UBERON:0002401	47.99	silver quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
caudate nucleus	UBERON:0001873	47.61	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
kidney epithelium	UBERON:0004819	47.39	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality
diaphragm	UBERON:0001103	47.05	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
nasal cavity mucosa	UBERON:0001826	46.98	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	46.92	gold quality
transverse colon	UBERON:0001157	46.65	gold quality
stomach	UBERON:0000945	46.63	gold quality
substantia nigra	UBERON:0002038	46.38	gold quality
putamen	UBERON:0001874	46.37	gold quality
frontal cortex	UBERON:0001870	46.30	gold quality
telencephalon	UBERON:0001893	45.94	gold quality
layer of synovial tissue	UBERON:0007616	45.76	gold quality
midbrain	UBERON:0001891	45.67	gold quality
neocortex	UBERON:0001950	45.63	gold quality
nasal cavity epithelium	UBERON:0005384	45.61	gold quality
tibia	UBERON:0000979	45.57	silver quality
hypothalamus	UBERON:0001898	45.53	gold quality
fundus of stomach	UBERON:0001160	45.43	gold quality
right adrenal gland cortex	UBERON:0035827	45.34	gold quality
spleen	UBERON:0002106	45.26	gold quality
cerebral cortex	UBERON:0000956	45.23	gold quality
forebrain	UBERON:0001890	45.03	gold quality
cingulate cortex	UBERON:0003027	44.83	gold quality
anterior cingulate cortex	UBERON:0009835	44.81	gold quality
right frontal lobe	UBERON:0002810	44.41	gold quality
amygdala	UBERON:0001876	44.36	gold quality
brain	UBERON:0000955	44.25	gold quality
Ammon’s horn	UBERON:0001954	44.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	43.52	gold quality
skin of hip	UBERON:0001554	43.47	silver quality
squamous epithelium	UBERON:0006914	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
right adrenal gland	UBERON:0001233	43.19	gold quality
stromal cell of endometrium	CL:0002255	42.98	silver quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
pancreatic ductal cell	CL:0002079	42.82	silver quality
bone marrow cell	CL:0002092	42.82	gold quality
descending thoracic aorta	UBERON:0002345	42.75	gold quality
epithelium of bronchus	UBERON:0002031	42.70	gold quality
bronchus	UBERON:0002185	42.58	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
granulocyte	CL:0000094	42.21	silver quality
temporal lobe	UBERON:0001871	42.11	gold quality
cartilage tissue	UBERON:0002418	42.04	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

HPA expression

RNA tissue specificity: Tissue enriched

51 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Salivary gland	tissue	160.3
Prostate	tissue	6.3
Lung	tissue	2.3
Nucleus accumbens	tissue	0.9
Pancreas	tissue	0.7
Lymph node	tissue	0.6
Skeletal muscle	tissue	0.6
Rectum	tissue	0.5
Basal ganglia	tissue	0.5
Postcentral gyrus	tissue	0.5
Breast	tissue	0.4
Testis	tissue	0.4
Colon	tissue	0.4
Putamen	tissue	0.4
Hippocampal formation	tissue	0.4
Ventral forebrain	tissue	0.4
Pituitary gland	tissue	0.3
Stomach 1	tissue	0.3
Amygdala	tissue	0.3
Liver	tissue	0.3
Gallbladder	tissue	0.3
Locus coeruleus	tissue	0.3
Hippocampus	tissue	0.3
Entorhinal cortex	tissue	0.3
Septum	tissue	0.3
Cervix	tissue	0.2
Cerebral cortex	tissue	0.2
Pons	tissue	0.2
Adipose tissue	tissue	0.2
Motor cortex	tissue	0.2
Tongue	tissue	0.2
Hypothalamus	tissue	0.2
Spleen	tissue	0.2
Thymus	tissue	0.2
Retrosplenial and cingulate cortex	tissue	0.2
Retrosplenial cortex	tissue	0.2
Temporal cortex	tissue	0.2
Insular cortex	tissue	0.2
Prefrontal cortex	tissue	0.1
Midbrain	tissue	0.1
Medulla oblongata	tissue	0.1
Thalamus	tissue	0.1
Superior colliculi	tissue	0.1
Cerebellum	tissue	0.1
Substantia nigra	tissue	0.1
Thyroid gland	tissue	0.1
Spinal cord	tissue	0.1
Corpus callosum	tissue	0.1
Tonsil	tissue	0.1
Periaqueductal gray	tissue	0.1
Occipital cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 188; highest nTPM — Arcuate nucleus (1.7), Lateral funiculus (white matter) (1.4), Parieto-temporal junction (white matter) (1.1), Corpus callosum, genu (white matter) (0.9), Corpus callosum, splenium (white matter) (0.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF4, TBX15

miRNA regulators (miRDB)

Targeting DNASE2B by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

17 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 2.43e-14, LOEUF 1.21, missense Z 0.677 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000370665 — one region, missense o/e 0.95.

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913283) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 5 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased bone mineral density	1
cataract	1
increased circulating HDL cholesterol level	1
abnormal vision	1
abnormal eye electrophysiology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Sus scrofa	O62855	82.6%	Diamond
Bos taurus	P56541	82.6%	Diamond
Acanthaster planci	Q75WF2	40.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC01461	ncRNA	103695366
CTBS	protein-coding	1486
GNG5	protein-coding	2787
RPF1	protein-coding	80135
SPATA1	protein-coding	100505741
SAMD13	protein-coding	148418

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, UniProt - Evidence at transcript level

Protein evidence: Evidence at transcript level

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)

Type	Positions
N-linked (glcnac…) asparagine	81, 103, 119, 278

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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

12 GO namespaces:

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

showing 15 of 639 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNASE2B	DNASE1L1	P49184	632
DNASE2B	BFSP1	Q12934	505
DNASE2B	CRYGS	P22914	500
DNASE2B	DNASE1L2	Q92874	478
DNASE2B	SOWAHA	Q2M3V2	464
DNASE2B	CRYGA	P11844	462
DNASE2B	LENEP	Q9Y5L5	452
DNASE2B	LGSN	Q5TDP6	445
DNASE2B	ENTREP1	Q15884	442
DNASE2B	FOXE3	Q13461	440
DNASE2B	TDRD7	Q8NHU6	437
DNASE2B	CRYBA2	P53672	434
DNASE2B	BFSP2	Q13515	424
DNASE2B	HSF4	Q9ULV5	418
DNASE2B	GRIFIN	A4D1Z8	408

IntAct

Human interaction partners of DNASE2B in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
ARSA	association	0.530	1
HEXA	association	0.350	1
LRP5	association	0.350	1

BioGRID (79 interactions; top human partners by supporting records): FUT11 (Affinity Capture-MS; 3 records), GALNS (Affinity Capture-MS; 3 records), GPR98 (Affinity Capture-MS; 3 records), IL17RA (Affinity Capture-MS; 3 records), PPP2R5D (Affinity Capture-MS; 3 records), PPP2R5E (Affinity Capture-MS; 3 records), SUCO (Affinity Capture-MS; 3 records), TMEM132A (Affinity Capture-MS; 3 records), TOR3A (Affinity Capture-MS; 3 records), TRAPPC2 (Affinity Capture-MS; 3 records), WIPI1 (Affinity Capture-MS; 3 records), YTHDF1 (Affinity Capture-MS; 3 records), AMD1 (Affinity Capture-MS; 2 records), ARSA (Affinity Capture-MS; 2 records), CERCAM (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for DNASE2B: 36 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 520):

Position(s)	Effect	Δscore	Sites
1:84398592	donor_gain	0.9900
1:84412334	acceptor_gain	0.9900
1:84412341	acceptor_gain	0.9900
1:84412502	donor_gain	0.9900
1:84414520	acceptor_gain	0.9900
1:84412347–84412348	acceptor_loss	0.9800	5
1:84412547–84412548	donor_loss	0.9800	6
1:84398538	donor_gain	0.9700
1:84398584	donor_gain	0.9700
1:84410996	donor_gain	0.9700

AlphaMissense

516 missense substitutions predicted likely pathogenic (of 2,363 scored), across 134 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D304	8	0.921	0.968
H305	8	0.870	0.931
D112	8	0.848	0.921
H126	8	0.841	0.927
D324	8	0.833	0.918
D249	8	0.809	0.911
C171	7	0.944	0.974
C340	7	0.942	0.974
C321	7	0.939	0.972
F148	7	0.928	0.975
C32	7	0.919	0.957
C279	7	0.899	0.943
W268	7	0.898	0.968
W308	7	0.892	0.983
N326	7	0.877	0.966
F43	7	0.861	0.968
C360	7	0.845	0.896
N111	7	0.811	0.966
D41	7	0.671	0.791
K128	6	0.942	0.991

HPA cancer prognostics

RNA cancer specificity: Group enriched (Prostate Adenocarcinoma, Skin Cutaneous Melanoma)

Disease associations

OMIM: gene MIM:608057 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST001325_9	Response to hepatitis C treatment	7e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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)

Via MONDO — disease-level, not drug-specific.