DMBT1

Summary

DMBT1 (deleted in malignant brain tumors 1, HGNC:2926) is a protein-coding gene on chromosome 10q26.13, encoding Scavenger receptor cysteine-rich domain-containing protein DMBT1 (Q9UGM3). May be considered as a candidate tumor suppressor gene for brain, lung, esophageal, gastric, and colorectal cancers.

Loss of sequences from human chromosome 10q has been associated with the progression of human cancers. This gene was originally isolated based on its deletion in a medulloblastoma cell line. This gene is expressed with transcripts of 6.0, 7.5, and 8.0 kb in fetal lung and with one transcript of 8.0 kb in adult lung, although the 7.5 kb transcript has not been characterized. The encoded protein precursor is a glycoprotein containing multiple scavenger receptor cysteine-rich (SRCR) domains separated by SRCR-interspersed domains (SID). Transcript variant 2 (8.0 kb) has been shown to bind surfactant protein D independently of carbohydrate recognition. This indicates that DMBT1 may not be a classical tumor suppressor gene, but rather play a role in the interaction of tumor cells and the immune system.

Source: NCBI Gene 1755 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 496 total — 1 likely-pathogenic
• MANE Select transcript: NM_001377530

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2926
Approved symbol	DMBT1
Name	deleted in malignant brain tumors 1
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	GP340, SALSA, Gp-340
Ensembl gene	ENSG00000187908
Ensembl biotype	protein_coding
OMIM	601969
Entrez	1755

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 17 protein_coding, 5 retained_intron

ENST00000330163, ENST00000338354, ENST00000344338, ENST00000368909, ENST00000368955, ENST00000368956, ENST00000619379, ENST00000652446, ENST00000653442, ENST00000654082, ENST00000655774, ENST00000656203, ENST00000657942, ENST00000663574, ENST00000663623, ENST00000664003, ENST00000664692, ENST00000664974, ENST00000666315, ENST00000667454, ENST00000668486, ENST00000866238

RefSeq mRNA: 5 — MANE Select: NM_001377530 NM_001320644, NM_001377530, NM_004406, NM_007329, NM_017579

CCDS: CCDS44490, CCDS44491, CCDS44492, CCDS91368

Canonical transcript exons

ENST00000338354 — 56 exons

Exon	Start	End
ENSE00001603791	122643122	122643736
ENSE00001628081	122632861	122632890
ENSE00001637864	122640040	122640449
ENSE00001654461	122637128	122637312
ENSE00001706275	122630961	122631281
ENSE00001739142	122635991	122636199
ENSE00001786834	122633191	122633341
ENSE00001799353	122631855	122631875
ENSE00002431864	122630288	122630490
ENSE00002432686	122605050	122605082
ENSE00002433470	122584322	122584351
ENSE00002433600	122582600	122582923
ENSE00002435552	122611218	122611247
ENSE00002436096	122593569	122593598
ENSE00002439352	122594496	122594528
ENSE00002439404	122573715	122573762
ENSE00002440719	122601797	122602120
ENSE00002441292	122600064	122600093
ENSE00002441342	122578718	122578759
ENSE00002441948	122600991	122601023
ENSE00002443680	122580866	122580895
ENSE00002451519	122590665	122590694
ENSE00002452206	122597025	122597054
ENSE00002452573	122617228	122617260
ENSE00002453235	122598774	122599097
ENSE00002454579	122586060	122586383
ENSE00002455617	122618017	122618340
ENSE00002460312	122621057	122621380
ENSE00002463456	122605856	122606179
ENSE00002464367	122591479	122591517
ENSE00002464912	122613974	122614297
ENSE00002475355	122565967	122565996
ENSE00002479569	122620253	122620291
ENSE00002481947	122585271	122585309
ENSE00002484394	122625277	122625303
ENSE00002488975	122570162	122570209
ENSE00002489010	122629840	122629993
ENSE00002492233	122579578	122579901
ENSE00002492459	122609915	122610238
ENSE00002494396	122581793	122581825
ENSE00002496410	122619308	122619337
ENSE00002498214	122609109	122609141
ENSE00002500691	122607159	122607188
ENSE00002501963	122595303	122595626
ENSE00002502423	122615277	122615306
ENSE00002502539	122570890	122570937
ENSE00002510955	122592272	122592595
ENSE00002511126	122588944	122589267
ENSE00002515425	122576399	122576722
ENSE00002518040	122613168	122613200
ENSE00002527923	122603100	122603129
ENSE00002531408	122577811	122577840
ENSE00002533153	122625933	122625965
ENSE00002533634	122572314	122572361
ENSE00002534429	122597974	122598012
ENSE00003900377	122560754	122560831

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 99.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8346 / max 580.8974, expressed in 40 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107462	1.4696	39
107460	0.2059	24
107461	0.1592	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.78	gold quality
trachea	UBERON:0003126	99.71	gold quality
jejunal mucosa	UBERON:0000399	99.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.44	gold quality
duodenum	UBERON:0002114	99.29	gold quality
ileal mucosa	UBERON:0000331	98.78	gold quality
palpebral conjunctiva	UBERON:0001812	95.61	gold quality
mucosa of transverse colon	UBERON:0004991	94.01	gold quality
nasal cavity mucosa	UBERON:0001826	93.56	gold quality
pancreatic ductal cell	CL:0002079	93.49	silver quality
saliva-secreting gland	UBERON:0001044	92.40	gold quality
small intestine	UBERON:0002108	92.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.58	gold quality
gall bladder	UBERON:0002110	91.30	gold quality
minor salivary gland	UBERON:0001830	90.62	gold quality
lower lobe of lung	UBERON:0008949	90.56	gold quality
vermiform appendix	UBERON:0001154	88.11	gold quality
jejunum	UBERON:0002115	88.02	gold quality
caecum	UBERON:0001153	87.53	gold quality
mouth mucosa	UBERON:0003729	87.06	gold quality
epithelial cell of pancreas	CL:0000083	86.56	gold quality
sperm	CL:0000019	86.16	gold quality
lung	UBERON:0002048	85.21	gold quality
upper lobe of lung	UBERON:0008948	85.21	gold quality
male germ cell	CL:0000015	84.60	gold quality
upper lobe of left lung	UBERON:0008952	84.57	gold quality
transverse colon	UBERON:0001157	83.00	gold quality
pharyngeal mucosa	UBERON:0000355	82.10	gold quality
tongue	UBERON:0001723	81.98	gold quality
rectum	UBERON:0001052	81.31	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	690.00
E-MTAB-9906	yes	686.68
E-HCAD-1	yes	73.43
E-CURD-114	yes	24.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2, NFKB, SOX9

miRNA regulators (miRDB)

18 targeting DMBT1, 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-4682	100.00	68.89	1258
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-4314	97.50	67.30	1369
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-571	95.38	66.54	671

Literature-anchored findings (GeneRIF, showing 40)

• may be involved in terminal differentiation of prostate and vas deferens, but no evidence implicating role in prostatic carcinogenesis (PMID:11550206)
• DMBT1 is likely to play a differential role in the genesis of digestive tract carcinomas. (PMID:11751412)
• DMBT1 polymorphisms are not likely primary targets of 10q loss in malignant gliomas and do not support a major role for DMBT1 in gliomagenesis. (PMID:11912156)
• Identification of two highly sialylated human tear-fluid isoforms: the major high-molecular-mass glycoproteins in human tears (PMID:12015815)
• Identification of the bacteria-binding peptide domain (PMID:12050164)
• DMBT1 and p16 alterations occur in low-grade astrocytomas, and might be considered as early genetic events. (PMID:12168116)
• mutational analysis of the entire coding region of DMBT1, employing SSCP analysis and direct DNA sequencing in 79 astrocytic gliomas. Five somatic mutations were detected.21 of the 27 SNP identified in this study have not been recognized previously. (PMID:12185598)
• Changes of DMBT1 expression and location reflect a time course that point to possible mechanisms for its role in epithelial cancer. (PMID:12203780)
• Analysis of loss of heterozygosity in melanoma resection specimens (PMID:12239452)
• The repetitive scavenger receptor cysteine-rich (SRCR) domains and SRCR-interspersed domains (SID) of DMBT1 define a complex multi-allele system that represents the major basis for the variability of DMBT1 in cancer. (PMID:12353266)
• heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of this protein (PMID:12368192)
• Intragenic homozygous deletion of DMBT1 is common in brain tumors and is likely a result of a germline deletion of 1 allele followed by loss of the second allele during tumor development (PMID:12672033)
• regulates mucosal homeostasis through the linking of mucosal defense and regeneration (PMID:12681477)
• present in bronchoalveolar lavage fluids and saliva and mediates specific adhesion to and aggregation of influenza A virus (PMID:12871854)
• Selective loss of the 10q25.3 region, including the DMBT1 gene, is not an initiating event in the genesis of astrocytoma grade II. (PMID:14603438)
• TFF2 and its putative receptor, DMBT1, were expressed non-specifically in biliary epithelial cells of the damaged small bile ducts, suggesting a cytoprotective role in biliary pathophysiology. (PMID:15101998)
• DMBT1(SAG) expression was analyzed in 20 salivary gland tumors and 14 tumor-flanking tissues. DMBT1(SAG) was upregulated in 10/14 tumor-flanking tissues, and a strong staining of the luminal content was observed in 14/20 cases. (PMID:15218048)
• Binding of IgA to salivary agglutinin, encoded by DMBT1, is specifically mediated by a peptide sequence on the scavenger receptor cysteine-rich domains. (PMID:15228387)
• The interaction of gp340 with gp120 is enhanced by prebinding of sCD4 to gp120, suggesting that gp340 inhibitory activity is mediated by blocking access of the gp120 to the chemokine receptor. (PMID:15242536)
• The redistribution and up-regulation of DMBT1 in normal and hyperplastic tissues flanking malignant tumours and its down-regulation in carcinomas suggests a potential role in breast cancer. (PMID:15301691)
• Results describe the minimal bacteria-binding site on DMBT1 (deleted in malignant brain tumors 1). (PMID:15355985)
• DMBT1 is an estrogen-responsive gene with a possible role in endometrial proliferation or differentiation (PMID:15564322)
• reported as new substrate for StcE protease of Escherichia coli O157-H7 in HEp-2 cells (PMID:15731026)
• involved in oral squamous cell carcinoma oncogenesis and/or progression (PMID:15754018)
• frequent abnormalities of the DMBT1 expression in the specimens of human gastric adenocarcinoma were detected (PMID:15760920)
• The applicability of the vector system by expression of the largest DMBT1 variant in a tetracycline-inducible mammalian expression system using the Chinese hamster ovary cell line. (PMID:15866713)
• DMBT1 and its glycosylation in the adenoma-carcinoma sequence leading to the adenocarcinoma phenotype. (PMID:16042587)
• salivary gp-340 can, in some cases, strongly antagonize certain antiviral activities of surfactant protein-D (PMID:16190864)
• gp340 is a normal component of the tear film of the human eye and may function as a bacterial agglutinin. (PMID:16790779)
• We have demonstrated that the N-terminal SRCR domain of gp340 directly interacts with HIV-1 gp120 and likely mediates anti-HIV-1 activity via this interaction (PMID:16796526)
• The glycoforms of saliva and lung gp-340 mediated differential aggregation of Le(b)- (Helicobacter pylori), sialylpolylactosamine- (Streptococcus suis) or sialic acid- (Streptococcus mutans) binding bacteria. (PMID:17243023)
• DMBT1 is a target gene for the intracellular pathogen receptor NOD2 via NF-kappaB activation. (PMID:17548659)
• A host protein, gp340, that is expressed on genital epithelium and binds the HIV envelope via a specific protein-protein interaction, was identified. (PMID:17709527)
• Our data showed pulmonary DMBT1 expression in hyaline membranes during respiratory distress syndrome and demonstrated that DMBT1 increases lung surface tension in vitro. (PMID:17908325)
• DMBT1 may play a role in intestinal mucosal protection and prevention of inflammation. Impaired DMBT1 function may contribute to the pathogenesis of Crohn’s disease. (PMID:17983803)
• these data strongly point to a role for DMBT1 as a molecule linking innate immune processes with regenerative processes–{review} (PMID:18020944)
• gp340-mediated aggregation reduced bacterial adhesion to human epithelial cells. (PMID:18452511)
• gp340, which is expressed by macrophages in vivo, may function to enhance infection in much the same manner (PMID:18641344)
• in conclusion, a common binding motif (RVEVLYxxxSW) within the scavenger receptor cysteine-rich (SRCR) domains is responsible for the broad bacteria-binding spectrum of DMBT1SAG (PMID:18713006)
• A proteomic analysis of proteins expressed in intraductal papillary mucinous neoplasms showed that DMBT1 and TGM2 were both upregulated in these lesions. (PMID:18849643)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000101017
danio_rerio		ENSDARG00000111315
mus_musculus	Dmbt1	ENSMUSG00000047517
rattus_norvegicus		ENSRNOG00000074425

Paralogs (15): CD6 (ENSG00000013725), CD5L (ENSG00000073754), LGALS3BP (ENSG00000108679), CD5 (ENSG00000110448), LOX (ENSG00000113083), LOXL3 (ENSG00000115318), LOXL1 (ENSG00000129038), LOXL2 (ENSG00000134013), LOXL4 (ENSG00000138131), SSC4D (ENSG00000146700), PRSS12 (ENSG00000164099), CD163 (ENSG00000177575), CD163L1 (ENSG00000177675), SSC5D (ENSG00000179954), SCART1 (ENSG00000214279)

Protein

Protein identifiers

Scavenger receptor cysteine-rich domain-containing protein DMBT1 — Q9UGM3 (reviewed: Q9UGM3)

Alternative names: Deleted in malignant brain tumors 1 protein, Glycoprotein 340, Hensin, Salivary agglutinin, Surfactant pulmonary-associated D-binding protein

All UniProt accessions (6): A0A590UIX5, A0A590UJ76, A0A590UJF8, A0A590UJZ9, A0A590UK99, Q9UGM3

UniProt curated annotations — full annotation on UniProt →

Function. May be considered as a candidate tumor suppressor gene for brain, lung, esophageal, gastric, and colorectal cancers. May play roles in mucosal defense system, cellular immune defense and epithelial differentiation. May play a role as an opsonin receptor for SFTPD and SPAR in macrophage tissues throughout the body, including epithelial cells lining the gastrointestinal tract. May play a role in liver regeneration. May be an important factor in fate decision and differentiation of transit-amplifying ductular (oval) cells within the hepatic lineage. Required for terminal differentiation of columnar epithelial cells during early embryogenesis. May function as a binding protein in saliva for the regulation of taste sensation. Binds to HIV-1 envelope protein and has been shown to both inhibit and facilitate viral transmission. Displays a broad calcium-dependent binding spectrum against both Gram-positive and Gram-negative bacteria, suggesting a role in defense against bacterial pathogens. Binds to a range of poly-sulfated and poly-phosphorylated ligands which may explain its broad bacterial-binding specificity. Inhibits cytoinvasion of S.enterica. Associates with the actin cytoskeleton and is involved in its remodeling during regulated exocytosis. Interacts with pancreatic zymogens in a pH-dependent manner and may act as a Golgi cargo receptor in the regulated secretory pathway of the pancreatic acinar cell.

Subunit / interactions. Interacts with LGALS3. Binds SFTPD and SPAR in a calcium-dependent manner. (Microbial infection) Interacts with HIV-1 glycoprotein 120. (Microbial infection) Interacts with S.aureus SraP; the interaction is inhibited by N-acetylneuraminic acid.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in alveolar and macrophage tissues. In some macrophages, expression is seen on the membrane, and in other macrophages, strongly expressed in the phagosome/phagolysosome compartments. Expressed in lung, trachea, salivary gland, small intestine and stomach. In pancreas, expressed in certain cells of the islets of Langerhans. In digestive tract, confined to tissues with large epithelial surfaces. In intestinal tissue, moderately expressed in epithelial cells of the midcrypts and the crypt base. Expression is significantly elevated in intestinal tissue from patients with inflammatory bowel disease (IBD), particularly in surface epithelial and Paneth cells, but not in IBD patients with mutant NOD2. Present in crypt bases of the duodenum, in crypt tops of the colon, and in collecting ducts of the cortical kidney. Expressed in stratified squamous epithelium of vagina and in outer luminar surface and basilar region of columnar epithelial cells in cervix (at protein level). Isoform 1 is secreted to the lumen of the respiratory tract.

Post-translational modifications. Highly N- and O-glycosylated. The O-glycans are heavily sulfated.

Disease relevance. Glioma (GLM) [MIM:137800] Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. The gene represented in this entry is involved in disease pathogenesis. Homozygous deletions may be the predominant mechanism of DMBT1 inactivation playing a role in carcinogenesis. DMBT1 is deleted in medulloblastoma and glioblastoma cell lines; point mutations have also been reported in patients with glioma. A loss or reduction of DMBT1 expression has been seen in esophageal, gastric, lung and colorectal carcinomas as well.

Domain organisation. The SRCR domains mediate binding to bacteria. The minimal bacterial-binding site is an 11-residue repeat of GRVEVLYRGSW where VEVL and W are critical residues.

Induction. Up-regulated in intestinal epithelial cells in response to pro-inflammatory stimuli including TNF and bacterial lipopolysaccharides (LPS).

Polymorphism. The number of SRCR and SRCR-interspersed domains is polymorphic in a variety of tumors and may represent the major site of alterations in cancer.

Similarity. Belongs to the DMBT1 family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q9UGM3-1	1, DMBT1/8kb.2	yes
Q9UGM3-2	2, DMBT1/6kb.1
Q9UGM3-3	3, DMBT1/8kb.1
Q9UGM3-4	4
Q9UGM3-6	6
Q9UGM3-7	7
Q9UGM3-8	8
Q9UGM3-5	5
Q9UGM3-9	9

RefSeq proteins (5): NP_001307573, NP_001364459, NP_004397, NP_015568, NP_060049 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000859	CUB_dom	Domain
IPR001190	SRCR	Domain
IPR001507	ZP_dom	Domain
IPR017977	ZP_dom_CS	Conserved_site
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR036772	SRCR-like_dom_sf	Homologous_superfamily
IPR042235	ZP-C_dom	Homologous_superfamily
IPR055355	ZP-C	Domain
IPR055356	ZP-N	Domain

Pfam: PF00100, PF00431, PF00530, PF23344

UniProt features (195 total): disulfide bond 47, sequence conflict 36, sequence variant 31, domain 17, strand 17, glycosylation site 14, splice variant 12, helix 10, region of interest 6, turn 2, signal peptide 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6SA5	X-RAY DIFFRACTION	1.29
6SAN	X-RAY DIFFRACTION	1.36
8J8D	X-RAY DIFFRACTION	1.51
6SA4	X-RAY DIFFRACTION	1.77
8J8T	X-RAY DIFFRACTION	1.81
8WZS	X-RAY DIFFRACTION	2.54

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGM3-F1	74.29	0.25

Functional residue map

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

Disulfide bonds (47): 127–191, 140–201, 171–181, 259–323, 272–333, 303–313, 388–452, 401–462, 432–442, 519–583, 532–593, 563–573, 627–691, 640–701, 671–681, 758–822, 771–832, 802–812, 887–951, 900–961 …

Glycosylation sites (14): 566, 737, 1712, 1745, 1818, 1832, 1842, 1889, 1998, 2120, 2188, 2233, 2240, 2256

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5683826	Surfactant metabolism

MSigDB gene sets: 136 (showing top): RNGTGGGC_UNKNOWN, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_MEDIATED_TRANSPORT, LEE_LIVER_CANCER_CIPROFIBRATE_DN, MODULE_66, MODULE_118, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_GRAM_NEGATIVE_BACTERIUM, LEE_LIVER_CANCER_DENA_DN, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_DEFENSE_RESPONSE_TO_GRAM_POSITIVE_BACTERIUM

GO Biological Process (10): defense response (GO:0006952), protein transport (GO:0015031), epithelial cell differentiation (GO:0030855), induction of bacterial agglutination (GO:0043152), innate immune response (GO:0045087), defense response to Gram-negative bacterium (GO:0050829), defense response to Gram-positive bacterium (GO:0050830), defense response to virus (GO:0051607), vesicle-mediated transport (GO:0016192), cell differentiation (GO:0030154)

GO Molecular Function (5): scavenger receptor activity (GO:0005044), zymogen binding (GO:0035375), pattern recognition receptor activity (GO:0038187), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), phagocytic vesicle membrane (GO:0030670), extracellular matrix (GO:0031012), zymogen granule membrane (GO:0042589), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
transport	2
defense response to bacterium	2
response to stress	1
intracellular protein localization	1
establishment of protein localization	1
cell differentiation	1
epithelium development	1
antibacterial humoral response	1
immune response	1
defense response to symbiont	1
defense response	1
response to virus	1
cellular process	1
cellular developmental process	1
cargo receptor activity	1
enzyme binding	1
signaling receptor activity	1
calcium ion binding	1
protein binding	1
binding	1
intracellular anatomical structure	1
endocytic vesicle membrane	1
phagocytic vesicle	1
external encapsulating structure	1
secretory granule membrane	1
zymogen granule	1
extracellular vesicle	1

Protein interactions and networks

STRING

1346 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMBT1	SFTPD	P35247	965
DMBT1	MUC5B	Q9HC84	891
DMBT1	ZNF320	A2RRD8	825
DMBT1	LTF	P02788	800
DMBT1	SRA1	Q9HD15	767
DMBT1	PDZK1IP1	Q13113	752
DMBT1	ALB	P02768	711
DMBT1	ITIH4	Q14624	699
DMBT1	LGALS3	P17931	693
DMBT1	PACC1	Q9H813	632
DMBT1	MUC7	Q8TAX7	622
DMBT1	LYZL1	Q6UWQ5	591
DMBT1	TFF3	Q07654	587
DMBT1	BIRC2	Q13490	578
DMBT1	LYZ	P00695	572
DMBT1	MGMT	P16455	572

IntAct

62 interactions, top by confidence:

A	B	Type	Score
PARD6B	PRKCI	psi-mi:“MI:0914”(association)	0.960
SMARCE1	ARID1A	psi-mi:“MI:0914”(association)	0.840
	MASP2	psi-mi:“MI:0915”(physical association)	0.750
C4B	C4A	psi-mi:“MI:0915”(physical association)	0.720
SFTPA1	DMBT1	psi-mi:“MI:0407”(direct interaction)	0.560
FRMD1	A2ML1	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
HBM	SCGB2A1	psi-mi:“MI:0914”(association)	0.530
ICE2	HP	psi-mi:“MI:0914”(association)	0.530
PCK2	IGHA1	psi-mi:“MI:0914”(association)	0.530
RIBC1	CNOT1	psi-mi:“MI:0914”(association)	0.530
SFTPD	DMBT1	psi-mi:“MI:0407”(direct interaction)	0.440
DMBT1	Sftpd	psi-mi:“MI:0407”(direct interaction)	0.440
spaP	DMBT1	psi-mi:“MI:0407”(direct interaction)	0.440
DMBT1	DMBT1	psi-mi:“MI:0407”(direct interaction)	0.440
	DMBT1	psi-mi:“MI:0407”(direct interaction)	0.440
MBL2	DMBT1	psi-mi:“MI:0407”(direct interaction)	0.440
DMBT1	FCN3	psi-mi:“MI:0407”(direct interaction)	0.440
DMBT1	FCN2	psi-mi:“MI:0407”(direct interaction)	0.440
DMBT1	FCN1	psi-mi:“MI:0407”(direct interaction)	0.440
DMBT1	C3	psi-mi:“MI:0407”(direct interaction)	0.440
METTL3	TUBAL3	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
GSK3B	PRSS37	psi-mi:“MI:0914”(association)	0.350
PRDM16	GAPDHS	psi-mi:“MI:0914”(association)	0.350
DISC1	AGRN	psi-mi:“MI:0914”(association)	0.350
CLK1	PIGR	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), DMBT1 (Affinity Capture-MS), BIRC2 (Affinity Capture-Western), DMBT1 (Affinity Capture-RNA), DMBT1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P0UTI6, A0A0P0UTQ7, A0A6P8HC43, B2CJ57, E9Q0N2, O42918, O49146, O96790, P01068, P01357, P05226, P05817, P0C589, P0DMZ8, P0DMZ9, P0DRJ4, P0DUT2, P14417, P25071, P29127, P30205, P32072, P37842, P58454, P69929, P81592, P83606, P86179, P86733, Q09180, Q1ELU5, Q28201, Q29428, Q43710, Q4A3R3, Q5DFZ7, Q5GC91, Q5GC92, Q5GC94, Q60997

Diamond homologs: A1L0T3, A1L1V4, A1L4H1, A5PJQ2, A6H737, A7E3W2, B4F6N6, B5DF27, B8A4W9, E1C3U7, F1QQC3, F1RD85, F7J220, G3V801, M9NDE3, O08762, O43866, O70513, P21757, P21758, P30203, P30204, P30205, P56730, P58022, P58215, P70117, P85521, Q05585, Q07797, Q08380, Q08B63, Q14DK5, Q24JV9, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q4A3R3, Q4G0T1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 82 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
Initial triggering of complement	7	82.5×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
complement activation, classical pathway	5	38.3×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	334
Likely benign	116
Benign	17

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1077193	Single allele	Likely pathogenic

SpliceAI

7954 predictions. Top by Δscore:

Variant	Effect	Δscore
10:122577809:A:AG	acceptor_gain	1.0000
10:122577810:G:GG	acceptor_gain	1.0000
10:122578709:T:A	acceptor_gain	1.0000
10:122578717:GAAA:G	acceptor_gain	1.0000
10:122578759:GGTA:G	donor_loss	1.0000
10:122578760:GTA:G	donor_loss	1.0000
10:122578761:T:G	donor_loss	1.0000
10:122580864:A:AG	acceptor_gain	1.0000
10:122580865:G:GG	acceptor_gain	1.0000
10:122580893:CAGGT:C	donor_loss	1.0000
10:122580894:AGGT:A	donor_loss	1.0000
10:122580895:GGT:G	donor_loss	1.0000
10:122580896:G:T	donor_loss	1.0000
10:122580897:T:A	donor_loss	1.0000
10:122581778:T:A	acceptor_gain	1.0000
10:122581781:T:TA	acceptor_gain	1.0000
10:122581784:A:AG	acceptor_gain	1.0000
10:122581785:A:G	acceptor_gain	1.0000
10:122581791:A:AG	acceptor_gain	1.0000
10:122581792:G:GG	acceptor_gain	1.0000
10:122581792:GA:G	acceptor_gain	1.0000
10:122581792:GAT:G	acceptor_gain	1.0000
10:122581792:GATA:G	acceptor_gain	1.0000
10:122581822:GCAG:G	donor_gain	1.0000
10:122581823:CAGGT:C	donor_loss	1.0000
10:122581824:AGGT:A	donor_loss	1.0000
10:122581825:GGTA:G	donor_loss	1.0000
10:122581826:G:A	donor_loss	1.0000
10:122581827:T:A	donor_loss	1.0000
10:122585263:A:AG	acceptor_gain	1.0000

AlphaMissense

16366 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:122576508:G:C	W131C	1.000
10:122576508:G:T	W131C	1.000
10:122579687:G:C	W263C	1.000
10:122579687:G:T	W263C	1.000
10:122582707:T:A	W392R	1.000
10:122582707:T:C	W392R	1.000
10:122582709:G:C	W392C	1.000
10:122582709:G:T	W392C	1.000
10:122586169:G:C	W523C	1.000
10:122586169:G:T	W523C	1.000
10:122589053:G:C	W631C	1.000
10:122589053:G:T	W631C	1.000
10:122592379:T:A	W762R	1.000
10:122592379:T:C	W762R	1.000
10:122592381:G:C	W762C	1.000
10:122592381:G:T	W762C	1.000
10:122595398:T:A	C887S	1.000
10:122595399:G:A	C887Y	1.000
10:122595399:G:C	C887S	1.000
10:122595412:G:C	W891C	1.000
10:122595412:G:T	W891C	1.000
10:122598883:G:C	W1022C	1.000
10:122598883:G:T	W1022C	1.000
10:122601906:G:C	W1151C	1.000
10:122601906:G:T	W1151C	1.000
10:122610024:G:C	W1280C	1.000
10:122610024:G:T	W1280C	1.000
10:122631067:G:C	W1915C	1.000
10:122631067:G:T	W1915C	1.000
10:122576494:T:A	C127S	0.999

dbSNP variants (sampled 300 via entrez): RS1000032887 (10:122618733 A>T), RS1000076290 (10:122643205 T>C), RS1000109035 (10:122592002 C>T), RS1000133241 (10:122623780 G>A), RS1000211874 (10:122626670 A>G), RS1000331081 (10:122620939 A>G), RS1000384999 (10:122620674 A>G), RS1000409550 (10:122564203 G>C), RS1000468792 (10:122581483 G>A,C), RS1000541435 (10:122591753 C>T), RS1000543771 (10:122587890 T>C), RS1000603610 (10:122627055 C>T), RS1000644121 (10:122629665 T>A), RS1000662271 (10:122569363 A>G), RS1000692910 (10:122632572 G>A)

Disease associations

OMIM: gene MIM:601969 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST007742_10	Iris heterochromicity	8.000000e-06
GCST007742_21	Iris heterochromicity	4.000000e-06
GCST007742_25	Iris heterochromicity	3.000000e-06
GCST012490_212	Femur bone mineral density x serum urate levels interaction	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009764	eye colour measurement
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

41 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression, increases reaction, affects binding, decreases expression, affects cotreatment	4
bisphenol A	increases expression, affects cotreatment, affects expression, increases abundance	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Aflatoxin B1	increases expression, increases methylation	2
ginger extract	affects cotreatment, affects expression, increases abundance	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
potassium persulfate	increases expression	1
sodium arsenite	decreases expression	1
zinc chromate	increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
tamibarotene	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
licochalcone B	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Fulvestrant	increases expression	1
Microplastics	increases abundance, increases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Cisplatin	affects response to substance	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Oils, Volatile	affects cotreatment, affects expression, increases abundance	1
Ozone	affects cotreatment, decreases expression, increases abundance	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome