DCBLD1

Summary

DCBLD1 (discoidin, CUB and LCCL domain containing 1, HGNC:21479) is a protein-coding gene on chromosome 6q22.1, encoding Discoidin, CUB and LCCL domain-containing protein 1 (Q8N8Z6).

Predicted to enable signaling receptor activity. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 285761 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 125 total — 1 pathogenic
• MANE Select transcript: NM_001366458

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21479
Approved symbol	DCBLD1
Name	discoidin, CUB and LCCL domain containing 1
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC46341, dJ94G16.1
Ensembl gene	ENSG00000164465
Ensembl biotype	protein_coding
Entrez	285761

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 8 protein_coding_CDS_not_defined, 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000296955, ENST00000338728, ENST00000424717, ENST00000478345, ENST00000481630, ENST00000487076, ENST00000525483, ENST00000528138, ENST00000528162, ENST00000533453, ENST00000533950, ENST00000534777, ENST00000904345, ENST00000939913, ENST00000939914, ENST00000960444

RefSeq mRNA: 4 — MANE Select: NM_001366458 NM_001366458, NM_001366459, NM_001366460, NM_173674

CCDS: CCDS34522, CCDS93995

Canonical transcript exons

ENST00000338728 — 15 exons

Exon	Start	End
ENSE00001894349	117547907	117549797
ENSE00001947740	117482674	117482893
ENSE00002432510	117503767	117503979
ENSE00002462479	117525362	117525434
ENSE00002466666	117539255	117539379
ENSE00002475116	117538620	117538835
ENSE00003488708	117537185	117537225
ENSE00003516194	117519816	117519950
ENSE00003535102	117543124	117543211
ENSE00003539379	117540918	117541025
ENSE00003574664	117521525	117521576
ENSE00003577132	117540668	117540815
ENSE00003600426	117544528	117544577
ENSE00003655653	117545478	117545597
ENSE00003668920	117532260	117532393

Expression profiles

Bgee: expression breadth ubiquitous, 218 present calls, max score 91.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1136 / max 82.2050, expressed in 1691 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69449	6.7933	1628
69450	2.4346	1154
69451	0.8857	517

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	91.58	gold quality
islet of Langerhans	UBERON:0000006	90.25	gold quality
stromal cell of endometrium	CL:0002255	90.24	gold quality
decidua	UBERON:0002450	89.12	gold quality
ileal mucosa	UBERON:0000331	87.03	gold quality
visceral pleura	UBERON:0002401	85.22	gold quality
endocervix	UBERON:0000458	84.84	gold quality
upper lobe of left lung	UBERON:0008952	84.27	gold quality
upper lobe of lung	UBERON:0008948	84.23	gold quality
gall bladder	UBERON:0002110	83.83	gold quality
ectocervix	UBERON:0012249	83.04	gold quality
endometrium	UBERON:0001295	82.96	gold quality
omental fat pad	UBERON:0010414	82.96	gold quality
peritoneum	UBERON:0002358	82.92	gold quality
sural nerve	UBERON:0015488	82.74	gold quality
pancreas	UBERON:0001264	82.66	gold quality
lung	UBERON:0002048	82.56	gold quality
right lung	UBERON:0002167	82.39	gold quality
adipose tissue of abdominal region	UBERON:0007808	82.32	gold quality
tibialis anterior	UBERON:0001385	81.90	silver quality
subcutaneous adipose tissue	UBERON:0002190	81.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.41	gold quality
rectum	UBERON:0001052	81.07	gold quality
colonic epithelium	UBERON:0000397	81.06	gold quality
apex of heart	UBERON:0002098	81.04	gold quality
uterine cervix	UBERON:0000002	80.78	gold quality
right lobe of liver	UBERON:0001114	80.75	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.57	gold quality
palpebral conjunctiva	UBERON:0001812	80.56	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.22	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.72
E-MTAB-8271	no	215.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting DCBLD1, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-1258	96.08	67.74	700
HSA-MIR-6891-3P	95.80	65.76	683

Literature-anchored findings (GeneRIF, showing 9)

• Two new signals were observed at genome-wide significance (P < 5 x 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases (PMID:28025329)
• Dynamic multi-site phosphorylation by Fyn and Abl drives the interaction between CRKL and the novel scaffolding receptors DCBLD1 and DCBLD2. (PMID:29025973)
• Integration of candidate lung adenocarcinoma (LUAD) risk SNPS with epigenomic marks from normal alveolar epithelium identified numerous candidate functional LUAD risk SNPs including rs6942067, which appears to affect DCBLD1 expression. (PMID:30212242)
• The DCBLD receptor family: emerging signaling roles in development, homeostasis and disease. (PMID:30902898)
• SNP rs17079281 decreases lung cancer risk through creating an YY1-binding site to suppress DCBLD1 expression. (PMID:32231272)
• FYN and ABL Regulate the Interaction Networks of the DCBLD Receptor Family. (PMID:32606017)
• DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma. (PMID:34140574)
• SNP rs9387478 at ROS1-DCBLD1 Locus is Significantly Associated with Lung Cancer Risk and Poor Survival in Indian Population. (PMID:36308382)
• Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression. (PMID:38291438)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dcbld1	ENSDARG00000015907
mus_musculus	Dcbld1	ENSMUSG00000019891
rattus_norvegicus	Dcbld1	ENSRNOG00000000407

Paralogs (1): RS1 (ENSG00000102104)

Protein

Protein identifiers

Discoidin, CUB and LCCL domain-containing protein 1 — Q8N8Z6 (reviewed: Q8N8Z6)

All UniProt accessions (2): Q8N8Z6, H0Y4G4

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N8Z6-1	1	yes
Q8N8Z6-2	2

RefSeq proteins (4): NP_001353387, NP_001353388, NP_001353389, NP_775945 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000421	FA58C	Domain
IPR000859	CUB_dom	Domain
IPR004043	LCCL	Domain
IPR008979	Galactose-bd-like_sf	Homologous_superfamily
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR036609	LCCL_sf	Homologous_superfamily
IPR050633	Neuropilin_MCO_CoagFactor	Family

Pfam: PF00431, PF00754, PF03815

UniProt features (27 total): glycosylation site 6, disulfide bond 4, domain 3, modified residue 2, topological domain 2, splice variant 2, sequence conflict 2, region of interest 2, signal peptide 1, chain 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N8Z6-F1	68.00	0.40

Functional residue map

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

Post-translational modifications (2): 513, 614

Disulfide bonds (4): 41–68, 94–112, 158–174, 178–200

Glycosylation sites (6): 64, 124, 277, 351, 418, 455

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 81 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, ZHANG_GATA6_TARGETS_DN, chr6q22, CHICAS_RB1_TARGETS_SENESCENT, LEE_BMP2_TARGETS_DN, FORTSCHEGGER_PHF8_TARGETS_UP, CSR_EARLY_UP.V1_UP, CSR_LATE_UP.V1_UP, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TAN_DN, ATF6_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): signaling receptor activity (GO:0038023)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molecular transducer activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DCBLD1	ROS1	P08922	609
DCBLD1	SLC35F1	Q5T1Q4	524
DCBLD1	CRKL	P46109	500
DCBLD1	LMBRD1	Q9NUN5	449
DCBLD1	FAM229B	Q4G0N7	446
DCBLD1	MRAP2	Q96G30	441
DCBLD1	OMA1	Q96E52	394
DCBLD1	GOPC	Q9HD26	379
DCBLD1	DCUN1D3	Q8IWE4	377
DCBLD1	KCTD11	Q693B1	370
DCBLD1	HACD1	B0YJ81	353
DCBLD1	IRF2BP2	Q7Z5L9	343
DCBLD1	ZCCHC14	Q8WYQ9	337
DCBLD1	SACK1B	Q5T0W9	337
DCBLD1	LRRC71	Q8N4P6	327

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
CRK	ARHGAP42	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
DCBLD1	PDIA3	psi-mi:“MI:0408”(disulfide bond)	0.440
HLA-DPA1	GXYLT2	psi-mi:“MI:0914”(association)	0.350
TNFSF8	NME4	psi-mi:“MI:0914”(association)	0.350
PCDH12	PCDH17	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
FAM234A	IFRD1	psi-mi:“MI:0914”(association)	0.350
RYK	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
CDH16	EGFR	psi-mi:“MI:0914”(association)	0.350
C1orf54	QSOX1	psi-mi:“MI:0914”(association)	0.350
CCNI2	ZNF609	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
KRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
HRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
KCNK3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (42): DCBLD1 (Affinity Capture-MS), DCBLD1 (Affinity Capture-MS), DCBLD1 (Affinity Capture-MS), DCBLD1 (Affinity Capture-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS), DCBLD1 (Proximity Label-MS)

ESM2 similar proteins: A7E3C4, B6ZK77, C5IAW9, D4A039, F1LW30, O00750, O08721, O08722, O08747, O70167, O70173, O75339, O75460, O95185, O95256, P17948, P35916, P35917, P35969, P53767, Q14956, Q5R7M3, Q66K08, Q68DX3, Q6UXZ4, Q6ZN44, Q761X5, Q7T2H2, Q7T2Z5, Q7TNJ4, Q80ZD9, Q86SJ2, Q8C008, Q8C8H8, Q8IZJ1, Q8JGT4, Q8K1S2, Q8K1S3, Q8K1S4, Q8N8Z6

Diamond homologs: B3EX01, B8JI71, B8VIV4, C6KFA3, F1RWC3, O08628, O08859, O14786, O35276, O35375, O57382, O60462, O60494, O70244, O75074, O88204, P07898, P13497, P28824, P35443, P42662, P42664, P42674, P49744, P56677, P60882, P70412, P78504, P79795, P79953, P82279, P97333, P97607, P98065, P98066, P98069, P98072, P98074, Q06441, Q15113

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	96
Likely benign	8
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1703230	Single allele	Pathogenic

SpliceAI

4381 predictions. Top by Δscore:

Variant	Effect	Δscore
6:117482889:GCTGG:G	donor_gain	1.0000
6:117482890:CTGGG:C	donor_loss	1.0000
6:117482892:GG:G	donor_gain	1.0000
6:117482893:GG:G	donor_gain	1.0000
6:117482893:GGTG:G	donor_loss	1.0000
6:117482894:G:C	donor_loss	1.0000
6:117482894:G:GG	donor_gain	1.0000
6:117482895:T:A	donor_loss	1.0000
6:117503763:CCA:C	acceptor_loss	1.0000
6:117503765:A:AG	acceptor_gain	1.0000
6:117503765:AGG:A	acceptor_loss	1.0000
6:117503765:AGGT:A	acceptor_gain	1.0000
6:117503766:G:GA	acceptor_gain	1.0000
6:117503766:GGT:G	acceptor_gain	1.0000
6:117503766:GGTG:G	acceptor_gain	1.0000
6:117519810:TTTTA:T	acceptor_loss	1.0000
6:117519811:TTTA:T	acceptor_loss	1.0000
6:117519812:TTA:T	acceptor_loss	1.0000
6:117519813:TA:T	acceptor_loss	1.0000
6:117519814:A:AC	acceptor_loss	1.0000
6:117519814:A:AG	acceptor_gain	1.0000
6:117519815:G:GA	acceptor_loss	1.0000
6:117519815:G:GG	acceptor_gain	1.0000
6:117519959:G:GT	donor_gain	1.0000
6:117521523:A:AG	acceptor_gain	1.0000
6:117521524:G:GG	acceptor_gain	1.0000
6:117521524:GATTT:G	acceptor_gain	1.0000
6:117521574:CAGGT:C	donor_loss	1.0000
6:117521577:G:GC	donor_loss	1.0000
6:117521577:G:GG	donor_gain	1.0000

AlphaMissense

4673 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:117519890:A:C	S134R	0.992
6:117519892:T:A	S134R	0.992
6:117519892:T:G	S134R	0.992
6:117525369:T:C	C174R	0.992
6:117532272:T:A	C200S	0.991
6:117532273:G:C	C200S	0.991
6:117503856:T:A	C68S	0.990
6:117503857:G:C	C68S	0.990
6:117525369:T:A	C174S	0.990
6:117525370:G:C	C174S	0.990
6:117532272:T:C	C200R	0.990
6:117547963:T:C	F558L	0.990
6:117547965:C:A	F558L	0.990
6:117547965:C:G	F558L	0.990
6:117503950:T:C	L99P	0.989
6:117503856:T:C	C68R	0.988
6:117519918:T:C	F143S	0.988
6:117519915:G:A	G142D	0.987
6:117519924:T:C	L145P	0.987
6:117525371:C:G	C174W	0.987
6:117525381:T:A	C178S	0.987
6:117525382:G:C	C178S	0.987
6:117519824:T:A	C112S	0.986
6:117519825:G:C	C112S	0.986
6:117519885:T:C	F132S	0.986
6:117519914:G:C	G142R	0.986
6:117540744:G:C	R393P	0.986
6:117521536:T:C	C158R	0.985
6:117525370:G:A	C174Y	0.985
6:117532273:G:A	C200Y	0.984

dbSNP variants (sampled 300 via entrez): RS1000037219 (6:117543994 T>G), RS1000051632 (6:117505973 C>T), RS1000075267 (6:117549975 G>A), RS1000138918 (6:117551433 G>T), RS1000171965 (6:117556515 T>C), RS1000185842 (6:117491927 C>G,T), RS1000186241 (6:117506939 C>T), RS1000204497 (6:117556241 A>G), RS1000247133 (6:117498470 T>C,G), RS1000253083 (6:117541326 G>A), RS1000299507 (6:117498162 C>T), RS1000305614 (6:117499389 G>A), RS1000311768 (6:117562956 A>C), RS1000340534 (6:117518235 G>A), RS1000450943 (6:117504361 A>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:617082

GenCC curated gene-disease

Mondo (1): congenital disorder of glycosylation, type IAA (MONDO:0014904)

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001519_8	Economic and political preferences	2.000000e-06
GCST001740_6	Lung cancer	4.000000e-10
GCST001787_13	Colorectal cancer	3.000000e-06
GCST001901_5	Response to irinotecan and platinum-based chemotherapy in non-small-cell lung cancer	4.000000e-07
GCST001956_83	Height	2.000000e-08
GCST004744_9	Lung adenocarcinoma	7.000000e-08
GCST007094_5	Diastolic blood pressure	1.000000e-08
GCST008103_77	Bipolar disorder	9.000000e-07
GCST008834_9	Non-small cell lung cancer	4.000000e-09
GCST011983_10	Fasting glucose	4.000000e-06
GCST90014033_47	Haemorrhoidal disease	2.000000e-12
GCST90026415_3	Mild obesity-related type 2 diabetes	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004827	economic and social preference
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17574269	Efficacy	3	cisplatin;irinotecan	Small cell carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17574269	DCBLD1	3	0.00	1	cisplatin;irinotecan

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
bisphenol A	decreases methylation, decreases expression	2
trichostatin A	affects cotreatment, increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bufotalin	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
salinomycin	decreases expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
manganese chloride	increases abundance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression	1

Clinical trials (associated diseases)

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