DPY19L3

Summary

DPY19L3 (dpy-19 like C-mannosyltransferase 3, HGNC:27120) is a protein-coding gene on chromosome 19q13.11, encoding Protein C-mannosyl-transferase DPY19L3 (Q6ZPD9). C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.

Enables mannosyltransferase activity. Predicted to be involved in protein glycosylation. Located in endoplasmic reticulum membrane.

Source: NCBI Gene 147991 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 113 total
• MANE Select transcript: NM_001172774

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27120
Approved symbol	DPY19L3
Name	dpy-19 like C-mannosyltransferase 3
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178904
Ensembl biotype	protein_coding
OMIM	613894
Entrez	147991

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000342179, ENST00000392250, ENST00000585597, ENST00000586427, ENST00000586987, ENST00000587077, ENST00000588648, ENST00000590651, ENST00000592142, ENST00000592503, ENST00000592832, ENST00000608291, ENST00000852723, ENST00000852724

RefSeq mRNA: 2 — MANE Select: NM_001172774 NM_001172774, NM_207325

CCDS: CCDS12422

Canonical transcript exons

ENST00000392250 — 19 exons

Exon	Start	End
ENSE00003477393	32463869	32463980
ENSE00003478320	32411239	32411372
ENSE00003500143	32468731	32468813
ENSE00003513014	32454939	32455040
ENSE00003527147	32480399	32480557
ENSE00003534766	32464728	32464784
ENSE00003548724	32453145	32453276
ENSE00003568495	32477522	32477654
ENSE00003569546	32463366	32463488
ENSE00003612116	32458351	32458509
ENSE00003622440	32408217	32408356
ENSE00003625142	32458100	32458173
ENSE00003655557	32439776	32439910
ENSE00003845864	32405770	32405909
ENSE00003849485	32482079	32485890
ENSE00003889961	32439112	32439235
ENSE00003890687	32437194	32437339
ENSE00003891882	32432716	32432806
ENSE00003892120	32436446	32436567

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 97.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.4031 / max 475.9939, expressed in 1784 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175050	7.4994	1610
175053	5.1285	1597
175051	1.9727	997
175049	1.8284	991
175052	0.9741	563

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	97.93	gold quality
germinal epithelium of ovary	UBERON:0001304	94.04	gold quality
secondary oocyte	CL:0000655	92.94	gold quality
parietal pleura	UBERON:0002400	92.24	gold quality
ganglionic eminence	UBERON:0004023	91.95	gold quality
visceral pleura	UBERON:0002401	91.38	gold quality
tendon of biceps brachii	UBERON:0008188	91.38	gold quality
cortical plate	UBERON:0005343	90.75	gold quality
ventricular zone	UBERON:0003053	90.66	gold quality
stromal cell of endometrium	CL:0002255	90.56	gold quality
pigmented layer of retina	UBERON:0001782	90.50	gold quality
medial globus pallidus	UBERON:0002477	90.44	gold quality
cartilage tissue	UBERON:0002418	90.20	gold quality
oviduct epithelium	UBERON:0004804	89.83	gold quality
endometrium	UBERON:0001295	89.14	gold quality
globus pallidus	UBERON:0001875	88.85	gold quality
esophagus squamous epithelium	UBERON:0006920	88.80	gold quality
skin of hip	UBERON:0001554	88.54	gold quality
trabecular bone tissue	UBERON:0002483	88.53	gold quality
tendon	UBERON:0000043	88.44	gold quality
bone marrow cell	CL:0002092	88.40	gold quality
epithelial cell of pancreas	CL:0000083	88.27	silver quality
adrenal tissue	UBERON:0018303	87.98	gold quality
calcaneal tendon	UBERON:0003701	87.58	gold quality
sural nerve	UBERON:0015488	87.27	gold quality
ileal mucosa	UBERON:0000331	86.59	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.41	gold quality
caudate nucleus	UBERON:0001873	86.40	gold quality
bone marrow	UBERON:0002371	86.23	gold quality
nucleus accumbens	UBERON:0001882	86.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.07
E-GEOD-124858	no	104.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

228 targeting DPY19L3, 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-8485	100.00	77.57	4731
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 3)

• DPY19L3 is the C-mannosyltransferase of Rspo1 at tryptophan(156). (PMID:26764097)
• Data indicate that N-glycosylations of C-mannosyltransferase DPY19L3 (DPY19L3) do not have any roles for its enzymatic activity. (PMID:29405629)
• DPY19L3 promotes vasculogenic mimicry by its C-mannosyltransferase activity. (PMID:38560568)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpy19l3	ENSDARG00000079013
mus_musculus	Dpy19l3	ENSMUSG00000043671
rattus_norvegicus	Dpy19l3	ENSRNOG00000021573
drosophila_melanogaster	CG6659	FBGN0030946

Paralogs (3): DPY19L4 (ENSG00000156162), DPY19L1 (ENSG00000173852), DPY19L2 (ENSG00000177990)

Protein

Protein identifiers

Protein C-mannosyl-transferase DPY19L3 — Q6ZPD9 (reviewed: Q6ZPD9)

Alternative names: Dpy-19-like protein 3, Protein dpy-19 homolog 3

All UniProt accessions (6): Q6ZPD9, K7ELB5, K7ELG1, K7ELH8, Q8N6Q4, S4R3D3

UniProt curated annotations — full annotation on UniProt →

Function. C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins. The reaction occurs on the luminal side of the endoplasmic reticulum and involves the transfer of a mannose unit from a dolichylphosphate mannose (Dol-P-Man) donor to an acceptor protein containing a WxxW or WxxC consensus sequence. C-mannosylates RSPO1, a Wnt signaling regulator, preferentially at the first Trp residue in the sequence WxxW. C-mannosylates the netrin receptor UNC5A, preferentially at the third tryptophan of WxxWxxWxxC sequence. Has no C-mannosyltransferase activity.

Subcellular location. Endoplasmic reticulum membrane Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed.

Domain organisation. The C-terminal luminal region is essential for C-mannosyltransferase activity.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the dpy-19 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6ZPD9-1	1	yes
Q6ZPD9-2	2

RefSeq proteins (2): NP_001166245, NP_997208 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018732	Dpy-19/Dpy-19-like	Family
IPR047465	Dpy19L3	Family

Pfam: PF10034

Enzyme classification (BRENDA):

• EC 2.4.1.B72 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• L-tryptophyl-[protein] + a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate = C-alpha-D-mannosyl-L-tryptophyl-[protein] + a di-trans,poly-cis-dolichyl phosphate + H(+) (RHEA:77219)

UniProt features (36 total): topological domain 14, transmembrane region 11, glycosylation site 2, splice variant 2, mutagenesis site 2, intramembrane region 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZPD9-F1	88.89	0.73

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 (2): 118, 704

Mutagenesis-validated functional residues (2):

Position	Phenotype
118	does not affect endoplasmic reticulum membrane localization. does not affect mannosyltransferase activity.
704	does not affect endoplasmic reticulum membrane localization. does not affect mannosyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 159 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GTGCCTT_MIR506, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, YYCATTCAWW_UNKNOWN, TGCCTTA_MIR124A, GRYDER_PAX3FOXO1_TOP_ENHANCERS, TAATTA_CHX10_01, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, AAGCACA_MIR218, GOMF_HEXOSYLTRANSFERASE_ACTIVITY, GOMF_MANNOSYLTRANSFERASE_ACTIVITY, GOMF_GLYCOSYLTRANSFERASE_ACTIVITY, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_DN

GO Biological Process (1): obsolete protein glycosylation (GO:0006486)

GO Molecular Function (3): mannosyltransferase activity (GO:0000030), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hexosyltransferase activity	1
catalytic activity	1
transferase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

496 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPY19L3	TSR3	Q9UJK0	615
DPY19L3	TSR1	Q2NL82	577
DPY19L3	TSR2	Q969E8	576
DPY19L3	CCDC126	Q96EE4	564
DPY19L3	PRPSAP1	Q14558	540
DPY19L3	PPP1R3G	B7ZBB8	517
DPY19L3	NLRP13	Q86W25	507
DPY19L3	UNC5A	Q6ZN44	505
DPY19L3	OR5AR1	Q8NGP9	502
DPY19L3	CHST10	O43529	499
DPY19L3	ZC3H8	Q8N5P1	494
DPY19L3	OR5M11	Q96RB7	493
DPY19L3	MTMR1	Q13613	479
DPY19L3	PRDM13	Q9H4Q3	473
DPY19L3	OR5M10	Q6IEU7	467

IntAct

37 interactions, top by confidence:

A	B	Type	Score
DDRGK1	UFL1	psi-mi:“MI:0914”(association)	0.710
THBS2	AP1G2	psi-mi:“MI:0914”(association)	0.530
C6	B3GLCT	psi-mi:“MI:0914”(association)	0.530
CFP	B3GLCT	psi-mi:“MI:0914”(association)	0.530
PBXIP1	GOLIM4	psi-mi:“MI:0914”(association)	0.530
vpr	AGPS	psi-mi:“MI:0914”(association)	0.460
RSPO3	DPY19L3	psi-mi:“MI:0915”(physical association)	0.400
K8.1	EXOC5	psi-mi:“MI:0914”(association)	0.350
DDRGK1	UFL1	psi-mi:“MI:0914”(association)	0.350
PAPLN	PKM	psi-mi:“MI:0914”(association)	0.350
CACNG4	MTX1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
DRD4	TNPO2	psi-mi:“MI:0914”(association)	0.350
SPON1	AHCYL1	psi-mi:“MI:0914”(association)	0.350
ISM2	PEX1	psi-mi:“MI:0914”(association)	0.350
C8B	PAPSS2	psi-mi:“MI:0914”(association)	0.350
PAPLN	SDHB	psi-mi:“MI:0914”(association)	0.350
TSPAN33	PDZD11	psi-mi:“MI:0914”(association)	0.350
PPY	DPY19L3	psi-mi:“MI:0914”(association)	0.350
CD226	TMED7-TICAM2	psi-mi:“MI:0914”(association)	0.350

BioGRID (43): DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Proximity Label-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), DPY19L3 (Proximity Label-MS)

ESM2 similar proteins: A2AWR3, A4IGI5, D3ZYP5, O18405, O88496, P38435, P52650, P58355, Q07175, Q0P4Y8, Q18864, Q28FA9, Q3KQE5, Q3KTM2, Q3U0Y2, Q4R5F4, Q4V3B8, Q4V8K1, Q53FP2, Q53P98, Q58EL2, Q5E9T5, Q5R9A7, Q5RCJ4, Q5RF50, Q68FV1, Q6GN30, Q6JAM9, Q6P2T0, Q6P8F8, Q6ZPD9, Q6ZQE4, Q71B07, Q7Z3F1, Q7ZVP8, Q7ZWN0, Q7ZY07, Q8NCS4, Q923B6, Q95L73

Diamond homologs: A2AJQ3, Q5R8N9, Q5RCJ4, Q6NXN4, Q6ZPD9, Q71B07, Q7Z388, A6X919, A8Y3M2, D4AD75, P0CW70, P34413, Q2PZI1, Q6NUT2, Q6ZN68

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	85
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3636 predictions. Top by Δscore:

Variant	Effect	Δscore
19:32408212:T:G	acceptor_gain	1.0000
19:32408213:CTAG:C	acceptor_loss	1.0000
19:32408215:A:AG	acceptor_gain	1.0000
19:32408215:AG:A	acceptor_gain	1.0000
19:32408216:G:GA	acceptor_gain	1.0000
19:32408216:GG:G	acceptor_gain	1.0000
19:32408216:GGA:G	acceptor_gain	1.0000
19:32408216:GGAGT:G	acceptor_gain	1.0000
19:32408330:TG:T	donor_gain	1.0000
19:32408331:G:GT	donor_gain	1.0000
19:32408352:ATCTG:A	donor_gain	1.0000
19:32408353:TCTG:T	donor_gain	1.0000
19:32408357:G:GG	donor_gain	1.0000
19:32408357:GTA:G	donor_loss	1.0000
19:32408358:T:A	donor_loss	1.0000
19:32439007:T:G	donor_gain	1.0000
19:32439007:T:TG	donor_gain	1.0000
19:32439011:G:GG	donor_gain	1.0000
19:32439105:T:TA	acceptor_gain	1.0000
19:32439106:GTGCA:G	acceptor_loss	1.0000
19:32439107:TGCAG:T	acceptor_loss	1.0000
19:32439108:GCA:G	acceptor_loss	1.0000
19:32439109:CA:C	acceptor_loss	1.0000
19:32439110:A:AG	acceptor_gain	1.0000
19:32439110:A:C	acceptor_loss	1.0000
19:32439111:G:GA	acceptor_gain	1.0000
19:32439111:G:T	acceptor_loss	1.0000
19:32439111:GA:G	acceptor_gain	1.0000
19:32439111:GAA:G	acceptor_gain	1.0000
19:32439111:GAAT:G	acceptor_gain	1.0000

AlphaMissense

4690 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:32432726:G:C	R83P	0.999
19:32432734:T:C	S86P	0.999
19:32432756:T:C	L93P	0.999
19:32439126:G:C	R204T	0.999
19:32439827:T:A	W258R	0.999
19:32439827:T:C	W258R	0.999
19:32458377:G:A	C397Y	0.999
19:32458388:T:C	F401L	0.999
19:32458390:T:A	F401L	0.999
19:32458390:T:G	F401L	0.999
19:32463882:T:A	W487R	0.999
19:32463882:T:C	W487R	0.999
19:32468773:T:C	F553L	0.999
19:32468775:C:A	F553L	0.999
19:32468775:C:G	F553L	0.999
19:32468798:T:C	L561P	0.999
19:32477556:A:C	S578R	0.999
19:32477558:C:A	S578R	0.999
19:32477558:C:G	S578R	0.999
19:32477572:C:A	A583D	0.999
19:32411358:T:C	F75L	0.998
19:32411360:T:A	F75L	0.998
19:32411360:T:G	F75L	0.998
19:32432741:G:C	R88T	0.998
19:32432744:C:T	T89I	0.998
19:32432753:G:A	G92D	0.998
19:32436509:G:C	R131P	0.998
19:32437275:A:C	S178R	0.998
19:32437277:C:A	S178R	0.998
19:32437277:C:G	S178R	0.998

dbSNP variants (sampled 300 via entrez): RS1000010110 (19:32475881 C>G,T), RS1000036432 (19:32434097 T>C), RS1000116439 (19:32410526 C>G), RS1000119926 (19:32447779 TA>T), RS1000168694 (19:32410891 G>A), RS1000172176 (19:32435268 G>A), RS1000173342 (19:32427144 C>G), RS1000218347 (19:32476660 C>A), RS1000294314 (19:32447657 A>T), RS1000321563 (19:32451523 A>G), RS1000366183 (19:32428480 G>T), RS1000373229 (19:32457631 A>G), RS1000433167 (19:32441839 T>G), RS1000456133 (19:32411821 C>T), RS1000456369 (19:32418223 CCT>C)

Disease associations

OMIM: gene MIM:613894 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000417_1	Bipolar disorder	2.000000e-06
GCST005232_15	Neuroticism	1.000000e-08
GCST008839_606	Height	3.000000e-09
GCST90017148_3	Brain asymmetrical skew (vertical)	3.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects expression, affects cotreatment	6
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
titanium dioxide	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, increases abundance	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Plant Extracts	affects cotreatment, increases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Gold Compounds	increases expression	1

Clinical trials (associated diseases)

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