DPM1

Summary

DPM1 (dolichyl-phosphate mannosyltransferase subunit 1, catalytic, HGNC:3005) is a protein-coding gene on chromosome 20q13.13, encoding Dolichol-phosphate mannosyltransferase subunit 1 (O60762). Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of proteins; catalytic subunit of…. It is a selective cancer dependency (DepMap: 16.5% of cell lines).

Dolichol-phosphate mannose (Dol-P-Man) serves as a donor of mannosyl residues on the lumenal side of the endoplasmic reticulum (ER). Lack of Dol-P-Man results in defective surface expression of GPI-anchored proteins. Dol-P-Man is synthesized from GDP-mannose and dolichol-phosphate on the cytosolic side of the ER by the enzyme dolichyl-phosphate mannosyltransferase. Human DPM1 lacks a carboxy-terminal transmembrane domain and signal sequence and is regulated by DPM2. Mutations in this gene are associated with congenital disorder of glycosylation type Ie. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8813 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital disorder of glycosylation type 1E (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 183 total — 10 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 81
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 16.5% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_003859

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3005
Approved symbol	DPM1
Name	dolichyl-phosphate mannosyltransferase subunit 1, catalytic
Location	20q13.13
Locus type	gene with protein product
Status	Approved
Aliases	MPDS, CDGIE
Ensembl gene	ENSG00000000419
Ensembl biotype	protein_coding
OMIM	603503
Entrez	8813

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 11 protein_coding, 8 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000371582, ENST00000371584, ENST00000371588, ENST00000413082, ENST00000466152, ENST00000494752, ENST00000681979, ENST00000682366, ENST00000682713, ENST00000682754, ENST00000683010, ENST00000683048, ENST00000683466, ENST00000684193, ENST00000684628, ENST00000684708, ENST00000858753, ENST00000858754, ENST00000922811, ENST00000922812, ENST00000922813, ENST00000970159

RefSeq mRNA: 4 — MANE Select: NM_003859 NM_001317034, NM_001317035, NM_001317036, NM_003859

CCDS: CCDS13434, CCDS82628, CCDS93059

Canonical transcript exons

ENST00000371588 — 9 exons

Exon	Start	End
ENSE00000662820	50940865	50940933
ENSE00001455614	50958363	50958532
ENSE00003503678	50945737	50945762
ENSE00003540320	50942031	50942126
ENSE00003540669	50945847	50945923
ENSE00003652000	50955186	50955285
ENSE00003671097	50948629	50948662
ENSE00003791430	50936148	50936262
ENSE00003900401	50934870	50935236

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 80.4632 / max 1639.8249, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187905	73.2603	1821
187906	5.1892	1666
187904	2.0137	1024

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelium of nasopharynx	UBERON:0001951	98.55	gold quality
germinal epithelium of ovary	UBERON:0001304	98.08	gold quality
sperm	CL:0000019	98.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.48	gold quality
male germ cell	CL:0000015	97.41	gold quality
oral cavity	UBERON:0000167	97.37	gold quality
skin of hip	UBERON:0001554	97.30	gold quality
gingiva	UBERON:0001828	97.26	gold quality
gingival epithelium	UBERON:0001949	97.25	gold quality
amniotic fluid	UBERON:0000173	97.23	gold quality
esophagus squamous epithelium	UBERON:0006920	97.19	gold quality
pharyngeal mucosa	UBERON:0000355	97.17	gold quality
superior surface of tongue	UBERON:0007371	97.10	gold quality
biceps brachii	UBERON:0001507	97.08	gold quality
parietal pleura	UBERON:0002400	97.07	gold quality
palpebral conjunctiva	UBERON:0001812	97.02	gold quality
bronchial epithelial cell	CL:0002328	96.89	gold quality
body of tongue	UBERON:0011876	96.87	gold quality
tibia	UBERON:0000979	96.85	gold quality
pleura	UBERON:0000977	96.83	gold quality
synovial joint	UBERON:0002217	96.80	gold quality
tongue	UBERON:0001723	96.67	gold quality
visceral pleura	UBERON:0002401	96.65	gold quality
penis	UBERON:0000989	96.61	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.60	gold quality
corpus epididymis	UBERON:0004359	96.55	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.54	gold quality
parotid gland	UBERON:0001831	96.49	gold quality
cauda epididymis	UBERON:0004360	96.41	gold quality
lower lobe of lung	UBERON:0008949	96.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting DPM1, 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-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-1911-3P	99.15	66.17	528
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-491-3P	98.88	68.86	1224
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-4724-3P	97.57	67.31	785

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 16.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• DPM1 modulates desmosomal adhesion and epidermal differentiation through SERPINB5. (PMID:38477878)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dpm1	ENSDARG00000057011
mus_musculus	Dpm1	ENSMUSG00000078919
rattus_norvegicus	Dpm1	ENSRNOG00000010993
drosophila_melanogaster	Dpm1	FBGN0032799
caenorhabditis_elegans		WBGENE00022044

Paralogs (1): ALG5 (ENSG00000120697)

Protein

Protein identifiers

Dolichol-phosphate mannosyltransferase subunit 1 — O60762 (reviewed: O60762)

Alternative names: Dolichol-phosphate mannose synthase subunit 1, Dolichyl-phosphate beta-D-mannosyltransferase subunit 1, Mannose-P-dolichol synthase subunit 1

All UniProt accessions (8): A0A0S2Z4Y5, A0A804HIB3, A0A804HIK9, A0A804HJ93, H0Y368, O60762, Q5QPJ9, Q5QPK2

UniProt curated annotations — full annotation on UniProt →

Function. Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of proteins; catalytic subunit of the dolichol-phosphate mannose (DPM) synthase complex.

Subunit / interactions. Component of the dolichol-phosphate mannose (DPM) synthase complex composed of DPM1, DPM2 and DPM3; within the complex, directly interacts with DPM3. This interaction stabilizes DPM1.

Subcellular location. Endoplasmic reticulum.

Disease relevance. Congenital disorder of glycosylation 1E (CDG1E) [MIM:608799] A form of congenital disorder of glycosylation, a multisystem disorder caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. Some CDG1E patients have features consistent with a dystroglycanopathy and congenital muscular dystrophy, including O-mannosylation defect, camptodactyly, elevated creatine kinase, motor delay and dystrophic changes on muscel biopsy. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 divalent metal cation.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the glycosyltransferase 2 family.

RefSeq proteins (4): NP_001303963, NP_001303964, NP_001303965, NP_003850* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001173	Glyco_trans_2-like	Domain
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily
IPR039528	DPM1-like	Family

Pfam: PF00535

Enzyme classification (BRENDA):

• EC 2.4.1.83 — dolichyl-phosphate beta-D-mannosyltransferase (BRENDA: 27 organisms, 37 substrates, 49 inhibitors, 37 Km, 9 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GDPMANNOSE	0.0003–0.007	11
GDP-MANNOSE	0.0002–0.0012	10
DOLICHYL PHOSPHATE	0.0003–0.0143	7
(6Z,10E,14E,18E,22E)-3,7,15,19,23,27-HEXAMETHYL-	0.0751	1
(6Z,10Z,14Z,18Z,22E,26E)-3,7,11,15,19,23,27-HEPT	0.0246	1
(6Z,10Z,14Z,18Z,22Z,26Z,30E,34E,38E)-3,7,11,15,1	0.0248	1
C110-DOLICHYL PHOSPHATE	0.0006	1
C120-DOLICHYL PHOSPHATE	0.0016	1
C55-UNDECAPRENYL PHOSPHATE	0.0012	1
C85-DOLICHYL PHOSPHATE	0.0023	1

Catalyzed reactions (Rhea), 1 shown:

• a di-trans,poly-cis-dolichyl phosphate + GDP-alpha-D-mannose = a di-trans,poly-cis-dolichyl beta-D-mannosyl phosphate + GDP (RHEA:21184)

UniProt features (29 total): binding site 13, sequence conflict 8, modified residue 3, sequence variant 3, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60762-F1	88.61	0.65

Functional residue map

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

Ligand- & substrate-binding residues (13): 120; 120; 147; 234; 240; 32; 34; 36; 63; 65; 118; 119 …

Post-translational modifications (3): 2, 3, 9

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-162699	Synthesis of dolichyl-phosphate mannose
R-HSA-4717374	Defective DPM1 causes DPM1-CDG
R-HSA-4719360	Defective DPM3 causes DPM3-CDG
R-HSA-4719377	Defective DPM2 causes DPM2-CDG
R-HSA-9918432	Maturation of DENV proteins

MSigDB gene sets: 355 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, MORF_RAB5A, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, KEGG_N_GLYCAN_BIOSYNTHESIS, MORF_RAD21, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MORF_PSMC2, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (11): dolichol-linked oligosaccharide biosynthetic process (GO:0006488), GPI anchor biosynthetic process (GO:0006506), GDP-mannose metabolic process (GO:0019673), protein O-linked glycosylation via mannose (GO:0035269), dolichyl monophosphate biosynthetic process (GO:0043048), response to oxygen levels (GO:0070482), dolichol phosphate mannose biosynthetic process (GO:0180047), obsolete protein glycosylation (GO:0006486), obsolete protein N-linked glycosylation via asparagine (GO:0018279), obsolete dolichol metabolic process (GO:0019348), obsolete protein mannosylation (GO:0035268)

GO Molecular Function (7): dolichyl-phosphate beta-D-mannosyltransferase activity (GO:0004582), D-mannose binding (GO:0005537), alcohol binding (GO:0043178), metal ion binding (GO:0046872), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (5): nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), dolichol-phosphate-mannose synthase complex (GO:0033185)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Diseases associated with glycosylation precursor biosynthesis	3
Post-translational modification: synthesis of GPI-anchored proteins	1
Synthesis of substrates in N-glycan biosythesis	1
Dengue Virus Genome Translation and Replication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glycolipid biosynthetic process	2
phospholipid biosynthetic process	2
intracellular membrane-bounded organelle	2
protein N-linked glycosylation	1
carbohydrate derivative biosynthetic process	1
GPI anchor metabolic process	1
glycerophospholipid biosynthetic process	1
GPI anchored protein biosynthesis	1
nucleotide-sugar metabolic process	1
protein O-linked glycosylation	1
response to abiotic stimulus	1
terpenoid biosynthetic process	1
mannosyltransferase activity	1
monosaccharide binding	1
small molecule binding	1
cation binding	1
binding	1
catalytic activity	1
transferase activity	1
cytoplasm	1
endomembrane system	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
mannosyltransferase complex	1

Protein interactions and networks

STRING

3220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DPM1	DPM2	O94777	999
DPM1	DPM3	Q9P2X0	999
DPM1	MPDU1	O75352	966
DPM1	DOLK	Q9UPQ8	811
DPM1	ALG12	Q9BV10	771
DPM1	ALG6	Q9Y672	770
DPM1	MBD3L2	Q8NHZ7	770
DPM1	POMGNT2	Q8NAT1	764
DPM1	GMPPB	Q9Y5P6	762
DPM1	B3GALNT2	Q8NCR0	743
DPM1	POMT2	Q9UKY4	742
DPM1	POMK	Q9H5K3	736
DPM1	RXYLT1	Q9Y2B1	735
DPM1	POMT1	Q9Y6A1	734
DPM1	DPAGT1	Q9H3H5	729

IntAct

133 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
DPM1	DPM3	psi-mi:“MI:0915”(physical association)	0.730
DPM3	DPM1	psi-mi:“MI:0915”(physical association)	0.730
DPM1	TDO2	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
DPM1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
ILK	HAX1	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
ILK	ILVBL	psi-mi:“MI:0914”(association)	0.530
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
DPM1	BSG	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (245): DPM1 (Affinity Capture-MS), DPM1 (Two-hybrid), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS), DPM1 (Affinity Capture-MS)

ESM2 similar proteins: A2AKQ0, A2VE55, A5GFZ5, B8B7Q4, F4JN00, O14494, O42602, O60762, O70152, O75352, O88956, P0CK96, P60588, Q15B89, Q1JQ93, Q28HF8, Q2M3R5, Q3ZCD7, Q4L208, Q4R8V4, Q52KD1, Q5PT50, Q5PT53, Q5RDC9, Q5XF09, Q5ZJ75, Q5ZJH8, Q64232, Q6DBP3, Q6DHK8, Q6NMB6, Q6ZL17, Q762D5, Q76EJ3, Q7T0V6, Q8C811, Q8GUJ1, Q8IVW8, Q8R4D1, Q8RXL8

Diamond homologs: A0A0H3M5A8, A0QZ12, A0QZ13, A1ADA6, A4WAM4, A5GFZ5, A7ZP72, A8A2C1, B1IXT3, B1LLK8, B1X8W7, B5YX45, B6I7J7, B7LAR9, B7LM77, B7M5T6, B7MG21, B7MXT5, B7N5L9, B7UFR6, C4ZU96, C5CBV8, C6DAW6, O14466, O53493, O60762, O70152, P0A598, P77757, P9WMY0, P9WMY1, Q0TFI8, Q1JQ93, Q1R9G1, Q31YK3, Q32DT4, Q3YZV2, Q48HZ2, Q54LP3, Q6D2F0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DPM1	“form complex”	“DPM complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 136 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
Cytokine Signaling in Immune system	13	5.4×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	6	22.8×	7e-05
cell surface receptor protein tyrosine kinase signaling pathway	11	17.2×	4e-08
positive regulation of fibroblast proliferation	5	13.3×	3e-03
hemopoiesis	5	12.1×	5e-03
protein autophosphorylation	9	11.8×	3e-05
obsolete positive regulation of NF-kappaB transcription factor activity	6	11.1×	2e-03
MAPK cascade	8	11.0×	1e-04
insulin receptor signaling pathway	5	10.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	3
Uncertain significance	79
Likely benign	66
Benign	5

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
100635	NM_003859.3(DPM1):c.373-5T>A	Pathogenic
100637	NC_000020.11:g.(50936263_50940865)_(50948664_50955185)del	Pathogenic
1444616	NM_003859.3(DPM1):c.571C>T (p.Arg191Ter)	Pathogenic
1454916	NM_003859.3(DPM1):c.173_174del (p.Asn57_Tyr58insTer)	Pathogenic
1455808	NM_003859.3(DPM1):c.52del (p.Glu18fs)	Pathogenic
2712030	NM_003859.3(DPM1):c.182del (p.Ile61fs)	Pathogenic
3631040	NM_003859.3(DPM1):c.564-1G>T	Pathogenic
570864	NM_003859.3(DPM1):c.331_343del (p.Gly111fs)	Pathogenic
6296	NM_003859.3(DPM1):c.274C>G (p.Arg92Gly)	Pathogenic
857465	NM_003859.3(DPM1):c.490_493del (p.Ile164fs)	Pathogenic
1098270	NM_003859.3(DPM1):c.371A>G (p.His124Arg)	Likely pathogenic
1343000	NM_003859.3(DPM1):c.274C>T (p.Arg92Ter)	Likely pathogenic
3911870	NM_003859.3(DPM1):c.225del (p.Glu76fs)	Likely pathogenic

SpliceAI

1600 predictions. Top by Δscore:

Variant	Effect	Δscore
20:50936143:CATA:C	donor_loss	1.0000
20:50936144:ATAC:A	donor_loss	1.0000
20:50936145:TAC:T	donor_loss	1.0000
20:50936147:CCTC:C	donor_loss	1.0000
20:50936176:G:A	donor_gain	1.0000
20:50936259:TAAT:T	acceptor_gain	1.0000
20:50936260:AAT:A	acceptor_gain	1.0000
20:50936260:AATC:A	acceptor_loss	1.0000
20:50936261:AT:A	acceptor_gain	1.0000
20:50936261:ATC:A	acceptor_loss	1.0000
20:50936262:TCT:T	acceptor_loss	1.0000
20:50936263:C:A	acceptor_loss	1.0000
20:50936263:C:CC	acceptor_gain	1.0000
20:50936264:T:A	acceptor_loss	1.0000
20:50942026:CCTA:C	donor_loss	1.0000
20:50942027:CTAC:C	donor_loss	1.0000
20:50942029:ACCT:A	donor_loss	1.0000
20:50942123:CTTC:C	acceptor_gain	1.0000
20:50942127:C:CC	acceptor_gain	1.0000
20:50945839:CCA:C	donor_gain	1.0000
20:50945843:TTA:T	donor_loss	1.0000
20:50945844:TACA:T	donor_loss	1.0000
20:50945845:A:AC	donor_gain	1.0000
20:50945845:A:AG	donor_loss	1.0000
20:50945846:C:A	donor_loss	1.0000
20:50945846:C:CC	donor_gain	1.0000
20:50945846:CA:C	donor_gain	1.0000
20:50945846:CATG:C	donor_gain	1.0000
20:50945846:CATGG:C	donor_gain	1.0000
20:50945919:AGTTC:A	acceptor_gain	1.0000

AlphaMissense

1679 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:50935222:A:C	F231L	1.000
20:50935222:A:T	F231L	1.000
20:50935224:A:G	F231L	1.000
20:50945866:T:A	D118V	1.000
20:50935215:G:T	R234S	0.999
20:50935223:A:G	F231S	0.999
20:50940870:A:C	S186R	0.999
20:50940870:A:T	S186R	0.999
20:50940872:T:G	S186R	0.999
20:50942086:G:T	R147S	0.999
20:50942097:A:T	V143D	0.999
20:50945859:A:C	D120E	0.999
20:50945859:A:T	D120E	0.999
20:50945860:T:A	D120V	0.999
20:50945860:T:G	D120A	0.999
20:50945861:C:G	D120H	0.999
20:50945865:A:C	D118E	0.999
20:50945865:A:T	D118E	0.999
20:50945866:T:G	D118A	0.999
20:50945867:C:G	D118H	0.999
20:50935214:C:G	R234P	0.998
20:50935223:A:C	F231C	0.998
20:50936262:T:A	R188S	0.998
20:50936262:T:G	R188S	0.998
20:50940933:G:C	S165R	0.998
20:50940933:G:T	S165R	0.998
20:50942032:T:G	S165R	0.998
20:50942042:T:A	R161S	0.998
20:50942042:T:G	R161S	0.998
20:50942043:C:A	R161I	0.998

dbSNP variants (sampled 300 via entrez): RS1000159167 (20:50952375 C>T), RS1000195999 (20:50955646 C>G), RS1000325062 (20:50945283 GTTGTGTGTGTGTGTGT>G), RS1000358015 (20:50958617 C>A,G,T), RS1000390667 (20:50948235 T>A), RS1000484708 (20:50951977 T>A), RS1000613188 (20:50935697 C>A), RS1000726687 (20:50960069 T>C,G), RS1000796625 (20:50953678 C>A,T), RS1000999570 (20:50955031 C>T), RS1001009250 (20:50947387 A>C,G), RS1001059818 (20:50939358 CTTTTTTGTTT>C), RS1001154681 (20:50955395 T>G), RS1001164477 (20:50950934 C>G,T), RS1001657193 (20:50958631 C>A,G,T)

Disease associations

OMIM: gene MIM:603503 | disease phenotypes: MIM:608799

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital disorder of glycosylation type 1E	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital disorder of glycosylation type 1E	Definitive	AR

Mondo (1): congenital disorder of glycosylation type 1E (MONDO:0012123)

Orphanet (1): DPM1-CDG (Orphanet:79322)

HPO phenotypes

81 total (30 of 81 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000243	Trigonocephaly
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000347	Micrognathia
HP:0000486	Strabismus
HP:0000488	Retinopathy
HP:0000494	Downslanted palpebral fissures
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0001009	Telangiectasia
HP:0001028	Hemangioma
HP:0001103	Abnormal macular morphology
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001337	Tremor
HP:0001395	Hepatic fibrosis
HP:0001397	Hepatic steatosis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001643	Patent ductus arteriosus
HP:0001744	Splenomegaly
HP:0001847	Long hallux

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008103_111	Bipolar disorder	4.000000e-06
GCST008115_15	Bipolar I disorder	6.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009963	bipolar I disorder

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535743	Congenital disorder of glycosylation type 1E (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2572 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.54	Kd	2897	nM	CHEMBL5653589
5.54	ED50	2897	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148259: Binding affinity to human DPM1 incubated for 45 mins by Kinobead based pull down assay	kd	2.8972	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	4
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
Cadmium Chloride	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
FR900359	decreases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
sodium arsenite	increases abundance, increases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
MT19c compound	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Piroxicam	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651301	Binding	Binding affinity to human DPM1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_DB04	GM20944	Finite cell line	Female
CVCL_SL14	HAP1 DPM1 (-) 1	Cancer cell line	Male
CVCL_SL15	HAP1 DPM1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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