DOLPP1

Summary

DOLPP1 (dolichyldiphosphatase 1, HGNC:29565) is a protein-coding gene on chromosome 9q34.11, encoding Dolichyldiphosphatase 1 (Q86YN1). Required for efficient N-glycosylation. It is a selective cancer dependency (DepMap: 20.6% of cell lines).

A similar gene has been characterized in mice and encodes dolichyl pyrophosphate (Dol-P-P) phosphatase. This protein dephosphorylates dolichyl pyrophosphate so that it may be re-utilized as a glycosyl carrier lipid by the oligosaccharyltransferase multisubunit complex in the ER. Alternative splicing results in multiple transcript variants and protein isoforms.

Source: NCBI Gene 57171 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 29 total
• Cancer dependency (DepMap): dependent in 20.6% of screened cell lines
• MANE Select transcript: NM_020438

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29565
Approved symbol	DOLPP1
Name	dolichyldiphosphatase 1
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	LSFR2
Ensembl gene	ENSG00000167130
Ensembl biotype	protein_coding
OMIM	614516
Entrez	57171

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000327812, ENST00000372546, ENST00000406974, ENST00000412363, ENST00000480255, ENST00000904143, ENST00000904144, ENST00000904145, ENST00000923819, ENST00000923820, ENST00000923821, ENST00000923822

RefSeq mRNA: 2 — MANE Select: NM_020438 NM_001135917, NM_020438

CCDS: CCDS48039, CCDS6918

Canonical transcript exons

ENST00000372546 — 8 exons

Exon	Start	End
ENSE00001110098	129086139	129086267
ENSE00001918381	129081111	129081207
ENSE00003497389	129085207	129085306
ENSE00003533906	129085518	129085616
ENSE00003556997	129085023	129085107
ENSE00003647993	129084668	129084768
ENSE00003673444	129086709	129086798
ENSE00003846345	129088971	129090438

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 92.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.6070 / max 155.3265, expressed in 1773 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98872	19.3565	1772
98873	0.2505	119

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	92.21	gold quality
mucosa of transverse colon	UBERON:0004991	91.89	gold quality
hair follicle	UBERON:0002073	89.13	gold quality
duodenum	UBERON:0002114	89.05	gold quality
lower esophagus mucosa	UBERON:0035834	88.07	gold quality
right lobe of liver	UBERON:0001114	87.11	gold quality
endometrium epithelium	UBERON:0004811	86.20	gold quality
tongue squamous epithelium	UBERON:0006919	86.15	silver quality
epithelium of nasopharynx	UBERON:0001951	86.05	silver quality
pancreatic ductal cell	CL:0002079	85.85	silver quality
jejunal mucosa	UBERON:0000399	85.38	gold quality
esophagus mucosa	UBERON:0002469	85.32	gold quality
gingival epithelium	UBERON:0001949	85.28	silver quality
epithelium of esophagus	UBERON:0001976	84.51	gold quality
esophagus squamous epithelium	UBERON:0006920	84.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.99	gold quality
transverse colon	UBERON:0001157	83.91	gold quality
colonic mucosa	UBERON:0000317	83.80	gold quality
liver	UBERON:0002107	83.63	gold quality
spinal cord	UBERON:0002240	83.62	gold quality
squamous epithelium	UBERON:0006914	83.58	gold quality
pharyngeal mucosa	UBERON:0000355	83.34	silver quality
right adrenal gland	UBERON:0001233	83.31	gold quality
small intestine	UBERON:0002108	83.08	gold quality
nipple	UBERON:0002030	83.06	gold quality
right adrenal gland cortex	UBERON:0035827	83.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.90	gold quality
embryo	UBERON:0000922	82.86	gold quality
ventral tegmental area	UBERON:0002691	82.76	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	133.59
E-ANND-3	yes	4.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting DOLPP1, 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-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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 20.6% of screened cell lines.

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dolpp1	ENSDARG00000036915
mus_musculus	Dolpp1	ENSMUSG00000026856
rattus_norvegicus	Dolpp1	ENSRNOG00000017663

Paralogs (2): PPT1 (ENSG00000131238), PPT2 (ENSG00000221988)

Protein

Protein identifiers

Dolichyldiphosphatase 1 — Q86YN1 (reviewed: Q86YN1)

Alternative names: Dolichyl pyrophosphate phosphatase 1

All UniProt accessions (3): Q86YN1, H7BXT6, H7C1Z8

UniProt curated annotations — full annotation on UniProt →

Function. Required for efficient N-glycosylation. Necessary for maintaining optimal levels of dolichol-linked oligosaccharides. Hydrolyzes dolichyl pyrophosphate at a very high rate and dolichyl monophosphate at a much lower rate. Does not act on phosphatidate.

Subcellular location. Endoplasmic reticulum membrane.

Pathway. Protein modification; protein glycosylation.

Similarity. Belongs to the dolichyldiphosphatase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86YN1-1	1	yes
Q86YN1-2	2

RefSeq proteins (2): NP_001129389, NP_065171* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000326	PAP2/HPO	Domain
IPR036938	PAP2/HPO_sf	Homologous_superfamily
IPR039667	Dolichyldiphosphatase_PAP2	Domain

Pfam: PF01569

Catalyzed reactions (Rhea), 1 shown:

• a di-trans,poly-cis-dolichyl diphosphate + H2O = a di-trans,poly-cis-dolichyl phosphate + phosphate + H(+) (RHEA:14385)

UniProt features (6 total): transmembrane region 4, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YN1-F1	89.92	0.70

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-446199	Synthesis of dolichyl-phosphate

MSigDB gene sets: 179 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_PROTEIN_N_LINKED_GLYCOSYLATION, KEGG_N_GLYCAN_BIOSYNTHESIS, GTTAAAG_MIR302B, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, MCAATNNNNNGCG_UNKNOWN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GATA1_01, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (4): protein N-linked glycosylation (GO:0006487), dolichyl monophosphate biosynthetic process (GO:0043048), obsolete protein glycosylation (GO:0006486), dolichyl diphosphate biosynthetic process (GO:0006489)

GO Molecular Function (2): dolichyldiphosphatase activity (GO:0047874), hydrolase activity (GO:0016787)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phospholipid biosynthetic process	2
glycoprotein biosynthetic process	1
dolichol-linked oligosaccharide biosynthetic process	1
polyprenyl diphosphate phosphatase activity	1
catalytic 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

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOLPP1	SRD5A3	Q9H8P0	725
DOLPP1	DHDDS	Q86SQ9	691
DOLPP1	DOLK	Q9UPQ8	690
DOLPP1	DPM1	O60762	647
DOLPP1	MPDU1	O75352	644
DOLPP1	ALG5	Q9Y673	616
DOLPP1	ALG6	Q9Y672	604
DOLPP1	NUS1	Q96E22	592
DOLPP1	DPM3	Q9P2X0	522
DOLPP1	ALG11	Q2TAA5	512
DOLPP1	DPAGT1	Q9H3H5	494
DOLPP1	ALG13	Q9NP73	487
DOLPP1	RPN2	P04844	474
DOLPP1	ALG8	Q9BVK2	457
DOLPP1	ALG12	Q9BV10	447

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DOLPP1	VSIG8	psi-mi:“MI:0914”(association)	0.530
DOLPP1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
PRKCB	CHEK1	psi-mi:“MI:0914”(association)	0.350
TCTN3	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270
TCTN2	TMEM120B	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (65): HEPHL1 (Affinity Capture-MS), SELENBP1 (Affinity Capture-MS), LYG2 (Affinity Capture-MS), ASS1 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), PKP3 (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), DOLPP1 (Proximity Label-MS), DOLPP1 (Proximity Label-MS), SELENBP1 (Affinity Capture-MS), HEPHL1 (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), LYG2 (Affinity Capture-MS), DOLPP1 (Positive Genetic)

ESM2 similar proteins: A1A5C7, A6H7A0, B0BMW8, B0CM95, B0KWE9, B1MTH4, B2KI79, O43688, O62772, O75147, P0CK96, P35438, P35439, P52875, P57791, Q05586, Q28D01, Q2KJ29, Q3KNV8, Q3SZQ2, Q3UHH2, Q4L208, Q4V899, Q5R1P0, Q5R890, Q5SP67, Q5ZJ75, Q7TPB4, Q86YN1, Q8BTQ0, Q8C6G8, Q8C811, Q8R4D1, Q8VDI9, Q8VE98, Q90812, Q9BWV1, Q9D9E0, Q9H6U8, Q9H7D7

Diamond homologs: B0CM95, B0KWE9, B1MTH4, B2KI79, O59747, P53223, Q6NLA5, Q86IX2, Q86YN1, Q9C2M6, Q9JMF7, O08564, O14494, O14495, O43688, O88956, P60588, P97544, Q04396, Q0VBU9, Q0WNG6, Q10022, Q2HJ61, Q3SZE3, Q3UMZ3, Q5VZY2, Q61469, Q6GQ62, Q6IQH6, Q86AF0, Q8K593, Q8LFD1, Q8NEB5, Q99JY8, Q9DAX2, Q9V576, Q9XI60, Q9ZU49, O88531, P45478

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1313 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129081203:TGCAG:T	donor_loss	1.0000
9:129081205:CAGGT:C	donor_loss	1.0000
9:129081206:AGG:A	donor_loss	1.0000
9:129081207:GG:G	donor_loss	1.0000
9:129081208:GT:G	donor_loss	1.0000
9:129082940:G:T	donor_gain	1.0000
9:129084657:T:TA	acceptor_gain	1.0000
9:129084662:T:TA	acceptor_gain	1.0000
9:129084663:GCCAG:G	acceptor_loss	1.0000
9:129084664:CCA:C	acceptor_loss	1.0000
9:129084666:A:AG	acceptor_gain	1.0000
9:129084666:A:C	acceptor_loss	1.0000
9:129084666:AG:A	acceptor_gain	1.0000
9:129084666:AGGT:A	acceptor_gain	1.0000
9:129084667:G:GG	acceptor_gain	1.0000
9:129084667:GG:G	acceptor_gain	1.0000
9:129084667:GGT:G	acceptor_gain	1.0000
9:129084667:GGTG:G	acceptor_gain	1.0000
9:129084667:GGTGA:G	acceptor_gain	1.0000
9:129084765:CACG:C	donor_gain	1.0000
9:129084765:CACGG:C	donor_loss	1.0000
9:129084767:CGGT:C	donor_loss	1.0000
9:129084769:G:GG	donor_gain	1.0000
9:129084769:GT:G	donor_loss	1.0000
9:129084770:T:A	donor_loss	1.0000
9:129085020:CAGAT:C	acceptor_loss	1.0000
9:129085021:A:AG	acceptor_gain	1.0000
9:129085021:AGA:A	acceptor_loss	1.0000
9:129085022:G:GG	acceptor_gain	1.0000
9:129085105:G:GT	donor_gain	1.0000

AlphaMissense

1535 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:129085616:G:T	R154M	0.999
9:129086738:A:C	D207A	0.999
9:129086767:T:C	F217L	0.999
9:129086769:T:A	F217L	0.999
9:129086769:T:G	F217L	0.999
9:129085075:A:T	K77I	0.998
9:129086212:T:A	W179R	0.998
9:129086212:T:C	W179R	0.998
9:129086737:G:C	D207H	0.998
9:129086738:A:T	D207V	0.998
9:129086750:T:C	I211T	0.998
9:129086786:G:C	R223P	0.998
9:129088977:A:C	R229S	0.998
9:129088977:A:T	R229S	0.998
9:129084700:A:C	S37R	0.997
9:129084702:C:A	S37R	0.997
9:129084702:C:G	S37R	0.997
9:129084727:G:C	G46R	0.997
9:129085076:A:C	K77N	0.997
9:129085076:A:T	K77N	0.997
9:129085616:G:C	R154T	0.997
9:129086180:G:A	G168E	0.997
9:129086192:G:A	G172E	0.997
9:129086735:G:C	R206P	0.997
9:129086768:T:C	F217S	0.997
9:129086773:T:G	Y219D	0.997
9:129086794:G:C	A226P	0.997
9:129088976:G:C	R229T	0.997
9:129084755:G:C	R55P	0.996
9:129085243:C:A	P100H	0.996

dbSNP variants (sampled 300 via entrez): RS1000059370 (9:129083164 A>G,T), RS1000148096 (9:129089346 A>G), RS1000233172 (9:129088479 G>A), RS1000603829 (9:129087616 G>A), RS1000804739 (9:129079137 T>C), RS1000974470 (9:129087465 G>A), RS1001412665 (9:129088092 C>T), RS1001735652 (9:129080499 T>A), RS1001736422 (9:129087891 G>A,C,T), RS1001852585 (9:129088154 A>C,G), RS1001873509 (9:129085962 T>G), RS1001925725 (9:129086337 G>A,T), RS1002210722 (9:129080725 C>A,G,T), RS1002922068 (9:129087359 A>G), RS1002927492 (9:129087630 C>T)

Disease associations

OMIM: gene MIM:614516 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003225_3	Pelvic organ prolapse (moderate/severe)	2.000000e-06
GCST006879_1	Blood metabolite levels	1.000000e-09
GCST006879_18	Blood metabolite levels	3.000000e-43
GCST006879_19	Blood metabolite levels	4.000000e-83
GCST006879_2	Blood metabolite levels	2.000000e-12
GCST006879_20	Blood metabolite levels	5.000000e-12
GCST006879_21	Blood metabolite levels	2.000000e-22
GCST006879_22	Blood metabolite levels	2.000000e-20
GCST010143_23	Meat-related diet	6.000000e-11
GCST011494_51	Daytime nap	4.000000e-12
GCST90002384_268	Hemoglobin	8.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0007828	daytime rest measurement
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Selenium	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1

Clinical trials (associated diseases)

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