GDPD2

Summary

GDPD2 (glycerophosphodiester phosphodiesterase domain containing 2, HGNC:25974) is a protein-coding gene on chromosome Xq13.1, encoding Glycerophosphoinositol inositolphosphodiesterase GDPD2 (Q9HCC8). Has glycerophosphoinositol inositolphosphodiesterase activity and specifically hydrolyzes glycerophosphoinositol, with no activity for other substrates such as glycerophosphoinositol 4-phosphate, glycerophosphocholine, glycerophosphoethanolamine, and glycerophosphoserine.

This gene encodes a member of the glycerophosphodiester phosphodiesterase enzyme family. The encoded protein hydrolyzes glycerophosphoinositol to produce inositol 1-phosphate and glycerol. This protein may have a role in osteoblast differentiation and growth. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 54857 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 123 total — 1 likely-pathogenic
• MANE Select transcript: NM_017711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25974
Approved symbol	GDPD2
Name	glycerophosphodiester phosphodiesterase domain containing 2
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Aliases	OBDPF, FLJ20207, GDE3
Ensembl gene	ENSG00000130055
Ensembl biotype	protein_coding
OMIM	300940
Entrez	54857

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374382, ENST00000453994, ENST00000472623, ENST00000536730, ENST00000538649, ENST00000913685

RefSeq mRNA: 4 — MANE Select: NM_017711 NM_001171191, NM_001171192, NM_001171193, NM_017711

CCDS: CCDS14402, CCDS55437, CCDS55438

Canonical transcript exons

ENST00000374382 — 16 exons

Exon	Start	End
ENSE00000815642	70426648	70426741
ENSE00001041567	70424976	70425089
ENSE00001041568	70423314	70423382
ENSE00001250214	70429493	70429714
ENSE00001325134	70429915	70430063
ENSE00001842830	70433034	70433381
ENSE00003465817	70432579	70432661
ENSE00003527751	70425763	70425856
ENSE00003550066	70426371	70426469
ENSE00003566794	70432912	70432940
ENSE00003577784	70426866	70427011
ENSE00003605088	70426052	70426111
ENSE00003618488	70425354	70425457
ENSE00003651661	70432307	70432454
ENSE00003671552	70427313	70427463
ENSE00003690966	70427137	70427219

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 94.63.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7649 / max 150.2183, expressed in 312 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196628	1.0494	283
196627	0.3444	175
196624	0.2178	111
196629	0.0781	32
196626	0.0426	18
196625	0.0231	10
196630	0.0095	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	94.63	gold quality
type B pancreatic cell	CL:0000169	92.33	gold quality
olfactory bulb	UBERON:0002264	92.18	gold quality
ileal mucosa	UBERON:0000331	89.95	silver quality
diaphragm	UBERON:0001103	87.79	gold quality
tongue squamous epithelium	UBERON:0006919	86.25	gold quality
skin of abdomen	UBERON:0001416	85.35	gold quality
upper arm skin	UBERON:0004263	85.07	gold quality
upper leg skin	UBERON:0004262	85.04	gold quality
cervix squamous epithelium	UBERON:0006922	84.76	gold quality
cauda epididymis	UBERON:0004360	84.36	gold quality
mucosa of transverse colon	UBERON:0004991	84.35	gold quality
jejunal mucosa	UBERON:0000399	83.41	gold quality
zone of skin	UBERON:0000014	83.37	gold quality
skin of leg	UBERON:0001511	82.71	gold quality
duodenum	UBERON:0002114	82.11	gold quality
ventricular zone	UBERON:0003053	81.37	gold quality
amygdala	UBERON:0001876	81.07	gold quality
skin of hip	UBERON:0001554	80.16	gold quality
nasal cavity epithelium	UBERON:0005384	79.76	gold quality
jejunum	UBERON:0002115	79.59	gold quality
hair follicle	UBERON:0002073	79.25	gold quality
triceps brachii	UBERON:0001509	79.19	gold quality
gluteal muscle	UBERON:0002000	79.00	gold quality
hypothalamus	UBERON:0001898	78.82	gold quality
nucleus accumbens	UBERON:0001882	78.71	gold quality
thymus	UBERON:0002370	78.20	gold quality
substantia nigra	UBERON:0002038	78.01	gold quality
cervix epithelium	UBERON:0004801	77.79	gold quality
epithelial cell of pancreas	CL:0000083	77.66	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	11.25
E-GEOD-99795	no	3.03
E-ANND-3	no	1.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting GDPD2, 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-6740-5P	100.00	65.64	932
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-26B-3P	98.71	67.49	1102
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-4287	97.55	67.24	1247
HSA-MIR-4685-3P	97.55	67.35	1255
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-4436B-5P	96.71	68.37	1346
HSA-MIR-6858-5P	96.05	64.59	1020

Literature-anchored findings (GeneRIF, showing 4)

• GDE3 is a novel seven-transmembrane protein with a GP-PDE-like extracellular motif expressed during osteoblast differentiation that accelerates the program of osteoblast differentiation and is involved in morphological change of cells (PMID:12933806)
• GDE3 substrate GroPIns is a candidate mediator for osteoblast proliferation (PMID:19596859)
• The results establish GDE3 as a negative regulator of the uPAR signaling network and, furthermore, highlight GPI-anchor hydrolysis as a cell-intrinsic mechanism to alter cell behavior. (PMID:28849762)
• Glycerophosphodiesterase 3 (GDE3) is a lysophosphatidylinositol-specific ectophospholipase C acting as an endocannabinoid signaling switch. (PMID:32917725)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gdpd2	ENSDARG00000073870
mus_musculus	Gdpd2	ENSMUSG00000019359
rattus_norvegicus	Gdpd2	ENSRNOG00000002800

Paralogs (5): GDE1 (ENSG00000006007), GDPD3 (ENSG00000102886), GDPD1 (ENSG00000153982), GDPD5 (ENSG00000158555), GDPD4 (ENSG00000178795)

Protein

Protein identifiers

Glycerophosphoinositol inositolphosphodiesterase GDPD2 — Q9HCC8 (reviewed: Q9HCC8)

Alternative names: Glycerophosphodiester phosphodiesterase 3, Glycerophosphodiester phosphodiesterase domain-containing protein 2, Osteoblast differentiation promoting factor

All UniProt accessions (1): Q9HCC8

UniProt curated annotations — full annotation on UniProt →

Function. Has glycerophosphoinositol inositolphosphodiesterase activity and specifically hydrolyzes glycerophosphoinositol, with no activity for other substrates such as glycerophosphoinositol 4-phosphate, glycerophosphocholine, glycerophosphoethanolamine, and glycerophosphoserine. Accelerates the program of osteoblast differentiation and growth. May play a role in remodeling of the actin cytoskeleton.

Subcellular location. Cell membrane. Cytoplasm. Cytoskeleton.

Similarity. Belongs to the glycerophosphoryl diester phosphodiesterase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9HCC8-1	1	yes
Q9HCC8-2	2
Q9HCC8-3	3

RefSeq proteins (4): NP_001164662, NP_001164663, NP_001164664, NP_060181* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017946	PLC-like_Pdiesterase_TIM-brl	Homologous_superfamily
IPR030395	GP_PDE_dom	Domain

Pfam: PF03009, PF13653

Enzyme classification (BRENDA):

• EC 3.1.4.46 — glycerophosphodiester phosphodiesterase (BRENDA: 38 organisms, 62 substrates, 23 inhibitors, 29 Km, 19 kcat entries)
• EC 4.6.1.14 — glycosylphosphatidylinositol diacylglycerol-lyase (BRENDA: 9 organisms, 47 substrates, 57 inhibitors, 10 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BIS(P-NITROPHENYL) PHOSPHATE	0.12–3.95	5
GLYCEROPHOSPHOCHOLINE	0.036–2	5
P-NITROPHENYL PHOSPHATE	0.12–49	5
MYRISTATE-LABELED VARIANT-SURFACE-GLYCOPROTEIN	0.0003–0.0021	5
GLYCEROPHOSPHOETHANOLAMINE	0.2–0.22	3
GLYCEROPHOSPHOGLYCEROL	0.2–0.62	3
BIS(P-NITROPHENYL PHOSPHATE)	3.5–7	2
GLYCEROPHOSPHOINOSITOL	0.39	2
GLYCEROPHOSPHOSERINE	0.66	2
BIS(4-NITROPHENYL) PHOSPHATE	3.56	1
BIS(GLYCEROPHOSPHO)GLYCEROL	0.6	1
ACETYLCHOLINESTERASE	0.0008	1
PHOSPHATIDYLINOSITOL	0.037	1

Catalyzed reactions (Rhea), 1 shown:

• sn-glycero-3-phospho-1D-myo-inositol + H2O = 1D-myo-inositol 1-phosphate + glycerol + H(+) (RHEA:14033)

UniProt features (22 total): topological domain 7, transmembrane region 6, binding site 3, splice variant 2, chain 1, domain 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCC8-F1	90.38	0.72

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 (3): 256; 258; 271

Glycosylation sites (1): 442

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): GOBP_OSTEOBLAST_DIFFERENTIATION, GGGTGGRR_PAX4_03, EFC_Q6, YGACNNYACAR_UNKNOWN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, MYOD_01, AML_Q6, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, NF1_Q6_01, TGCTGAY_UNKNOWN, GOBP_ACTIN_FILAMENT_ORGANIZATION, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, PPAR_DR1_Q2, GOBP_LIPID_METABOLIC_PROCESS, BERTUCCI_INVASIVE_CARCINOMA_DUCTAL_VS_LOBULAR_DN

GO Biological Process (3): lipid metabolic process (GO:0006629), actin filament organization (GO:0007015), positive regulation of osteoblast differentiation (GO:0045669)

GO Molecular Function (5): glycerophosphodiester phosphodiesterase activity (GO:0008889), metal ion binding (GO:0046872), glycerophosphoinositol inositolphosphodiesterase activity (GO:0047394), phosphoric diester hydrolase activity (GO:0008081), hydrolase activity (GO:0016787)

GO Cellular Component (6): cytoplasm (GO:0005737), actin filament (GO:0005884), plasma membrane (GO:0005886), lamellipodium (GO:0030027), cytoskeleton (GO:0005856), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphoric diester hydrolase activity	2
cellular anatomical structure	2
primary metabolic process	1
actin cytoskeleton organization	1
supramolecular fiber organization	1
osteoblast differentiation	1
positive regulation of cell differentiation	1
regulation of osteoblast differentiation	1
cation binding	1
phosphoric ester hydrolase activity	1
catalytic activity	1
intracellular anatomical structure	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GDPD2	ISL2	Q96A47	597
GDPD2	MNX1	P50219	545
GDPD2	PRDX1	P35703	505
GDPD2	GDPD3	Q7L5L3	461
GDPD2	OLIG2	Q13516	423
GDPD2	ISL1	P20663	411
GDPD2	SBDS	Q9Y3A5	410
GDPD2	SF3B3	Q15393	409
GDPD2	NANOS3	P60323	402
GDPD2	OPRD1	P41143	395
GDPD2	PLCD4	Q9BRC7	394
GDPD2	TEDDM1	Q5T9Z0	381
GDPD2	PATE2	Q6UY27	362
GDPD2	GDE1	Q9NZC3	358
GDPD2	DNAJC17	Q9NVM6	341

IntAct

44 interactions, top by confidence:

A	B	Type	Score
GDPD2	DRD2	psi-mi:“MI:0915”(physical association)	0.370
P		psi-mi:“MI:0914”(association)	0.350
GDPD2		psi-mi:“MI:0915”(physical association)	0.000
nhaD	GDPD2	psi-mi:“MI:0915”(physical association)	0.000
metE	GDPD2	psi-mi:“MI:0915”(physical association)	0.000
GDPD2	ezrA	psi-mi:“MI:0915”(physical association)	0.000
metH	GDPD2	psi-mi:“MI:0915”(physical association)	0.000
	GDPD2	psi-mi:“MI:0915”(physical association)	0.000
ilvE2	GDPD2	psi-mi:“MI:0915”(physical association)	0.000
GDPD2	pyrB	psi-mi:“MI:0915”(physical association)	0.000
GDPD2	sufB	psi-mi:“MI:0915”(physical association)	0.000
moeA1	GDPD2	psi-mi:“MI:0915”(physical association)	0.000
proW	GDPD2	psi-mi:“MI:0915”(physical association)	0.000
GDPD2	kefB	psi-mi:“MI:0915”(physical association)	0.000
recA	GDPD2	psi-mi:“MI:0915”(physical association)	0.000
GDPD2	pqiB2	psi-mi:“MI:0915”(physical association)	0.000
GDPD2	nirC	psi-mi:“MI:0915”(physical association)	0.000
queA	GDPD2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): GDPD2 (Two-hybrid), GDPD2 (Two-hybrid), GDPD2 (Two-hybrid), GDPD2 (Two-hybrid), GDPD2 (Two-hybrid)

ESM2 similar proteins: A0A140LIJ0, A1L3G9, A4IFL1, B9X187, O18968, O70491, P08033, P08034, P28230, P35212, P36380, P51915, P60572, Q02738, Q059Y8, Q0V8E7, Q1LXZ7, Q28FG4, Q29559, Q4QR83, Q5E9Z5, Q5FVF4, Q5FWS4, Q5JW98, Q5R7B4, Q5T197, Q5T1A1, Q60HF7, Q640M6, Q6GMB1, Q6WGK6, Q7SY10, Q7TNJ0, Q8BXV2, Q8C2L6, Q8C9E8, Q8CE93, Q8CEG0, Q8N5C1, Q8NDZ6

Diamond homologs: A0A8F4N283, O07592, O30405, P09394, P37965, P47535, P54527, P75367, P9WLF0, P9WLF1, Q06282, Q08959, Q3T0T0, Q3TT99, Q640M6, Q6W3E5, Q7L5L3, Q8RB32, Q95JR7, Q99LY2, Q9C907, Q9ESM6, Q9HCC8, Q9JL56, Q9NZC3, Q9SD81, O14169, P10908, P9WMU2, P9WMU3, Q3KTM2, Q9JL55, Q8N9F7, Q8WTR4, Q9CRY7, P47625, P75212, Q9FGT9, Q9LVN0, O07244

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	38
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
559404	Single allele	Likely pathogenic

SpliceAI

2681 predictions. Top by Δscore:

Variant	Effect	Δscore
X:70425454:A:AG	donor_gain	1.0000
X:70425458:G:GG	donor_gain	1.0000
X:70426108:CAAGG:C	donor_loss	1.0000
X:70426112:G:T	donor_loss	1.0000
X:70426113:T:A	donor_loss	1.0000
X:70426366:CCCA:C	acceptor_loss	1.0000
X:70426367:CCA:C	acceptor_loss	1.0000
X:70426368:CAGGT:C	acceptor_loss	1.0000
X:70426370:G:GT	acceptor_loss	1.0000
X:70427012:G:GA	donor_loss	1.0000
X:70427012:G:GG	donor_gain	1.0000
X:70427133:CCAGC:C	acceptor_loss	1.0000
X:70427134:CAG:C	acceptor_loss	1.0000
X:70427135:A:AG	acceptor_gain	1.0000
X:70427135:A:AT	acceptor_loss	1.0000
X:70427135:AGCT:A	acceptor_gain	1.0000
X:70427135:AGCTG:A	acceptor_gain	1.0000
X:70427136:G:GA	acceptor_gain	1.0000
X:70427136:GC:G	acceptor_gain	1.0000
X:70427136:GCT:G	acceptor_gain	1.0000
X:70427136:GCTG:G	acceptor_gain	1.0000
X:70427136:GCTGG:G	acceptor_gain	1.0000
X:70427138:T:A	acceptor_gain	1.0000
X:70427219:GGTGA:G	donor_loss	1.0000
X:70427220:G:A	donor_loss	1.0000
X:70427226:G:T	donor_gain	1.0000
X:70427311:A:AG	acceptor_gain	1.0000
X:70427312:G:GG	acceptor_gain	1.0000
X:70427460:AGAG:A	donor_loss	1.0000
X:70427461:GAG:G	donor_gain	1.0000

AlphaMissense

3494 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:70426998:G:C	R230P	0.993
X:70427151:C:A	N239K	0.992
X:70427151:C:G	N239K	0.992
X:70432399:T:A	V467D	0.989
X:70427329:T:C	F268L	0.988
X:70427331:C:A	F268L	0.988
X:70427331:C:G	F268L	0.988
X:70429921:T:A	W389R	0.988
X:70429921:T:C	W389R	0.988
X:70427202:G:C	E256D	0.987
X:70427202:G:T	E256D	0.987
X:70427455:T:C	F310L	0.987
X:70427457:C:A	F310L	0.987
X:70427457:C:G	F310L	0.987
X:70426994:C:G	H229D	0.986
X:70427218:A:C	S262R	0.984
X:70427313:C:A	S262R	0.984
X:70427313:C:G	S262R	0.984
X:70427357:G:C	R277T	0.984
X:70427357:G:T	R277M	0.984
X:70427147:A:T	E238V	0.983
X:70427358:G:C	R277S	0.983
X:70427358:G:T	R277S	0.983
X:70427150:A:T	N239I	0.982
X:70427144:C:A	P237H	0.981
X:70432377:T:A	W460R	0.981
X:70432377:T:C	W460R	0.981
X:70427330:T:C	F268S	0.980
X:70427342:A:T	D272V	0.980
X:70427404:A:C	S293R	0.980

dbSNP variants (sampled 300 via entrez): RS1000211326 (X:70433874 G>C), RS1000491069 (X:70424254 G>A), RS1000571794 (X:70422269 T>C), RS1000689775 (X:70422838 C>A), RS1001092267 (X:70426178 T>C), RS1001116585 (X:70433438 G>A,T), RS1001367419 (X:70425244 G>A,T), RS1001587816 (X:70424894 C>T), RS1002579439 (X:70428382 TA>T), RS1003135980 (X:70427848 G>A,C), RS1003373180 (X:70429804 C>A,T), RS1003469917 (X:70425158 C>G,T), RS1003561689 (X:70428679 G>C), RS1003592763 (X:70429127 G>T), RS1003856747 (X:70423192 G>A)

Disease associations

OMIM: gene MIM:300940 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
Valproic Acid	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenite	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
bisphenol S	increases methylation	1
prothioconazole	increases expression	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	decreases expression	1

Clinical trials (associated diseases)

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