PDE4DIP

Summary

PDE4DIP (phosphodiesterase 4D interacting protein, HGNC:15580) is a protein-coding gene on chromosome 1q21.2, encoding Myomegalin (Q5VU43). Functions as an anchor sequestering components of the cAMP-dependent pathway to Golgi and/or centrosomes. It is a selective cancer dependency (DepMap: 55.9% of cell lines).

The protein encoded by this gene serves to anchor phosphodiesterase 4D to the Golgi/centrosome region of the cell. Defects in this gene may be a cause of myeloproliferative disorder (MBD) associated with eosinophilia. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9659 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 148 total — 2 pathogenic, 2 likely-pathogenic
• Cancer dependency (DepMap): dependent in 55.9% of screened cell lines
• MANE Select transcript: NM_001395426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15580
Approved symbol	PDE4DIP
Name	phosphodiesterase 4D interacting protein
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0477, KIAA0454, MMGL
Ensembl gene	ENSG00000178104
Ensembl biotype	protein_coding
OMIM	608117
Entrez	9659

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 29 protein_coding, 15 retained_intron, 13 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay

ENST00000313431, ENST00000369347, ENST00000369349, ENST00000369351, ENST00000369354, ENST00000369356, ENST00000460027, ENST00000464924, ENST00000467859, ENST00000469668, ENST00000477941, ENST00000479369, ENST00000479408, ENST00000481227, ENST00000491426, ENST00000494734, ENST00000496263, ENST00000524974, ENST00000525630, ENST00000526182, ENST00000526445, ENST00000526664, ENST00000527901, ENST00000528060, ENST00000528129, ENST00000529945, ENST00000530062, ENST00000530130, ENST00000530472, ENST00000533259, ENST00000533768, ENST00000533845, ENST00000534367, ENST00000534466, ENST00000534536, ENST00000585156, ENST00000610852, ENST00000612094, ENST00000613995, ENST00000616206, ENST00000617031, ENST00000617248, ENST00000617454, ENST00000617527, ENST00000618462, ENST00000618504, ENST00000619981, ENST00000620605, ENST00000621371, ENST00000695765, ENST00000695766, ENST00000695767, ENST00000695768, ENST00000695769, ENST00000695770, ENST00000695771, ENST00000695772, ENST00000695773, ENST00000695794, ENST00000695795, ENST00000704840, ENST00000706647, ENST00000706648

RefSeq mRNA: 49 — MANE Select: NM_001395426 NM_001002810, NM_001002811, NM_001002812, NM_001195260, NM_001195261, NM_001198832, NM_001198834, NM_001350520, NM_001350521, NM_001350522, NM_001350523, NM_001377392, NM_001377393, NM_001395297, NM_001395298, NM_001395299, NM_001395300, NM_001395301, NM_001395302, NM_001395303, NM_001395304, NM_001395305, NM_001395306, NM_001395307, NM_001395308, NM_001395309, NM_001395310, NM_001395311, NM_001395312, NM_001395313, NM_001395314, NM_001395315, NM_001395316, NM_001395317, NM_001395318, NM_001395319, NM_001395320, NM_001395321, NM_001395322, NM_001395323, NM_001395324, NM_001395325, NM_001395326, NM_001395327, NM_001395328, NM_001395329, NM_001395426, NM_014644, NM_022359

CCDS: CCDS72887, CCDS72888, CCDS72890, CCDS72891, CCDS72892, CCDS72893, CCDS72894, CCDS91040, CCDS91041, CCDS91042, CCDS91043, CCDS91044, CCDS91045, CCDS91046

Canonical transcript exons

ENST00000695795 — 47 exons

Exon	Start	End
ENSE00003650480	148929197	148929273
ENSE00003688558	148889784	148889894
ENSE00003721034	148863250	148863305
ENSE00003738218	148932113	148932288
ENSE00003739322	149024445	149024684
ENSE00003749895	148937747	148937864
ENSE00003964941	149029787	149029925
ENSE00003964942	149026715	149026831
ENSE00003964943	148962196	148962288
ENSE00003964944	149028560	149028703
ENSE00003964945	148967726	148967905
ENSE00003964946	149008444	149008495
ENSE00003964947	148968836	148969030
ENSE00003964949	149021029	149021153
ENSE00003964950	149009568	149009791
ENSE00003964951	148961837	148961956
ENSE00003964952	149016299	149016550
ENSE00003964953	149030232	149030278
ENSE00003964954	148974514	148974605
ENSE00003964956	149007201	149007436
ENSE00003964957	149001591	149002026
ENSE00003964960	149018542	149018661
ENSE00003964961	148931800	148931923
ENSE00003964965	148998143	148998375
ENSE00003964966	149004909	149005437
ENSE00003964968	148965484	148965642
ENSE00003964969	148966543	148966656
ENSE00003964970	148960654	148960785
ENSE00003964971	148991885	148991973
ENSE00003964972	149010443	149010595
ENSE00003964973	148981270	148981397
ENSE00003964975	149012591	149012776
ENSE00003964976	149020147	149020336
ENSE00003964977	148977937	148978053
ENSE00003964978	148979737	148979849
ENSE00003964979	149027401	149027627
ENSE00003964980	148962428	148962640
ENSE00003964981	148966839	148966976
ENSE00003964982	149002850	149003042
ENSE00003964983	148972511	148972592
ENSE00003964984	148978278	148978415
ENSE00003964988	149017748	149017879
ENSE00003964989	148972180	148972344
ENSE00003964990	149003611	149003730
ENSE00003964991	148868471	148868622
ENSE00003965054	148844428	148844794
ENSE00003996405	149031944	149033016

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.1708 / max 108.5483, expressed in 1526 samples.

FANTOM5 promoters (23 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5010	2.2741	1121
5009	1.0202	639
5011	0.7794	487
5008	0.3353	182
5004	0.2256	31
5006	0.1592	79
4998	0.1331	50
5007	0.0656	16
5014	0.0633	21
5001	0.0575	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.77	gold quality
gastrocnemius	UBERON:0001388	99.63	gold quality
right atrium auricular region	UBERON:0006631	99.63	gold quality
muscle of leg	UBERON:0001383	99.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.48	gold quality
cerebellar hemisphere	UBERON:0002245	99.35	gold quality
calcaneal tendon	UBERON:0003701	99.20	gold quality
cerebellar cortex	UBERON:0002129	99.19	gold quality
mucosa of stomach	UBERON:0001199	99.09	gold quality
right frontal lobe	UBERON:0002810	98.86	gold quality
popliteal artery	UBERON:0002250	98.79	gold quality
tibial artery	UBERON:0007610	98.78	gold quality
thoracic aorta	UBERON:0001515	98.69	gold quality
ascending aorta	UBERON:0001496	98.68	gold quality
descending thoracic aorta	UBERON:0002345	98.66	gold quality
aorta	UBERON:0000947	98.65	gold quality
peripheral nervous system	UBERON:0000010	98.64	gold quality
nerve	UBERON:0001021	98.64	gold quality
tibial nerve	UBERON:0001323	98.64	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.61	gold quality
right coronary artery	UBERON:0001625	98.44	gold quality
cortical plate	UBERON:0005343	98.43	gold quality
left coronary artery	UBERON:0001626	98.35	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.06	gold quality
lower esophagus	UBERON:0013473	98.02	gold quality
cerebellum	UBERON:0002037	98.01	gold quality
spinal cord	UBERON:0002240	97.93	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	967.80
E-GEOD-93593	yes	783.77
E-MTAB-9067	yes	295.97
E-CURD-119	yes	26.14
E-CURD-112	yes	19.27
E-HCAD-10	yes	18.93
E-ANND-3	yes	16.39
E-GEOD-135922	yes	9.90
E-MTAB-10042	yes	9.73
E-MTAB-11268	no	2237.92
E-MTAB-7606	no	892.92
E-MTAB-7316	no	32.76

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting PDE4DIP, 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-4789-5P	99.98	70.76	2721
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-154-3P	99.50	70.05	831
HSA-MIR-487A-3P	99.50	69.95	840
HSA-MIR-4677-3P	99.49	67.91	1246
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-922	99.02	67.23	1838
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-648	98.64	66.13	553
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-3201	97.16	65.42	1044
HSA-MIR-370-3P	97.09	64.92	1221
HSA-MIR-6872-3P	97.08	66.99	750

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 55.9% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• MMGL-antibody is significantly with a favorable prognosis. Consequently, MMGL-anatibodies may be a useful tumor marker to diagnose and establish a prognosis in patients with esophageal squamous cell carcinoma. (PMID:17143517)
• A role of the SANS-myomegalin complex in microtubule-dependent inner segment cargo transport towards the ciliary base of photoreceptor cells. (PMID:21767579)
• PDE4DIP genetic variation was associated with increased risk for ischemic stroke. (PMID:25961151)
• A specific isoform of myomegalin, termed “SMYLE,” promotes microtubule assembly and function. (PMID:29162697)
• analysis of the recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma (PMID:30030436)
• Bioinformatic Analysis Reveals Phosphodiesterase 4D-Interacting Protein as a Key Frontal Cortex Dementia Switch Gene. (PMID:32471155)
• Myomegalin regulates Hedgehog pathway by controlling PDE4D at the centrosome. (PMID:34260267)
• Epistatic interaction of PDE4DIP and DES mutations in familial atrial fibrillation with slow conduction. (PMID:34289528)
• PDE4DIP contributes to colorectal cancer growth and chemoresistance through modulation of the NF1/RAS signaling axis. (PMID:37355626)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pde4dip	ENSDARG00000054723
mus_musculus	Pde4dip	ENSMUSG00000038170
rattus_norvegicus	Pde4dip	ENSRNOG00000018220

Paralogs (1): CDK5RAP2 (ENSG00000136861)

Protein

Protein identifiers

Myomegalin — Q5VU43 (reviewed: Q5VU43)

Alternative names: Cardiomyopathy-associated protein 2, Phosphodiesterase 4D-interacting protein

All UniProt accessions (27): A0A075B749, A0A087WVQ4, A0A087WWI2, A0A087WWK4, A0A087WWY1, A0A087WX83, A0A087X041, A0A087X0I1, A0A087X229, A0A8Q3SI09, A0A8Q3SI11, A0A8Q3SI21, A0A8Q3SI65, A0A8Q3SI71, A0A8Q3SI83, A0A8Q3WM32, A0A994J5E0, A0A9L9PY76, Q5VU43, E9PJK3, E9PJU0, E9PNE0, E9PQG4, E9PS60, H0YCH7, H0YCY0, H0YEW6

UniProt curated annotations — full annotation on UniProt →

Function. Functions as an anchor sequestering components of the cAMP-dependent pathway to Golgi and/or centrosomes. Participates in microtubule dynamics, promoting microtubule assembly. Depending upon the cell context, may act at the level of the Golgi apparatus or that of the centrosome. In complex with AKAP9, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. In complex with AKAP9, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension from the centrosome to the cell periphery, a crucial process for directed cell migration, mitotic spindle orientation and cell-cycle progression.

Subunit / interactions. Interacts with PDE4D. Isoform 13 interacts with MAPRE1 and MAPRE3. Isoform 13 forms a pericentrosomal complex with AKAP9, CDK5RAP2 and EB1/MAPRE1; within this complex, may mediate MAPRE1-binding to CDK5RAP2. Interaction of isoform 13 with AKAP9 stabilizes both proteins. Isoform 13 interacts (via N-terminus) with CAMSAP2; this interaction is much stronger in the presence of AKAP9. In complex with AKAP9, Isoform 13 recruits CAMSAP2 to the Golgi apparatus. Isoform 13 interacts with unglycosylated LGALS3BP; this interaction may connect the pericentrosomal complex to the gamma-tubulin ring complex (gamma-TuRC) to promote microtubule assembly and acetylation.

Subcellular location. Golgi apparatus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome Cytoplasm. Centrosome.

Tissue specificity. Highly expressed in adult and fetal heart, in skeletal muscle and, to a lower extent, in brain and placenta.

Disease relevance. A chromosomal aberration involving PDE4DIP may be the cause of a myeloproliferative disorder (MBD) associated with eosinophilia. Translocation t(1;5)(q23;q33) that forms a PDE4DIP-PDGFRB fusion protein.

Domain organisation. Residues 1-150 are involved in AKAP9-binding.

Miscellaneous. Mutagenesis at position 311-312:LP->AA (loss of MAPRE1- and MAPRE3-binding and loss of association with microtubule ends, no effect on AKAP9- and CDK5RAP2-binding, relocalizes from EB1/MAPRE1 microtubule ends to centrosomal area).

Isoforms (12)

UniProt ID	Names	Canonical?
Q5VU43-1	1	yes
Q5VU43-2	2
Q5VU43-3	3
Q5VU43-4	4
Q5VU43-6	6
Q5VU43-7	7
Q5VU43-8	8
Q5VU43-9	9
Q5VU43-10	10
Q5VU43-11	11
Q5VU43-12	12
Q5VU43-13	13, Myomegalin variant 8, MMG, MMG8, Short myomegalin-like EB1 binding protein, SMYLE

RefSeq proteins (49): NP_001002810, NP_001002811, NP_001002812, NP_001182189, NP_001182190, NP_001185761, NP_001185763, NP_001337449, NP_001337450, NP_001337451, NP_001337452, NP_001364321, NP_001364322, NP_001382226, NP_001382227, NP_001382228, NP_001382229, NP_001382230, NP_001382231, NP_001382232, NP_001382233, NP_001382234, NP_001382235, NP_001382236, NP_001382237, NP_001382238, NP_001382239, NP_001382240, NP_001382241, NP_001382242, NP_001382243, NP_001382244, NP_001382245, NP_001382246, NP_001382247, NP_001382248, NP_001382249, NP_001382250, NP_001382251, NP_001382252, NP_001382253, NP_001382254, NP_001382255, NP_001382256, NP_001382257, NP_001382258, NP_001382355, NP_055459, NP_071754 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010630	Olduvai_dom	Domain
IPR012943	Cnn_1N	Domain
IPR052593	MT-associated_AKAP9-binding	Family
IPR056273	CDK5RAP2_MYOME_CC	Domain

Pfam: PF06758, PF07989, PF23246

UniProt features (87 total): sequence conflict 25, sequence variant 18, splice variant 14, coiled-coil region 13, region of interest 6, compositionally biased region 5, modified residue 3, chain 1, domain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VU43-F1	58.74	0.02

Functional residue map

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

Catalytic / active sites (1): 742–743 (breakpoint for insertion to form pde4dip-pdgfrb fusion protein)

Post-translational modifications (3): 704, 252, 252

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 293 (showing top): GOBP_REGULATION_OF_GOLGI_ORGANIZATION, GCM_MAP4K4, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MICROTUBULE_NUCLEATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOCC_MICROTUBULE_ORGANIZING_CENTER, MARTINEZ_RB1_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (6): centrosome cycle (GO:0007098), astral microtubule organization (GO:0030953), protein-containing complex assembly (GO:0065003), positive regulation of microtubule nucleation (GO:0090063), regulation of Golgi organization (GO:1903358), microtubule cytoskeleton organization (GO:0000226)

GO Molecular Function (4): enzyme binding (GO:0019899), molecular adaptor activity (GO:0060090), protein binding (GO:0005515), zinc ion binding (GO:0008270)

GO Cellular Component (8): nucleus (GO:0005634), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), centrosome (GO:0005813), myofibril (GO:0030016), microtubule organizing center (GO:0005815), cytoskeleton (GO:0005856), cortical microtubule plus-end (GO:1903754)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
cell cycle process	1
microtubule organizing center organization	1
spindle organization	1
cytoplasmic microtubule organization	1
cellular component assembly	1
protein-containing complex organization	1
microtubule nucleation	1
regulation of microtubule nucleation	1
positive regulation of microtubule polymerization	1
Golgi organization	1
regulation of organelle organization	1
cytoskeleton organization	1
microtubule-based process	1
protein binding	1
molecular_function	1
transition metal ion binding	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
centriole	1
microtubule organizing center	1
contractile muscle fiber	1
microtubule cytoskeleton	1
intracellular membraneless organelle	1
cortical microtubule	1
cytoplasmic microtubule plus-end	1

Protein interactions and networks

STRING

1584 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDE4DIP	PDE4D	Q08499	979
PDE4DIP	AKAP9	Q99996	928
PDE4DIP	PDGFRB	P09619	709
PDE4DIP	MYBPC3	Q14896	673
PDE4DIP	MAPRE3	Q9UPY8	595
PDE4DIP	KRAS	P01116	523
PDE4DIP	TRIP11	Q15643	516
PDE4DIP	NEDD1	Q8NHV4	495
PDE4DIP	CAMSAP2	Q08AD1	494
PDE4DIP	GOLGA2	Q08379	492
PDE4DIP	ATP2A2	P16614	472
PDE4DIP	ITSN2	Q9NZM3	456
PDE4DIP	OR51Q1	Q8NH59	451
PDE4DIP	CDK5R2	Q13319	450
PDE4DIP	FGFR2	P18443	450
PDE4DIP	GART	P22102	450

IntAct

249 interactions, top by confidence:

A	B	Type	Score
MAPRE1	PDE4DIP	psi-mi:“MI:0915”(physical association)	0.800
PDE4DIP	PRPF31	psi-mi:“MI:0915”(physical association)	0.780
PRPF31	PDE4DIP	psi-mi:“MI:0915”(physical association)	0.780
PDE4DIP	NAA10	psi-mi:“MI:0915”(physical association)	0.740
NAA10	PDE4DIP	psi-mi:“MI:0915”(physical association)	0.740
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
PRKACA	VAPB	psi-mi:“MI:0914”(association)	0.730
	PRKAR1A	psi-mi:“MI:0914”(association)	0.700
PDE4DIP	SDCBP	psi-mi:“MI:0915”(physical association)	0.670
LMO4	PDE4DIP	psi-mi:“MI:0915”(physical association)	0.670
PDE4DIP	LMO4	psi-mi:“MI:0915”(physical association)	0.670
SDCBP	PDE4DIP	psi-mi:“MI:0915”(physical association)	0.670
PDE4DIP	rep	psi-mi:“MI:0915”(physical association)	0.660
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640

BioGRID (313): PDE4DIP (Two-hybrid), PDE4DIP (Two-hybrid), PDE4DIP (Two-hybrid), PDE4DIP (Two-hybrid), PDE4DIP (Two-hybrid), PDE4DIP (Two-hybrid), PDE4DIP (Two-hybrid), UTP14C (Two-hybrid), FCHSD2 (Two-hybrid), MAPRE1 (Two-hybrid), MTUS2 (Two-hybrid), TFIP11 (Two-hybrid), PRPF31 (Two-hybrid), ZNF581 (Two-hybrid), CHCHD3 (Two-hybrid)

ESM2 similar proteins: A0PJP4, A0PJT0, A1A600, A2A6T1, A4IFK7, D3YV10, D3ZUQ0, G9G127, P97817, Q08379, Q0IHE5, Q0P4J3, Q17QG3, Q499E4, Q5EBL4, Q5RCR6, Q5RD32, Q5VU43, Q5XIA0, Q5XJA2, Q5ZJA3, Q61043, Q62839, Q6AYA0, Q6DFC2, Q6IP02, Q6NZT2, Q80YF0, Q86X02, Q86YS3, Q8BH60, Q8BQP8, Q8C2K1, Q8IYE1, Q8N4C6, Q91WG2, Q921M4, Q92574, Q969X0, Q96CN9

Diamond homologs: A0A087WUL8, B4DH59, P0C2Y1, P0DPF2, P0DPF3, Q32LC2, Q3BBV0, Q3BBV2, Q5TAG4, Q5TI25, Q5VU43, Q5VWK0, Q6P3W6, Q86T75, Q86XG9, Q8N660, Q96M43, Q9H094, A0A096LNW5, A2RUV0, G3I6Z6, O35516, P0DPK3, P0DPK4, P10040, P21783, P46530, P46531, Q01705, Q04721, Q04756, Q07008, Q20911, Q7Z3S9, Q80YT7, Q99466, Q9QW30, Q9UM47, P54623, Q19UN5

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PDE4DIP	up-regulates	MYBPC3	binding
PDE4DIP	up-regulates	PRKAR1A	binding
PDE4DIP	up-regulates	PRKAR2A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 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
PKA activation in glucagon signalling	6	57.6×	3e-08
PKA activation	6	54.4×	4e-08
PKA-mediated phosphorylation of CREB	6	48.9×	7e-08
DARPP-32 events	6	40.8×	2e-07
Anti-inflammatory response favouring Leishmania parasite infection	6	33.8×	6e-07
Leishmania parasite growth and survival	6	33.8×	6e-07
Calmodulin induced events	6	32.6×	7e-07
CaM pathway	6	32.6×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial cell response to laminar fluid shear stress	6	44.4×	2e-06
renal water homeostasis	6	30.9×	1e-05
adenylate cyclase-activating G protein-coupled receptor signaling pathway	7	8.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	2
Uncertain significance	3
Likely benign	14
Benign	8

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1174534	NM_001395426.1(PDE4DIP):c.835-7507G>A	Pathogenic
1711137	GRCh37/hg19 1q21.1(chr1:144893419-144937891)x1	Pathogenic
1174535	NM_001395426.1(PDE4DIP):c.3874C>T (p.Arg1292Cys)	Likely pathogenic
1174537	NM_001395426.1(PDE4DIP):c.4630A>G (p.Ile1544Val)	Likely pathogenic

SpliceAI

6874 predictions. Top by Δscore:

Variant	Effect	Δscore
1:148889857:T:TA	donor_gain	1.0000
1:148889893:C:CT	donor_gain	1.0000
1:148889893:CC:C	donor_gain	1.0000
1:148889893:CCC:C	donor_gain	1.0000
1:148889893:CCCG:C	donor_gain	1.0000
1:148889893:CCCGC:C	donor_gain	1.0000
1:148889894:A:AC	donor_gain	1.0000
1:148889894:AC:A	donor_gain	1.0000
1:148889894:ACC:A	donor_gain	1.0000
1:148889894:ACCCG:A	donor_gain	1.0000
1:148889895:CAC:C	donor_loss	1.0000
1:148889896:TCA:T	donor_loss	1.0000
1:148926472:T:A	donor_gain	1.0000
1:148929193:T:C	acceptor_loss	1.0000
1:148929194:C:CC	acceptor_gain	1.0000
1:148929195:TCTGA:T	acceptor_loss	1.0000
1:148929196:TT:T	acceptor_gain	1.0000
1:148929197:GTT:G	acceptor_gain	1.0000
1:148929198:TGTT:T	acceptor_gain	1.0000
1:148929199:ATGTT:A	acceptor_gain	1.0000
1:148929272:C:CA	donor_gain	1.0000
1:148929272:CC:C	donor_gain	1.0000
1:148929272:CCA:C	donor_gain	1.0000
1:148929272:CCAT:C	donor_gain	1.0000
1:148929272:CCATG:C	donor_gain	1.0000
1:148929273:A:AC	donor_gain	1.0000
1:148929273:AC:A	donor_gain	1.0000
1:148929273:ACCAT:A	donor_loss	1.0000
1:148931798:CC:C	acceptor_gain	1.0000
1:148931799:CC:C	acceptor_gain	1.0000

AlphaMissense

15844 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:148889818:T:C	L22P	0.999
1:148889824:T:C	L24P	0.999
1:148889797:T:C	L15P	0.998
1:148889811:T:C	F20L	0.998
1:148889813:C:A	F20L	0.998
1:148889813:C:G	F20L	0.998
1:148929207:T:C	L51P	0.998
1:148978282:T:C	L814P	0.998
1:148889788:T:C	L12P	0.997
1:148889801:G:C	K16N	0.997
1:148889801:G:T	K16N	0.997
1:148889827:G:C	R25P	0.997
1:148889810:C:A	N19K	0.996
1:148889810:C:G	N19K	0.996
1:148889812:T:C	F20S	0.996
1:148889820:A:G	K23E	0.996
1:148889822:G:C	K23N	0.996
1:148889822:G:T	K23N	0.996
1:148889835:T:C	F28L	0.996
1:148889837:C:A	F28L	0.996
1:148889837:C:G	F28L	0.996
1:149007332:T:C	L1516P	0.996
1:149017790:T:C	L1854P	0.996
1:148889812:T:G	F20C	0.995
1:148889826:C:A	R25S	0.995
1:148889839:T:C	L29P	0.995
1:148979780:T:C	L873P	0.995
1:149017802:T:C	L1858P	0.995
1:149017810:T:C	S1861P	0.995
1:148889814:A:C	S21R	0.994

dbSNP variants (sampled 300 via entrez): RS1002928 (1:148952088 C>G,T), RS10045281 (1:148833292 A>G), RS10157122 (1:148841590 G>A,T), RS10158139 (1:148928075 C>G,T), RS10159285 (1:148926242 A>G), RS1020363 (1:148894534 C>A,T), RS1025970 (1:148900789 G>A,C), RS1025971 (1:148900125 T>C), RS1025972 (1:148899988 C>T), RS1037047 (1:148849060 C>T), RS1037048 (1:148849084 T>C), RS1037049 (1:148849089 C>A), RS1037051 (1:148849303 C>T), RS10465476 (1:148887689 A>T), RS10494237 (1:148975885 G>A,C)

Disease associations

OMIM: gene MIM:608117 | 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
GCST001368_9	Capecitabine sensitivity	2.000000e-06
GCST011161_1	Macrovascular complications in type 2 diabetes	6.000000e-10
GCST011381_7	Cutaneous mastocytosis	8.000000e-08
GCST011383_7	Mastocytosis	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010977	macrovascular complications of diabetes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	9
trichostatin A	affects cotreatment, increases expression, affects expression	4
bisphenol A	increases expression	2
sodium arsenite	affects methylation, increases expression	2
Arsenic Trioxide	affects expression, increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	affects expression, increases expression	2
Lead	affects expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	increases expression, increases methylation	2
Tretinoin	affects cotreatment, affects expression, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bis(tri-n-butyltin)oxide	affects expression	1
lead acetate	affects cotreatment, increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc protoporphyrin	affects cotreatment, increases expression	1
butyraldehyde	decreases expression	1
nickel sulfate	decreases expression	1
vanadyl sulfate	increases expression	1
triacsin C	decreases expression	1
pentanal	increases expression	1

Clinical trials (associated diseases)

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