PLEKHM3

Summary

PLEKHM3 (pleckstrin homology domain containing M3, HGNC:34006) is a protein-coding gene on chromosome 2q33.3, encoding Pleckstrin homology domain-containing family M member 3 (Q6ZWE6). Involved in skeletal muscle differentiation.

Predicted to enable zinc ion binding activity. Predicted to be involved in myoblast differentiation. Predicted to be located in Golgi apparatus.

Source: NCBI Gene 389072 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001080475

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34006
Approved symbol	PLEKHM3
Name	pleckstrin homology domain containing M3
Location	2q33.3
Locus type	gene with protein product
Status	Approved
Aliases	DAPR
Ensembl gene	ENSG00000178385
Ensembl biotype	protein_coding
OMIM	619186
Entrez	389072

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000343987, ENST00000427836, ENST00000447645, ENST00000457206, ENST00000877374, ENST00000877375, ENST00000877376

RefSeq mRNA: 1 — MANE Select: NM_001080475 NM_001080475

CCDS: CCDS42808

Canonical transcript exons

ENST00000427836 — 8 exons

Exon	Start	End
ENSE00001505270	208001030	208001957
ENSE00001579025	207930926	207931119
ENSE00001582596	207946367	207946512
ENSE00001583075	207861105	207861262
ENSE00001617497	207821288	207828496
ENSE00001769349	208025389	208025527
ENSE00001774136	207976651	207977586
ENSE00003643374	207908514	207908577

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 88.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8078 / max 108.5483, expressed in 1679 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33423	7.8078	1679

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	88.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.99	gold quality
primary visual cortex	UBERON:0002436	87.95	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.24	gold quality
corpus callosum	UBERON:0002336	86.80	gold quality
anterior cingulate cortex	UBERON:0009835	86.00	gold quality
hypothalamus	UBERON:0001898	85.77	gold quality
cerebral cortex	UBERON:0000956	85.65	gold quality
prefrontal cortex	UBERON:0000451	85.50	gold quality
frontal cortex	UBERON:0001870	85.29	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.06	gold quality
cortical plate	UBERON:0005343	84.82	gold quality
right frontal lobe	UBERON:0002810	84.74	gold quality
substantia nigra	UBERON:0002038	84.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.83	gold quality
Ammon’s horn	UBERON:0001954	83.65	gold quality
brain	UBERON:0000955	83.41	gold quality
nucleus accumbens	UBERON:0001882	82.85	gold quality
amygdala	UBERON:0001876	82.66	gold quality
temporal lobe	UBERON:0001871	82.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	81.77	gold quality
ganglionic eminence	UBERON:0004023	81.72	gold quality
cerebellar cortex	UBERON:0002129	81.59	gold quality
cerebellar hemisphere	UBERON:0002245	81.55	gold quality
cerebellum	UBERON:0002037	81.53	gold quality
right lung	UBERON:0002167	81.30	gold quality
putamen	UBERON:0001874	81.26	gold quality
caudate nucleus	UBERON:0001873	81.14	gold quality
right adrenal gland cortex	UBERON:0035827	81.12	gold quality
right adrenal gland	UBERON:0001233	81.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-2983	no	563.84
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

368 targeting PLEKHM3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
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-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4682	100.00	68.89	1258
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-3689D	100.00	66.14	1181
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-656-3P	100.00	72.15	2788

Literature-anchored findings (GeneRIF, showing 2)

• DAPR is a novel gene that binds to PKB/AKT and is a critical component for the differentiation of skeletal muscle myoblast cells into myotubes. (PMID:19028694)
• CircPLEKHM3 is down-regulated in ovarian cancer. Patients with a lower circPLEKHM3 expression have a worse prognosis. CircPLEKHM3 was found to act as a tumor suppressor that inhibits cell proliferation. (PMID:31623606)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plekhm3	ENSDARG00000030633
mus_musculus	Plekhm3	ENSMUSG00000051344
rattus_norvegicus	Plekhm3	ENSRNOG00000023760
drosophila_melanogaster	Plekhm1	FBGN0034694
caenorhabditis_elegans		WBGENE00013093

Paralogs (4): RUBCNL (ENSG00000102445), DEF8 (ENSG00000140995), RUBCN (ENSG00000145016), PLEKHM1 (ENSG00000225190)

Protein

Protein identifiers

Pleckstrin homology domain-containing family M member 3 — Q6ZWE6 (reviewed: Q6ZWE6)

Alternative names: Differentiation associated protein

All UniProt accessions (3): Q6ZWE6, C9J119, H7C0J9

UniProt curated annotations — full annotation on UniProt →

Function. Involved in skeletal muscle differentiation. May act as a scaffold protein for AKT1 during muscle differentiation.

Subunit / interactions. Interacts with AKT1.

Subcellular location. Cytoplasm. Golgi apparatus. Cell membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZWE6-1	1	yes
Q6ZWE6-2	2
Q6ZWE6-3	3

RefSeq proteins (1): NP_001073944* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR025258	RH_dom	Domain
IPR037812	PLEKHM3_PH_1	Domain
IPR051366	DEF8	Family

Pfam: PF00169, PF13901

UniProt features (8 total): splice variant 3, domain 2, chain 1, zinc finger region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZWE6-F1	65.18	0.29

Functional residue map

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

Post-translational modifications (1): 132

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 171 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_MYOBLAST_DIFFERENTIATION, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, GSE14415_INDUCED_TREG_VS_FOXP3_KO_INDUCED_TREG_DN, GSE14415_INDUCED_TREG_VS_TCONV_DN, ALKBH3_TARGET_GENES, ARNT2_TARGET_GENES, DIDO1_TARGET_GENES, FOXN3_TARGET_GENES, GLI4_TARGET_GENES, GTF2E2_TARGET_GENES, HMG20B_TARGET_GENES, NFE2L1_TARGET_GENES

GO Biological Process (1): myoblast differentiation (GO:0045445)

GO Molecular Function (2): zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (4): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell differentiation	1
muscle structure development	1
transition metal ion binding	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

364 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLEKHM3	GDAP1	Q8TB36	506
PLEKHM3	CCNYL1	Q8N7R7	441
PLEKHM3	AKT1	P31749	439
PLEKHM3	C1QBP	Q07021	433
PLEKHM3	PIANP	Q8IYJ0	433
PLEKHM3	SAAL1	Q96ER3	407
PLEKHM3	LRRCC1	Q9C099	406
PLEKHM3	TANGO6	Q9C0B7	402
PLEKHM3	PILRA	Q9UKJ1	391
PLEKHM3	PRAMEF20	Q5VT98	381
PLEKHM3	SLC7A13	Q8TCU3	370
PLEKHM3	IFIH1	Q9BYX4	370
PLEKHM3	ZNF385B	Q569K4	361
PLEKHM3	ISOC1	Q96CN7	353
PLEKHM3	FASTKD1	Q53R41	353

IntAct

26 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
PLEKHM3	PCNA	psi-mi:“MI:0915”(physical association)	0.370
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAQ	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
PLEKHM3	ENDOD1	psi-mi:“MI:0914”(association)	0.350
RAB9A	SNAP23	psi-mi:“MI:2364”(proximity)	0.270
LTK	AIP	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	PLEKHG3	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (73): PLEKHM3 (Proximity Label-MS), PLEKHM3 (Affinity Capture-RNA), PLEKHM3 (Proximity Label-MS), PLEKHM3 (Proximity Label-MS), PLEKHM3 (Proximity Label-MS), PLEKHM3 (Proximity Label-MS), PLEKHM3 (Proximity Label-MS), PLEKHM3 (Proximity Label-MS), PLEKHM3 (Proximity Label-MS), PLEKHM3 (Affinity Capture-RNA), ENDOD1 (Affinity Capture-MS), KIF1A (Affinity Capture-MS), ATAD3C (Affinity Capture-MS), XPO4 (Affinity Capture-MS), KIAA1549 (Affinity Capture-MS)

ESM2 similar proteins: A2RT67, A2RUS2, A4IJ06, F1LQX4, F1R7R1, G9CGD6, O88842, O95170, O95267, P52734, P98174, Q05AA6, Q0GNC1, Q13474, Q13905, Q17R89, Q28CB1, Q3U0J8, Q3ZBK7, Q4VX76, Q5BKC9, Q5F3G0, Q5JS13, Q5RAS2, Q5RDX5, Q5SSM3, Q641K1, Q69ZK0, Q6NTL4, Q6ZM86, Q6ZWE6, Q70Z35, Q7Z628, Q8BL80, Q8BM47, Q8BRH3, Q8CGF6, Q8CHT1, Q8IV61, Q8IZC4

Diamond homologs: A5PJM7, A7E316, O01738, Q08AW4, Q22744, Q3TD16, Q4V8I4, Q5PQS0, Q6DDJ3, Q6DJB3, Q6ZN54, Q6ZWE6, Q7T0P6, Q7TSI1, Q80U62, Q8BM47, Q92622, Q99J78, Q9H714, Q9VTT9, Q9Y4G2, Q08DX0, Q8BIJ7, Q8IWE5, Q8TEQ0, Q96T51, Q9D3S3, P34125, P09215, P28867, Q05655, Q5PU49, Q9Z1S3, Q5R4V2, Q5R5R4, Q7L099, Q8WXA3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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
Activation of BAD and translocation to mitochondria	7	280.5×	6e-15
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	247.5×	1e-14
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	247.5×	1e-14
Activation of BH3-only proteins	7	182.9×	1e-13
RHO GTPases activate PKNs	7	116.9×	2e-12
Intrinsic Pathway for Apoptosis	7	107.9×	3e-12
FOXO-mediated transcription	5	88.4×	2e-08
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	65.0×	3e-12

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	96.4×	1e-07
intracellular protein localization	7	38.6×	5e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2120 predictions. Top by Δscore:

Variant	Effect	Δscore
2:207861099:CTGTA:C	donor_loss	1.0000
2:207861100:TGTA:T	donor_loss	1.0000
2:207861101:GTACC:G	donor_loss	1.0000
2:207861102:TACCT:T	donor_loss	1.0000
2:207861103:ACC:A	donor_loss	1.0000
2:207861104:CCT:C	donor_loss	1.0000
2:207908509:CTTA:C	donor_loss	1.0000
2:207908510:TTA:T	donor_loss	1.0000
2:207908511:TA:T	donor_loss	1.0000
2:207908513:C:A	donor_loss	1.0000
2:207908513:CCTG:C	donor_gain	1.0000
2:207930920:TCTTA:T	donor_loss	1.0000
2:207930921:CTTAC:C	donor_loss	1.0000
2:207930922:TTA:T	donor_loss	1.0000
2:207930923:TAC:T	donor_loss	1.0000
2:207930924:A:AC	donor_gain	1.0000
2:207930925:C:A	donor_loss	1.0000
2:207930925:C:CA	donor_gain	1.0000
2:207930925:CCTG:C	donor_gain	1.0000
2:207931117:CAC:C	acceptor_gain	1.0000
2:207931118:ACCTA:A	acceptor_loss	1.0000
2:207931119:CCTA:C	acceptor_loss	1.0000
2:207931120:C:CC	acceptor_gain	1.0000
2:207931120:CT:C	acceptor_loss	1.0000
2:207931121:T:C	acceptor_loss	1.0000
2:207946362:CCTA:C	donor_loss	1.0000
2:207946364:TACCT:T	donor_loss	1.0000
2:207946366:C:CG	donor_loss	1.0000
2:207946509:CAGC:C	acceptor_gain	1.0000
2:207946510:AGC:A	acceptor_gain	1.0000

AlphaMissense

5030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:207861125:A:C	F696L	1.000
2:207861125:A:T	F696L	1.000
2:207861127:A:G	F696L	1.000
2:207861161:A:C	C684W	1.000
2:207861162:C:T	C684Y	1.000
2:207861163:A:G	C684R	1.000
2:207861167:G:C	F682L	1.000
2:207861167:G:T	F682L	1.000
2:207861169:A:G	F682L	1.000
2:207861171:C:T	G681E	1.000
2:207861182:A:C	C677W	1.000
2:207861183:C:G	C677S	1.000
2:207861183:C:T	C677Y	1.000
2:207861184:A:G	C677R	1.000
2:207861184:A:T	C677S	1.000
2:207861191:G:C	C674W	1.000
2:207861192:C:T	C674Y	1.000
2:207861193:A:G	C674R	1.000
2:207861213:G:T	A667D	1.000
2:207908521:A:G	L648P	1.000
2:207930958:G:C	C618W	1.000
2:207930959:C:T	C618Y	1.000
2:207930960:A:G	C618R	1.000
2:207930989:A:G	L608P	1.000
2:207931097:A:G	F572S	1.000
2:207946387:A:G	W558R	1.000
2:207946387:A:T	W558R	1.000
2:207946407:G:T	P551Q	1.000
2:207946466:G:C	C531W	1.000
2:207946467:C:T	C531Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000006933 (2:207864621 T>C), RS1000017108 (2:207965918 A>G), RS1000028238 (2:207966425 TCTC>T), RS1000051977 (2:207997643 T>C), RS1000069809 (2:207874166 G>C,T), RS1000085363 (2:207912601 T>C), RS1000092486 (2:208005644 C>T), RS1000111857 (2:207904314 G>A,C), RS1000113876 (2:207857706 C>T), RS1000117870 (2:207837576 G>C), RS1000128094 (2:207956521 A>G), RS1000135699 (2:207825391 C>A), RS1000143935 (2:207992609 T>C), RS1000146960 (2:208015288 A>C,G), RS1000169407 (2:207945192 G>C,T)

Disease associations

OMIM: gene MIM:619186 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006979_86	Heel bone mineral density	9.000000e-15
GCST011494_100	Daytime nap	3.000000e-12
GCST90016675_3	Pancreas fat	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0007828	daytime rest measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, affects cotreatment, decreases expression	7
bisphenol A	decreases expression, increases expression	2
trichostatin A	affects expression, decreases expression	2
sodium arsenite	decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
arsenite	affects binding, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Panobinostat	decreases expression, affects cotreatment	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	affects expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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