PDZD11

Summary

PDZD11 (PDZ domain containing 11, HGNC:28034) is a protein-coding gene on chromosome Xq13.1, encoding PDZ domain-containing protein 11 (Q5EBL8). Mediates docking of ADAM10 to zonula adherens by interacting with PLEKHA7 which is required for PLEKHA7 to interact with the ADAM10-binding protein TSPAN33.

Predicted to enable protein-macromolecule adaptor activity. Involved in pore complex assembly. Located in basolateral plasma membrane and cytosol. Part of pore complex.

Source: NCBI Gene 51248 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_016484

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28034
Approved symbol	PDZD11
Name	PDZ domain containing 11
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000120509
Ensembl biotype	protein_coding
OMIM	300632
Entrez	51248

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 28 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000239666, ENST00000374454, ENST00000473667, ENST00000486461, ENST00000695560, ENST00000695561, ENST00000859554, ENST00000859555, ENST00000859556, ENST00000859557, ENST00000859558, ENST00000859559, ENST00000859560, ENST00000859561, ENST00000859562, ENST00000859563, ENST00000924462, ENST00000924463, ENST00000924464, ENST00000924465, ENST00000924466, ENST00000924467, ENST00000924468, ENST00000924469, ENST00000924470, ENST00000924471, ENST00000967454, ENST00000967455, ENST00000967456, ENST00000967457

RefSeq mRNA: 6 — MANE Select: NM_016484 NM_001370174, NM_001370175, NM_001370176, NM_001370177, NM_001370178, NM_016484

CCDS: CCDS14400

Canonical transcript exons

ENST00000239666 — 7 exons

Exon	Start	End
ENSE00000672292	70287732	70287830
ENSE00000672294	70287276	70287336
ENSE00003527296	70289255	70289354
ENSE00003529566	70288430	70288513
ENSE00003550337	70288117	70288173
ENSE00003964286	70286595	70287116
ENSE00003964289	70289860	70289927

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 97.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.0938 / max 465.3557, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199529	52.0938	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	97.50	gold quality
left ventricle myocardium	UBERON:0006566	96.10	gold quality
parotid gland	UBERON:0001831	95.91	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.89	gold quality
hypothalamus	UBERON:0001898	95.74	gold quality
prefrontal cortex	UBERON:0000451	95.59	gold quality
myocardium	UBERON:0002349	95.59	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.48	gold quality
nasal cavity epithelium	UBERON:0005384	95.43	gold quality
substantia nigra	UBERON:0002038	95.38	gold quality
amygdala	UBERON:0001876	95.29	gold quality
anterior cingulate cortex	UBERON:0009835	95.25	gold quality
embryo	UBERON:0000922	95.08	gold quality
ganglionic eminence	UBERON:0004023	95.08	gold quality
midbrain	UBERON:0001891	95.02	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.94	gold quality
substantia nigra pars compacta	UBERON:0001965	94.85	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.57	gold quality
pigmented layer of retina	UBERON:0001782	94.50	gold quality
stromal cell of endometrium	CL:0002255	94.49	gold quality
retina	UBERON:0000966	94.47	gold quality
rectum	UBERON:0001052	94.46	gold quality
caudate nucleus	UBERON:0001873	94.46	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.43	gold quality
nucleus accumbens	UBERON:0001882	94.37	gold quality
putamen	UBERON:0001874	94.36	gold quality
islet of Langerhans	UBERON:0000006	94.35	gold quality
pancreatic ductal cell	CL:0002079	94.34	silver quality
frontal cortex	UBERON:0001870	94.27	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting PDZD11, 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-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6875-3P	99.82	70.26	2983

Literature-anchored findings (GeneRIF, showing 4)

• PDZD11 is an interacting partner with sodium-dependent multivitamin transporter in intestinal epithelial cells and that this interaction affects SMVT function and cell biology. (PMID:21183659)
• PDZD11 forms a complex with nectin-1 and nectin-3, and its PDZ domain interacts directly with the PDZ-binding motif of nectin-1. (PMID:27044745)
• Cooperative binding of the tandem WW domains of PLEKHA7 to PDZD11 promotes conformation-dependent interaction with tetraspanin 33. (PMID:32371390)
• The PLEKHA7-PDZD11 complex regulates the localization of the calcium pump PMCA and calcium handling in cultured cells. (PMID:35714771)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdzd11	ENSDARG00000053194
mus_musculus	Pdzd11	ENSMUSG00000015668
rattus_norvegicus	Pdzd11	ENSRNOG00000084220
drosophila_melanogaster	veli	FBGN0039269
caenorhabditis_elegans		WBGENE00002996

Paralogs (3): LIN7B (ENSG00000104863), LIN7A (ENSG00000111052), LIN7C (ENSG00000148943)

Protein

Protein identifiers

PDZ domain-containing protein 11 — Q5EBL8 (reviewed: Q5EBL8)

Alternative names: ATPase-interacting PDZ protein, Plasma membrane calcium ATPase-interacting single-PDZ protein

All UniProt accessions (1): Q5EBL8

UniProt curated annotations — full annotation on UniProt →

Function. Mediates docking of ADAM10 to zonula adherens by interacting with PLEKHA7 which is required for PLEKHA7 to interact with the ADAM10-binding protein TSPAN33.

Subunit / interactions. Interacts with ATP2B1, ATP2B2, ATP2B3, ATP2B4 and ATP7A. Interacts with PLEKHA7 (via WW domains) at zonula adherens; this interaction is essential for the interaction between PLEKHA7 and the ADAM10-binding protein TSPAN33. Interacts with SLC5A6.

Subcellular location. Secreted Cytoplasm. Cell junction. Adherens junction. Cell membrane.

Tissue specificity. Widely expressed (at protein level).

Isoforms (2)

UniProt ID	Names	Canonical?
Q5EBL8-1	1, AIPP1a	yes
Q5EBL8-2	2, AIPP1b

RefSeq proteins (6): NP_001357103, NP_001357104, NP_001357105, NP_001357106, NP_001357107, NP_057568* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR051109	MAM_complex_regulator	Family

Pfam: PF00595

UniProt features (4 total): chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5EBL8-F1	81.99	0.34

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-196780	Biotin transport and metabolism
R-HSA-199220	Vitamin B5 (pantothenate) metabolism
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-6803544	Ion influx/efflux at host-pathogen interface
R-HSA-936837	Ion transport by P-type ATPases

MSigDB gene sets: 164 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_VESICLE_LOCALIZATION, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY

GO Biological Process (4): neurotransmitter secretion (GO:0007269), regulation of synaptic assembly at neuromuscular junction (GO:0008582), pore complex assembly (GO:0046931), synaptic vesicle transport (GO:0048489)

GO Molecular Function (2): protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (11): extracellular region (GO:0005576), cytosol (GO:0005829), cell-cell junction (GO:0005911), adherens junction (GO:0005912), basolateral plasma membrane (GO:0016323), pore complex (GO:0046930), presynapse (GO:0098793), cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	2
SLC-mediated transmembrane transport	1
Antimicrobial peptides	1
Ion channel transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
neurotransmitter transport	1
chemical synaptic transmission	1
establishment of localization in cell	1
presynapse	1
signal release from synapse	1
regulation of developmental growth	1
synaptic assembly at neuromuscular junction	1
regulation of synapse assembly	1
regulation of neuromuscular junction development	1
protein-containing complex assembly	1
transport	1
cellular process	1
establishment of vesicle localization	1
synaptic vesicle localization	1
protein binding	1
molecular adaptor activity	1
binding	1
cytoplasm	1
anchoring junction	1
cell-cell junction	1
basal plasma membrane	1
plasma membrane region	1
membrane protein complex	1
synapse	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDZD11	KIF4A	O95239	806
PDZD11	ATP7A	Q04656	776
PDZD11	PLEKHA7	Q6IQ23	767
PDZD11	TSPAN33	Q86UF1	665
PDZD11	AFDN	P55196	625
PDZD11	SLC5A6	Q9Y289	609
PDZD11	CGNL1	Q0VF96	495
PDZD11	NECTIN3	Q9NQS3	482
PDZD11	PLEKHA5	Q9HAU0	467
PDZD11	MISP	Q8IVT2	446
PDZD11	SMCO4	Q9NRQ5	436
PDZD11	MED31	Q9Y3C7	435
PDZD11	ITM2C	Q9NQX7	431
PDZD11	SNTA1	Q13424	400
PDZD11	WWC3	Q9ULE0	394

IntAct

103 interactions, top by confidence:

A	B	Type	Score
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
PLEKHA5	PDZD11	psi-mi:“MI:0915”(physical association)	0.720
PDZD11	PLEKHA5	psi-mi:“MI:0915”(physical association)	0.720
PDZD11	ATP7A	psi-mi:“MI:0915”(physical association)	0.610
ATP7A	PDZD11	psi-mi:“MI:0915”(physical association)	0.610
PDZD11	SLC5A6	psi-mi:“MI:0915”(physical association)	0.600
SLC5A6	PDZD11	psi-mi:“MI:0915”(physical association)	0.600
PDZD11	SLC5A6	psi-mi:“MI:0403”(colocalization)	0.600
SUMO1	CBX4	psi-mi:“MI:0914”(association)	0.600
PDZD11	MAGI2	psi-mi:“MI:0915”(physical association)	0.560
rep	SBNO1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
TGM5	UBB	psi-mi:“MI:0914”(association)	0.530
GINM1	ADCY9	psi-mi:“MI:0914”(association)	0.530
Tax	TAX1BP3	psi-mi:“MI:0914”(association)	0.520
	PDZD11	psi-mi:“MI:0915”(physical association)	0.490
PDZD11		psi-mi:“MI:0915”(physical association)	0.490
ABCC4	PDZD11	psi-mi:“MI:0407”(direct interaction)	0.440
KIR3DL3	PDZD11	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (84): PLEKHA5 (Two-hybrid), PDZD11 (Affinity Capture-MS), PDZD11 (Affinity Capture-MS), PDZD11 (Proximity Label-MS), PDZD11 (Proximity Label-MS), PDZD11 (Proximity Label-MS), PDZD11 (Proximity Label-MS), PDZD11 (Proximity Label-MS), PDZD11 (Affinity Capture-MS), PDZD11 (Affinity Capture-MS), PDZD11 (Affinity Capture-MS), PDZD11 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), PDZD11 (Affinity Capture-MS), PDZD11 (Affinity Capture-MS)

ESM2 similar proteins: A5PKA5, A6QLK6, O14508, O54865, O75382, P09851, P16068, P20595, P20936, P49138, P50904, P57790, P62993, P62994, Q02153, Q07883, Q13588, Q14145, Q3UHD6, Q3ZCI3, Q4R539, Q4ZHR9, Q5EBL8, Q5PR73, Q5R4J7, Q5R4Q7, Q5R6S2, Q5R774, Q5RKN4, Q5ZLD3, Q5ZLT5, Q60631, Q684M4, Q7YRV6, Q861R0, Q8K4V4, Q8N653, Q8TC17, Q95KD9, Q96HU8

Diamond homologs: A0A0G2K2P5, A0A8P0N4K0, C5IAW9, F1LW30, O08721, O08722, O08747, O62683, O95049, O95185, O97758, P39447, P57105, Q07157, Q0P5E6, Q13424, Q28626, Q32LE7, Q3T0C9, Q5EBL8, Q5ZIK2, Q61234, Q6NXB2, Q6QA76, Q6R653, Q6UXZ4, Q6ZN44, Q761X5, Q7KRY7, Q7T2Z5, Q80VW5, Q86UL8, Q8IV45, Q8IZJ1, Q8JGT4, Q8K1S2, Q8K1S3, Q8K1S4, Q95168, Q9CZG9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PDZD11	“up-regulates activity”	TSPAN33	binding
PLEKHA7	“up-regulates activity”	PDZD11	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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	5	53.6×	6e-06
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	5	47.3×	6e-06
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	5	47.3×	6e-06
Activation of BH3-only proteins	5	35.0×	3e-05
RHO GTPases activate PKNs	5	22.3×	2e-04
Intrinsic Pathway for Apoptosis	5	20.6×	3e-04
G2/M Checkpoints	8	15.1×	6e-06
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	13.0×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2211 predictions. Top by Δscore:

Variant	Effect	Δscore
X:70282290:GAA:G	donor_gain	1.0000
X:70282329:G:GT	donor_gain	1.0000
X:70282331:A:T	donor_gain	1.0000
X:70282856:G:GG	donor_gain	1.0000
X:70283374:G:GG	donor_gain	1.0000
X:70283626:T:A	donor_loss	1.0000
X:70283938:T:A	acceptor_gain	1.0000
X:70283943:C:CA	acceptor_gain	1.0000
X:70283945:TCCA:T	acceptor_loss	1.0000
X:70283946:CCA:C	acceptor_loss	1.0000
X:70283948:A:AC	acceptor_loss	1.0000
X:70283948:A:AG	acceptor_gain	1.0000
X:70283949:G:GA	acceptor_gain	1.0000
X:70283949:GA:G	acceptor_gain	1.0000
X:70283949:GAC:G	acceptor_gain	1.0000
X:70283949:GACA:G	acceptor_gain	1.0000
X:70283949:GACAA:G	acceptor_gain	1.0000
X:70284040:AAAGG:A	donor_loss	1.0000
X:70284042:AGG:A	donor_loss	1.0000
X:70284044:G:GA	donor_loss	1.0000
X:70284045:T:A	donor_loss	1.0000
X:70284240:T:A	acceptor_gain	1.0000
X:70287274:A:AC	donor_gain	1.0000
X:70287275:C:CT	donor_gain	1.0000
X:70287333:CAGC:C	acceptor_gain	1.0000
X:70287727:CTCA:C	donor_loss	1.0000
X:70287728:TCA:T	donor_loss	1.0000
X:70287729:CAC:C	donor_loss	1.0000
X:70287731:CCTTG:C	donor_gain	1.0000
X:70287827:TCAC:T	acceptor_gain	1.0000

AlphaMissense

922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:70288169:C:T	G59E	1.000
X:70287323:A:G	L114P	0.999
X:70287781:T:G	Q93P	0.999
X:70287784:T:C	D92G	0.999
X:70287796:A:G	L88P	0.999
X:70287818:A:G	S81P	0.999
X:70288124:A:T	I74N	0.999
X:70288126:G:C	F73L	0.999
X:70288126:G:T	F73L	0.999
X:70288128:A:G	F73L	0.999
X:70288160:A:C	I62S	0.999
X:70288160:A:G	I62T	0.999
X:70288160:A:T	I62N	0.999
X:70288166:A:G	F60S	0.999
X:70288170:C:G	G59R	0.999
X:70288170:C:T	G59R	0.999
X:70287290:C:G	R125P	0.998
X:70287323:A:T	L114Q	0.998
X:70287335:G:T	A110D	0.998
X:70287778:A:T	V94D	0.998
X:70287784:T:A	D92V	0.998
X:70287784:T:G	D92A	0.998
X:70287796:A:T	L88Q	0.998
X:70287811:G:T	A83E	0.998
X:70288122:A:G	S75P	0.998
X:70288124:A:C	I74S	0.998
X:70288154:C:T	G64E	0.998
X:70288155:C:G	G64R	0.998
X:70288155:C:T	G64R	0.998
X:70288165:A:C	F60L	0.998

dbSNP variants (sampled 300 via entrez): RS1002108254 (X:70289897 T>C), RS1003676719 (X:70288970 C>A), RS1004016687 (X:70291480 G>C), RS1004070386 (X:70291103 C>T), RS1004243191 (X:70287573 TCCTC>T), RS1007415639 (X:70286176 G>A), RS1007586723 (X:70287876 A>G), RS1007636919 (X:70288510 C>A,G), RS1008367388 (X:70288984 A>G), RS1008419626 (X:70288704 C>A), RS1010760416 (X:70289751 G>A,C), RS1011023298 (X:70286567 T>C), RS1012541889 (X:70286457 G>C), RS1017157081 (X:70288004 C>A,T), RS1017310097 (X:70291441 G>A)

Disease associations

OMIM: gene MIM:300632 | 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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation, affects methylation, decreases methylation	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Cyclosporine	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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