MPDZ

Summary

MPDZ (multiple PDZ domain crumbs cell polarity complex component, HGNC:7208) is a protein-coding gene on chromosome 9p23, encoding Multiple PDZ domain protein (O75970). Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses.

The protein encoded by this gene has multiple PDZ domains, which are hallmarks of protein-protein interactions. The encoded protein is known to interact with the HTR2C receptor and may cause it to clump at the cell surface. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 8777 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hydrocephalus, nonsyndromic, autosomal recessive 2 (Strong, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 2,027 total — 83 pathogenic, 45 likely-pathogenic
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001378778

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7208
Approved symbol	MPDZ
Name	multiple PDZ domain crumbs cell polarity complex component
Location	9p23
Locus type	gene with protein product
Status	Approved
Aliases	MUPP1
Ensembl gene	ENSG00000107186
Ensembl biotype	protein_coding
OMIM	603785
Entrez	8777

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 20 protein_coding, 4 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000319198, ENST00000319217, ENST00000381017, ENST00000433359, ENST00000437441, ENST00000438511, ENST00000447879, ENST00000494251, ENST00000535169, ENST00000536827, ENST00000538841, ENST00000539508, ENST00000540202, ENST00000541718, ENST00000542239, ENST00000542806, ENST00000545857, ENST00000546205, ENST00000883517, ENST00000883518, ENST00000883519, ENST00000918415, ENST00000959908, ENST00000959909, ENST00000959910, ENST00000959911, ENST00000959912, ENST00000959913

RefSeq mRNA: 18 — MANE Select: NM_001378778 NM_001261406, NM_001261407, NM_001330637, NM_001375413, NM_001375416, NM_001375417, NM_001375418, NM_001375419, NM_001375420, NM_001375421, NM_001375422, NM_001375423, NM_001375424, NM_001375425, NM_001375426, NM_001375427, NM_001378778, NM_003829

CCDS: CCDS47951, CCDS59119, CCDS59120, CCDS83342

Canonical transcript exons

ENST00000319217 — 47 exons

Exon	Start	End
ENSE00000689662	13143466	13143564
ENSE00001487238	13105707	13107111
ENSE00001619314	13221372	13221500
ENSE00001621914	13224374	13224583
ENSE00001641589	13219559	13219768
ENSE00001644434	13205036	13205107
ENSE00001664917	13223571	13223710
ENSE00001669588	13147548	13147658
ENSE00001678863	13247635	13247801
ENSE00001718719	13193167	13193313
ENSE00001731016	13192131	13192295
ENSE00001741916	13222233	13222446
ENSE00001761630	13196121	13196230
ENSE00001775725	13190114	13190299
ENSE00001776738	13205916	13206099
ENSE00002273569	13279400	13279692
ENSE00002297104	13250300	13250372
ENSE00003458356	13113011	13113054
ENSE00003472884	13216774	13216862
ENSE00003476912	13112024	13112146
ENSE00003488913	13183418	13183585
ENSE00003494769	13126516	13126590
ENSE00003501892	13175752	13175875
ENSE00003506780	13176136	13176417
ENSE00003537016	13125216	13125390
ENSE00003545978	13136712	13136803
ENSE00003559792	13123153	13123298
ENSE00003566023	13122087	13122170
ENSE00003566620	13158018	13158110
ENSE00003570625	13113931	13114021
ENSE00003574899	13188784	13188993
ENSE00003585111	13119502	13119649
ENSE00003594396	13110636	13110740
ENSE00003595337	13186270	13186386
ENSE00003606619	13115248	13115334
ENSE00003614456	13150511	13150688
ENSE00003619475	13126680	13126772
ENSE00003624775	13109952	13110064
ENSE00003632421	13108936	13109059
ENSE00003634357	13136092	13136182
ENSE00003637445	13168366	13168564
ENSE00003650040	13162691	13162795
ENSE00003659361	13121739	13121932
ENSE00003680079	13133824	13133904
ENSE00003681758	13139987	13140149
ENSE00003684553	13217180	13217294
ENSE00003691004	13137957	13138153

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 97.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0457 / max 229.6578, expressed in 1438 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99961	5.5736	1335
99959	1.8726	901
99960	1.3322	749
99957	0.8350	498
99958	0.4221	236
99947	0.2643	75
99946	0.2519	81
99953	0.1534	38
99954	0.1134	38
99948	0.0964	47

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	97.63	gold quality
corpus callosum	UBERON:0002336	97.55	gold quality
ventricular zone	UBERON:0003053	97.25	gold quality
subthalamic nucleus	UBERON:0001906	96.87	gold quality
inferior vagus X ganglion	UBERON:0005363	96.80	gold quality
choroid plexus epithelium	UBERON:0003911	96.61	gold quality
lateral globus pallidus	UBERON:0002476	95.87	gold quality
superior vestibular nucleus	UBERON:0007227	95.72	gold quality
blood vessel layer	UBERON:0004797	95.64	gold quality
vena cava	UBERON:0004087	95.50	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.37	gold quality
urethra	UBERON:0000057	95.33	gold quality
pigmented layer of retina	UBERON:0001782	95.32	gold quality
heart right ventricle	UBERON:0002080	95.29	gold quality
sural nerve	UBERON:0015488	95.27	gold quality
substantia nigra pars compacta	UBERON:0001965	95.15	gold quality
pons	UBERON:0000988	95.11	gold quality
cranial nerve II	UBERON:0000941	95.06	gold quality
myocardium	UBERON:0002349	94.99	gold quality
pericardium	UBERON:0002407	94.98	gold quality
cauda epididymis	UBERON:0004360	94.71	gold quality
medulla oblongata	UBERON:0001896	94.58	gold quality
trigeminal ganglion	UBERON:0001675	94.55	gold quality
left ventricle myocardium	UBERON:0006566	94.47	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.31	gold quality
ventral tegmental area	UBERON:0002691	94.26	gold quality
tibial artery	UBERON:0007610	94.14	gold quality
popliteal artery	UBERON:0002250	94.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.12	gold quality
liver	UBERON:0002107	94.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

118 targeting MPDZ, 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-3163	100.00	77.23	8605
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-4776-3P	100.00	68.73	1340
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-153-5P	99.89	73.86	6317
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

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 25)

• Results indicate that the coxsackievirus and adenovirus receptor interacts with multi-PDZ domain protein 1 (MUPP1) and is involved in MUPP1 recruitment to the tight junction. (PMID:15364909)
• The predominant expression profile of MUPP1 in sperm in the apical acrosomal region of different mammalian species suggests that this PDZ-domain protein may be involved in organizing signaling molecules mediating primary reactions of fertilization. (PMID:16452527)
• The results revealed prominent MUPP1 expression which was restricted to the apical acrosomal region and, most notably, to the equatorial segment of the acrosome[MUPP1] (PMID:16452527)
• the apparent occurrence of an unusual TG 3’ splice site in intron 39 is discussed (PMID:17672918)
• MUPP1 binds to the G protein-coupled MT(1) melatonin receptor and directly regulates its G(i)-dependent signal transduction (PMID:18378672)
• An interaction between the human somatostatin receptor 3 and the multiple PDZ protein MUPP1 was identified. (PMID:19071123)
• Exploratory haplotype and single nucleotide polymorphisms association analyses suggest a possible association between the MPDZ gene and alcohol dependence but not alcohol withdrawal seizures. (PMID:19175764)
• Results suggest that signaling mediated by Pals1, which has a higher affinity for Patj than for MUPP1 and is involved in the activation of the Par6-aPKC complex, is of principal importance for the function of Patj in epithelial cells. (PMID:19255144)
• MUPP1 and Kir4.2 may participate in a protein complex in the nephron that could regulate transport of K(+) as well as other ions. (PMID:19420109)
• These data suggest that NMDA receptor complex formation, localization, and downstream signaling may be abnormal in schizophrenia as PSD95, SynGAP and MUPP1 expression is altered. (PMID:19483657)
• The data indicates potential association between variation in mpdz NMDA dependent AMPA trafficking and alcohol dependence. (PMID:21762291)
• Our data strongly support the candidacy of MPDZ as a novel congenital hydrocephalus disease gene. (PMID:23240096)
• MUPP-1 controls the PALS-1/PATJ complex levels at the post-translational level. (PMID:23880463)
• The replication association of rs1324183 (MPDZ-NF1B) with KC in our population and the results, which are identical to those in different populations, suggest that rs1324183 (MPDZ-NF1B) is a common genetic risk for Keratoconus. (PMID:25675348)
• two peptides (SIAPNV(-COOH) and SIVMNV(-COOH)) were identified to have considerably improved affinity with K d increase by ~tenfold relative to wild type peptide. Thus, the two peptides are considered as promising lead entities to develop therapeutic molecular agents with high efficacy and specificity to target CaMKIIalpha-MUPP1 interaction. (PMID:26984442)
• Phenotypic spectrum of congenital hydrocephalus is associated with 5 recessive MPDZ alleles. (PMID:28556411)
• Tumor angiogenesis was enhanced upon endothelial-specific inactivation of MPDZ leading to an excessively branched and poorly functional vessel network resulting in tumor hypoxia through DLL4-induced Notch signaling. (PMID:29620522)
• This study confirmed the association of SNP rs1324183 in MPDZ-NF1B with keratoconus and revealed the association of this SNP with keratoconus severity and corneal parameters. It is thus a putative genetic marker for monitoring the progression of keratoconus to a severe form and facilitating early intervention. (PMID:30002070)
• DAPLE and MPDZ function as cooperative partners at apical junctions. (PMID:31268831)
• Observation of nine previously reported and 10 non-reported SLC4A11 mutations among 20 Iranian CHED probands and identification of an MPDZ mutation as possible cause of CHED and FECD in one family. (PMID:31420327)
• MPDZ as a novel epigenetic silenced tumor suppressor inhibits growth and progression of lung cancer through the Hippo-YAP pathway. (PMID:34108620)
• ADAMTS1, MPDZ, MVD, and SEZ6: candidate genes for autosomal recessive nonsyndromic hearing impairment. (PMID:34135477)
• Evaluating the association between MPDZ-NF1B rs1324183 and keratoconus in an independent northwestern Chinese population. (PMID:35305607)
• Retinal manifestations in autosomal recessive MPDZ maculopathy: report of two cases and literature review. (PMID:36594712)
• MPDZ is associated with immune infiltration and regulates migration and invasion by switching YAP1 phosphorylation in colorectal cancer. (PMID:37949382)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mpdz	ENSMUSG00000028402
rattus_norvegicus	Mpdz	ENSRNOG00000007894
caenorhabditis_elegans		WBGENE00001492
caenorhabditis_elegans		WBGENE00021406

Paralogs (5): LNX1 (ENSG00000072201), PATJ (ENSG00000132849), LNX2 (ENSG00000139517), STXBP4 (ENSG00000166263), FRMPD2 (ENSG00000170324)

Protein

Protein identifiers

Multiple PDZ domain protein — O75970 (reviewed: O75970)

Alternative names: Multi-PDZ domain protein 1

All UniProt accessions (11): O75970, A0A075B6R8, B7ZB24, F5H1U9, F5H8D6, F8WDQ8, H0YF96, H0YFZ6, H0YGQ3, H0YH70, H3BM19

UniProt curated annotations — full annotation on UniProt →

Function. Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses. Promotes clustering of HT2RC at the cell surface.

Subunit / interactions. Interacts with CLDN5, DLG4, GRIN1, F11R/JAM, CLDN1, NG2, CRB1, MPP4 and PALS1. Interacts with HTR2A, HTR2B, HTR2C, PLEKHA1/TAPP1, PLEKHA2/TAPP2, CXADR, SYNGAP1, CAMK2A and CAMK2B. Interacts with FAT4 (via cytoplasmic domain). Interacts with DLL1. (Microbial infection) Interacts with human adenovirus type 9 E4-ORF1 protein. (Microbial infection) Interacts with human papillomavirus 18/HPV18 protein E6.

Subcellular location. Cell membrane. Apical cell membrane. Postsynaptic density. Cell projection. Dendrite. Cell junction. Tight junction. Synapse. Synaptosome.

Tissue specificity. Expressed in heart, brain, placenta, liver, skeletal muscle, kidney and pancreas.

Disease relevance. Hydrocephalus, congenital, 2, with or without brain or eye anomalies (HYC2) [MIM:615219] A form of congenital hydrocephalus, a disease characterized by onset in utero of enlarged ventricles due to accumulation of ventricular cerebrospinal fluid. HYC2 affected individuals have variable neurologic impairment. Some individuals have other brain abnormalities, including lissencephaly, thinning of the corpus callosum, and neuronal heterotopia. Most patients have delayed motor development and some have delayed intellectual development and/or seizures. Additional congenital features, including cardiac septal defects, iris coloboma, and non-specific dysmorphic features, may be observed. HYC2 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PDZ domain 1 binds NG2. The PDZ domains 7 and 10 bind the Ad9 E4-ORF1 oncoprotein. The PDZ domain 9 binds F11R. The PDZ domain 10 binds the C-terminus of CLDN1 and KIT and the C-terminal PDZ-binding motif of HTR2C. The PDZ domain 13 binds CXADR. The PDZ domain 2 binds CAMK2A and CAMK2B. The PDZ domains 10 and 13 bind PLEKHA1 and PLEKHA2. The PDZ domain 13 binds SYNGAP1.

Isoforms (4)

UniProt ID	Names	Canonical?
O75970-1	1	yes
O75970-2	2
O75970-3	3
O75970-5	4

RefSeq proteins (18): NP_001248335, NP_001248336, NP_001317566, NP_001362342, NP_001362345, NP_001362346, NP_001362347, NP_001362348, NP_001362349, NP_001362350, NP_001362351, NP_001362352, NP_001362353, NP_001362354, NP_001362355, NP_001362356, NP_001365707, NP_003820 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR004172	L27_dom	Domain
IPR015132	L27_2	Domain
IPR032078	MPDZ_u10	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR036892	L27_dom_sf	Homologous_superfamily
IPR051342	PDZ_scaffold	Family

Pfam: PF00595, PF09045, PF16667

UniProt features (95 total): strand 38, helix 15, domain 14, sequence variant 10, modified residue 7, region of interest 3, compositionally biased region 2, splice variant 2, chain 1, mutagenesis site 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
2IWN	X-RAY DIFFRACTION	1.35
2QG1	X-RAY DIFFRACTION	1.4
2OPG	X-RAY DIFFRACTION	1.5
2IWO	X-RAY DIFFRACTION	1.7
2FCF	X-RAY DIFFRACTION	1.76
2IWQ	X-RAY DIFFRACTION	1.8
2FNE	X-RAY DIFFRACTION	1.83
2IWP	X-RAY DIFFRACTION	2.15
2O2T	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75970-F1	63.98	0.14

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 (7): 230, 483, 790, 1078, 1170, 1818, 1824

Mutagenesis-validated functional residues (1):

Position	Phenotype
147–150	loss of interaction with camk2a.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KEGG_TIGHT_JUNCTION, GOBP_CELL_JUNCTION_ORGANIZATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP, GOCC_APICOLATERAL_PLASMA_MEMBRANE, GOCC_APICAL_PLASMA_MEMBRANE, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GOBP_CELL_JUNCTION_ASSEMBLY, GOCC_NEURON_PROJECTION, LE_EGR2_TARGETS_DN, GOBP_CELL_CELL_JUNCTION_ASSEMBLY, GOCC_CELL_CELL_JUNCTION, SARTIPY_BLUNTED_BY_INSULIN_RESISTANCE_DN

GO Biological Process (1): tight junction assembly (GO:0120192)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (13): cytoplasm (GO:0005737), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), postsynaptic density (GO:0014069), apical plasma membrane (GO:0016324), apicolateral plasma membrane (GO:0016327), dendrite (GO:0030425), apical part of cell (GO:0045177), membrane (GO:0016020), cell projection (GO:0042995), neuron projection (GO:0043005), synapse (GO:0045202), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
plasma membrane region	2
cell junction	2
cell-cell junction assembly	1
tight junction organization	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
asymmetric synapse	1
postsynaptic specialization	1
apical part of cell	1
neuron projection	1
dendritic tree	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MPDZ	PALS1	Q8N3R9	978
MPDZ	AMOT	Q4VCS5	897
MPDZ	OCLN	Q16625	889
MPDZ	TJP3	O95049	855
MPDZ	CGN	Q9P2M7	854
MPDZ	PATJ	Q8NI35	848
MPDZ	TJP1	Q07157	840
MPDZ	TJP2	Q9UDY2	816
MPDZ	F11R	Q9Y624	793
MPDZ	KCNV2	Q8TDN2	784
MPDZ	IER5	Q5VY09	765
MPDZ	MARVELD2	Q8N4S9	737
MPDZ	GABBR1	Q9UBS5	728
MPDZ	GJD2	Q9UKL4	721
MPDZ	NFIB	O00712	682

IntAct

1498 interactions, top by confidence:

A	B	Type	Score
PALS1	LIN7A	psi-mi:“MI:0914”(association)	0.870
YAP1	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.780
PLEKHA1	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.770
HTR2C	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.650
MPDZ	CYSLTR2	psi-mi:“MI:0407”(direct interaction)	0.620
CYSLTR2	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.620
HTR2A	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.620
MPDZ	ABCA1	psi-mi:“MI:0407”(direct interaction)	0.610
ABCA1	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.610
MPDZ	SMCHD1	psi-mi:“MI:0914”(association)	0.590
SMCHD1	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.590
CFTR	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.570
MPDZ	PTEN	psi-mi:“MI:0407”(direct interaction)	0.540
MPDZ	PTEN	psi-mi:“MI:0915”(physical association)	0.540
Tax	MPDZ	psi-mi:“MI:0915”(physical association)	0.540
NET1	MPDZ	psi-mi:“MI:0915”(physical association)	0.540
E6	MPDZ	psi-mi:“MI:0915”(physical association)	0.540
CREBBP	MPDZ	psi-mi:“MI:0915”(physical association)	0.540
GP1	MPDZ	psi-mi:“MI:0915”(physical association)	0.540
CREBBP	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.540
MPDZ	CREBBP	psi-mi:“MI:0407”(direct interaction)	0.540
E6	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.540

BioGRID (149): MPDZ (Affinity Capture-RNA), MPDZ (Affinity Capture-RNA), MPDZ (Affinity Capture-RNA), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS), MPDZ (Synthetic Lethality), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS), MPDZ (Affinity Capture-MS)

ESM2 similar proteins: B2GUY1, E2QYC9, E7F1U2, E7FDW2, E9Q9W7, F1MAD2, O15018, O54960, O55164, O75970, P68907, Q12923, Q13009, Q4L1J4, Q5RBI7, Q60610, Q63ZW7, Q64512, Q69ZS0, Q6AWC2, Q6DJR2, Q6IVY4, Q6RHR9, Q6XZF7, Q6ZMN7, Q80VW5, Q810W9, Q8N680, Q8NI35, Q8TEW0, Q8VBX6, Q92870, Q96QZ7, Q99N50, Q99NH2, Q9BYG5, Q9D3A8, Q9DBR4, Q9DDT2, Q9EQZ7

Diamond homologs: A0A8C0TYJ0, A0A8P0N4K0, B4F7E7, D3ZAA9, E2QY99, E2QYC9, E7FDW2, F1MAD2, G5ECY0, O14910, O15018, O55164, O75970, O84033, O88382, O88951, O88952, P15454, P31006, P31007, P31016, P46195, P57105, P68907, P70175, P78352, P93757, Q0P5F3, Q0SS73, Q0TPK6, Q12959, Q13425, Q13884, Q14160, Q15700, Q16774, Q24210, Q255A8, Q28C55, Q2KIB6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 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
Signaling by Hippo	5	29.2×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
hippo signaling	5	32.7×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

2027 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	83
Likely pathogenic	45
Uncertain significance	1003
Likely benign	723
Benign	58

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1027378	NM_001378778.1(MPDZ):c.5125_5126insGTAT (p.Tyr1709fs)	Pathogenic
1071173	NC_000009.11:g.(?13136071)(13136201_?)del	Pathogenic
1204727	NM_001378778.1(MPDZ):c.1735C>T (p.Arg579Ter)	Pathogenic
1323286	NM_001378778.1(MPDZ):c.414del (p.Phe138fs)	Pathogenic
1371165	NM_001378778.1(MPDZ):c.2508del (p.Asp837fs)	Pathogenic
1447384	NM_001378778.1(MPDZ):c.960del (p.Val321fs)	Pathogenic
1451543	NM_001378778.1(MPDZ):c.3130C>T (p.Arg1044Ter)	Pathogenic
1452904	NM_001378778.1(MPDZ):c.3363_3364del (p.Ile1122fs)	Pathogenic
1454932	NM_001378778.1(MPDZ):c.5492del (p.Phe1831fs)	Pathogenic
1456451	NM_001378778.1(MPDZ):c.3016G>T (p.Glu1006Ter)	Pathogenic
1458966	NM_001378778.1(MPDZ):c.1364_1365del (p.Val455fs)	Pathogenic
1459014	NM_001378778.1(MPDZ):c.4210C>T (p.Gln1404Ter)	Pathogenic
1459553	NM_001378778.1(MPDZ):c.2248C>T (p.Arg750Ter)	Pathogenic
1807690	GRCh37/hg19 9p23(chr9:13122130-13649715)x3	Pathogenic
1895790	NM_001378778.1(MPDZ):c.64C>T (p.Arg22Ter)	Pathogenic
1909200	NM_001378778.1(MPDZ):c.5993del (p.Gly1998fs)	Pathogenic
1917776	NM_001378778.1(MPDZ):c.4929dup (p.Val1644fs)	Pathogenic
1959874	NM_001378778.1(MPDZ):c.5045del (p.Gly1682fs)	Pathogenic
1959982	NM_001378778.1(MPDZ):c.3343dup (p.Ser1115fs)	Pathogenic
1974700	NM_001378778.1(MPDZ):c.1938_1942del (p.Asp647fs)	Pathogenic
1979076	NM_001378778.1(MPDZ):c.5147_5148del (p.Lys1716fs)	Pathogenic
1992798	NM_001378778.1(MPDZ):c.77dup (p.Asp26fs)	Pathogenic
2000707	NM_001378778.1(MPDZ):c.5320_5327del (p.Met1774fs)	Pathogenic
2020688	NM_001378778.1(MPDZ):c.3857_3858del (p.Glu1286fs)	Pathogenic
2028458	NM_001378778.1(MPDZ):c.779T>A (p.Leu260Ter)	Pathogenic
2029103	NM_001378778.1(MPDZ):c.2629del (p.Leu877fs)	Pathogenic
2050675	NM_001378778.1(MPDZ):c.5013_5014del (p.Trp1672fs)	Pathogenic
2065003	NM_001378778.1(MPDZ):c.3564del (p.Lys1188fs)	Pathogenic
2068125	NM_001378778.1(MPDZ):c.4198G>T (p.Glu1400Ter)	Pathogenic
2087661	NM_001378778.1(MPDZ):c.4079T>A (p.Leu1360Ter)	Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

13518 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:13108952:T:A	K2017I	1.000
9:13108955:A:T	V2016D	1.000
9:13109000:A:T	I2001K	1.000
9:13109006:A:G	F1999S	1.000
9:13121853:A:G	L1706P	1.000
9:13121880:A:G	L1697P	1.000
9:13123172:C:T	G1645E	1.000
9:13123178:A:T	I1643N	1.000
9:13123184:A:G	L1641P	1.000
9:13138072:A:G	L1362P	1.000
9:13206047:A:G	L448S	1.000
9:13216781:A:C	I428S	1.000
9:13216781:A:G	I428T	1.000
9:13221442:A:G	F269S	1.000
9:13107008:A:G	L2057P	0.999
9:13107021:C:G	A2053P	0.999
9:13107059:A:T	V2040D	0.999
9:13107068:A:C	I2037S	0.999
9:13107068:A:G	I2037T	0.999
9:13107068:A:T	I2037N	0.999
9:13107086:A:G	L2031P	0.999
9:13107086:A:T	L2031Q	0.999
9:13108942:A:C	F2020L	0.999
9:13108942:A:T	F2020L	0.999
9:13108944:A:G	F2020L	0.999
9:13108951:T:A	K2017N	0.999
9:13108951:T:G	K2017N	0.999
9:13108953:T:C	K2017E	0.999
9:13108981:G:C	S2007R	0.999
9:13108981:G:T	S2007R	0.999

dbSNP variants (sampled 300 via entrez): RS1000002558 (9:13172405 G>A,C,T), RS1000022952 (9:13196320 C>T), RS1000045370 (9:13194838 A>T), RS1000047497 (9:13272704 A>G), RS1000058885 (9:13266148 C>T), RS1000069544 (9:13231529 C>A,G), RS1000071055 (9:13202459 C>T), RS1000111781 (9:13131962 T>C), RS1000112708 (9:13154397 A>C), RS1000129986 (9:13231134 G>C), RS1000131069 (9:13137508 C>A,T), RS1000157344 (9:13137687 T>A,G), RS1000162909 (9:13173865 G>C), RS1000163268 (9:13246720 G>A), RS1000221262 (9:13179514 A>G)

Disease associations

OMIM: gene MIM:603785 | disease phenotypes: MIM:615219, MIM:156000, MIM:615502, MIM:236600

GenCC curated gene-disease

Disease	Classification	Inheritance
hydrocephalus, nonsyndromic, autosomal recessive 2	Strong	Autosomal recessive

Mondo (5): hydrocephalus, nonsyndromic, autosomal recessive 2 (MONDO:0014085), Meniere disease (MONDO:0007972), CTCF-related neurodevelopmental disorder (MONDO:0014213), intellectual disability (MONDO:0001071), congenital hydrocephalus (MONDO:0016349)

Orphanet (4): Congenital hydrocephalus (Orphanet:2185), CTCF-related neurodevelopmental disorder (Orphanet:363611), NON RARE IN EUROPE: Menière disease (Orphanet:45360), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001806_10	Corneal structure	8.000000e-09
GCST005667_41	Central corneal thickness	6.000000e-12
GCST006288_479	Heel bone mineral density	9.000000e-06
GCST006288_665	Heel bone mineral density	4.000000e-10
GCST006979_153	Heel bone mineral density	3.000000e-25
GCST007160_20	Refractive astigmatism	2.000000e-06
GCST008315_7	Corneal hysteresis	5.000000e-06
GCST010244_108	Triglyceride levels	7.000000e-09
GCST011391_3	Corneal hysteresis	4.000000e-86
GCST90000025_463	Appendicular lean mass	7.000000e-11
GCST90000654_26	Central corneal thickness	2.000000e-25

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0005213	central corneal thickness
EFO:0009270	heel bone mineral density
EFO:0010066	corneal hysteresis
EFO:0004530	triglyceride measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008575	Meniere Disease	C09.218.568.217.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	affects cotreatment, increases expression, decreases expression, increases abundance	3
bisphenol A	increases expression, increases methylation	2
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance	2
methacrylaldehyde	increases abundance, affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases expression	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
testosterone enanthate	affects expression	1
methyleugenol	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
potassium chromate(VI)	decreases expression	1
coumarin	affects phosphorylation	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1

Cellosaurus cell lines

29 cell lines: 29 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0325	HuT78B1	Cancer cell line	Male
CVCL_0337	HuT 78	Cancer cell line	Male
CVCL_1240	H9	Cancer cell line	Male
CVCL_1734	SW982	Cancer cell line	Female
CVCL_3514	H9/HTLV-IIIB	Cancer cell line	Male
CVCL_9472	PM1	Cancer cell line	Male
CVCL_D3XT	HuT 78/HIV-1 FRE-3 clone B4A	Cancer cell line	Male
CVCL_D3XU	HuT 78/HIV-1 FRE-3 clone C9A	Cancer cell line	Male
CVCL_D3XV	HuT 78/HIV-1 FRE-3 clone D5A	Cancer cell line	Male
CVCL_D3XW	HuT 78/HIV-1 FRE-3 clone E2D	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01574313	PHASE4	COMPLETED	Effect of Stellate Ganglion Block on Meniere’s Disease
NCT02529475	PHASE4	TERMINATED	Evaluation of Inner Ear and Brain Structures With Contrast-enhanced MRI in Healthy Subjects (HYDROPS)
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT03664674	PHASE3	COMPLETED	Phase 3 Study of OTO-104 in Subjects With Unilateral Meniere’s Disease
NCT04677972	PHASE3	COMPLETED	SPI-1005 for the Treatment of Meniere’s Disease
NCT05851508	PHASE3	RECRUITING	The Effecttiveness of Intratympanic Methylprednisolon Injections Compared to Placebo in the Treatment of Vertigo Attacks in Meniere’s Disease
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT05420350	PHASE2	UNKNOWN	Lamotrigine and Bupropion for Meniere’s Disease
NCT06544434	PHASE2	RECRUITING	Laser Acupuncture for Meniere Disease
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT04674735	PHASE1	WITHDRAWN	Safety of APSLXR in Patients Presenting Vertigo of Vestibular Origin or Meniere’s Disease
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT04218123	PHASE2/PHASE3	COMPLETED	Assessing the Efficacy of a Serotonin and Norepinephrine Reuptake Inhibitor for Improving Meniere’s Disease Outcomes
NCT04766853	PHASE1/PHASE2	COMPLETED	Verification of the Efficacy/safety of the Intratympanic Drug Delivery for Hearing Loss
NCT04794842	EARLY_PHASE1	UNKNOWN	Comparing Topical Tetracaine Drops to Topical Focal Phenol for Local Anesthesia During Intratympanic Steroid Injection
NCT00599560	Not specified	COMPLETED	Vasopressin and V2 Receptor in Meniere’s Disease
NCT02371798	Not specified	WITHDRAWN	Unilateral Meniere Disease: Can Double Dose Gadolinium and Delayed Imaging Make the Diagnosis?
NCT03520322	Not specified	TERMINATED	A Study of a Mastoid Device in Subjects With Ménière’s Disease
NCT03795675	Not specified	ACTIVE_NOT_RECRUITING	CI Following VS Removal or Labyrinthectomy
NCT04370366	Not specified	RECRUITING	Imaging of Endolymphatic Hydrops at 7T MRI
NCT04569175	Not specified	COMPLETED	Non Enhanced Labyrinth Imaging for the Detection of Endolymphatic Hydrops in Meniere’s Disease NELI Study
NCT04686695	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation Treatment on Meniere Disease
NCT04835688	Not specified	UNKNOWN	Ventilation Tube Insertion for Unilateral Menière’s Disease
NCT04902963	Not specified	COMPLETED	What is the Tympanic Membrane Healing Time After Insertion of a Gelfoam PE Tube?
NCT04935970	Not specified	UNKNOWN	Metabolic Disorders and Vertigo
NCT05322538	Not specified	NOT_YET_RECRUITING	Menier’s Disease - Bone Density Study
NCT05328895	Not specified	COMPLETED	Transcutaneous Auricular Vagus Nerve Stimulation for Meniere Disease
NCT05424302	Not specified	RECRUITING	Effect of Peripheral Vestibular Disease Location on Outcomes Following Home-based Virtual Reality Vestibular Therapy
NCT05582148	Not specified	UNKNOWN	Meniere Disease and Hearing Aids