MPDZ

multiple PDZ domain crumbs cell polarity complex component, the group of Crumbs complex|PDZ domain containing

Basic information

Region (hg38): 9:13105706-13279692

Links

ENSG00000107186 ∙ NCBI:8777 ∙ OMIM:603785 ∙ HGNC:7208 ∙ Uniprot:O75970 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hydrocephalus, nonsyndromic, autosomal recessive 2 (Limited), mode of inheritance: AR
• hydrocephalus, nonsyndromic, autosomal recessive 2 (Moderate), mode of inheritance: AR
• hydrocephalus, nonsyndromic, autosomal recessive 2 (Strong), mode of inheritance: AR
• hydrocephalus, nonsyndromic, autosomal recessive 2 (Moderate), mode of inheritance: AR
• hydrocephalus, nonsyndromic, autosomal recessive 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hydrocephalus, congenital, 2, with or without brain or eye anomalies	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Ophthalmologic	23240096

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MPDZ gene.

• not_provided (1639 variants)
• Inborn_genetic_diseases (384 variants)
• Hydrocephalus,_nonsyndromic,_autosomal_recessive_2 (87 variants)
• MPDZ-related_disorder (82 variants)
• not_specified (27 variants)
• Meniere_disease (7 variants)
• Intellectual_disability-feeding_difficulties-developmental_delay-microcephaly_syndrome (1 variants)
• Nonsyndromic_hearing_impairment (1 variants)
• Congenital_hydrocephalus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MPDZ gene is commonly pathogenic or not. These statistics are base on transcript: NM_001378778.1. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	354	19	383
missense		1	894	54	19	968
nonsense	29	11	2			42
start loss			1			1
frameshift	35	13	1			49
splice donor/acceptor (+/-2bp)		34	3			37
Total	64	59	911	408	38

Highest pathogenic variant AF is 0.0000743811

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MPDZ	protein_coding	protein_coding	ENST00000541718	45	173887

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.80e-38	0.131	124419	0	288	124707	0.00116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.98	1312	1.04e+3	1.26	0.0000530	13163
Missense in Polyphen		491	422.11	1.1632		5098
Synonymous	-3.71	466	375	1.24	0.0000198	4033
Loss of Function	2.47	73	99.6	0.733	0.00000560	1246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00311	0.00309
Ashkenazi Jewish	0.00130	0.00129
East Asian	0.00126	0.00122
Finnish	0.00107	0.00107
European (Non-Finnish)	0.00112	0.00103
Middle Eastern	0.00126	0.00122
South Asian	0.000836	0.000817
Other	0.00135	0.00132

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Interacts with HTR2C and provokes its clustering at the cell surface (By similarity). Member of the NMDAR signaling complex that may play a role in control of AMPAR potentiation and synaptic plasticity in excitatory synapses. {ECO:0000250, ECO:0000269|PubMed:11150294, ECO:0000269|PubMed:15312654}.
• Disease: DISEASE: 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 impairement. 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. {ECO:0000269|PubMed:23240096}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tight junction - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.154

Intolerance Scores

• loftool: 0.998
• rvis_EVS: 1.39
• rvis_percentile_EVS: 94.64

Haploinsufficiency Scores

• pHI: 0.389
• ghis: 0.476

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.655

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mpdz
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hearing/vestibular/ear phenotype

Gene ontology

• Biological process: cell adhesion;viral process
• Cellular component: cytoplasm;bicellular tight junction;postsynaptic density;apical plasma membrane;apicolateral plasma membrane;dendrite;cytoplasmic vesicle;Schmidt-Lanterman incisure;postsynaptic membrane
• Molecular function: protein binding;protein C-terminus binding