MPP4

protein-coding

MAGUK p55 scaffold protein 4, the group of PDZ domain containing|Membrane associated guanylate kinases

Gene summary

This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) protein family, with an N-terminal PDZ domain, a central src homology 3 region (SH3), and a C-terminal guanylate kinase-like (GUK) domain. The protein is localized to the outer limiting membrane in the retina, and is thought to function in photoreceptor polarity and the organization of specialized intercellular junctions. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Previous symbols:

DLG6

MANE transcript

NM_033066.3

Inheritance

—

ClinVar variants

P:1U:97B:6

Top phenotype

Strabismus

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr2:201,644,870-201,698,694

External References & Databases

Ensembl (ENSG00000082126)

Transcript & Mutation Effects

hg38 • Region Span ~53.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MPP4 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 98

not providedTotal: 4

StrabismusTotal: 1

Generalized hypotoniaTotal: 1

Wide nasal bridgeTotal: 1

High palateTotal: 1

Global developmental delayTotal: 1

SeizureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033066.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense	1 clinvar		97 clinvar	3 clinvar		101
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	1	0	97	6	0	104

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033066.3	RefSeq	NP_149055.2	21	MANE Select
ENST00000409474.8	Ensembl	ENSP00000387278.3	21	MANE Select
NM_001438024.1	RefSeq	NP_001424953.1	17	Standard
ENST00000315506.11	Ensembl	ENSP00000319363.7	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Tight junction - Homo sapiens (human)

Biological Process

biological_process
protein localization to synapse

Molecular Function

protein binding

Cellular Component

cytosol
cell-cell adherens junction
actin cytoskeleton
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409474
Coding exons: 21
Length: 53825
Individuals with no LoFs: 124456
Homozygous LoFs: 0
Heterozygous LoFs: 190
Defined: 124646
p: 0.000762

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.454	316	340	0.931	0.0000180	4175
Missense (PolyPhen)		105	117.55	0.8932		1384
Synonymous	0.530	116	123	0.939	0.00000702	1141
Loss of Function	1.26	32	40.7	0.786	0.00000203	479

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0036	0.0036	notable
Latino/Admixed American	0.0010	0.00099	notable
Ashkenazi Jewish	0.00061	0.00060	rare
East Asian	0.00028	0.00028	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00061	0.00058	rare
South Asian	0.00065	0.00059	rare
Other	0.00067	0.00066	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in retinal photoreceptors development. {ECO:0000250}.;

Recessive Scores

pRec: 0.0908

Intolerance Scores

LoFtool: 0.693
RVIS EVS: -0.46
RVIS percentile EVS: 23.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.453

Gene Damage Prediction

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