PLEKHA7

protein-coding

pleckstrin homology domain containing A7, the group of Pleckstrin homology domain containing

Gene summary

Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001329630.2

Inheritance

ClinVar variants

P:4U:222B:52

Top phenotype

PLEKHA7-related disorder

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr11:16,777,297-17,014,415

External References & Databases

Ensembl (ENSG00000166689)

Transcript & Mutation Effects

hg38 • Region Span ~237.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cleft lip/palateMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0016044

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLEKHA7 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 216

PLEKHA7-related disorderTotal: 51

not providedTotal: 8

Cleft lip with or without cleft palateTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001329630.2. 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			3 clinvar	28 clinvar	5 clinvar	36
missense		3 clinvar	217 clinvar	15 clinvar	4 clinvar	239
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	0	4	222	43	9	278

Highest pathogenic variant AF is 0.000024782257

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001329630.2	RefSeq	NP_001316559.1	27	MANE Select
ENST00000531066.6	Ensembl	ENSP00000435389.1	27	MANE Select
NM_001329631.2	RefSeq	NP_001316560.1	23	Standard
NM_001410960.1	RefSeq	NP_001397889.1	27	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
plekha7a	Danio rerio	Structure: atrioventricular canal Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

plekha7a

Danio rerio

Structure: atrioventricular canal

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Stabilization and expansion of the E-cadherin adherens junction

Biological Process

cell-cell adhesion mediated by cadherin
zonula adherens maintenance
epithelial cell-cell adhesion

Molecular Function

protein binding
delta-catenin binding

Cellular Component

nucleus
centrosome
cytosol
zonula adherens
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355661
Coding exons: 23
Length: 236149
Individuals with no LoFs: 125702
Homozygous LoFs: 0
Heterozygous LoFs: 46
Defined: 125748
p: 0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.214	665	681	0.977	0.0000425	7240
Missense (PolyPhen)		187	216.51	0.8637		2237
Synonymous	-0.155	282	279	1.01	0.0000176	2252
Loss of Function	4.77	27	70.1	0.385	0.00000452	666

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.000054	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00023	0.00020	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for zonula adherens biogenesis and maintenance. Acts via its interaction with KIAA1543/Nezha, which anchors microtubules at their minus-ends to zonula adherens, leading to the recruitment of KIFC3 kinesin to the junctional site. {ECO:0000269|PubMed:19041755}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.771
RVIS EVS: -1.39
RVIS percentile EVS: 4.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.856

Gene Damage Prediction

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