PLEKHO1

protein-coding

pleckstrin homology domain containing O1, the group of Pleckstrin homology domain containing

Gene summary

Predicted to be involved in regulation of myoblast fusion. Predicted to act upstream of or within several processes, including lamellipodium morphogenesis; myoblast fusion; and myoblast migration. Located in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_016274.6

Inheritance

—

ClinVar variants

U:70B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr1:150,149,183-150,164,720

External References & Databases

Ensembl (ENSG00000023902)

Transcript & Mutation Effects

hg38 • Region Span ~15.5 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 PLEKHO1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016274.6. 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			1 clinvar	2 clinvar	1 clinvar	4
missense			66 clinvar	1 clinvar		67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	70	3	1	74

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016274.6	RefSeq	NP_057358.2	6	MANE Select
ENST00000369124.5	Ensembl	ENSP00000358120.4	6	MANE Select
NM_001304722.2	RefSeq	NP_001291651.1	2	Standard
NM_001304723.2	RefSeq	NP_001291652.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
plekho1b	Danio rerio	Structure: fast muscle myoblast Quality: irregular spatial pattern abnormal

Gene / Model

Organism

Observed Phenotype

plekho1b

Danio rerio

Structure: fast muscle myoblast

Quality: irregular spatial pattern

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

myoblast fusion
regulation of cell shape
myoblast migration
lamellipodium morphogenesis

Molecular Function

protein binding

Cellular Component

nucleus
cytoplasm
ruffle membrane
muscle cell projection membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000369124
Coding exons: 6
Length: 15544
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0693	244	247	0.988	0.0000148	2628
Missense (PolyPhen)		83	99.348	0.83545		1068
Synonymous	-0.288	105	101	1.04	0.00000567	837
Loss of Function	3.19	4	19.0	0.210	0.00000113	201

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein (CP). May function to target CK2 to the plasma membrane thereby serving as an adapter to facilitate the phosphorylation of CP by protein kinase 2 (CK2). Appears to target ATM to the plasma membrane. Appears to also inhibit tumor cell growth by inhibiting AKT- mediated cell-survival. Also implicated in PI3K-regulated muscle differentiation, the regulation of AP-1 activity (plasma membrane bound AP-1 regulator that translocates to the nucleus) and the promotion of apoptosis induced by tumor necrosis factor TNF. When bound to PKB, it inhibits it probably by decreasing PKB level of phosphorylation. {ECO:0000269|PubMed:14729969, ECO:0000269|PubMed:15706351, ECO:0000269|PubMed:15831458, ECO:0000269|PubMed:16325375, ECO:0000269|PubMed:16987810, ECO:0000269|PubMed:17197158, ECO:0000269|PubMed:17942896}.;

Recessive Scores

pRec: 0.0873

Intolerance Scores

LoFtool: 0.380
RVIS EVS: -0.47
RVIS percentile EVS: 23.43

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.552

Gene Damage Prediction

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