PLEKHH2

protein-coding

pleckstrin homology, MyTH4 and FERM domain containing H2, the group of Pleckstrin homology domain containing|FERM domain containing

Gene summary

Predicted to enable actin binding activity. Predicted to be involved in negative regulation of actin filament depolymerization. Located in cytoplasm; lamellipodium; and plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_172069.4

Inheritance

—

ClinVar variants

U:240B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.76

Max pathogenic AF

—

Genomic locus

chr2:43,637,260-43,767,987

External References & Databases

Ensembl (ENSG00000152527)

Transcript & Mutation Effects

hg38 • Region Span ~130.7 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 PLEKHH2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 283

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172069.4. 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			4 clinvar	2 clinvar		6
missense			232 clinvar	7 clinvar		239
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	240	9	0	249

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172069.4	RefSeq	NP_742066.2	29	MANE Select
ENST00000282406.9	Ensembl	ENSP00000282406.4	29	MANE Select
ENST00000490038.1	Ensembl	ENSP00000430377.1	3	Standard
ENST00000491692.5	Ensembl	ENSP00000427746.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of actin filament depolymerization

Molecular Function

actin binding
protein binding
identical protein binding

Cellular Component

nucleoplasm
cytoplasm
cytosol
plasma membrane
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000282406
Coding exons: 29
Length: 130715
Individuals with no LoFs: 125603
Homozygous LoFs: 0
Heterozygous LoFs: 145
Defined: 125748
p: 0.000577

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.72	893	759	1.18	0.0000382	9754
Missense (PolyPhen)		147	140.76	1.0443		1801
Synonymous	-1.87	308	269	1.15	0.0000136	2802
Loss of Function	2.02	63	82.9	0.760	0.00000443	1019

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00082	0.00080	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00095	0.00092	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00062	0.00061	rare
South Asian	0.00088	0.00085	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: In the kidney glomerulus may play a role in linking podocyte foot processes to the glomerular basement membrane. May be involved in stabilization of F-actin by attenuating its depolymerization. Can recruit TGFB1I1 from focal adhesions to podocyte lamellipodia.;

Recessive Scores

pRec: 0.0910

Intolerance Scores

LoFtool: 0.614
RVIS EVS: -0.82
RVIS percentile EVS: 11.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.310

Gene Damage Prediction

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