PLEKHF2

protein-coding

pleckstrin homology and FYVE domain containing 2, the group of Zinc fingers FYVE-type|Pleckstrin homology domain containing

Gene summary

Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in endosome organization and endosome to lysosome transport. Located in transport vesicle. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_024613.4

Inheritance

—

ClinVar variants

U:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr8:95,115,642-95,156,698

External References & Databases

Ensembl (ENSG00000175895)

Transcript & Mutation Effects

hg38 • Region Span ~41.1 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 PLEKHF2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 13

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024613.4. 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						0
missense			13 clinvar			13
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	13	0	0	13

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024613.4	RefSeq	NP_078889.1	1	MANE Select
ENST00000315367.4	Ensembl	ENSP00000322373.3	1	MANE Select
ENST00000519516.1	Ensembl	ENSP00000427792.1	1	Standard
ENST00000519516.2	Ensembl	ENSP00000427792.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein transport

Molecular Function

protein binding
phosphatidylinositol binding
metal ion binding

Cellular Component

endoplasmic reticulum
transport vesicle
early endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315367
Coding exons: 1
Length: 22881
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.88	76	138	0.549	0.00000747	1659
Missense (PolyPhen)		21	63.929	0.32849		762
Synonymous	1.76	31	46.2	0.671	0.00000221	474
Loss of Function	2.38	0	6.60	0.00	3.80e-7	94

Population LoF Frequency

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

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in early endosome fusion upstream of RAB5, hence regulating receptor trafficking and fluid-phase transport. Enhances cellular sensitivity to TNF-induced apoptosis (PubMed:18288467). {ECO:0000269|PubMed:18288467, ECO:0000269|PubMed:19995552, ECO:0000269|PubMed:22816767}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

RVIS EVS: -0.12
RVIS percentile EVS: 44.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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