PLEKHA3

protein-coding

pleckstrin homology domain containing A3, the group of Pleckstrin homology domain containing

Gene summary

Enables identical protein binding activity; molecular carrier activity; and phosphatidylinositol-4-phosphate binding activity. Predicted to be involved in endosome organization; receptor recycling; and retrograde transport, endosome to Golgi. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_019091.4

Inheritance

—

ClinVar variants

P:1U:22B:1

Top phenotype

Hypercholesterolemia, familial, 1

gnomAD constraint

pLI —, LoF o/e 0.35

Max pathogenic AF

—

Genomic locus

chr2:178,480,457-178,516,463

External References & Databases

Ensembl (ENSG00000116095)

Transcript & Mutation Effects

hg38 • Region Span ~36.0 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 PLEKHA3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 22

Hypercholesterolemia, familial, 1Total: 1

TTN-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019091.4. 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			1 clinvar			1
missense	1 clinvar		21 clinvar	1 clinvar		23
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	22	1	0	24

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019091.4	RefSeq	NP_061964.3	8	MANE Select
ENST00000234453.10	Ensembl	ENSP00000234453.4	8	MANE Select
ENST00000421187.1	Ensembl	ENSP00000396136.1	4	Standard
ENST00000453653.5	Ensembl	ENSP00000416186.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
Synthesis of PIPs at the plasma membrane
PI Metabolism
Phospholipid metabolism

Biological Process

phosphatidylinositol biosynthetic process
biological_process
ER to Golgi ceramide transport
ceramide transport
intermembrane lipid transfer

Molecular Function

lipid binding
phosphatidylinositol-4-phosphate binding
ceramide 1-phosphate binding
ceramide 1-phosphate transporter activity

Cellular Component

Golgi membrane
Golgi apparatus
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000234453
Coding exons: 8
Length: 35995
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125729
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.41	108	158	0.685	0.00000784	1978
Missense (PolyPhen)		25	53.895	0.46387		686
Synonymous	1.18	42	52.9	0.794	0.00000269	550
Loss of Function	2.47	6	17.0	0.353	9.74e-7	206

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in Golgi to cell surface membrane traffic. Induces membrane tubulation. Binds preferentially to phosphatidylinositol 4-phosphate (PtdIns4P). {ECO:0000269|PubMed:15107860}.;

Recessive Scores

pRec: 0.127

Intolerance Scores

LoFtool: 0.759
RVIS EVS: -0.12
RVIS percentile EVS: 44.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.336

Gene Damage Prediction

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