PHLDA3

protein-coding

pleckstrin homology like domain family A member 3

Gene summary

Enables phosphatidylinositol phosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; and positive regulation of apoptotic process. Located in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_012396.5

Inheritance

—

ClinVar variants

U:19

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.29

Max pathogenic AF

—

Genomic locus

chr1:201,464,278-201,469,237

External References & Databases

Ensembl (ENSG00000174307)

Transcript & Mutation Effects

hg38 • Region Span ~5.0 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 PHLDA3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012396.5. 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			18 clinvar			18
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	19	0	0	19

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012396.5	RefSeq	NP_036528.1	1	MANE Select
ENST00000367311.5	Ensembl	ENSP00000356280.3	1	MANE Select
ENST00000367309.1	Ensembl	ENSP00000356278.1	1	Standard
ENST00000367309.2	Ensembl	ENSP00000356278.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

anatomical structure morphogenesis
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
positive regulation of apoptotic process
negative regulation of protein kinase B signaling

Molecular Function

phosphatidylinositol-4,5-bisphosphate binding
phosphatidylinositol-3,4,5-trisphosphate binding
phosphatidylinositol-5-phosphate binding
phosphatidylinositol-3-phosphate binding
phosphatidylinositol-3,4-bisphosphate binding

Cellular Component

cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367311
Coding exons: 1
Length: 3746
Individuals with no LoFs: 125658
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125689
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.150	75	78.8	0.952	0.00000370	802
Missense (PolyPhen)		26	23.962	1.0851		268
Synonymous	-2.03	55	38.9	1.41	0.00000182	287
Loss of Function	1.21	1	3.41	0.294	1.46e-7	35

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	0.0014	0.0014	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: p53/TP53-regulated repressor of Akt/AKT1 signaling. Represses AKT1 by preventing AKT1-binding to membrane lipids, thereby inhibiting AKT1 translocation to the cellular membrane and activation. Contributes to p53/TP53-dependent apoptosis by repressing AKT1 activity. Its direct transcription regulation by p53/TP53 may explain how p53/TP53 can negatively regulate AKT1. May act as a tumor suppressor. {ECO:0000269|PubMed:19203586}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.114
RVIS EVS: 0.17
RVIS percentile EVS: 65.33

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	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium