PLEKHA4

protein-coding

pleckstrin homology domain containing A4, the group of Pleckstrin homology domain containing

Gene summary

This gene encodes a pleckstrin homology (PH) domain-containing protein. The PH domain is found near the N-terminus and contains a putative phosphatidylinositol 3, 4, 5-triphosphate-binding motif (PPBM). Elevated expression of this gene has been observed in some melanomas. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

MANE transcript

NM_020904.3

Inheritance

—

ClinVar variants

U:172B:6

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr19:48,837,092-48,868,617

External References & Databases

Ensembl (ENSG00000105559)

Transcript & Mutation Effects

hg38 • Region Span ~31.5 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 PLEKHA4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 161

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020904.3. 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			3 clinvar	2 clinvar		5
missense			163 clinvar	4 clinvar		167
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	172	6	0	178

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020904.3	RefSeq	NP_065955.2	19	MANE Select
ENST00000263265.11	Ensembl	ENSP00000263265.5	19	MANE Select
NM_001161354.2	RefSeq	NP_001154826.1	15	Standard
NM_001438306.1	RefSeq	NP_001425235.1	19	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

Molecular Function

phosphatidylinositol-3-phosphate binding

Cellular Component

cellular_component
cytoplasm
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263265
Coding exons: 19
Length: 31536
Individuals with no LoFs: 125620
Homozygous LoFs: 0
Heterozygous LoFs: 127
Defined: 125747
p: 0.000505

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.610	456	494	0.923	0.0000320	4848
Missense (PolyPhen)		136	158.36	0.85883		1534
Synonymous	0.153	199	202	0.986	0.0000126	1747
Loss of Function	2.50	26	43.9	0.592	0.00000268	424

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00071	0.00068	rare
Latino/Admixed American	0.00036	0.00035	rare
Ashkenazi Jewish	0.00022	0.00020	rare
East Asian	0.00044	0.00044	rare
Finnish	0.00025	0.00023	rare
European (Non-Finnish)	0.00050	0.00048	rare
South Asian	0.00099	0.00098	rare
Other	0.00069	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds specifically to phosphatidylinositol 3-phosphate (PtdIns3P), but not to other phosphoinositides. {ECO:0000269|PubMed:11001876}.;

Recessive Scores

pRec: 0.0835

Intolerance Scores

LoFtool: 0.916
RVIS EVS: 0.03
RVIS percentile EVS: 55.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.988

Gene Damage Prediction

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