PLEKHA5

protein-coding

pleckstrin homology domain containing A5, the group of Pleckstrin homology domain containing

Gene summary

Predicted to enable phosphatidylinositol phosphate binding activity. Predicted to act upstream of or within reproductive system development. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001256470.2

Inheritance

ClinVar variants

P:2U:151B:28

Top phenotype

PLEKHA5-related disorder

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr12:19,129,669-19,376,400

External References & Databases

Ensembl (ENSG00000052126)

Transcript & Mutation Effects

hg38 • Region Span ~246.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cleft lip/palateMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0016044

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLEKHA5 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 131

PLEKHA5-related disorderTotal: 30

not providedTotal: 5

Cleft lip with or without cleft palateTotal: 5

Bilateral cleft lipTotal: 1

Hypercholesterolemia, familial, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001256470.2. 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			2 clinvar	14 clinvar	2 clinvar	18
missense		1 clinvar	138 clinvar	8 clinvar	4 clinvar	151
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	1	1	151	22	6	181

Highest pathogenic variant AF is 0.000005502154

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 166 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001256470.2	RefSeq	NP_001243399.1	31	MANE Select
ENST00000429027.7	Ensembl	ENSP00000404296.2	31	MANE Select
NM_001143821.3	RefSeq	NP_001137293.2	27	Standard
NM_001190860.3	RefSeq	NP_001177789.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
EGFR1
Synthesis of PIPs at the plasma membrane
PI Metabolism

Biological Process

biological_process
reproductive system development

Molecular Function

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

Cellular Component

nucleoplasm
cytosol
postsynaptic density
membrane
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000429027
Coding exons: 31
Length: 246687
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125743
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.24	580	670	0.865	0.0000344	8389
Missense (PolyPhen)		217	295.73	0.73379		3659
Synonymous	1.33	211	237	0.890	0.0000126	2370
Loss of Function	7.93	3	79.0	0.0380	0.00000429	953

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000073	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0968

Intolerance Scores

LoFtool: 0.273
RVIS EVS: -0.42
RVIS percentile EVS: 25.79

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.745

Gene Damage Prediction

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