PHLDB2

protein-coding

pleckstrin homology like domain family B member 2, the group of Pleckstrin homology domain containing

Gene summary

Enables cadherin binding activity. Involved in several processes, including basement membrane organization; negative regulation of cellular component organization; and negative regulation of wound healing, spreading of epidermal cells. Located in several cellular components, including basal cortex; focal adhesion; and podosome. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001134438.2

Inheritance

—

ClinVar variants

U:166B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr3:111,732,497-111,976,517

External References & Databases

Ensembl (ENSG00000144824)

Transcript & Mutation Effects

hg38 • Region Span ~244.0 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 PHLDB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 161

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001134438.2. 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			1 clinvar		2 clinvar	3
missense			159 clinvar	5 clinvar	5 clinvar	169
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	166	5	7	178

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 123 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001134438.2	RefSeq	NP_001127910.1	17	MANE Select
ENST00000431670.7	Ensembl	ENSP00000405405.2	17	MANE Select
NM_001134437.2	RefSeq	NP_001127909.1	17	Standard
NM_001134439.2	RefSeq	NP_001127911.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in muscle cell - TarBase
Regulation of Microtubule Cytoskeleton
EGFR1

Biological Process

microtubule cytoskeleton organization
regulation of gastrulation
regulation of epithelial to mesenchymal transition
establishment of protein localization
negative regulation of stress fiber assembly

Molecular Function

protein binding
cadherin binding

Cellular Component

cytosol
plasma membrane
focal adhesion
cell leading edge
intermediate filament cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000431670
Coding exons: 17
Length: 244021
Individuals with no LoFs: 125661
Homozygous LoFs: 0
Heterozygous LoFs: 87
Defined: 125748
p: 0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.376	650	678	0.959	0.0000367	8277
Missense (PolyPhen)		164	181.05	0.90585		2141
Synonymous	-0.674	261	248	1.05	0.0000130	2367
Loss of Function	4.01	23	55.1	0.417	0.00000297	706

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00030	0.00029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00028	0.00027	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00041	0.00040	rare
South Asian	0.00050	0.00049	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Seems to be involved in the assembly of the postsynaptic apparatus. May play a role in acetyl-choline receptor (AChR) aggregation in the postsynaptic membrane (By similarity). {ECO:0000250, ECO:0000269|PubMed:12376540}.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.801
RVIS EVS: 0.48
RVIS percentile EVS: 78.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.963

Gene Damage Prediction

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