PHLDB1

protein-coding

pleckstrin homology like domain family B member 1, the group of Pleckstrin homology domain containing|MicroRNA protein coding host genes

Gene summary

Involved in basement membrane organization. Located in basal cortex. Implicated in osteogenesis imperfecta. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001144758.3

Inheritance

ClinVar variants

P:2U:212B:12

Top phenotype

Osteogenesis imperfecta, type XXIII

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr11:118,606,440-118,658,031

External References & Databases

Ensembl (ENSG00000019144)

Transcript & Mutation Effects

hg38 • Region Span ~51.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

osteogenesis imperfecta, type 23MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957988

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Osteogenesis imperfecta, type XXIIIAR

Manifestation: Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: The use of bisphosphonates has been described as beneficial

Refs: 36543534

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PHLDB1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 199

not providedTotal: 13

Osteogenesis imperfecta, type 23Total: 2

Diamond-Blackfan anemia 9Total: 1

PHLDB1-related conditionTotal: 1

Bardet-Biedl syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001144758.3. 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			2 clinvar	5 clinvar	1 clinvar	8
missense			208 clinvar	5 clinvar	1 clinvar	214
nonsense						0
start loss						0
frameshift	2 clinvar					2
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	2	0	212	10	2	226

Highest pathogenic variant AF is 6.840853e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 160 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001144758.3	RefSeq	NP_001138230.1	22	MANE Select
ENST00000600882.6	Ensembl	ENSP00000469820.1	22	MANE Select
NM_001144759.3	RefSeq	NP_001138231.1	20	Standard
NM_015157.4	RefSeq	NP_055972.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of gastrulation
regulation of epithelial to mesenchymal transition
regulation of microtubule cytoskeleton organization
positive regulation of basement membrane assembly involved in embryonic body morphogenesis

Cellular Component

basal cortex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361417
Coding exons: 22
Length: 51587
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.47	732	853	0.858	0.0000558	8763
Missense (PolyPhen)		212	268.52	0.78952		2674
Synonymous	0.726	316	333	0.949	0.0000189	2991
Loss of Function	5.53	15	62.0	0.242	0.00000349	676

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.122

Intolerance Scores

LoFtool: 0.650
RVIS EVS: -1.85
RVIS percentile EVS: 2.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.261

Gene Damage Prediction

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