POSTN

protein-coding

periostin, the group of Gla domain containing

Gene summary

This gene encodes a secreted extracellular matrix protein that functions in tissue development and regeneration, including wound healing, and ventricular remodeling following myocardial infarction. The encoded protein binds to integrins to support adhesion and migration of epithelial cells. This protein plays a role in cancer stem cell maintenance and metastasis. Mice lacking this gene exhibit cardiac valve disease, and skeletal and dental defects. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2015]

MANE transcript

NM_006475.3

Inheritance

—

ClinVar variants

U:122B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr13:37,562,583-37,598,844

External References & Databases

Ensembl (ENSG00000133110)

Transcript & Mutation Effects

hg38 • Region Span ~36.3 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 POSTN variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 111

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006475.3. 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	1 clinvar	3 clinvar	6
missense			114 clinvar	4 clinvar	1 clinvar	119
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	122	5	4	131

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 50 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006475.3	RefSeq	NP_006466.2	23	MANE Select
ENST00000379747.9	Ensembl	ENSP00000369071.4	23	MANE Select
NM_001135934.2	RefSeq	NP_001129406.1	21	Standard
NM_001135935.2	RefSeq	NP_001129407.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Hypothesized Pathways in Pathogenesis of Cardiovascular Disease
Amplification and Expansion of Oncogenic Pathways as Metastatic Traits

Biological Process

skeletal system development
response to hypoxia
negative regulation of cell-matrix adhesion
regulation of systemic arterial blood pressure
cell adhesion

Molecular Function

extracellular matrix structural constituent
protein binding
heparin binding
metal ion binding
cell adhesion molecule binding

Cellular Component

extracellular space
trans-Golgi network
extracellular matrix
neuromuscular junction
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379747
Coding exons: 23
Length: 36262
Individuals with no LoFs: 125652
Homozygous LoFs: 0
Heterozygous LoFs: 96
Defined: 125748
p: 0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.852	393	443	0.886	0.0000225	5479
Missense (PolyPhen)		151	186.67	0.8089		2295
Synonymous	-0.617	166	156	1.06	0.00000850	1565
Loss of Function	3.00	22	43.3	0.508	0.00000219	570

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00031	rare
Latino/Admixed American	0.000094	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00028	0.00027	rare
Finnish	0.0016	0.0016	notable
European (Non-Finnish)	0.00031	0.00031	rare
South Asian	0.00034	0.00033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Induces cell attachment and spreading and plays a role in cell adhesion (PubMed:12235007). Enhances incorporation of BMP1 in the fibronectin matrix of connective tissues, and subsequent proteolytic activation of lysyl oxidase LOX (By similarity). {ECO:0000250|UniProtKB:Q62009, ECO:0000269|PubMed:12235007}.;

Recessive Scores

pRec: 0.744

Intolerance Scores

LoFtool: 0.0534
RVIS EVS: 0.27
RVIS percentile EVS: 70.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.198

Gene Damage Prediction

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