PPHLN1

protein-coding

periphilin 1

Gene summary

The protein encoded by this gene is one of the several proteins that become sequentially incorporated into the cornified cell envelope during the terminal differentiation of keratinocyte at the outer layers of epidermis. This protein interacts with periplakin, which is known as a precursor of the cornified cell envelope. The cellular localization pattern and insolubility of this protein suggest that it may play a role in epithelial differentiation and contribute to epidermal integrity and barrier formation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

MANE transcript

NM_201439.2

Inheritance

—

ClinVar variants

U:49B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr12:42,238,447-42,459,715

External References & Databases

Ensembl (ENSG00000134283)

Transcript & Mutation Effects

hg38 • Region Span ~221.3 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 PPHLN1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 44

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_201439.2. 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						0
missense			47 clinvar	1 clinvar		48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	49	1	0	50

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 136 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_201439.2	RefSeq	NP_958847.1	9	MANE Select
ENST00000358314.12	Ensembl	ENSP00000351066.7	9	MANE Select
NM_001143787.2	RefSeq	NP_001137259.1	11	Standard
NM_001143788.2	RefSeq	NP_001137260.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

keratinization
negative regulation of transcription, DNA-templated

Molecular Function

RNA binding
protein binding

Cellular Component

nucleoplasm
chromosome
Golgi apparatus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000395568
Coding exons: 12
Length: 221269
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.762	224	258	0.867	0.0000146	2952
Missense (PolyPhen)		36	53.118	0.67773		715
Synonymous	0.229	88	90.8	0.969	0.00000506	869
Loss of Function	2.26	17	30.5	0.557	0.00000186	339

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the HUSH complex, a multiprotein complex that mediates epigenetic repression. The HUSH complex is recruited to genomic loci rich in H3K9me3 and is probably required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3. In the HUSH complex, contributes to the maintenance of the complex at chromatin (PubMed:26022416). Acts as a transcriptional corepressor and regulates the cell cycle, probably via the HUSH complex (PubMed:15474462, PubMed:17963697). May be involved in epithelial differentiation by contributing to epidermal integrity and barrier formation (Probable). {ECO:0000269|PubMed:15474462, ECO:0000269|PubMed:17963697, ECO:0000269|PubMed:26022416, ECO:0000305|PubMed:12853457}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.0364
RVIS EVS: -0.25
RVIS percentile EVS: 36.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.768

Gene Damage Prediction

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