GeneBe

LORICRIN

protein-coding

loricrin cornified envelope precursor protein, the group of Cornified envelope precursor family

Gene summary

This gene encodes loricrin, a major protein component of the cornified cell envelope found in terminally differentiated epidermal cells. Mutations in this gene are associated with Vohwinkel's syndrome and progressive symmetric erythrokeratoderma, both inherited skin diseases. [provided by RefSeq, Jul 2008]

Previous symbols:
  • LOR

MANE transcript

NM_000427.3

Inheritance

AD

ClinVar variants

P:8U:88B:27

Top phenotype

Vohwinkel syndrome, variant form

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr1:153,259,687-153,262,124

External References & Databases

Ensembl (ENSG00000203782)NCBI Gene (4014)OMIM (152445)HGNC:6663GenCCUniProt (P23490)AlphaFoldClinVar (LORICRIN)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~2.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

loricrin keratodermaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011396

Submitter: Labcorp Genetics (formerly Invitae)

loricrin keratodermaSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011396

Submitter: Orphanet

loricrin keratodermaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011396

Submitter: PanelApp Australia

loricrin keratodermaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011396

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Vohwinkel syndrome, variant formAD

Manifestation: Dermatologic

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

Refs: 8673107; 9326323; 9326398; 16403113Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LORICRIN variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 81
not providedTotal: 62
Loricrin keratodermaTotal: 9
LOR-related disordersTotal: 2
Moyamoya angiopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000427.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
11
clinvar
2
clinvar
 14
missense
84
clinvar
11
clinvar
3
clinvar
 98
nonsense
2
clinvar
1
clinvar
 3
start loss
0
frameshift
4
clinvar
2
clinvar
2
clinvar
 8
splice donor/acceptor (+/-2bp)
0
Total4488225123

Highest pathogenic variant AF is 0.000010525153

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000427.3RefSeqNP_000418.21MANE Select
ENST00000368742.4EnsemblENSP00000357731.31MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Keratinization
  • Developmental Biology
  • Formation of the cornified envelope

Biological Process

  • cytoskeleton organization
  • peptide cross-linking
  • keratinocyte differentiation
  • cornification

Molecular Function

  • structural molecule activity
  • structural constituent of cytoskeleton
  • protein binding
  • structural constituent of epidermis
  • protein binding, bridging

Cellular Component

  • cornified envelope
  • nucleoplasm
  • cytoplasm
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000368742
Coding exons
1
Length
2423
Individuals with no LoFs
117110
Homozygous LoFs
0
Heterozygous LoFs
6
Defined
117116
p
0.0000256
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.8741411151.230.000005651903
Missense (PolyPhen)61.57913.799541
Synonymous-0.3325753.91.060.00000272724
Loss of Function1.4914.360.2301.89e-762

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.000310.00031rare
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000290.000029rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Major keratinocyte cell envelope protein.;
Disease
DISEASE: Vohwinkel syndrome with ichthyosis (VSI) [MIM:604117]: A variant form of Vohwinkel syndrome without hearing loss and associated with ichthyosiform dermatosis. Clinical features include palmoplantar keratoderma, pseudoainhum and ichthyosis. Compact hyperkeratosis with round retained nuclei and hypergranulosis is observed on skin biopsies. {ECO:0000269|PubMed:12072018, ECO:0000269|PubMed:12615358, ECO:0000269|PubMed:9326323}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.579

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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