LORICRIN

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

Basic information

Region (hg38): 1:153259687-153262124

Previous symbols: [ "LOR" ]

Links

ENSG00000203782 ∙ NCBI:4014 ∙ OMIM:152445 ∙ HGNC:6663 ∙ Uniprot:P23490 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• loricrin keratoderma (Strong), mode of inheritance: AD
• loricrin keratoderma (Supportive), mode of inheritance: AD
• loricrin keratoderma (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vohwinkel syndrome, variant form	AD	General	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	Dermatologic	8673107; 9326323; 9326398; 16403113

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LORICRIN gene.

• Loricrin keratoderma (2 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LORICRIN gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	5	10
missense			38	4	6	48
nonsense		2	1			3
start loss						0
frameshift	3	1				4
inframe indel			6	3	3	12
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	3	3	45	12	14

Variants in LORICRIN

This is a list of pathogenic ClinVar variants found in the LORICRIN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-153261004-A-G		not specified	Uncertain significance (Dec 06, 2023)
1-153261010-GGCGGCGGTGGCGGTGGCGGCGGCA-G			Uncertain significance (May 04, 2022)
1-153261012-C-CGGCGGT			Benign (Jan 29, 2024)
1-153261012-C-CGGCGGTGGCGGT			Likely benign (Apr 13, 2022)
1-153261016-G-A		not specified	Uncertain significance (Feb 15, 2023)
1-153261024-T-TGGCGGCGGC			Uncertain significance (Jan 05, 2023)
1-153261031-G-A			Uncertain significance (Mar 11, 2023)
1-153261034-A-G			Benign (Jan 29, 2024)
1-153261052-G-A		not specified	Uncertain significance (May 15, 2024)
1-153261059-T-TCGG		Loricrin keratoderma	Conflicting classifications of pathogenicity (Nov 27, 2023)
1-153261064-G-C		not specified	Uncertain significance (Aug 26, 2022)
1-153261070-G-T		not specified	Uncertain significance (Aug 17, 2022)
1-153261091-G-T		not specified	Uncertain significance (Jun 18, 2024)
1-153261093-T-C			Benign (Feb 01, 2023)
1-153261102-C-T			Benign (Jan 25, 2024)
1-153261124-T-C		not specified	Uncertain significance (Jun 23, 2023)
1-153261129-T-G			Likely benign (Sep 01, 2023)
1-153261139-T-G			Uncertain significance (Oct 03, 2023)
1-153261179-T-C		not specified	Likely benign (Oct 21, 2021)
1-153261202-G-C		not specified	Uncertain significance (Jan 10, 2023)
1-153261204-T-A			Likely benign (Mar 29, 2018)
1-153261209-G-A		not specified	Uncertain significance (Dec 28, 2022)
1-153261218-A-ACTCCGGCGGCGGCGGCTC			Uncertain significance (Jul 28, 2023)
1-153261220-T-A		not specified	Uncertain significance (Jan 09, 2024)
1-153261221-C-G		not specified	Conflicting classifications of pathogenicity (Dec 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LORICRIN	protein_coding	protein_coding	ENST00000368742	1	2423

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.335	0.610	117110	0	6	117116	0.0000256

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.874	141	115	1.23	0.00000565	1903
Missense in Polyphen		6	1.5791	3.7995		41
Synonymous	-0.332	57	53.9	1.06	0.00000272	724
Loss of Function	1.49	1	4.36	0.230	1.89e-7	62

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000311	0.000309
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000292	0.0000285
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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.
• Pathway: Keratinization;Developmental Biology;Formation of the cornified envelope (Consensus)

Haploinsufficiency Scores

• pHI: 0.213
• hipred: N
• hipred_score: 0.238
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.579

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lor
• Phenotype: immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cytoskeleton organization;peptide cross-linking;keratinocyte differentiation;cornification
• Cellular component: cornified envelope;nucleoplasm;cytoplasm;cytosol
• Molecular function: structural molecule activity;structural constituent of cytoskeleton;protein binding;structural constituent of epidermis;protein binding, bridging