LIPN
protein-codinglipase family member N, the group of Lipases
Gene summary
The gene encodes a lipase that is highly expressed in granular keratinocytes in the epidermis, and plays a role in the differentiation of keratinocytes. Mutations in this gene are associated with lamellar ichthyosis type 4. [provided by RefSeq, Dec 2011]
- LIPL4
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013495
Submitter: G2P
Inheritance Pattern: AR
Disease ID:MONDO:0013495
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0017778
Submitter: Orphanet
Inheritance Pattern: Unknown
Disease ID:MONDO:0013495
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
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
Comments: There are suggestions that treatment may be tailored by more precise (ie, genetic) diagnosis
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LIPN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001102469.2. 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 | 1 | 4 | 3 | 8 | ||
| missense | 70 | 6 | 2 | 78 | ||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | 1 | 3 | ||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 1 | 77 | 11 | 5 | 94 |
Highest pathogenic variant AF is 0.00002425533
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001095939.1 | 9 | MANE Select | |
| Ensembl | ENSP00000383923.1 | 9 | MANE Select | |
| Ensembl | ENSP00000761333.1 | 6 | Standard | |
| RefSeq | XP_005270106.1 | 9 | Standard |
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
- lipid catabolic process
- cellular lipid metabolic process
- cornification
Molecular Function
- lipoprotein lipase activity
- lipase activity
Cellular Component
- extracellular region
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000404459
- Coding exons
- 9
- Length
- 16837
- Individuals with no LoFs
- 124501
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 93
- Defined
- 124594
- p
- 0.000373
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0970 | 211 | 207 | 1.02 | 0.00000995 | 2626 |
| Missense (PolyPhen) | 78 | 79.935 | 0.97579 | 1046 | ||
| Synonymous | 0.657 | 63 | 70.0 | 0.900 | 0.00000336 | 709 |
| Loss of Function | 1.75 | 10 | 18.0 | 0.554 | 8.43e-7 | 237 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00013 | rare |
| Latino/Admixed American | 0.00056 | 0.00055 | rare |
| Ashkenazi Jewish | 0.0030 | 0.0030 | notable |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00019 | 0.00019 | rare |
| European (Non-Finnish) | 0.00031 | 0.00028 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0.00050 | 0.00050 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a highly specific role in the last step of keratinocyte differentiation. May have an essential function in lipid metabolism of the most differentiated epidermal layers. {ECO:0000269|PubMed:17562024}.;
- Disease
- DISEASE: Ichthyosis, congenital, autosomal recessive 8 (ARCI8) [MIM:613943]: A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs. {ECO:0000269|PubMed:21439540}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.686
- RVIS EVS
- 0.6
- RVIS percentile EVS
- 82.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.134
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |