IVL

protein-coding

involucrin, the group of Cornified envelope precursor family

Gene summary

Involucrin, a component of the keratinocyte crosslinked envelope, is found in the cytoplasm and crosslinked to membrane proteins by transglutaminase. This gene is mapped to 1q21, among calpactin I light chain, trichohyalin, profillaggrin, loricrin, and calcyclin. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005547.4

Inheritance

—

ClinVar variants

U:121B:27

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e —

Max pathogenic AF

—

Genomic locus

chr1:152,908,546-152,911,886

External References & Databases

Ensembl (ENSG00000163207)

Transcript & Mutation Effects

hg38 • Region Span ~3.3 kb

Loading mutation effect viewer...

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 IVL variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 127

not providedTotal: 22

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005547.4. 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				10 clinvar	4 clinvar	14
missense			121 clinvar	8 clinvar	4 clinvar	133
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	121	19	8	148

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005547.4	RefSeq	NP_005538.2	1	MANE Select
ENST00000368764.4	Ensembl	ENSP00000357753.3	1	MANE Select
ENST00001145455.1	Ensembl	ENSP00000809455.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Corticotropin-releasing hormone signaling pathway
Hair Follicle Development- Induction (Part 1 of 3)
Keratinization
Developmental Biology
Formation of the cornified envelope

Biological Process

response to UV-B
peptide cross-linking
isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine
keratinocyte differentiation
cornification

Molecular Function

structural molecule activity
protein binding
protein binding, bridging

Cellular Component

cornified envelope
cytoplasm
centrosome
cytosol
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368764
Coding exons: 1
Length: 3342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.37	355	250	1.42	0.0000109	3772
Missense (PolyPhen)		50	44.232	1.1304		710
Synonymous	-0.958	127	114	1.11	0.00000524	1028
Loss of Function

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia.;

Intolerance Scores

LoFtool: 0.945
RVIS EVS: 0.53
RVIS percentile EVS: 81.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.211

Gene Damage Prediction

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