ASPRV1

protein-coding

aspartic peptidase retroviral like 1, the group of Gag like LTR retrotransposon derived genes|Peptidase family A28

Gene summary

Filaggrin is a structural protein that is crucial for in the development and maintenance of the skin barrier. This gene encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. Expression is found primarily in the epidermis and inner root sheath of hair follicles. [provided by RefSeq, May 2017]

MANE transcript

NM_152792.4

Inheritance

ClinVar variants

P:3U:40B:8

Top phenotype

Ichythosis, lamellar, autosomal dominant

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr2:69,960,089-69,961,631

External References & Databases

Ensembl (ENSG00000244617)

Transcript & Mutation Effects

hg38 • Region Span ~1.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ichthyosis, lamellar, autosomal dominantMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007812

Submitter: Ambry Genetics

ichthyosis, lamellar, autosomal dominantSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007812

Submitter: PanelApp Australia

ichthyosis, lamellar, autosomal dominantMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007812

Submitter: G2P

Clinical Genomic Database (CGD)

Ichythosis, lamellar, autosomal dominantAD

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: 32516568

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ASPRV1 variants in ClinVar

5 Conditions Cataloged

Inborn genetic diseasesTotal: 43

Autosomal dominant lamellar ichthyosisTotal: 4

not specifiedTotal: 2

ASPRV1-related conditionTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152792.4. 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				2 clinvar		2
missense	3 clinvar		39 clinvar	6 clinvar		48
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	3	0	40	8	0	51

Highest pathogenic variant AF is 6.840488e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152792.4	RefSeq	NP_690005.3	1	MANE Select
ENST00000320256.6	Ensembl	ENSP00000315383.5	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

protein processing
skin development

Molecular Function

aspartic-type endopeptidase activity

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000320256
Coding exons: 1
Length: 2172
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.130	192	197	0.974	0.0000110	2229
Missense (PolyPhen)		54	66.742	0.80909		831
Synonymous	-1.26	106	90.8	1.17	0.00000551	738
Loss of Function	1.07	4	7.07	0.566	3.68e-7	80

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

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.392
RVIS EVS: -0.25
RVIS percentile EVS: 36.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0283

Gene Damage Prediction

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