PADI1

protein-coding

peptidyl arginine deiminase 1, the group of Peptidyl arginine deiminases

Gene summary

This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. The type I enzyme is involved in the late stages of epidermal differentiation, where it deiminates filaggrin and keratin K1, which maintains hydration of the stratum corneum, and hence the cutaneous barrier function. This enzyme may also play a role in hair follicle formation. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]

MANE transcript

NM_013358.3

Inheritance

—

ClinVar variants

U:113B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr1:17,205,128-17,246,007

External References & Databases

Ensembl (ENSG00000142623)

Transcript & Mutation Effects

hg38 • Region Span ~40.9 kb

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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 PADI1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 117

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013358.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			112 clinvar	6 clinvar	1 clinvar	119
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	113	7	1	121

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013358.3	RefSeq	NP_037490.2	16	MANE Select
ENST00000375471.5	Ensembl	ENSP00000364620.4	16	MANE Select
ENST00001140326.1	Ensembl	ENSP00000810547.1	16	Standard
XM_011541307.3	RefSeq	XP_011539609.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Chromatin modifying enzymes
Chromatin organization
protein citrullination

Biological Process

protein citrullination
histone citrullination

Molecular Function

protein-arginine deiminase activity
calcium ion binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375471
Coding exons: 16
Length: 40880
Individuals with no LoFs: 125197
Homozygous LoFs: 1
Heterozygous LoFs: 550
Defined: 125748
p: 0.00219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.05	446	388	1.15	0.0000222	4345
Missense (PolyPhen)		205	183.5	1.1172		2047
Synonymous	-1.56	185	160	1.16	0.00000962	1285
Loss of Function	0.948	26	31.8	0.818	0.00000151	373

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00099	0.00098	rare
Latino/Admixed American	0.0013	0.0013	notable
Ashkenazi Jewish	0.0028	0.0028	notable
East Asian	0.0023	0.0023	notable
Finnish	0.0064	0.0064	notable
European (Non-Finnish)	0.0022	0.0022	notable
South Asian	0.00059	0.00059	rare
Other	0.0028	0.0028	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the deimination of arginine residues of proteins. {ECO:0000269|PubMed:12416996, ECO:0000269|PubMed:27393304}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.875
RVIS EVS: -0.46
RVIS percentile EVS: 23.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.488

Gene Damage Prediction

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