PADI3

protein-coding

peptidyl arginine deiminase 3, the group of Peptidyl arginine deiminases|MicroRNA protein coding host genes

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 III enzyme modulates hair structural proteins, such as filaggrin in the hair follicle and trichohyalin in the inner root sheath, during hair follicle formation. Together with the type I enzyme, this enzyme may also play a role in terminal differentiation of the epidermis. This gene exists in a cluster with four other paralogous genes. [provided by RefSeq, Jul 2008]

MANE transcript

NM_016233.2

Inheritance

ClinVar variants

P:11U:124B:16

Top phenotype

Uncombable hair syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr1:17,249,098-17,284,233

External References & Databases

Ensembl (ENSG00000142619)

Transcript & Mutation Effects

hg38 • Region Span ~35.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

uncombable hair syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0008621

Submitter: Orphanet

uncombable hair syndrome 1LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0020736

Submitter: Labcorp Genetics (formerly Invitae)

uncombable hair syndrome 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020736

Submitter: Ambry Genetics

uncombable hair syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020736

Submitter: PanelApp Australia

uncombable hair syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020736

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

uncombable hair syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020736

Submitter: G2P

Clinical Genomic Database (CGD)

Uncombable hair syndrome 1AR

Manifestation: Dermatologic

Intervention: General

Rationale: The clinical relevance of the condition is unclear

Refs: 27866708

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PADI3 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 123

not providedTotal: 12

PADI3-related disorderTotal: 12

not specifiedTotal: 7

Central centrifugal cicatricial alopeciaTotal: 6

Uncombable hair syndrome 1Total: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016233.2. 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			2 clinvar	8 clinvar	1 clinvar	11
missense	4 clinvar	4 clinvar	122 clinvar	6 clinvar	1 clinvar	137
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	2 clinvar					2
Total	6	5	124	14	2	151

Highest pathogenic variant AF is 0.007560879

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016233.2	RefSeq	NP_057317.2	16	MANE Select
ENST00000375460.3	Ensembl	ENSP00000364609.3	16	MANE Select
ENST00001069418.1	Ensembl	ENSP00000739224.1	2	Standard
XM_011541571.3	RefSeq	XP_011539873.1	15	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
identical protein binding

Cellular Component

nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000375460
Coding exons: 16
Length: 35136
Individuals with no LoFs: 125563
Homozygous LoFs: 0
Heterozygous LoFs: 185
Defined: 125748
p: 0.000736

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.169	400	410	0.977	0.0000248	4379
Missense (PolyPhen)		136	143.89	0.9452		1599
Synonymous	0.365	167	173	0.965	0.0000110	1298
Loss of Function	1.81	20	30.8	0.649	0.00000140	354

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0016	0.0016	notable
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00033	0.00032	rare
European (Non-Finnish)	0.00078	0.00077	rare
South Asian	0.0016	0.0016	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the deimination of arginine residues of proteins. {ECO:0000269|PubMed:27866708}.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.908
RVIS EVS: 1.85
RVIS percentile EVS: 97.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.119

Gene Damage Prediction

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