CELA2A

protein-coding

chymotrypsin like elastase 2A, the group of Chymotrypsin like elastases

Gene summary

Elastases form a subfamily of serine proteases that hydrolyze many proteins in addition to elastin. Humans have six elastase genes which encode the structurally similar proteins elastase 1, 2, 2A, 2B, 3A, and 3B. Like most of the human elastases, elastase 2A is secreted from the pancreas as a zymogen. In other species, elastase 2A has been shown to preferentially cleave proteins after leucine, methionine, and phenylalanine residues. [provided by RefSeq, May 2009]

MANE transcript

NM_033440.3

Inheritance

ClinVar variants

P:5U:41B:5

Top phenotype

Abdominal obesity-metabolic syndrome 4

gnomAD constraint

pLI —, LoF o/e 1.33

Max pathogenic AF

—

Genomic locus

chr1:15,456,728-15,472,091

External References & Databases

Ensembl (ENSG00000142615)

Transcript & Mutation Effects

hg38 • Region Span ~15.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

abdominal obesity-metabolic syndrome 4LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0032837

Submitter: Labcorp Genetics (formerly Invitae)

abdominal obesity-metabolic syndrome 4LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032837

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Abdominal obesity-metabolic syndrome 4AD

Manifestation: Cardiovascular; Endocrine

Intervention: Cardiovascular

Rationale: Among other features, individuals have been described with relatively early-onset cardiac disease, including myocardial infarction, and awareness may allow early interventions to ameliorate cardiovascular and related sequelae

Refs: 31358993

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CELA2A variants in ClinVar

8 Conditions Cataloged

not specifiedTotal: 37

Abdominal obesity-metabolic syndrome 4Total: 8

not providedTotal: 5

Hypertensive disorderTotal: 4

HypertriglyceridemiaTotal: 4

DiabetesTotal: 4

Coronary artery disorderTotal: 4

CELA2A-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033440.3. 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			2 clinvar			2
missense	1 clinvar	2 clinvar	38 clinvar	5 clinvar		46
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar					1
Total	2	3	41	5	0	51

Highest pathogenic variant AF is 0.00010968609

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033440.3	RefSeq	NP_254275.1	8	MANE Select
ENST00000359621.5	Ensembl	ENSP00000352639.4	8	MANE Select
ENST00000967096.1	Ensembl	ENSP00000637155.1	7	Standard
ENST00000967096.2	Ensembl	ENSP00000637155.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Protein digestion and absorption - Homo sapiens (human)
Pancreatic secretion - Homo sapiens (human)
Keratinization
Developmental Biology
Formation of the cornified envelope

Biological Process

proteolysis
cornification

Molecular Function

endopeptidase activity
serine-type endopeptidase activity
serine hydrolase activity

Cellular Component

extracellular region
extracellular space
cytosol
keratohyalin granule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359621
Coding exons: 8
Length: 15364
Individuals with no LoFs: 125665
Homozygous LoFs: 1
Heterozygous LoFs: 80
Defined: 125746
p: 0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0359	172	173	0.992	0.0000111	1732
Missense (PolyPhen)		64	64.39	0.99394		697
Synonymous	-0.352	83	79.0	1.05	0.00000573	554
Loss of Function	-1.21	21	15.8	1.33	7.78e-7	150

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00086	0.00080	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00065	0.00065	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00075	0.00075	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts upon elastin.;

Intolerance Scores

LoFtool: 0.325
RVIS EVS: -0.45
RVIS percentile EVS: 24.33

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.148

Gene Damage Prediction

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