ADAM19

protein-coding

ADAM metallopeptidase domain 19, the group of ADAM metallopeptidase domain containing

Gene summary

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has been demonstrated to be an active metalloproteinase, which may be involved in normal physiological processes such as cell migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. It is proposed to play a role in pathological processes, such as cancer, inflammatory diseases, renal diseases, and Alzheimer's disease. [provided by RefSeq, May 2013]

MANE transcript

NM_033274.5

Inheritance

—

ClinVar variants

U:122B:17

Top phenotype

Lung adenocarcinoma

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr5:157,395,534-157,575,775

External References & Databases

Ensembl (ENSG00000135074)

Transcript & Mutation Effects

hg38 • Region Span ~180.2 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 ADAM19 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 122

not providedTotal: 9

Lung adenocarcinomaTotal: 3

Squamous cell carcinomaTotal: 2

Abnormality of neuronal migrationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033274.5. 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 clinvar	1 clinvar	5
missense			115 clinvar	9 clinvar	5 clinvar	129
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	122	11	6	139

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033274.5	RefSeq	NP_150377.1	23	MANE Select
ENST00000257527.9	Ensembl	ENSP00000257527.5	23	MANE Select
ENST00000517374.5	Ensembl	ENSP00000431027.1	12	Standard
ENST00000517905.1	Ensembl	ENSP00000428654.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mesodermal Commitment Pathway
Invadopodia formation
Extracellular matrix organization

Biological Process

placenta development
membrane protein ectodomain proteolysis
positive regulation of gene expression
extracellular matrix organization
positive regulation of cell-cell adhesion mediated by cadherin

Molecular Function

metalloendopeptidase activity
protein binding
SH3 domain binding
metal ion binding

Cellular Component

nucleus
Golgi apparatus
plasma membrane
integral component of membrane
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000257527
Coding exons: 23
Length: 180242
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.88	409	531	0.770	0.0000304	5970
Missense (PolyPhen)		133	206.89	0.64286		2345
Synonymous	0.465	203	212	0.959	0.0000133	1806
Loss of Function	4.40	17	50.9	0.334	0.00000293	557

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.000098	0.000098	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Participates in the proteolytic processing of beta-type neuregulin isoforms which are involved in neurogenesis and synaptogenesis, suggesting a regulatory role in glial cell. Also cleaves alpha-2 macroglobulin. May be involved in osteoblast differentiation and/or osteoblast activity in bone (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.131

Intolerance Scores

LoFtool: 0.452
RVIS EVS: 0.92
RVIS percentile EVS: 89.57

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.440

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High