ADAM15

protein-coding

ADAM metallopeptidase domain 15, the group of ADAM metallopeptidase domain containing

Gene summary

The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as a EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

MANE transcript

NM_207197.3

Inheritance

—

ClinVar variants

U:160B:17

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr1:155,050,566-155,062,775

External References & Databases

Ensembl (ENSG00000143537)

Transcript & Mutation Effects

hg38 • Region Span ~12.2 kb

Loading mutation effect viewer...

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 ADAM15 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 142

not providedTotal: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_207197.3. 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			6 clinvar	5 clinvar		11
missense			138 clinvar	11 clinvar	1 clinvar	150
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			12 clinvar			12
Total	0	0	160	16	1	177

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 124 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_207197.3	RefSeq	NP_997080.1	23	MANE Select
ENST00000356955.7	Ensembl	ENSP00000349436.2	23	MANE Select
NM_001261464.2	RefSeq	NP_001248393.1	21	Standard
NM_001261465.2	RefSeq	NP_001248394.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Invadopodia formation
Extracellular matrix organization
Degradation of the extracellular matrix
Alpha9 beta1 integrin signaling events

Biological Process

angiogenesis
negative regulation of cell-matrix adhesion
immune response to tumor cell
proteolysis
apoptotic process

Molecular Function

metalloendopeptidase activity
integrin binding
protein binding
metallopeptidase activity
SH3 domain binding

Cellular Component

acrosomal vesicle
plasma membrane
adherens junction
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356955
Coding exons: 23
Length: 12211
Individuals with no LoFs: 125629
Homozygous LoFs: 0
Heterozygous LoFs: 119
Defined: 125748
p: 0.000473

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	433	500	0.865	0.0000290	5463
Missense (PolyPhen)		156	192.72	0.80945		2233
Synonymous	1.42	177	203	0.874	0.0000113	1831
Loss of Function	2.35	33	51.1	0.646	0.00000298	501

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00083	0.00080	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.0011	0.0010	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00044	0.00042	rare
South Asian	0.00069	0.00069	rare
Other	0.00085	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Active metalloproteinase with gelatinolytic and collagenolytic activity. Plays a role in the wound healing process. Mediates both heterotypic intraepithelial cell/T-cell interactions and homotypic T-cell aggregation. Inhibits beta-1 integrin-mediated cell adhesion and migration of airway smooth muscle cells. Suppresses cell motility on or towards fibronectin possibly by driving alpha-v/beta-1 integrin (ITAGV-ITGB1) cell surface expression via ERK1/2 inactivation. Cleaves E-cadherin in response to growth factor deprivation. Plays a role in glomerular cell migration. Plays a role in pathological neovascularization. May play a role in cartilage remodeling. May be proteolytically processed, during sperm epididymal maturation and the acrosome reaction. May play a role in sperm-egg binding through its disintegrin domain. {ECO:0000269|PubMed:12091380, ECO:0000269|PubMed:15358598, ECO:0000269|PubMed:15818704, ECO:0000269|PubMed:17416588, ECO:0000269|PubMed:17575078, ECO:0000269|PubMed:18387333, ECO:0000269|PubMed:18434311}.;

Recessive Scores

pRec: 0.138

Intolerance Scores

LoFtool: 0.987
RVIS EVS: -0.57
RVIS percentile EVS: 19.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.687

Gene Damage Prediction

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