ADAMTS15

protein-coding

ADAM metallopeptidase with thrombospondin type 1 motif 15, the group of ADAM metallopeptidases with thrombospondin type 1 motif

Gene summary

This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. ADAMTS family members share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The encoded preproprotein is proteolytically processed to generate the mature enzyme, which may play a role in versican processing during skeletal muscle development. This gene may function as a tumor suppressor in colorectal and breast cancers. [provided by RefSeq, May 2016]

MANE transcript

NM_139055.4

Inheritance

ClinVar variants

P:5U:160B:16

Top phenotype

Arthrogryposis, distal, type 12

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr11:130,448,645-130,476,645

External References & Databases

Ensembl (ENSG00000166106)

Transcript & Mutation Effects

hg38 • Region Span ~28.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

arthrogryposis, distal, type 12MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0957819

Submitter: G2P

arthrogryposis, distal, type 12STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0957819

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Arthrogryposis, distal, type 12AR

Manifestation: Craniofacial; Dental; Musculoskeletal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 35962790

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ADAMTS15 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 158

not providedTotal: 14

Arthrogryposis, distal, type 12Total: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_139055.4. 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	3 clinvar	13
missense	1 clinvar	1 clinvar	157 clinvar	4 clinvar	1 clinvar	164
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	3	2	160	12	4	181

Highest pathogenic variant AF is 0.0000020530929

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_139055.4	RefSeq	NP_620686.1	8	MANE Select
ENST00000299164.4	Ensembl	ENSP00000299164.2	8	MANE Select
ENST00000948453.1	Ensembl	ENSP00000618512.1	8	Standard
ENST00000948453.2	Ensembl	ENSP00000618512.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Post-translational protein modification
Metabolism of proteins
O-glycosylation of TSR domain-containing proteins
O-linked glycosylation

Biological Process

proteolysis

Molecular Function

metalloendopeptidase activity
heparin binding
zinc ion binding
extracellular matrix binding

Cellular Component

extracellular space
cell surface
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299164
Coding exons: 8
Length: 27664
Individuals with no LoFs: 125712
Homozygous LoFs: 0
Heterozygous LoFs: 36
Defined: 125748
p: 0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.508	553	588	0.941	0.0000354	6054
Missense (PolyPhen)		240	269.78	0.88961		2799
Synonymous	-0.682	280	266	1.05	0.0000170	2033
Loss of Function	2.80	15	32.1	0.467	0.00000151	367

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.318
RVIS EVS: 0.68
RVIS percentile EVS: 84.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.252

Gene Damage Prediction

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