ADAMTS14

protein-coding

ADAM metallopeptidase with thrombospondin type 1 motif 14, 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 motif) protein family. Members of the family 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. This enzyme cleaves amino-terminal propeptides from type I procollagen, a necessary step in the formation of collagen fibers. Mutations in this gene may be associated with osteoarthritis in human patients. [provided by RefSeq, May 2016]

MANE transcript

NM_080722.4

Inheritance

—

ClinVar variants

U:249B:24

Top phenotype

Fraser syndrome 3

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr10:70,672,506-70,762,441

External References & Databases

Ensembl (ENSG00000138316)

Transcript & Mutation Effects

hg38 • Region Span ~89.9 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 ADAMTS14 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 259

not providedTotal: 12

Fraser syndrome 3Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_080722.4. 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			1 clinvar	5 clinvar	2 clinvar	8
missense			246 clinvar	17 clinvar		263
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	249	22	2	273

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_080722.4	RefSeq	NP_542453.2	22	MANE Select
ENST00000373207.2	Ensembl	ENSP00000362303.1	22	MANE Select
NM_139155.3	RefSeq	NP_631894.2	22	Standard
ENST00000373208.5	Ensembl	ENSP00000362304.1	22	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Collagen biosynthesis and modifying enzymes
Post-translational protein modification
Metabolism of proteins
Collagen formation
Extracellular matrix organization

Biological Process

proteolysis
collagen fibril organization
collagen catabolic process

Molecular Function

metalloendopeptidase activity
metal ion binding

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373208
Coding exons: 22
Length: 89639
Individuals with no LoFs: 125643
Homozygous LoFs: 0
Heterozygous LoFs: 105
Defined: 125748
p: 0.000418

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.295	746	769	0.970	0.0000492	7886
Missense (PolyPhen)		307	335.22	0.91582		3394
Synonymous	-0.462	317	307	1.03	0.0000194	2467
Loss of Function	3.41	32	60.6	0.528	0.00000350	612

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00054	0.00053	rare
South Asian	0.00036	0.00036	rare
Other	0.00066	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has a aminoprocollagen type I activity processing activity in the absence of ADAMTS2. Seems to be synthesized as a latent enzyme that requires activation to display aminoprocollagen peptidase activity.;

Recessive Scores

pRec: 0.123

Intolerance Scores

LoFtool: 0.730
RVIS EVS: -0.55
RVIS percentile EVS: 19.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.106

Gene Damage Prediction

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