TLL2

protein-coding

tolloid like 2, the group of Astacins

Gene summary

This gene encodes an astacin-like zinc-dependent metalloprotease and is a subfamily member of the metzincin family. Unlike other family members, a similar protein in mice does not cleave procollagen C-propeptides or chordin. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012465.4

Inheritance

—

ClinVar variants

U:177B:12

Top phenotype

Hand tremor

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr10:96,364,608-96,513,926

External References & Databases

Ensembl (ENSG00000095587)

Transcript & Mutation Effects

hg38 • Region Span ~149.3 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 TLL2 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 174

not providedTotal: 9

Hand tremorTotal: 2

EMG: neuropathic changesTotal: 2

Proximal amyotrophyTotal: 2

Muscular atrophyTotal: 2

Spinal muscular atrophyTotal: 2

Tongue fasciculationsTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012465.4. 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			3 clinvar		2 clinvar	5
missense			172 clinvar	6 clinvar	4 clinvar	182
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	177	6	6	189

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012465.4	RefSeq	NP_036597.1	21	MANE Select
ENST00000357947.4	Ensembl	ENSP00000350630.3	21	MANE Select
ENST00000881335.1	Ensembl	ENSP00000551394.1	20	Standard
ENST00000881335.2	Ensembl	ENSP00000551394.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Crosslinking of collagen fibrils
Assembly of collagen fibrils and other multimeric structures
Collagen biosynthesis and modifying enzymes
Collagen formation
Extracellular matrix organization

Biological Process

proteolysis
multicellular organism development
extracellular matrix disassembly
cell differentiation
negative regulation of skeletal muscle tissue growth

Molecular Function

metalloendopeptidase activity
serine-type endopeptidase activity
calcium ion binding
zinc ion binding

Cellular Component

extracellular region

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357947
Coding exons: 21
Length: 149313
Individuals with no LoFs: 125520
Homozygous LoFs: 0
Heterozygous LoFs: 228
Defined: 125748
p: 0.000907

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.447	596	628	0.950	0.0000379	6706
Missense (PolyPhen)		200	204.55	0.97777		2130
Synonymous	1.61	224	257	0.872	0.0000177	1886
Loss of Function	0.623	50	55.0	0.909	0.00000284	611

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0012	0.0012	notable
Latino/Admixed American	0.00076	0.00075	rare
Ashkenazi Jewish	0.00012	0.000099	rare
East Asian	0.0014	0.0014	notable
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00095	0.00091	rare
South Asian	0.0016	0.0015	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protease which specifically processes pro-lysyl oxidase. Required for the embryonic development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.;

Recessive Scores

pRec: 0.102

Intolerance Scores

LoFtool: 0.760
RVIS EVS: 0.35
RVIS percentile EVS: 73.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.204

Gene Damage Prediction

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