GeneBe

ARSL

arylsulfatase L, the group of Sulfatases

Basic information

Region (hg38): X:2934045-2968475

Previous symbols: [ "CDPX", "CDPX1", "ARSE" ]

Links

ENSG00000157399 ∙ NCBI:415 ∙ OMIM:300180 ∙ HGNC:719 ∙ Uniprot:P51690 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • X-linked chondrodysplasia punctata 1 (Supportive), mode of inheritance: XL
  • X-linked chondrodysplasia punctata 1 (Definitive), mode of inheritance: XL
  • X-linked chondrodysplasia punctata 1 (Strong), mode of inheritance: XL
  • X-linked chondrodysplasia punctata 1 (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Chondrodysplasia punctata 1, X-linked recessiveXLMusculoskeletalIndividuals may demonstrate cervical spine stenosis and/or instability, and surveillance may be beneficial to detect and treat (eg, with placement of a cervical collar or spinal fusion) spinal sequelaeCraniofacial; Musculoskeletal; Neurologic7720070; 9863597; 12567415; 18348268; 20301713; 20523025; 23462608; 23470839

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ARSL gene.

  • Chondrodysplasia_punctata,_brachytelephalangic,_autosomal (295 variants)
  • not_provided (106 variants)
  • X-linked_chondrodysplasia_punctata_1 (51 variants)
  • Inborn_genetic_diseases (46 variants)
  • not_specified (18 variants)
  • Connective_tissue_disorder (12 variants)
  • ARSL-related_disorder (11 variants)
  • Dystonia,_early-onset,_and/or_spastic_paraplegia (1 variants)
  • Intellectual_disability (1 variants)
  • See_cases (1 variants)
  • Coffin-Siris_syndrome_1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ARSL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000047.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
134
clinvar
7
clinvar
 141
missense
8
clinvar
14
clinvar
99
clinvar
31
clinvar
7
clinvar
 159
nonsense
5
clinvar
4
clinvar
 9
start loss
0
frameshift
5
clinvar
2
clinvar
1
clinvar
 8
splice donor/acceptor (+/-2bp)
6
clinvar
 6
Total 18 26 100 165 14

Highest pathogenic variant AF is 0.000155544

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
ARSLprotein_codingprotein_codingENST00000381134 1033588
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.5900.410125742141257470.0000199
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.951732620.6600.00002233844
Missense in Polyphen551170.470081690
Synonymous0.6121101180.9290.00001171191
Loss of Function2.98315.80.1900.00000122234

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00007610.0000615
Ashkenazi Jewish0.000.00
East Asian0.00007220.0000544
Finnish0.000.00
European (Non-Finnish)0.00003680.0000264
Middle Eastern0.00007220.0000544
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: May be essential for the correct composition of cartilage and bone matrix during development. Has no activity toward steroid sulfates.;
Disease
DISEASE: Chondrodysplasia punctata 1, X-linked recessive (CDPX1) [MIM:302950]: A clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. CDPX1 is a congenital defect of bone and cartilage development characterized by aberrant bone mineralization, severe underdevelopment of nasal cartilage, and distal phalangeal hypoplasia. This disease can also be induced by inhibition with the drug warfarin. {ECO:0000269|PubMed:12567415, ECO:0000269|PubMed:7720070, ECO:0000269|PubMed:9409863}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Estrogen metabolism;Metabolism of lipids;Post-translational protein modification;Metabolism of proteins;The activation of arylsulfatases;Gamma carboxylation, hypusine formation and arylsulfatase activation;Androgen and estrogen biosynthesis and metabolism;Metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

pRec
0.0978

Intolerance Scores

loftool
0.124
rvis_EVS
0.29
rvis_percentile_EVS
71.51

Haploinsufficiency Scores

pHI
0.167
hipred
N
hipred_score
0.403
ghis
0.385

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.974

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Gene ontology

Biological process
skeletal system development
Cellular component
endoplasmic reticulum lumen;Golgi apparatus;Golgi stack;extracellular exosome
Molecular function
arylsulfatase activity;metal ion binding