ARSL

arylsulfatase L, the group of Sulfatases

Basic information

Region (hg38): X:2934044-2968475

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 (Definitive), mode of inheritance: XLR
• 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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Chondrodysplasia punctata 1, X-linked recessive	XL	Musculoskeletal	Individuals 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 sequelae	Craniofacial; Musculoskeletal; Neurologic	7720070; 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 (174 variants)
• not provided (121 variants)
• X-linked chondrodysplasia punctata 1 (39 variants)
• not specified (23 variants)
• Connective tissue disorder (15 variants)
• Inborn genetic diseases (11 variants)
• ARSL-related condition (1 variants)
• See cases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	58	12	71
missense	2	10	61	13	11	97
nonsense	2	3				5
start loss						0
frameshift	4					4
inframe indel	1		1			2
splice donor/acceptor (+/-2bp)		5				5
splice region				5	1	6
non coding			3	46	50	99
Total	9	18	66	117	73

Highest pathogenic variant AF is 0.00000890

Variants in ARSL

This is a list of pathogenic ClinVar variants found in the ARSL region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-2934558-C-G			Benign (Aug 14, 2018)
X-2934561-C-T			Benign (Aug 14, 2018)
X-2934665-A-G			Benign (Jun 26, 2018)
X-2934843-C-T		Chondrodysplasia punctata, brachytelephalangic, autosomal	Uncertain significance (Jul 29, 2023)
X-2934859-C-T		X-linked chondrodysplasia punctata 1 • See cases • Chondrodysplasia punctata, brachytelephalangic, autosomal	Pathogenic/Likely pathogenic (Jan 03, 2024)
X-2934870-G-A		X-linked chondrodysplasia punctata 1	Pathogenic (Mar 01, 2003)
X-2934874-C-T		not specified • Chondrodysplasia punctata, brachytelephalangic, autosomal	Benign (Feb 01, 2024)
X-2934891-G-A			Pathogenic (Oct 24, 2016)
X-2934898-C-T		Chondrodysplasia punctata, brachytelephalangic, autosomal	Benign (Dec 21, 2023)
X-2934908-A-C		X-linked chondrodysplasia punctata 1 • Chondrodysplasia punctata, brachytelephalangic, autosomal	Conflicting classifications of pathogenicity (Jan 31, 2024)
X-2934910-G-A		not specified • X-linked chondrodysplasia punctata 1 • Chondrodysplasia punctata, brachytelephalangic, autosomal	Benign (Feb 01, 2024)
X-2934916-C-G		not specified • Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (Mar 14, 2023)
X-2934930-G-T		not specified • Chondrodysplasia punctata, brachytelephalangic, autosomal	Uncertain significance (Aug 12, 2022)
X-2934937-A-G		Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (Sep 21, 2023)
X-2934943-G-A		Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (May 20, 2023)
X-2934949-T-A		Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (Dec 10, 2022)
X-2934959-T-A		Chondrodysplasia punctata, brachytelephalangic, autosomal	Uncertain significance (Sep 19, 2022)
X-2934967-C-T		Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (May 12, 2023)
X-2934969-C-T		Chondrodysplasia punctata, brachytelephalangic, autosomal	Uncertain significance (Oct 05, 2022)
X-2934970-C-T		Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (Nov 17, 2023)
X-2934973-C-T		Connective tissue disorder • Chondrodysplasia punctata, brachytelephalangic, autosomal	Conflicting classifications of pathogenicity (Sep 20, 2023)
X-2934976-C-T		Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (Oct 06, 2023)
X-2934982-T-C		Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (Jul 25, 2023)
X-2934983-C-T		Chondrodysplasia punctata, brachytelephalangic, autosomal	Likely benign (Jan 29, 2024)
X-2934984-G-A		Chondrodysplasia punctata, brachytelephalangic, autosomal	Pathogenic (Mar 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ARSL	protein_coding	protein_coding	ENST00000381134	10	33588

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.590	0.410	125742	1	4	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.95	173	262	0.660	0.0000223	3844
Missense in Polyphen		55	117	0.47008		1690
Synonymous	0.612	110	118	0.929	0.0000117	1191
Loss of Function	2.98	3	15.8	0.190	0.00000122	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000761	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000722	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000368	0.0000264
Middle Eastern	0.0000722	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

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

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

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