ARSL

Summary

ARSL (arylsulfatase L, HGNC:719) is a protein-coding gene on chromosome Xp22.33, encoding Arylsulfatase L (P51690). Exhibits arylsulfatase activity towards the artificial substrate 4-methylumbelliferyl sulfate.

Arylsulfatase E is a member of the sulfatase family. It is glycosylated postranslationally and localized to the golgi apparatus. Sulfatases are essential for the correct composition of bone and cartilage matrix. X-linked chondrodysplasia punctata, a disease characterized by abnormalities in cartilage and bone development, has been linked to mutations in this gene. Alternative splicing results in multiple transcript variants. A pseudogene related to this gene is located on the Y chromosome.

Source: NCBI Gene 415 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked chondrodysplasia punctata 1 (Definitive, ClinGen)
• GWAS associations: 2
• Clinical variants (ClinVar): 540 total — 23 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 65
• MANE Select transcript: NM_000047

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:719
Approved symbol	ARSL
Name	arylsulfatase L
Location	Xp22.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000157399
Ensembl biotype	protein_coding
OMIM	300180
Entrez	415

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 28 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000381134, ENST00000438544, ENST00000483425, ENST00000540563, ENST00000545496, ENST00000672027, ENST00000672097, ENST00000672606, ENST00000672761, ENST00000673032, ENST00000681960, ENST00000681963, ENST00000682184, ENST00000682364, ENST00000682745, ENST00000683071, ENST00000683191, ENST00000683290, ENST00000683677, ENST00000683854, ENST00000683958, ENST00000684045, ENST00000684077, ENST00000684117, ENST00000684364, ENST00000684687, ENST00000684738, ENST00000879212, ENST00000879213, ENST00000879214, ENST00000879215, ENST00000879216, ENST00000879217, ENST00000879218, ENST00000879219, ENST00000968859

RefSeq mRNA: 5 — MANE Select: NM_000047 NM_000047, NM_001282628, NM_001282631, NM_001369079, NM_001369080

CCDS: CCDS14122, CCDS75948, CCDS75949

Canonical transcript exons

ENST00000381134 — 11 exons

Exon	Start	End
ENSE00000664472	2953143	2953265
ENSE00000664473	2949304	2949727
ENSE00000664474	2945998	2946134
ENSE00000664475	2943065	2943199
ENSE00000664477	2936742	2936863
ENSE00001434586	2955416	2955537
ENSE00001434877	2958274	2958435
ENSE00001617708	2938095	2938257
ENSE00003595756	2960378	2960420
ENSE00003889263	2964224	2964341
ENSE00003891345	2934521	2935190

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 93.60.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8867 / max 199.4155, expressed in 323 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198304	1.8779	197
198306	0.7508	173
198307	0.1675	88
198305	0.0904	57

Top tissues by expression

278 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	93.60	gold quality
liver	UBERON:0002107	92.23	gold quality
right lobe of liver	UBERON:0001114	91.62	gold quality
pancreas	UBERON:0001264	90.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.00	gold quality
mucosa of transverse colon	UBERON:0004991	87.33	gold quality
adult mammalian kidney	UBERON:0000082	86.43	gold quality
rectum	UBERON:0001052	86.15	gold quality
islet of Langerhans	UBERON:0000006	85.97	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.54	gold quality
colonic mucosa	UBERON:0000317	85.16	gold quality
ileal mucosa	UBERON:0000331	81.73	gold quality
duodenum	UBERON:0002114	81.19	gold quality
kidney	UBERON:0002113	81.00	gold quality
gall bladder	UBERON:0002110	80.23	gold quality
transverse colon	UBERON:0001157	80.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.07	silver quality
ventricular zone	UBERON:0003053	77.42	gold quality
cortex of kidney	UBERON:0001225	76.53	gold quality
large intestine	UBERON:0000059	76.48	gold quality
intestine	UBERON:0000160	76.21	gold quality
colon	UBERON:0001155	76.18	gold quality
stromal cell of endometrium	CL:0002255	75.88	gold quality
small intestine	UBERON:0002108	74.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.88	gold quality
nephron tubule	UBERON:0001231	74.82	gold quality
pancreatic ductal cell	CL:0002079	74.72	silver quality
jejunal mucosa	UBERON:0000399	74.29	gold quality
metanephros cortex	UBERON:0010533	73.62	gold quality
kidney epithelium	UBERON:0004819	73.03	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.88
E-MTAB-9388	yes	11.03
E-MTAB-8271	yes	6.39

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting ARSL, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-5087	98.01	69.09	965
HSA-MIR-1236-5P	96.62	66.38	856
HSA-MIR-4765	93.11	66.17	737
HSA-MIR-4508	90.37	59.62	240
HSA-MIR-4732-5P	90.07	64.77	412

Literature-anchored findings (GeneRIF, showing 4)

• Clinical and molecular analysis of ARSE in CDPX1 patients supports heterogeneity for CDPX1-like phenotypes and sorting these out will help to define the biological pathway and genetic contributors. [ARSE] (PMID:18348268)
• Results show that Around 40 perdcent of male patients with brachytelephalangic chondrodysplasia punctata do not have detectable ARSE mutations or known maternal etiological factors. (PMID:23470839)
• Data indicate that the neonatal detection test sensitivity obtained was 95% with a positive predictive value of 1 in the analyses for both the arylsulfatase E (ARSE) and melanoma antigen family H1 (MAGEH1) genes. (PMID:25366798)
• Evidence for high breakpoint variability in 46, XX, SRY-positive testicular disorder and frequent ARSE deletion that may be associated with short stature. (PMID:36026611)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	sulf2a	ENSDARG00000018423
danio_rerio	gnsb	ENSDARG00000098296
danio_rerio	arsib	ENSDARG00000117075
rattus_norvegicus	Arsl	ENSRNOG00000028350
drosophila_melanogaster	CG18278	FBGN0033836
drosophila_melanogaster	CG7408	FBGN0036765
drosophila_melanogaster	CG7402	FBGN0036768
drosophila_melanogaster	Sulf1	FBGN0040271
drosophila_melanogaster	CG32191	FBGN0052191
drosophila_melanogaster	CG30059	FBGN0260475
caenorhabditis_elegans		WBGENE00006308
caenorhabditis_elegans		WBGENE00006309
caenorhabditis_elegans		WBGENE00006310

Paralogs (16): ARSD (ENSG00000006756), IDS (ENSG00000010404), ARSF (ENSG00000062096), ARSA (ENSG00000100299), STS (ENSG00000101846), ARSB (ENSG00000113273), GNS (ENSG00000135677), SULF1 (ENSG00000137573), GALNS (ENSG00000141012), ARSG (ENSG00000141337), ARSK (ENSG00000164291), ARSJ (ENSG00000180801), SGSH (ENSG00000181523), ARSI (ENSG00000183876), SULF2 (ENSG00000196562), ARSH (ENSG00000205667)

Protein

Protein identifiers

Arylsulfatase L — P51690 (reviewed: P51690)

Alternative names: Arylsulfatase E

All UniProt accessions (13): P51690, A0A5F9ZHU0, A0A5F9ZHX8, A0A5F9ZHZ5, A0A804HHU6, A0A804HIF5, A0A804HIX6, A0A804HJ07, A0A804HJF6, A0A804HK35, C9J5G7, F5GYY5, F5H324

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits arylsulfatase activity towards the artificial substrate 4-methylumbelliferyl sulfate. May be essential for the correct composition of cartilage and bone matrix during development. Has no activity toward steroid sulfates.

Subcellular location. Golgi apparatus. Golgi stack.

Tissue specificity. Expressed in the pancreas, liver and kidney.

Post-translational modifications. N-glycosylated. The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by millimolar concentrations of warfarin.

Cofactor. Binds 1 Ca(2+) ion per subunit.

Similarity. Belongs to the sulfatase family.

RefSeq proteins (5): NP_000038, NP_001269557, NP_001269560, NP_001356008, NP_001356009 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000917	Sulfatase_N	Domain
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR024607	Sulfatase_CS	Conserved_site
IPR050738	Sulfatase	Family

Pfam: PF00884, PF14707

Catalyzed reactions (Rhea), 1 shown:

• an aryl sulfate + H2O = a phenol + sulfate + H(+) (RHEA:17261)

UniProt features (29 total): sequence variant 11, binding site 8, glycosylation site 4, active site 2, signal peptide 1, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51690-F1	92.57	0.87

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (2): 86 (nucleophile); 147

Ligand- & substrate-binding residues (8): 354; 378; 46; 47; 86 (via 3-oxoalanine); 145; 301; 353

Post-translational modifications (1): 86

Glycosylation sites (4): 58, 125, 258, 344

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-1663150	The activation of arylsulfatases
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-163841	Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 237 (showing top): MORF_RAGE, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, MODULE_16, MORF_FANCG, WINTER_HYPOXIA_METAGENE, SCHLOSSER_SERUM_RESPONSE_DN, MORF_PML, REACTOME_SPHINGOLIPID_METABOLISM, MORF_IKBKG, MORF_MT4, GOCC_GOLGI_STACK, MORF_ORC1L, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, GOCC_ORGANELLE_SUBCOMPARTMENT, MODULE_13

GO Biological Process (1): skeletal system development (GO:0001501)

GO Molecular Function (3): arylsulfatase activity (GO:0004065), metal ion binding (GO:0046872), hydrolase activity (GO:0016787)

GO Cellular Component (5): endoplasmic reticulum lumen (GO:0005788), Golgi apparatus (GO:0005794), Golgi stack (GO:0005795), extracellular exosome (GO:0070062), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Gamma carboxylation, hypusinylation, hydroxylation, and arylsulfatase activation	1
Glycosphingolipid metabolism	1
Post-translational protein modification	1
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
sulfuric ester hydrolase activity	1
cation binding	1
catalytic activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
Golgi apparatus subcompartment	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARSL	SHOX	O15266	915
ARSL	EBP	Q15125	833
ARSL	XG	P55808	750
ARSL	ANOS1	P23352	698
ARSL	CD99	P14209	683
ARSL	VCX3A	Q9NNX9	595
ARSL	ALB	P02768	509
ARSL	MGP	P08493	506
ARSL	SOX3	P35714	505
ARSL	GBA1	P04062	499
ARSL	PRKX	P51817	483
ARSL	RAN	P17080	482
ARSL	PNPLA4	P41247	458
ARSL	FGF2	P09038	443
ARSL	XPO5	Q9HAV4	439

IntAct

7 interactions, top by confidence:

A	B	Type	Score
rep	BMPR1B	psi-mi:“MI:0914”(association)	0.350
ARSL	FBXO21	psi-mi:“MI:0914”(association)	0.350
ARSL	COQ6	psi-mi:“MI:0915”(physical association)	0.000
ARSL	TMEM259	psi-mi:“MI:0915”(physical association)	0.000
ARSL	NDN	psi-mi:“MI:0915”(physical association)	0.000
TNK2	ARSL	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): COQ6 (Two-hybrid), NDN (Two-hybrid), ARSE (Affinity Capture-MS), ARSE (Proximity Label-MS), ARSE (Proximity Label-MS), ARSE (Proximity Label-MS), ARSE (Proximity Label-MS), ARSE (Proximity Label-MS), ARSE (Proximity Label-MS), ARSE (Proximity Label-MS), ZDHHC13 (Affinity Capture-MS), VAC14 (Affinity Capture-MS), SUMF1 (Affinity Capture-MS), CLPTM1L (Affinity Capture-MS), MTOR (Affinity Capture-MS)

ESM2 similar proteins: O14792, O35310, O43529, O54702, P21709, P51690, P51839, Q08BL3, Q08BN9, Q14BT6, Q16WU7, Q29G54, Q5E9W5, Q5EA41, Q5RBZ6, Q5U2X4, Q5U3T0, Q5YB40, Q5ZIE4, Q60750, Q60HH5, Q66H69, Q6AXM1, Q6GNS1, Q6PGK7, Q6W3E9, Q6W3F0, Q6XQH0, Q7Q297, Q7T3S5, Q80V53, Q8BSL4, Q8IZT8, Q8K0J2, Q8NCG5, Q8NCH0, Q8NCL4, Q92035, Q92179, Q96SM3

Diamond homologs: P08842, P14000, P15289, P15589, P20713, P34059, P50427, P50428, P50473, P51689, P51690, P54793, Q08DD1, Q32KH5, Q32KH8, Q32KH9, Q32KJ6, Q32KJ9, Q3TYD4, Q571E4, Q5FYA8, Q5FYB0, Q60HH5, Q8BM89, Q8WNQ7, Q9X759, T2KMG4, T2KN90, P22304, P31447, Q08890, Q32KI9, Q32KJ8, Q5FYB1, Q96EG1, P33727, P50430, Q32KH7, Q8A2F6, Q8A2H2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

540 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	23
Likely pathogenic	21
Uncertain significance	114
Likely benign	213
Benign	71

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
11524	NM_000047.3(ARSL):c.332G>C (p.Arg111Pro)	Pathogenic
11525	NM_000047.3(ARSL):c.410G>T (p.Gly137Val)	Pathogenic
11526	NM_000047.3(ARSL):c.733G>C (p.Gly245Arg)	Pathogenic
11527	NM_000047.3(ARSL):c.1475G>A (p.Cys492Tyr)	Pathogenic
11528	NM_000047.3(ARSL):c.1732C>T (p.Pro578Ser)	Pathogenic
1683207	NM_000047.3(ARSL):c.74del (p.Leu25fs)	Pathogenic
1723873	NM_000047.3(ARSL):c.916A>G (p.Thr306Ala)	Pathogenic
1809739	NM_000047.3(ARSL):c.1009_1010del (p.Leu337fs)	Pathogenic
2138468	NM_000047.3(ARSL):c.1618C>T (p.Arg540Ter)	Pathogenic
2709852	NM_000047.3(ARSL):c.131_140del (p.Met44fs)	Pathogenic
279691	NM_000047.3(ARSL):c.1300G>A (p.Gly434Ser)	Pathogenic
279692	NM_000047.3(ARSL):c.1711C>T (p.Gln571Ter)	Pathogenic
3244441	NC_000023.10:g.(?2852873)(2878441_?)del	Pathogenic
3382548	NM_000047.3(ARSL):c.827del (p.Leu276fs)	Pathogenic
3382779	NM_000047.3(ARSL):c.294C>A (p.Tyr98Ter)	Pathogenic
3384622	NM_000047.3(ARSL):c.1742G>A (p.Trp581Ter)	Pathogenic
3721569	NM_000047.3(ARSL):c.30T>A (p.Cys10Ter)	Pathogenic
430164	NM_000047.3(ARSL):c.1387G>A (p.Ala463Thr)	Pathogenic
4847304	NM_000047.3(ARSL):c.983G>A (p.Trp328Ter)	Pathogenic
503608	NM_000047.3(ARSL):c.123TCT[1] (p.Leu43del)	Pathogenic
657917	NC_000023.11:g.(?2934812)(2960420_?)del	Pathogenic
832204	NC_000023.11:g.(?2934812)(2958455_?)del	Pathogenic
851645	NM_000047.3(ARSL):c.1158del (p.Ile387fs)	Pathogenic
1066074	NM_000047.3(ARSL):c.217G>A (p.Gly73Ser)	Likely pathogenic
1200861	NM_000047.3(ARSL):c.854G>A (p.Arg285Lys)	Likely pathogenic
1683205	NM_000047.3(ARSL):c.185+1G>A	Likely pathogenic
1698854	NM_000047.3(ARSL):c.1219G>T (p.Glu407Ter)	Likely pathogenic
1805736	NM_000047.3(ARSL):c.430G>A (p.Gly144Arg)	Likely pathogenic
21031	NM_000047.3(ARSL):c.119T>G (p.Ile40Ser)	Likely pathogenic
253340	GRCh37/hg19 Xp22.33(chrX:2873380-2878978)x2	Likely pathogenic

SpliceAI

1630 predictions. Top by Δscore:

Variant	Effect	Δscore
X:2943059:TCTTA:T	donor_loss	1.0000
X:2943060:CTTAC:C	donor_loss	1.0000
X:2943061:TTACC:T	donor_loss	1.0000
X:2943062:TACCT:T	donor_loss	1.0000
X:2943195:CCGTC:C	acceptor_gain	1.0000
X:2943196:CGTC:C	acceptor_gain	1.0000
X:2943196:CGTCC:C	acceptor_gain	1.0000
X:2943197:GTCCT:G	acceptor_loss	1.0000
X:2943198:TCCTG:T	acceptor_loss	1.0000
X:2943199:CCTGC:C	acceptor_loss	1.0000
X:2943200:C:CC	acceptor_gain	1.0000
X:2943200:CTG:C	acceptor_loss	1.0000
X:2943201:T:C	acceptor_loss	1.0000
X:2945993:CTTA:C	donor_loss	1.0000
X:2945995:TA:T	donor_loss	1.0000
X:2945997:CCTA:C	donor_gain	1.0000
X:2946091:CGTG:C	acceptor_gain	1.0000
X:2946092:G:C	acceptor_gain	1.0000
X:2946094:G:C	acceptor_gain	1.0000
X:2946094:G:GC	acceptor_gain	1.0000
X:2953264:CCCTT:C	acceptor_gain	1.0000
X:2953276:T:C	acceptor_gain	1.0000
X:2953276:T:TC	acceptor_gain	1.0000
X:2955412:TGACC:T	donor_loss	1.0000
X:2955413:GACCT:G	donor_loss	1.0000
X:2955414:A:AC	donor_gain	1.0000
X:2955415:C:CC	donor_gain	1.0000
X:2955534:AGTC:A	acceptor_gain	1.0000
X:2955535:GTC:G	acceptor_gain	1.0000
X:2955535:GTCC:G	acceptor_loss	1.0000

AlphaMissense

3858 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:2949722:A:G	W146R	0.996
X:2949722:A:T	W146R	0.996
X:2955456:G:C	S89R	0.996
X:2955456:G:T	S89R	0.996
X:2955458:T:G	S89R	0.996
X:2949657:A:C	F167L	0.993
X:2949657:A:T	F167L	0.993
X:2949659:A:G	F167L	0.993
X:2949720:C:A	W146C	0.993
X:2949720:C:G	W146C	0.993
X:2949724:T:A	K145I	0.991
X:2938154:A:C	S410R	0.988
X:2938154:A:T	S410R	0.988
X:2938156:T:G	S410R	0.988
X:2949658:A:G	F167S	0.987
X:2955465:G:C	C86W	0.986
X:2943133:T:A	D353V	0.985
X:2943136:G:C	S352W	0.985
X:2949658:A:C	F167C	0.984
X:2955457:C:A	S89I	0.983
X:2958322:T:A	D46V	0.983
X:2935174:T:A	K476N	0.980
X:2935174:T:G	K476N	0.980
X:2958319:T:A	D47V	0.978
X:2949648:G:C	F170L	0.977
X:2949648:G:T	F170L	0.977
X:2949650:A:G	F170L	0.977
X:2936766:C:G	A463P	0.976
X:2955436:C:T	G96D	0.976
X:2955453:T:A	R90S	0.976

dbSNP variants (sampled 300 via entrez): RS1000053789 (X:2960096 C>A,T), RS1000206108 (X:2952364 G>A,T), RS1000489617 (X:2951629 A>G), RS1000771387 (X:2950110 C>T), RS1000789092 (X:2962080 C>G,T), RS1001045694 (X:2965814 T>A), RS1001097369 (X:2965355 G>A), RS1001211575 (X:2969582 C>G,T), RS1001383274 (X:2955832 C>T), RS1001434814 (X:2946208 A>G), RS1001664356 (X:2969344 C>T), RS1001717121 (X:2962766 A>G), RS1001770912 (X:2962532 G>A), RS1001866334 (X:2963441 T>C), RS1002294302 (X:2962878 A>C)

Disease associations

OMIM: gene MIM:300180 | disease phenotypes: MIM:602497, MIM:302950, MIM:135900, MIM:609943, MIM:614562, MIM:619681

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked chondrodysplasia punctata 1	Definitive	X-linked

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
X-linked chondrodysplasia punctata 1	Definitive	XL

Mondo (7): chondrodysplasia punctata, brachytelephalangic, autosomal (MONDO:0011238), X-linked chondrodysplasia punctata 1 (MONDO:0010555), connective tissue disorder (MONDO:0003900), epilepsy (MONDO:0005027), Coffin-Siris syndrome 1 (MONDO:0007617), dystonia, early-onset, and/or spastic paraplegia (MONDO:0859215), intellectual disability (MONDO:0001071)

Orphanet (3): Brachytelephalangic chondrodysplasia punctata (Orphanet:79345), Coffin-Siris syndrome (Orphanet:1465), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000135	Hypogonadism
HP:0000252	Microcephaly
HP:0000327	Hypoplasia of the maxilla
HP:0000365	Hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000420	Short nasal septum
HP:0000455	Broad nasal tip
HP:0000457	Depressed nasal ridge
HP:0000458	Anosmia
HP:0000518	Cataract
HP:0000609	Optic nerve hypoplasia
HP:0000919	Abnormality of the costochondral junction
HP:0000925	Abnormality of the vertebral column
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001643	Patent ductus arteriosus
HP:0001742	Nasal congestion
HP:0001857	Short distal phalanx of toe
HP:0002000	Short columella
HP:0002020	Gastroesophageal reflux
HP:0002099	Asthma
HP:0002205	Recurrent respiratory infections
HP:0002341	Cervical cord compression
HP:0002643	Neonatal respiratory distress
HP:0002777	Tracheal stenosis
HP:0002787	Tracheal calcification
HP:0002789	Tachypnea
HP:0002871	Central apnea

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001263_33	Height	6.000000e-12
GCST001290_4	Height	5.000000e-12

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D003240	Connective Tissue Diseases	C17.300
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression, decreases methylation, increases mutagenesis	3
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, affects expression	2
methylmercuric chloride	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
sodium arsenite	increases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
K 7174	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	decreases expression	1
Ivermectin	decreases expression	1
Phenobarbital	affects expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Triclosan	increases expression	1
Warfarin	decreases activity	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies