ADAMTSL4

ADAMTS like 4, the group of ADAMTS like|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:150549369-150560937

Previous symbols: [ "TSRC1" ]

Links

ENSG00000143382

∙ NCBI:54507 ∙ OMIM:610113 ∙ HGNC:19706 ∙ Uniprot:Q6UY14 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

ectopia lentis 2, isolated, autosomal recessive (Strong), mode of inheritance: AR
ectopia lentis et pupillae (Strong), mode of inheritance: AR
isolated ectopia lentis (Supportive), mode of inheritance: AD
ectopia lentis et pupillae (Strong), mode of inheritance: AR
ectopia lentis 2, isolated, autosomal recessive (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ectopia lentis et pupillae; Ectopia lentis 2, isolated, autosomal recessive	AR	Ophthalmologic; Pharmacogenomic	Although management related to some manifestations may be made through clinical observations (eg, related to amblyopia), surveillance related to intraocular pressure monitoring may be beneficial to allow prompt interventions; preventive measures (eg, related to contact sports) may be beneficial; Agents that may contribute to glaucoma should be avoided	Ophthalmologic	2377351; 19200529; 20702823; 21051722; 22736615; 2338190

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADAMTSL4 gene.

not_provided (1202 variants)
Inborn_genetic_diseases (210 variants)
Ectopia_lentis_2,_isolated,_autosomal_recessive (170 variants)
Ectopia_lentis_et_pupillae (122 variants)
ADAMTSL4-related_disorder (48 variants)
not_specified (8 variants)
Ectopia_lentis (5 variants)
Craniosynostosis_with_ectopia_lentis (4 variants)
Isolated_ectopia_lentis (2 variants)
See_cases (2 variants)
Craniosynostosis_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADAMTSL4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000019032.6. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	368 clinvar	10 clinvar	387
missense	2 clinvar	4 clinvar	466 clinvar	33 clinvar	4 clinvar	509
nonsense	44 clinvar	8 clinvar				52
start loss						0
frameshift	80 clinvar	13 clinvar	4 clinvar			97
splice donor/acceptor (+/-2bp)	1 clinvar	12 clinvar	1 clinvar			14
Total	127	37	480	401	14

Highest pathogenic variant AF is 0.001757404

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADAMTSL4	protein_coding	protein_coding	ENST00000271643	17	11530

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.60e-28	0.00265	125228	1	519	125748	0.00207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0800	666	672	0.991	0.0000450	6801
Missense in Polyphen		251	255.98	0.98055		2556
Synonymous	0.337	259	266	0.974	0.0000166	2357
Loss of Function	0.979	47	54.8	0.857	0.00000316	534

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00321	0.00306
Ashkenazi Jewish	0.000398	0.000397
East Asian	0.000832	0.000816
Finnish	0.00213	0.00208
European (Non-Finnish)	0.00319	0.00313
Middle Eastern	0.000832	0.000816
South Asian	0.000787	0.000784
Other	0.00181	0.00179

dbNSFP

Source: dbNSFP

Function: FUNCTION: Positive regulation of apoptosis. May facilitate FBN1 microfibril biogenesis. {ECO:0000269|PubMed:16364318, ECO:0000269|PubMed:21989719}.;
Disease: DISEASE: Ectopia lentis 2, isolated, autosomal recessive (ECTOL2) [MIM:225100]: An ocular abnormality characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation. {ECO:0000269|PubMed:19200529}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ectopia lentis et pupillae (ECTOLP) [MIM:225200]: An ocular abnormality characterized by displacement of the lenses and the pupils, associated with other ocular anomalies, but without systemic manifestations. The condition is usually bilateral, with the lenses and pupils displaced in opposite directions. Additional signs include enlarged corneal diameter, increased corneal astigmatism, increased anterior chamber depth, thinning and flattening of the iris with loss of crypts, angle malformation caused by enlarged iris processes, persistent pupillary membrane, loss of zonular fibers, tilted disk, and increased axial length. Secondary manifestations include refractive errors, glaucoma, early cataract development, and retinal detachment. Membrane formation on the posterior aspect of the iris has been observed both in histologic sections and on ultrasound biomicroscopy. {ECO:0000269|PubMed:20702823}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Post-translational protein modification;Metabolism of proteins;O-glycosylation of TSR domain-containing proteins;O-linked glycosylation (Consensus)

Recessive Scores

pRec: 0.0987

Intolerance Scores

loftool: 0.989
rvis_EVS: 0
rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

pHI: 0.107
hipred: N
hipred_score: 0.170
ghis: 0.458

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.853

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Adamtsl4
Phenotype: pigmentation phenotype; vision/eye phenotype;

Gene ontology

Biological process: epithelial cell development;proteolysis;apoptotic process;extracellular matrix organization;positive regulation of apoptotic process
Cellular component: cellular_component;interstitial matrix;endoplasmic reticulum lumen;collagen-containing extracellular matrix
Molecular function: protease binding;protein binding;peptidase activity