ADAMTSL4

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

Basic information

Region (hg38): 1:150549368-150560937

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

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 (850 variants)
• Ectopia lentis 2, isolated, autosomal recessive (175 variants)
• Ectopia lentis et pupillae (114 variants)
• Inborn genetic diseases (64 variants)
• Ectopia lentis et pupillae;Ectopia lentis 2, isolated, autosomal recessive (15 variants)
• not specified (8 variants)
• ADAMTSL4-related condition (7 variants)
• Ectopia lentis (6 variants)
• See cases (2 variants)
• Ectopia lentis 2, isolated, autosomal recessive;Ectopia lentis et pupillae (2 variants)
• Isolated ectopia lentis (1 variants)
• Craniosynostosis with ectopia lentis (1 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.

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			8	171	14	193
missense	1	1	387	20	7	416
nonsense	30	3	1			34
start loss						0
frameshift	39	7	5			51
inframe indel			4			4
splice donor/acceptor (+/-2bp)		3	1			4
splice region			11	24	1	36
non coding			20	79	46	145
Total	70	14	426	270	67

Highest pathogenic variant AF is 0.00118

Variants in ADAMTSL4

This is a list of pathogenic ClinVar variants found in the ADAMTSL4 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-150549422-C-T		Ectopia lentis 2, isolated, autosomal recessive	Uncertain significance (Jan 19, 2018)
1-150549837-C-T		Ectopia lentis 2, isolated, autosomal recessive	Benign (Jan 13, 2018)
1-150549880-G-A		Ectopia lentis 2, isolated, autosomal recessive	Uncertain significance (Jan 12, 2018)
1-150551891-CA-C			Benign (Nov 05, 2020)
1-150551891-C-CA			Benign (Feb 03, 2021)
1-150551992-G-A			Likely benign (Aug 16, 2019)
1-150552288-G-A			Uncertain significance (Oct 05, 2022)
1-150552294-G-T			Uncertain significance (Jan 24, 2024)
1-150552297-C-G			Uncertain significance (Apr 03, 2023)
1-150552317-A-AG			Benign (Sep 01, 2022)
1-150552320-G-C			Likely benign (Mar 02, 2023)
1-150552322-C-T			Likely benign (Sep 27, 2023)
1-150552323-C-T			Likely benign (Jan 20, 2024)
1-150552325-C-T			Likely benign (Jan 13, 2024)
1-150552326-G-A			Likely benign (May 23, 2023)
1-150552328-G-A			Likely benign (Aug 09, 2023)
1-150552528-G-C			Likely benign (Jan 29, 2024)
1-150552529-C-A			Likely benign (Jul 25, 2023)
1-150552530-C-A			Likely benign (Dec 30, 2023)
1-150552530-C-T			Likely benign (Feb 26, 2023)
1-150552531-T-C			Likely benign (Oct 31, 2023)
1-150552534-G-T			Likely benign (Aug 23, 2023)
1-150552535-G-A			Likely benign (Sep 09, 2023)
1-150552546-C-G			Likely benign (Aug 30, 2023)
1-150552548-G-A			Pathogenic (Sep 08, 2023)

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