ADAMTSL4 (ADAMTS like 4)

Gene

• Entrez ID: 54507
• Gene name: ADAMTS like 4
• Gene symbol: ADAMTSL4
• Synonyms (NCBI Gene): ADAMTSL-4, ECTOL2, TSRC1
• Chromosome: 1
• Chromosome location: 1q21.2
• Summary: This gene is a member of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-like gene family and encodes a protein with seven thrombospondin type 1 repeats. The thrombospondin type 1 repeat domain is found in many proteins with divers

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs781691587	G>A	Likely-pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant, non coding transcript variant, downstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023704	hsa-miR-1-3p	Microarray	18668037
MIRT766873	hsa-miR-34a	CLIP-seq
MIRT766874	hsa-miR-34c-5p	CLIP-seq
MIRT766875	hsa-miR-449a	CLIP-seq
MIRT766876	hsa-miR-449b	CLIP-seq
MIRT1925929	hsa-miR-1827	CLIP-seq
MIRT1925930	hsa-miR-4753-3p	CLIP-seq
MIRT766873	hsa-miR-34a	CLIP-seq
MIRT766874	hsa-miR-34c-5p	CLIP-seq
MIRT766875	hsa-miR-449a	CLIP-seq
MIRT766876	hsa-miR-449b	CLIP-seq
MIRT2674508	hsa-miR-1207-5p	CLIP-seq
MIRT2674509	hsa-miR-1321	CLIP-seq
MIRT1925929	hsa-miR-1827	CLIP-seq
MIRT2674510	hsa-miR-1909	CLIP-seq
MIRT2674511	hsa-miR-3162-5p	CLIP-seq
MIRT2674512	hsa-miR-3612	CLIP-seq
MIRT2674513	hsa-miR-4688	CLIP-seq
MIRT2674514	hsa-miR-4739	CLIP-seq
MIRT2674515	hsa-miR-4756-5p	CLIP-seq
MIRT2674516	hsa-miR-4763-3p	CLIP-seq
MIRT2674517	hsa-miR-650	CLIP-seq
MIRT2674518	hsa-miR-940	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002020	Function	Protease binding	IPI	16364318
GO:0002064	Process	Epithelial cell development	IEA
GO:0005515	Function	Protein binding	IPI	16189514, 16364318, 19060904, 23088713, 24722188, 25416956, 25910212, 26871637, 29758265, 32296183, 32814053
GO:0005576	Component	Extracellular region	IEA
GO:0005614	Component	Interstitial matrix	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	TAS
GO:0006915	Process	Apoptotic process	IEA
GO:0030198	Process	Extracellular matrix organization	IEA
GO:0031012	Component	Extracellular matrix	HDA	28327460
GO:0031012	Component	Extracellular matrix	HDA	25037231
GO:0031012	Component	Extracellular matrix	IEA
GO:0042802	Function	Identical protein binding	IPI	32296183
GO:0043065	Process	Positive regulation of apoptotic process	IDA	16364318
GO:0070285	Process	Pigment cell development	IEA

Other IDs

• MIM: 610113
• HGNC: 19706
• e!Ensembl: ENSG00000143382

Protein

• UniProt ID: Q6UY14
• Protein name: ADAMTS-like protein 4 (ADAMTSL-4) (Thrombospondin repeat-containing protein 1)
• Protein function: Positive regulation of apoptosis. May facilitate FBN1 microfibril biogenesis.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00090	TSP_1	48 → 82	Thrombospondin type 1 domain	Domain
  PF05986	ADAM_spacer1	485 → 600	ADAM-TS Spacer 1	Family
  PF19030	TSP1_ADAMTS	727 → 783		Domain
  PF19030	TSP1_ADAMTS	786 → 841		Domain
  PF19030	TSP1_ADAMTS	845 → 908		Domain
  PF19030	TSP1_ADAMTS	914 → 970		Domain
  PF19030	TSP1_ADAMTS	974 → 1025		Domain
  PF08686	PLAC	1033 → 1063	PLAC (protease and lacunin) domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in colon, heart, leukocyte, liver, lung, skeletal muscle, spleen, testis and placenta. Weaker expression in bone marrow, brain tissue, kidney and pancreas. Expression studies in fetal tissues reveal strong expression in heart
• Sequence:

  MENWTGRPWLYLLLLLSLPQLCLDQEVLSGHSLQTPTEEGQGPEGVWGPWVQWASCSQPC
  GVGVQRRSRTCQLPTVQLHPSLPLPPRPPRHPEALLPRGQGPRPQTSPETLPLYRTQSRG
  RGGPLRGPASHLGREETQEIRAARRSRLRDPIKPGMFGYGRVPFALPLHRNRRHPRSPPR
  SELSLISSRGEEAIPSPTPRAEPFSANGSPQTELPPTELSVHTPSPQAEPLSPETAQTEV
  APRTRPAPLRHHPRAQASGTEPPSPTHSLGEGGFFRASPQPRRPSSQGWASPQVAGRRPD
  PFPSVPRGRGQQGQGPWGTGGTPHGPRLEPDPQHPGAWLPLLSNGPHASSLWSLFAPSSP
  IPRCSGESEQLRACSQAPCPPEQPDPRALQCAAFNSQEFMGQLYQWEPFTEVQGSQRCEL
  NCRPRGFRFYVRHTEKVQDGTLCQPGAPDICVAGRCLSPGCDGILGSGRRPDGCGVCGGD
  DSTCRLVSGNLTDRGGPLGYQKILWIPAGALRLQIAQLRPSSNYLALRGPGGRSIINGNW
  AVDPPGSYRAGGTVFRYNRPPREEGKGESLSAEGPTTQPVDVYMIFQEENPGVFYQYVIS
  SPPPILENPTPEPPVPQLQPEILRVEPPLAPAPRPARTPGTLQRQVRIPQMPAPPHPRTP
  LGSPAAYWKRVGHSACSASCGKGVWRPIFLCISRESGEELDERSCAAGARPPASPEPCHG
  TPCPPYWEAGEWTSCSRSCGPGTQHRQLQCRQEFGGGGSSVPPERCGHLPRPNITQSCQL
  RLCGHWEVGSPWSQCSVRCGRGQRSRQVRCVGNNGDEVSEQECASGPPQPPSREACDMGP
  CTTAWFHSDWSSKCSAECGTGIQRRSVVCLGSGAALGPGQGEAGAGTGQSCPTGSRPPDM
  RACSLGPCERTWRWYTGPWGECSSECGSGTQRRDIICVSKLGTEFNVTSPSNCSHLPRPP
  ALQPCQGQACQDRWFSTPWSPCSRSCQGGTQTREVQCLSTNQTLSTRCPPQLRPSRKRPC
  NSQPCSQRPDDQCKDSSPHCPLVVQARLCVYPYYTATCCRSCAHVLERSPQDPS

• Sequence length: 1074

Pathways

Reactome:

Defective B3GALTL causes Peters-plus syndrome (PpS)
O-glycosylation of TSR domain-containing proteins

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
ADAMTSL4-related disorder	Pathogenic; Likely pathogenic	rs748115277, rs1461665171, rs746118823	RCV005057283 RCV004749770 RCV003418950 RCV003427939	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Craniosynostosis with ectopia lentis	Likely pathogenic; Pathogenic	rs747160538, rs1364255987, rs755516700, rs199473693	RCV004594589 RCV002243462 RCV004594817 RCV002243679	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ectopia lentis	Pathogenic	rs199473693	RCV000844602	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ectopia lentis 2, isolated, autosomal recessive	Likely pathogenic; Pathogenic	rs747160538, rs1461665171, rs757032537, rs2101584597, rs118203985, rs2101584216, rs763535661, rs199530808, rs2526788248, rs755516700, rs2526708427, rs757318536, rs781691587, rs587776927, rs199473693, rs794726688, rs368482584, rs794726689	RCV005040376 RCV003339791 RCV002290795 RCV002053867 RCV000001414 RCV002249229 RCV002272647 RCV005036850 RCV005036923 RCV005356509 RCV004595360 RCV003338592 RCV002506033 RCV000032752 RCV000032754 RCV000032755 RCV000032757 RCV000032758 RCV002466415	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ectopia lentis et pupillae	Pathogenic; Likely pathogenic	rs1672096009, rs747160538, rs1461665171, rs754966903, rs757032537, rs2101584597, rs768395332, rs199530808, rs2526788248, rs755516700, rs757318536, rs781691587, rs199473693, rs794726688, rs368482584	RCV001533172 RCV005040376 RCV003147695 RCV002293543 RCV003339803 RCV002053867 RCV005406489 RCV005036850 RCV005036923 RCV005356509 RCV003338593 RCV002293436 RCV000032753 RCV000032756 RCV001281006 RCV000032759	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Isolated ectopia lentis	Likely pathogenic; Pathogenic	rs754125407, rs2526718012	RCV001449734 RCV004018319	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CRANIOSYNOSTOSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Craniosynostosis syndrome	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ECTOPIA LENTIS ISOLATED	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ECTOPIA LENTIS WITH ECTOPIA OF PUPIL	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	17312329		★☆☆☆☆ Found in Text Mining only
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	17312329		★☆☆☆☆ Found in Text Mining only
Anaplasia	Anaplasia	BEFREE	26405179		★☆☆☆☆ Found in Text Mining only
Burkitt Lymphoma	Burkitt lymphoma	Pubtator	36354023	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	16364318		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	17312329		★☆☆☆☆ Found in Text Mining only
Class III malocclusion	Malocclusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital ectopic pupil	Congenital anomaly of eye	HPO_DG			★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	BEFREE	26905423		★☆☆☆☆ Found in Text Mining only
Coronary Artery Dissection Spontaneous	Spontaneous coronary artery dissection	Pubtator	36103205	Associate	★☆☆☆☆ Found in Text Mining only
Ectopia Lentis	Ectopia Lentis	LHGDN	19200529		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ectopia Lentis	Ectopia lentis	Pubtator	19200529, 25053872, 37107549	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ectopia Lentis	Ectopia Lentis	BEFREE	20141359, 20564469, 26405179, 26653794, 28394649, 28642162, 31282960		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ectopia Lentis	Ectopia Lentis	CLINVAR_DG	20564469, 20702823, 21051722, 28642162		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ectopia Lentis	Ectopia Lentis	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ectopia Lentis	Ectopia Lentis	ORPHANET_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
ECTOPIA LENTIS 2, ISOLATED, AUTOSOMAL RECESSIVE	Ectopia lentis	CLINVAR_DG	20564469, 20702823, 21051722, 22736615, 22871183, 25975359		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ECTOPIA LENTIS 2, ISOLATED, AUTOSOMAL RECESSIVE	Ectopia lentis	GENOMICS_ENGLAND_DG	20702823		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
ECTOPIA LENTIS 2, ISOLATED, AUTOSOMAL RECESSIVE	Ectopia lentis	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ectopia lentis isolated	Ectopia Lentis Isolated	BEFREE	19200529, 21051722, 21858451, 21989719, 22736615, 22871183, 25957949, 25975359		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ectopia lentis isolated	Ectopia Lentis Isolated	ORPHANET_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ectopia Lentis with Ectopia of Pupil	Ectopia Lentis	BEFREE	20702823, 21989719		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ectopia Lentis with Ectopia of Pupil	Ectopia Lentis	GENOMICS_ENGLAND_DG	20702823		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ectopia Lentis with Ectopia of Pupil	Ectopia Lentis	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ectopia Lentis with Ectopia of Pupil	Ectopia Lentis	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ectopia Lentis, Isolated, Autosomal Recessive	Ectopia Lentis Isolated	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Familial ectopia lentis	Ectopia Lentis	ORPHANET_DG			★☆☆☆☆ Found in Text Mining only
Geleophysic dysplasia	Geleophysic Dysplasia	BEFREE	21858451		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	30728876	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	30728876		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Isolated ectopia lentis	Isolated Ectopia Lentis	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	28107202	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	16364318		★☆☆☆☆ Found in Text Mining only
Marfan Syndrome	Marfan Syndrome	BEFREE	20564469, 28394649		★☆☆☆☆ Found in Text Mining only
Microspherophakia	Microspherophakia	Pubtator	40025527	Associate	★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	Pubtator	29346494	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	28107202		★☆☆☆☆ Found in Text Mining only
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	28107202	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	28107202		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	16364318		★☆☆☆☆ Found in Text Mining only
Purpura, Thrombotic Thrombocytopenic	Thrombotic thrombocytopenic purpura	BEFREE	21880666		★☆☆☆☆ Found in Text Mining only