EXTL3

exostosin like glycosyltransferase 3, the group of Exostosin glycosyltransferase family

Basic information

Region (hg38): 8:28600469-28756561

Links

ENSG00000012232 ∙ NCBI:2137 ∙ OMIM:605744 ∙ HGNC:3518 ∙ Uniprot:O43909 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• immunoskeletal dysplasia with neurodevelopmental abnormalities (Strong), mode of inheritance: AR
• immunoskeletal dysplasia with neurodevelopmental abnormalities (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunoskeletal dysplasia with neurodevelopmental abnormalities	AR	Allergy/Immunology/Infectious	The condition can include severe combined immunodeficiency, and awareness may allow preventive measures and early and aggressive treatment of infections	Allergy/Immunology/Infectious; Musculoskeletal; Neurologic	28148688; 28132690

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXTL3 gene.

• not_provided (485 variants)
• Inborn_genetic_diseases (101 variants)
• EXTL3-related_disorder (11 variants)
• Immunoskeletal_dysplasia_with_neurodevelopmental_abnormalities (11 variants)
• not_specified (1 variants)
• Familial_meningioma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXTL3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001440.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	223	9	233
missense	1	1	246	8		256
nonsense		1	6			7
start loss			1			1
frameshift			5			5
splice donor/acceptor (+/-2bp)				1		1
Total	1	2	259	232	9

Highest pathogenic variant AF is 0.000008673328

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXTL3	protein_coding	protein_coding	ENST00000220562	5	155131

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000250	0.999	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	458	556	0.824	0.0000394	6005
Missense in Polyphen		91	176.92	0.51436		1866
Synonymous	-1.29	259	234	1.11	0.0000165	1919
Loss of Function	2.94	13	30.5	0.426	0.00000172	346

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000167	0.000167
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Glycosyltransferase which regulates the biosynthesis of heparan sulfate (HS). Important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs) (PubMed:28132690, PubMed:28148688). Required for the function of REG3A in regulating keratinocyte proliferation and differentiation (PubMed:22727489). {ECO:0000269|PubMed:22727489, ECO:0000269|PubMed:28132690, ECO:0000269|PubMed:28148688}.
• Pathway: Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human);XBP1(S) activates chaperone genes;heparan sulfate biosynthesis (late stages);heparan sulfate biosynthesis (Consensus)

Recessive Scores

• pRec: 0.177

Intolerance Scores

• loftool: 0.0851
• rvis_EVS: -1.79
• rvis_percentile_EVS: 2.24

Haploinsufficiency Scores

• pHI: 0.349
• hipred: Y
• hipred_score: 0.575
• ghis: 0.490

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.700

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Extl3
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: extl3
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: organization quality

Gene ontology

• Biological process: protein glycosylation;heparan sulfate proteoglycan biosynthetic process;positive regulation of cell growth;IRE1-mediated unfolded protein response
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;integral component of membrane
• Molecular function: glucuronyl-galactosyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity;transferase activity, transferring glycosyl groups;metal ion binding