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

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.

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.

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			1	197	9	207
missense		1	208	6		215
nonsense		1	5			6
start loss			1			1
frameshift			3			3
inframe indel			4			4
splice donor/acceptor (+/-2bp)				1		1
splice region			3	8		11
non coding				15	1	16
Total	0	2	222	219	10

Variants in EXTL3

This is a list of pathogenic ClinVar variants found in the EXTL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-28716061-T-C			Uncertain significance (Nov 27, 2023)
8-28716064-C-CA			Uncertain significance (May 13, 2022)
8-28716065-A-G			Likely benign (Oct 25, 2022)
8-28716068-C-T		EXTL3-related disorder	Likely benign (Sep 21, 2023)
8-28716077-G-A			Uncertain significance (Oct 24, 2022)
8-28716081-C-T		Immunoskeletal dysplasia with neurodevelopmental abnormalities • Inborn genetic diseases	Uncertain significance (Sep 19, 2022)
8-28716082-G-A		Inborn genetic diseases	Uncertain significance (Oct 16, 2023)
8-28716084-A-G			Uncertain significance (May 19, 2022)
8-28716089-G-T			Likely benign (Dec 07, 2022)
8-28716092-C-T			Benign (Dec 11, 2023)
8-28716094-C-T			Uncertain significance (May 22, 2022)
8-28716095-G-A		EXTL3-related disorder	Likely benign (Nov 27, 2023)
8-28716101-C-T			Likely benign (Nov 23, 2022)
8-28716104-A-T			Likely benign (Jan 02, 2021)
8-28716120-C-T			Likely benign (Apr 15, 2023)
8-28716123-C-T			Uncertain significance (Oct 13, 2023)
8-28716124-G-A			Uncertain significance (Aug 16, 2022)
8-28716135-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
8-28716136-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
8-28716138-A-G			Uncertain significance (May 30, 2021)
8-28716141-C-G			Uncertain significance (Feb 18, 2022)
8-28716141-C-T		Inborn genetic diseases	Uncertain significance (Nov 10, 2024)
8-28716142-G-A			Uncertain significance (Aug 02, 2022)
8-28716156-A-T			Uncertain significance (Aug 09, 2022)
8-28716163-C-T			Uncertain significance (Dec 11, 2023)

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