EXTL1

protein-coding

exostosin like glycosyltransferase 1, the group of Exostosin glycosyltransferase family

Gene summary

This gene is a member of the multiple exostoses (EXT) family of glycosyltransferases, which function in the chain polymerization of heparan sulfate and heparin. The encoded protein harbors alpha 1,4- N-acetylglucosaminyltransferase activity, and is involved in chain elongation of heparan sulfate and possibly heparin. [provided by RefSeq, Jul 2008]

MANE transcript

NM_004455.3

Inheritance

—

ClinVar variants

U:106B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.75

Max pathogenic AF

—

Genomic locus

chr1:26,019,884-26,036,464

External References & Databases

Ensembl (ENSG00000158008)

Transcript & Mutation Effects

hg38 • Region Span ~16.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to EXTL1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 115

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004455.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			104 clinvar	12 clinvar		116
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	106	12	0	118

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004455.3	RefSeq	NP_004446.2	11	MANE Select
ENST00000374280.4	Ensembl	ENSP00000363398.3	11	MANE Select
ENST00000882616.1	Ensembl	ENSP00000552675.1	10	Standard
ENST00000882616.2	Ensembl	ENSP00000552675.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycosaminoglycan biosynthesis - heparan sulfate / heparin - Homo sapiens (human)
HH-Ncore
XBP1(S) activates chaperone genes
heparan sulfate biosynthesis (late stages)
heparan sulfate biosynthesis

Biological Process

skeletal system development
protein glycosylation
IRE1-mediated unfolded protein response

Molecular Function

glucuronosyl-N-acetylglucosaminyl-proteoglycan 4-alpha-N-acetylglucosaminyltransferase activity

Cellular Component

endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000374280
Coding exons: 11
Length: 16581
Individuals with no LoFs: 125399
Homozygous LoFs: 1
Heterozygous LoFs: 347
Defined: 125747
p: 0.00138

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.904	336	386	0.871	0.0000215	4295
Missense (PolyPhen)		114	147.78	0.77143		1780
Synonymous	0.171	160	163	0.983	0.00000918	1459
Loss of Function	1.22	21	27.9	0.752	0.00000128	303

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0024	0.0023	notable
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0.0022	0.0017	notable
East Asian	0.00011	0.00011	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.0021	0.0021	notable
South Asian	0.00070	0.00065	rare
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable glycosyltransferase. {ECO:0000250}.;

Recessive Scores

pRec: 0.0936

Intolerance Scores

LoFtool: 0.179
RVIS EVS: 0.71
RVIS percentile EVS: 85.82

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.666

Gene Damage Prediction

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