ALG13

ALG13 UDP-N-acetylglucosaminyltransferase subunit, the group of UDP-N-acetylglucosaminyltransferase subunits|Tudor domain containing|OTU domain containing

Basic information

Region (hg38): X:111665810-111760649

Previous symbols: [ "GLT28D1", "CXorf45" ]

Links

ENSG00000101901 ∙ NCBI:79868 ∙ OMIM:300776 ∙ HGNC:30881 ∙ Uniprot:Q9NP73 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 36 (Strong), mode of inheritance: XLD
• developmental and epileptic encephalopathy, 36 (Limited), mode of inheritance: XL
• developmental and epileptic encephalopathy, 36 (Strong), mode of inheritance: XL
• non-syndromic X-linked intellectual disability (Supportive), mode of inheritance: XL
• developmental and epileptic encephalopathy, 36 (Supportive), mode of inheritance: XL
• developmental and epileptic encephalopathy, 36 (Strong), mode of inheritance: XL
• developmental and epileptic encephalopathy, 36 (Strong), mode of inheritance: XL
• developmental and epileptic encephalopathy (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 36	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	22492991; 23033978; 23934111; 24781210; 26138355
One patient has been reported with a phenotype described as consistent with a congenital disorder of glycosylation, but subsequent patients did not have similar features

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG13 gene.

• Developmental and epileptic encephalopathy, 36 (745 variants)
• not provided (215 variants)
• not specified (82 variants)
• Inborn genetic diseases (69 variants)
• ALG13-related condition (4 variants)
• See cases (2 variants)
• Intellectual disability (2 variants)
• Congenital disorder of glycosylation (2 variants)
• Neurodevelopmental delay;Seizure;Hypotonia (1 variants)
• Neurodevelopmental delay (1 variants)
• Infantile spasms;Global developmental delay;Osteopenia;Microcephaly;Cerebral visual impairment (1 variants)
• Rare genetic intellectual disability (1 variants)
• Developmental and epileptic encephalopathy, 1;Congenital disorder of glycosylation (1 variants)
• SUDDEN INFANT DEATH SYNDROME (1 variants)
• Seizure (1 variants)
• Developmental and epileptic encephalopathy, 1 (1 variants)
• Microcephaly;Seizure;Neurodevelopmental delay;Hypotonia (1 variants)
• Microcephaly;Neurodevelopmental delay;Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG13 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			3	193	12	208
missense	2	5	320	45	8	380
nonsense			2			2
start loss						0
frameshift			3			3
inframe indel			19	21	4	44
splice donor/acceptor (+/-2bp)			3			3
splice region			14	28	5	47
non coding			2	129	16	147
Total	2	5	352	388	40

Variants in ALG13

This is a list of pathogenic ClinVar variants found in the ALG13 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-111680917-TG-T			Benign (Aug 20, 2019)
X-111681192-G-A		not specified	Likely benign (Mar 06, 2018)
X-111681205-G-A			Likely benign (Apr 24, 2018)
X-111681210-A-G		not specified • ALG13-related disorder	Likely benign (Aug 30, 2019)
X-111681212-C-T		not specified	Likely benign (Feb 10, 2017)
X-111681218-C-T		Inborn genetic diseases	Uncertain significance (Sep 06, 2017)
X-111681224-G-A		Developmental and epileptic encephalopathy, 36	Likely benign (Dec 02, 2023)
X-111681228-G-A		Developmental and epileptic encephalopathy, 36	Uncertain significance (Aug 15, 2022)
X-111681230-G-A		Developmental and epileptic encephalopathy, 36	Likely benign (May 23, 2023)
X-111681231-T-C		not specified • Developmental and epileptic encephalopathy, 36 • Inborn genetic diseases	Likely benign (Jan 24, 2024)
X-111681239-C-T		Developmental and epileptic encephalopathy, 36	Likely benign (Mar 08, 2023)
X-111681240-G-C		Developmental and epileptic encephalopathy, 36	Uncertain significance (Jul 09, 2020)
X-111681245-G-A		Developmental and epileptic encephalopathy, 36	Likely benign (Apr 22, 2023)
X-111681248-C-T		Developmental and epileptic encephalopathy, 36	Likely benign (Jan 22, 2024)
X-111681251-C-G		Developmental and epileptic encephalopathy, 36	Likely benign (May 24, 2023)
X-111681253-G-A		Developmental and epileptic encephalopathy, 36	Uncertain significance (Nov 14, 2021)
X-111681254-C-T		Developmental and epileptic encephalopathy, 36	Likely benign (Oct 15, 2023)
X-111681260-C-A		not specified • Developmental and epileptic encephalopathy, 36	Benign/Likely benign (Jan 31, 2024)
X-111681261-G-A		Developmental and epileptic encephalopathy, 36	Uncertain significance (Sep 01, 2021)
X-111681261-G-T		Developmental and epileptic encephalopathy, 36	Uncertain significance (Sep 01, 2021)
X-111681268-T-A		Infantile spasms;Global developmental delay;Osteopenia;Microcephaly;Cerebral visual impairment • Congenital disorder of glycosylation • See cases	Likely pathogenic (Dec 21, 2022)
X-111681269-T-TGCG		Developmental and epileptic encephalopathy, 36	Uncertain significance (Aug 27, 2021)
X-111681272-G-A		not specified • Developmental and epileptic encephalopathy, 36	Likely benign (Nov 14, 2023)
X-111681277-T-C			Uncertain significance (May 31, 2016)
X-111681278-G-A		Developmental and epileptic encephalopathy, 36	Likely benign (Apr 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG13	protein_coding	protein_coding	ENST00000394780	27	94835

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000205	122973	1	0	122974	0.00000407

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.15	332	396	0.838	0.0000287	7384
Missense in Polyphen		81	131.87	0.61424		2443
Synonymous	-0.722	153	142	1.08	0.0000106	2178
Loss of Function	5.51	2	39.2	0.0510	0.00000272	801

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000127	0.00000909
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Isoform 1: Possible multifunctional enzyme with both glycosyltransferase and deubiquitinase activities.
• Disease: DISEASE: Epileptic encephalopathy, early infantile, 36 (EIEE36) [MIM:300884]: A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. Some EIEE36 patients may present with an abnormal isoelectric focusing of serum transferrin, consistent with a diagnostic classification of congenital disorder of glycosylation type I. Congenital disorders of glycosylation result in a wide variety of clinical features, such as defects in the nervous system development, psychomotor retardation, dysmorphic features, hypotonia, coagulation disorders, and immunodeficiency. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions. {ECO:0000269|PubMed:22492991, ECO:0000269|PubMed:23033978, ECO:0000269|PubMed:23934111, ECO:0000269|PubMed:26138355, ECO:0000269|PubMed:27476654}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: N-Glycan biosynthesis - Homo sapiens (human);Post-translational protein modification;Metabolism of proteins;dolichyl-diphosphooligosaccharide biosynthesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Intolerance Scores

• loftool: 0.273
• rvis_EVS: -1
• rvis_percentile_EVS: 8.37

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.314
• ghis: 0.651

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.133

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg13
• Phenotype: growth/size/body region 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); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; embryo phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: alg13
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curled

Gene ontology

• Biological process: dolichol-linked oligosaccharide biosynthetic process;proteolysis
• Cellular component: endoplasmic reticulum membrane
• Molecular function: RNA binding;N-acetylglucosaminyldiphosphodolichol N-acetylglucosaminyltransferase activity;thiol-dependent ubiquitinyl hydrolase activity