ALG14

ALG14 UDP-N-acetylglucosaminyltransferase subunit, the group of UDP-N-acetylglucosaminyltransferase subunits

Basic information

Region (hg38): 1:94974404-95072951

Links

ENSG00000172339 ∙ NCBI:199857 ∙ OMIM:612866 ∙ HGNC:28287 ∙ Uniprot:Q96F25 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 15 (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 15 (Strong), mode of inheritance: AR
• congenital myasthenic syndromes with glycosylation defect (Supportive), mode of inheritance: AR
• myopathy, epilepsy, and progressive cerebral atrophy (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 15 (Strong), mode of inheritance: AR
• congenital disorder of glycosylation (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital 15	AR	Musculoskeletal; Neurologic	Individuals have been described as manifesting with progressive weakness, and have been reported who have demonstrated long-term benefit from medical treatment (with anticholinesterase medication)	Musculoskeletal; Neurologic	23404334

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ALG14 gene.

• Congenital myasthenic syndrome 15 (108 variants)
• not provided (28 variants)
• Myopathy, epilepsy, and progressive cerebral atrophy (18 variants)
• Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (18 variants)
• Inborn genetic diseases (17 variants)
• not specified (5 variants)
• Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies;Congenital myasthenic syndrome 15;Myopathy, epilepsy, and progressive cerebral atrophy (1 variants)
• ALG14-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALG14 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	20	1	22
missense			68	4		72
nonsense			1			1
start loss						0
frameshift			2			2
inframe indel			2			2
splice donor/acceptor (+/-2bp)			2			2
splice region			2	3	1	6
non coding				15	3	18
Total	0	0	76	39	4

Variants in ALG14

This is a list of pathogenic ClinVar variants found in the ALG14 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-94983086-C-T		Congenital myasthenic syndrome 15	Uncertain significance (Aug 23, 2022)
1-94983094-G-A		Congenital myasthenic syndrome 15	Likely benign (Dec 20, 2022)
1-94983101-G-A		Congenital myasthenic syndrome 15 • Inborn genetic diseases • Myopathy, epilepsy, and progressive cerebral atrophy • Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies	Uncertain significance (Apr 11, 2023)
1-94983106-G-A		Congenital myasthenic syndrome 15	Likely benign (May 15, 2023)
1-94983108-G-A		Congenital myasthenic syndrome 15	Uncertain significance (Mar 18, 2022)
1-94983118-T-C		Congenital myasthenic syndrome 15	Likely benign (Oct 15, 2023)
1-94983127-C-T		Congenital myasthenic syndrome 15	Likely benign (Oct 08, 2022)
1-94983128-G-A		Congenital myasthenic syndrome 15 • Inborn genetic diseases • Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies • Myopathy, epilepsy, and progressive cerebral atrophy	Uncertain significance (Apr 11, 2023)
1-94983157-A-T		Congenital myasthenic syndrome 15	Uncertain significance (Aug 30, 2022)
1-94983167-A-G		Congenital myasthenic syndrome 15	Uncertain significance (Aug 27, 2021)
1-94983175-G-A		Congenital myasthenic syndrome 15	Likely benign (Jan 05, 2024)
1-94983176-G-C		Congenital myasthenic syndrome 15	Uncertain significance (Dec 11, 2023)
1-94983178-C-G		Congenital myasthenic syndrome 15	Uncertain significance (Dec 18, 2021)
1-94983181-G-A		Congenital myasthenic syndrome 15	Likely benign (Oct 22, 2023)
1-94983187-C-T		Congenital myasthenic syndrome 15	Likely benign (Jan 03, 2023)
1-94983188-G-A		Congenital myasthenic syndrome 15	Uncertain significance (Aug 31, 2022)
1-94983192-C-T		Congenital myasthenic syndrome 15 • Inborn genetic diseases • Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies • Myopathy, epilepsy, and progressive cerebral atrophy	Uncertain significance (Apr 11, 2023)
1-94983194-A-C		Congenital myasthenic syndrome 15 • Inborn genetic diseases	Uncertain significance (Jan 02, 2024)
1-94983195-C-T		Congenital myasthenic syndrome 15 • Myopathy, epilepsy, and progressive cerebral atrophy • Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies • Inborn genetic diseases	Uncertain significance (Apr 11, 2023)
1-94983196-A-C		Congenital myasthenic syndrome 15	Likely benign (Dec 21, 2023)
1-94983197-C-A		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
1-94983198-G-T		Congenital myasthenic syndrome 15	Uncertain significance (Sep 16, 2019)
1-94983203-A-T			Uncertain significance (Nov 05, 2018)
1-94983210-C-A		Congenital myasthenic syndrome 15	Uncertain significance (Aug 30, 2023)
1-94983214-G-A		Congenital myasthenic syndrome 15	Likely benign (Nov 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ALG14	protein_coding	protein_coding	ENST00000370205	4	98539

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000937	0.819	125702	0	43	125745	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.266	118	126	0.933	0.00000661	1376
Missense in Polyphen		36	46.126	0.78048		493
Synonymous	0.552	45	50.0	0.901	0.00000280	461
Loss of Function	1.15	6	9.90	0.606	5.71e-7	100

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000300	0.000300
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000247	0.000246
Middle Eastern	0.0000544	0.0000544
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in protein N-glycosylation. May play a role in the second step of the dolichol-linked oligosaccharide pathway. May anchor the catalytic subunit ALG13 to the ER. {ECO:0000269|PubMed:16100110}.
• Disease: DISEASE: Myasthenic syndrome, congenital, 15 (CMS15) [MIM:616227]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness. {ECO:0000269|PubMed:23404334}. 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;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation;N-Glycan biosynthesis (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.410
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.82

Haploinsufficiency Scores

• pHI: 0.294
• hipred: N
• hipred_score: 0.301
• ghis: 0.490

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.255

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Alg14

Gene ontology

• Biological process: dolichol-linked oligosaccharide biosynthetic process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane;nuclear membrane;UDP-N-acetylglucosamine transferase complex
• Molecular function: N-acetylglucosaminyldiphosphodolichol N-acetylglucosaminyltransferase activity