RXYLT1

ribitol xylosyltransferase 1, the group of Glycosyltransferase family 8

Basic information

Region (hg38): 12:63779833-63809792

Previous symbols: [ "TMEM5" ]

Links

ENSG00000118600 ∙ NCBI:10329 ∙ OMIM:605862 ∙ HGNC:13530 ∙ Uniprot:Q9Y2B1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 (Strong), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy, type A (Supportive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 (Definitive), mode of inheritance: AR
• muscle-eye-brain disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 10	AR	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; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic	23217329

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RXYLT1 gene.

• not_provided (372 variants)
• Inborn_genetic_diseases (58 variants)
• Muscular_dystrophy-dystroglycanopathy_(congenital_with_brain_and_eye_anomalies),_type_a,_10 (30 variants)
• not_specified (20 variants)
• RXYLT1-related_disorder (6 variants)
• Walker-Warburg_congenital_muscular_dystrophy (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RXYLT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014254.3. 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	112	1	114
missense	1	2	149	6	1	159
nonsense	10	4	1			15
start loss		1	1			2
frameshift	20	6	4			30
splice donor/acceptor (+/-2bp)	1	8				9
Total	32	21	156	118	2

Highest pathogenic variant AF is 0.0000576466

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RXYLT1	protein_coding	protein_coding	ENST00000261234	6	29756

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000107	0.941	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.730	199	230	0.865	0.0000110	2897
Missense in Polyphen		71	84.043	0.84481		1032
Synonymous	0.332	85	89.0	0.955	0.00000474	809
Loss of Function	1.82	13	22.3	0.583	0.00000110	265

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00113	0.000984
Ashkenazi Jewish	0.00	0.00
East Asian	0.000110	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000181	0.000176
Middle Eastern	0.000110	0.000109
South Asian	0.000236	0.000229
Other	0.00189	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: UDP-xylosyltransferase involved in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N- acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate- 6-)mannose), a carbohydrate structure present in alpha- dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:25279699, PubMed:27130732, PubMed:27733679, PubMed:27601598). Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyzes the transfer of UDP-D- xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan (PubMed:27130732, PubMed:27733679). {ECO:0000269|PubMed:25279699, ECO:0000269|PubMed:27601598, ECO:0000269|PubMed:27733679, ECO:0000305|PubMed:27130732}.
• Disease: DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A10 (MDDGA10) [MIM:615041]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:23217329, ECO:0000269|PubMed:23519211, ECO:0000269|PubMed:27130732, ECO:0000269|PubMed:27212206, ECO:0000269|PubMed:27733679}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mannose type O-glycan biosynthesis - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.0856

Intolerance Scores

• rvis_EVS: 0.22
• rvis_percentile_EVS: 68.27

Haploinsufficiency Scores

• pHI: 0.0935
• hipred: N
• hipred_score: 0.362
• ghis: 0.496

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Rxylt1

Zebrafish Information Network

• Gene name: rxylt1
• Affected structure: myotome
• Phenotype tag: abnormal
• Phenotype quality: broken

Gene ontology

• Biological process: protein O-linked mannosylation
• Cellular component: Golgi membrane;nucleoplasm;Golgi apparatus;integral component of plasma membrane
• Molecular function: ribitol beta-1,4-xylosyltransferase activity