RXYLT1

Chr 12AR

ribitol xylosyltransferase 1

Also known as: HP10481, MDDGA10, TMEM5

NCBI Gene: 10329 ENSG00000118600 UniProt: Q9Y2B1 OMIM: 605862

This gene encodes a glycosyltransferase that catalyzes xylose transfer to ribitol 5-phosphate in the biosynthesis of phosphorylated O-mannosyl trisaccharides on alpha-dystroglycan, which are required for binding laminin-containing extracellular proteins. Mutations cause autosomal recessive muscular dystrophy-dystroglycanopathy with congenital brain and eye anomalies, featuring cobblestone lissencephaly. The gene shows low constraint against loss-of-function variants in the population.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a type II transmembrane protein that is thought to have glycosyltransferase function. Mutations in this gene result in cobblestone lissencephaly. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2013]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.931 OMIM phenotype

Clinical Summary— RXYLT1

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Gene-Disease Validity (ClinGen)

muscle-eye-brain disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

57 unique Pathogenic / Likely Pathogenic· 174 VUS of 459 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.000

Z-score 1.82

OE 0.58 (0.38–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.73Z-score

OE missense 0.86 (0.77–0.97)

199 obs / 230.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.38–0.93)

0≤0.351.4

Missense OE?0.86 (0.77–0.97)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 13 / 22.3Missense obs/exp: 199 / 230.2Syn Z: 0.33

ClinVar Variant Classifications

459 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36

Likely Pathogenic21

VUS174

Likely Benign200

Benign14

Conflicting6

Pathogenic

Likely Pathogenic

174

VUS

200

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	34	1	1	0	36
Likely Pathogenic	18	3	0	0	21
VUS	6	152	15	1	174
Likely Benign	0	5	76	119	200
Benign	0	2	11	1	14
Conflicting	—				6
Total	58	163	103	121	451

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

7 pathogenic / likely-pathogenic (of 8) ClinVar copy-number / structural variants overlap RXYLT1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →