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SLC29A3 – Dysosteosclerosis

Dysosteosclerosis is an autosomal recessive sclerosing bone dysplasia characterized by platyspondyly (HP:0000926), metaphyseal osteosclerosis, and paucity of osteoclasts. Whole-exome sequencing in two unrelated probands identified biallelic missense variants in SLC29A3, including c.1346C>T (p.Thr449Met) (PMID:22875837).

Functional studies demonstrated expression of Slc29a3 in murine osteoclasts in vivo and revealed markedly reduced osteoclast differentiation and demineralization capacity in patient monocytes, consistent with a loss-of-function mechanism (PMID:22875837).

References

  • Human molecular genetics • 2012 • Whole-exome sequencing identifies mutations in the nucleoside transporter gene SLC29A3 in dysosteosclerosis, a form of osteopetrosis. PMID:22875837

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

Two unrelated probands with biallelic missense variants; no segregation beyond index cases; functional data supportive

Genetic Evidence

Limited

Identification of homozygous and compound heterozygous missense variants in two probands (c.1346C>T (p.Thr449Met), etc.) in AR pattern below ClinGen threshold

Functional Evidence

Moderate

Expression in osteoclasts in vivo and reduced osteoclast differentiation and resorptive function in patient cells