Skeletal dysplasia

Gene: RAB34

Green List (high evidence)

Comment on list classification: There are four unrelated families reported with biallelic RAB34 variants and with Orofaciodigital syndrome XX, which includes skeletal phenotypes and cleft lip/ palate. There is also functional evidence available from mouse model that recapitulates human phenotype. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 2 Nov 2026, 6:23 p.m. | Last Modified: 2 Nov 2026, 6:23 p.m.

Panel Version: 10.28

PMID:37384395 (2023) reported the identification of biallelic missense variants in a novel disease-causing ciliary gene RAB34 in four individuals from three unrelated families.Three different variants were identified in total - p.Arg211His, p.Gly202Val & p.Glu218Lys. Affected individuals presented with a novel form of Orofaciodigital syndrome (OFDS) accompanied by cardiac, cerebral, skeletal and anorectal defects. All probands presented with bilateral cleft palate/lip and bilateral hand and feet polydactyly.

PMID: 37619988 (2023) reported a foetus with an atypical skeletal ciliopathy phenotype and compound heterozygous variants in the RAB34 gene. The affected fetus had multiple malformations, including posterior neck edema, micrognathia, low-set and small ears, auricular hypoplasia, cleft lip and palate, short extremities, and a combination of rarely occurring pre- and postaxial polydactyly. The foetus was identified with compound heterozygous variants in the RAB34 gene: p.Ile85Thr & p.Arg231Ter variants.

PMID:30301781 (2018) demonstrated that Rab34 localizes to cilia, and that its mutation results in significant decrease of ciliogenesis in both cultured cells and mice. The study also showed that Rab34 mutant mice exhibit polydactyly, and cleft-lip and -palate. These phenotypes are consistent with observations that nonciliated Rab34 mutant cells fail to respond to Hedgehog signaling and that processing of full-length Gli3 to its C-terminally truncated form is reduced in Rab34 mutant embryos.

This gene has been associated with relevant phenotypes in OMIM (MIM #620718) and Gene2Phenotype (with 'moderate' rating on the DD panel) and both these records were last accessed on 02 November 2026.
Sources: Literature

Created: 2 Nov 2026, 6:18 p.m. | Last Modified: 2 Nov 2026, 6:25 p.m.

Panel Version: 10.28

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Orofaciodigital syndrome XX, OMIM:620718; orofaciodigital syndrome 20, MONDO:0958230

Publications

• 30301781
• 37384395
• 37619988