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GDI1 |
- 1
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- GDI1 (HGNC:4226) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- GDP dissociation inhibitor 1
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- MRX48, MRX41, GDIL
- Alias symbols
- RABGDIA, XAP-4, OPHN2, FLJ41411
- %HI
- 30.35(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0.99(Read more about gnomAD pLI score)
- LOEUF
- 0.19(Read more about gnomAD LOEUF score)
- Cytoband
- Xq28
- Genomic Coordinates
-
GRCh37/hg19: chrX:153665500-153671814 NCBI Ensembl UCSC GRCh38/hg38: chrX:154437154-154443467 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001493.3 ENST00000447750.7 (Read more about MANE Select)
- Function
- Regulates the GDP/GTP exchange reaction of most Rab proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Promotes the dissociation of GDP-bound Rab proteins from the membrane and inhibits their activation. Promotes the dissociation of RAB1A, RAB3A, RAB5A and RAB10 from membranes. {ECO:0000269|PubMed:23815289}. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- intellectual disability, X-linked 41 Monarch
-
PUBMED:
9620768
D’Adamo et al (1998) identified a nonsense variant in GDI1 (c.C>T; p.R70X) in a three-generation family (MRX48) presenting with X-linked intellectual disability. The variant was not observed in a group of 100 diverse normal controls. Western-blot analysis of lymphocytes from an affected family member demonstrated an absence of GDI1 protein. The authors state, “affected and nonaffected relatives and obligate carriers were analysed and the mutations were shown to segregate with the disease by sequence analysis and restriction enzyme digestion (a novel DdeI site is introduced by the mutation in family MRX48; data not shown).” Family MRX48 was first described by des Portes (PMID: 9106537; 1997) in which intellectual disability segregated with seven affected males and one mildly affected female (IV-6) in three generations. Obligate-carrier females (I-2, III-12) were not affected. Obligate-carrier female II-2 presented with borderline intellectual function with poor speech and difficulties in counting, writing, and reading. The variability of clinical expression in obligate-carrier females could be explained by skewed X-inactivation. Pairwise linkage analysis with 35 informative markers indicated a significant linkage between disease and several marks in Xq28, a 5.5-6.0 Mb segment.
-
PUBMED:
22002931
Strobl-Wildemann et al (2011) identified a frameshift variant in GDI1 (c.1185_1186delAG; Ser396ProfsX15) in a five-generation family presenting with X-linked intellectual disability. Of the seventeen family members tested the variant was present in 7 affected males, absent in 5 unaffected males, present in 2 unaffected females, and present in 2 mildly affected females (Figure 1). The variant segregated with disease.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
