GLMN
  • 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
GLMN (HGNC:14373) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
glomulin, FKBP associated protein
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
VMGLOM
Alias symbols
FAP48, FAP68, GLML, GVM, FKBPAP
%HI
14.69(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.01(Read more about gnomAD pLI score)
LOEUF
1.71(Read more about gnomAD LOEUF score)
Cytoband
1p22.1
Genomic Coordinates
GRCh37/hg19: chr1:92711959-92764544 NCBI Ensembl UCSC
GRCh38/hg38: chr1:92246402-92370844 NCBI Ensembl UCSC
MANE Select Transcript
NM_053274.3 ENST00000370360.8 (Read more about MANE Select)
Function
[Isoform 1]: Regulatory component of cullin-RING-based SCF (SKP1-Cullin-F-box protein) E3 ubiquitin-protein ligase complexes (PubMed:22405651, PubMed:22748924). Inhibits E3 ubiquitin ligase activity by binding to RBX1 (via RING domain) and inhibiting its interaction with the E2 ubiquitin-conjugating enzyme CDC34 (PubMed:22405651, PubMed:22748924). Inhibits RBX1-mediated neddylation of CUL1 (PubMed:22405651). Required for normal stability and normal cellular levels of key components of SCF ubiqui... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-5310
ClinGen Curation ID:
CCID:007220
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Read full report...
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Read full report...
Last Evaluated:
07/18/2013

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 11845407
    Brouillard et al. (2002) identified an intragenic deletion and 13 sequence-level mutations (predicted to result in a loss-of-function) in the GLMN gene in 14 unrelated families with autosomal dominant glomuvenous malformations (GVMs), including an 8.4 kb intragenic deletion removing exons 8-13 and two nonsense mutations. Acquisition of a somatic ‘second hit’ GLMN mutation was demonstrated for one individual in this cohort, supporting a 2-hit mode of inheritance for GVMs. The authors also report that, amongst the families studied, observed penetrance of the mutations was 88.6% and rose to 92.7% at age 20 years.
  • PUBMED: 15689436
    Brouillard et al. (2005) reported 3 novel frameshift mutations and identify 23 additional families with GLMN mutations and GVM.
  • PUBMED: 22092580
    Borroni et al. (2011) describe a novel frameshift mutation (p.Leu374LeufsX4 ) segregating with the phenotype in a family with multiple GVMs. The mutation was absent in 190 controls.
HI Evidence Comments:
Alterations at the GLMN locus are associated with autosomal dominant hereditary glomuvenous malformations (GVMs). Penetrance of this phenotype is age-dependent and may be incomplete; expressivity is variable. Somatic 'second hit' mutations are hypothesized to be responsible for the expression of GVMs. Reported mutations are predicted to result in a loss-of-function, however whole gene deletions have not been reported at the time of this literature search.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000001.10) (NC_000001.11)