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)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
07/18/2013
Haploinsufficiency (HI) Score Details
HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- glomuvenous malformation Monarch
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)