GeneBe

GLMN

protein-coding

glomulin, FKBP associated protein

Gene summary

This gene encodes a phosphorylated protein that is a member of a Skp1-Cullin-F-box-like complex. The protein is essential for normal development of the vasculature and mutations in this gene have been associated with glomuvenous malformations, also called glomangiomas. Multiple splice variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

Previous symbols:
  • VMGLOM

MANE transcript

NM_053274.3

Inheritance

AD

ClinVar variants

P:69U:70B:28

Top phenotype

Glomuvenous malformations

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr1:92,246,402-92,298,987

External References & Databases

Ensembl (ENSG00000174842)NCBI Gene (11146)OMIM (601749)HGNC:14373GenCCUniProt (Q92990)AlphaFoldClinVar (GLMN)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~52.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

glomuvenous malformationSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007672

Submitter: Genomics England PanelApp

glomuvenous malformationSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007672

Submitter: Labcorp Genetics (formerly Invitae)

glomuvenous malformationDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007672

Submitter: G2P

glomuvenous malformationSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007672

Submitter: Orphanet

glomuvenous malformationSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007672

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Glomuvenous malformationsAD

Manifestation: Cardiovascular; Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 11845407; 23375657Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GLMN variants in ClinVar

10 Conditions Cataloged
Glomuvenous malformationTotal: 84
Inborn genetic diseasesTotal: 65
not providedTotal: 43
not specifiedTotal: 21
GLMN-related disorderTotal: 18
GLMN-related disordersTotal: 12
Vascular skin disordersTotal: 7
Blue rubber bleb nevusTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_053274.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
5
clinvar
1
clinvar
 7
missense
61
clinvar
14
clinvar
8
clinvar
 83
nonsense
7
clinvar
13
clinvar
1
clinvar
 21
start loss
0
frameshift
10
clinvar
25
clinvar
4
clinvar
 39
splice donor/acceptor (+/-2bp)
3
clinvar
11
clinvar
3
clinvar
 17
Total204970199167

Highest pathogenic variant AF is 0.00009810776

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 60 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_053274.3RefSeqNP_444504.118MANE Select
ENST00000370360.8EnsemblENSP00000359385.318MANE Select
NM_001319683.2RefSeqNP_001306612.117Standard
ENST00000463560.1EnsemblENSP00000468973.19Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Immune System
  • Adaptive Immune System
  • Antigen processing: Ubiquitination & Proteasome degradation
  • Class I MHC mediated antigen processing & presentation

Biological Process

  • vasculogenesis
  • neural tube closure
  • negative regulation of protein ubiquitination
  • regulation of proteasomal ubiquitin-dependent protein catabolic process
  • regulation of gene expression, epigenetic

Molecular Function

  • hepatocyte growth factor receptor binding
  • protein binding
  • ubiquitin protein ligase binding
  • ubiquitin-protein transferase inhibitor activity

Cellular Component

  • cytoplasm
  • cullin-RING ubiquitin ligase complex
  • Cul2-RING ubiquitin ligase complex
  • Cul3-RING ubiquitin ligase complex
  • Cul4A-RING E3 ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000370360
Coding exons
18
Length
52586
Individuals with no LoFs
125631
Homozygous LoFs
0
Heterozygous LoFs
111
Defined
125742
p
0.000441
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.9542372820.8400.00001243921
Missense (PolyPhen)6079.4980.754731111
Synonymous-0.14710098.11.020.000004301023
Loss of Function2.022538.50.6490.00000174507

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000990.00098rare
Latino/Admixed American0.000350.00026rare
Ashkenazi Jewish00.0absent
East Asian0.000760.00076rare
Finnish0.0000920.000092rare
European (Non-Finnish)0.000450.00045rare
South Asian0.000590.00059rare
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
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 ubiquitin ligase complexes, including FBXW7, RBX1, CUL1, CUL2, CUL3, CUL4A, and thereby contributes to the regulation of CCNE1 and MYC levels (By similarity). Essential for normal development of the vasculature (PubMed:11845407). Contributes to the regulation of RPS6KB1 phosphorylation (PubMed:11571281). {ECO:0000250|UniProtKB:Q8BZM1, ECO:0000269|PubMed:11571281, ECO:0000269|PubMed:11845407, ECO:0000269|PubMed:22405651, ECO:0000269|PubMed:22748924}.;
Disease
DISEASE: Glomuvenous malformations (GVMs) [MIM:138000]: Characterized by the presence of smooth-muscle-like glomus cells in the media surrounding distended vascular lumens. {ECO:0000269|PubMed:11845407, ECO:0000269|PubMed:22405651}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.112

Intolerance Scores

LoFtool
0.918
RVIS EVS
1.29
RVIS percentile EVS
93.8

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.540

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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