GLMN

glomulin, FKBP associated protein

Basic information

Region (hg38): 1:92246402-92298987

Previous symbols: [ "VMGLOM" ]

Links

ENSG00000174842

∙ NCBI:11146 ∙ OMIM:601749 ∙ HGNC:14373 ∙ Uniprot:Q92990 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

glomuvenous malformation (Strong), mode of inheritance: AD
glomuvenous malformation (Definitive), mode of inheritance: AD
glomuvenous malformation (Strong), mode of inheritance: AD
glomuvenous malformation (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Glomuvenous malformations	AD	General	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	Cardiovascular; Dermatologic	11845407; 23375657

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLMN gene.

Glomuvenous_malformation (69 variants)
Inborn_genetic_diseases (56 variants)
not_provided (37 variants)
GLMN-related_disorder (9 variants)
not_specified (3 variants)
Blue_rubber_bleb_nevus (2 variants)
Vascular_skin_disorders (1 variants)
Venous_malformation (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLMN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000053274.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar	1 clinvar	1 clinvar	1 clinvar	2 clinvar	6
missense			51 clinvar	11 clinvar	9 clinvar	71
nonsense	5 clinvar	6 clinvar				11
start loss						0
frameshift	10 clinvar	14 clinvar	1 clinvar			25
splice donor/acceptor (+/-2bp)	2 clinvar	9 clinvar				11
Total	18	30	53	12	11

Highest pathogenic variant AF is 0.0000981078

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLMN	protein_coding	protein_coding	ENST00000370360	18	52586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.15e-12	0.907	125631	0	111	125742	0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.954	237	282	0.840	0.0000124	3921
Missense in Polyphen		60	79.498	0.75473		1111
Synonymous	-0.147	100	98.1	1.02	0.00000430	1023
Loss of Function	2.02	25	38.5	0.649	0.00000174	507

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00134	0.00133
Ashkenazi Jewish	0.00	0.00
East Asian	0.000762	0.000761
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000450	0.000448
Middle Eastern	0.000762	0.000761
South Asian	0.000588	0.000588
Other	0.000163	0.000163

dbNSFP

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.;
Pathway: Immune System;Adaptive Immune System;Antigen processing: Ubiquitination & Proteasome degradation;Class I MHC mediated antigen processing & presentation (Consensus)

Recessive Scores

pRec: 0.112

Intolerance Scores

loftool: 0.918
rvis_EVS: 1.29
rvis_percentile_EVS: 93.8

Haploinsufficiency Scores

pHI: 0.276
hipred: Y
hipred_score: 0.663
ghis: 0.426

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.540

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Glmn
Phenotype: embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: vasculogenesis;neural tube closure;negative regulation of protein ubiquitination;regulation of proteasomal ubiquitin-dependent protein catabolic process;regulation of gene expression, epigenetic;negative regulation of T cell proliferation;positive regulation of phosphorylation;muscle cell differentiation;positive regulation of interleukin-2 biosynthetic process;positive regulation of cytokine secretion
Cellular component: cytoplasm;cullin-RING ubiquitin ligase complex;Cul2-RING ubiquitin ligase complex;Cul3-RING ubiquitin ligase complex;Cul4A-RING E3 ubiquitin ligase complex
Molecular function: hepatocyte growth factor receptor binding;protein binding;ubiquitin protein ligase binding;ubiquitin-protein transferase inhibitor activity