GLMN

glomulin, FKBP associated protein

Basic information

Region (hg38): 1:92246401-92298987

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 (64 variants)
• not provided (44 variants)
• Inborn genetic diseases (15 variants)
• not specified (5 variants)
• GLMN-related condition (2 variants)
• Blue rubber bleb nevus (2 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	1	2	4
missense			17		13	30
nonsense	5	3				8
start loss						0
frameshift	8	9	2			19
inframe indel	1					1
splice donor/acceptor (+/-2bp)	2	5				7
splice region			1	1	3	5
non coding			4	4	20	28
Total	16	17	24	5	35

Highest pathogenic variant AF is 0.0000461

Variants in GLMN

This is a list of pathogenic ClinVar variants found in the GLMN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-92246415-C-G		Glomuvenous malformation	Benign (Nov 12, 2018)
1-92246438-A-C		Glomuvenous malformation	Uncertain significance (Jan 13, 2018)
1-92246595-G-A			Likely pathogenic (May 13, 2018)
1-92246626-GAA-G		Glomuvenous malformation	Uncertain significance (Sep 01, 2023)
1-92246627-A-G		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
1-92246709-C-T			Benign (May 12, 2021)
1-92247041-GAA-G		not specified	Benign (Nov 12, 2018)
1-92247091-G-A		Inborn genetic diseases	Uncertain significance (Apr 13, 2023)
1-92247095-C-T		Glomuvenous malformation	Likely benign (Jan 12, 2018)
1-92247100-C-A		Blue rubber bleb nevus	Pathogenic (-)
1-92247304-CAG-C			Benign (May 12, 2021)
1-92247877-C-T		Glomuvenous malformation	Likely pathogenic (Aug 21, 2023)
1-92247981-T-A		Glomuvenous malformation	Benign (Jan 12, 2018)
1-92247996-A-G		Glomuvenous malformation	Uncertain significance (Jan 13, 2018)
1-92248000-TGAAA-T		Glomuvenous malformation	Likely benign (Jun 14, 2016)
1-92262619-A-G			Benign (Nov 12, 2018)
1-92262861-A-T		Glomuvenous malformation	Likely pathogenic (Aug 02, 2021)
1-92262862-CTTGA-C			Likely pathogenic (Oct 23, 2020)
1-92262884-T-A		Inborn genetic diseases	Uncertain significance (Aug 10, 2023)
1-92262939-AAT-A		Glomuvenous malformation	Likely benign (Oct 16, 2023)
1-92263622-CCTAT-C			Pathogenic (Dec 17, 2022)
1-92263655-AC-A		Glomuvenous malformation	Pathogenic (Feb 24, 2020)
1-92263676-CA-C		Glomuvenous malformation • GLMN-related disorder	Pathogenic/Likely pathogenic (Jul 05, 2023)
1-92263708-T-TA		Glomuvenous malformation	Pathogenic/Likely pathogenic (Dec 30, 2022)
1-92263713-C-T			Pathogenic (Mar 03, 2022)

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