GLDN

gliomedin

Basic information

Region (hg38): 15:51341655-51408005

Previous symbols: [ "COLM" ]

Links

ENSG00000186417

∙ NCBI:342035 ∙ OMIM:608603 ∙ HGNC:29514 ∙ Uniprot:Q6ZMI3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

lethal congenital contracture syndrome 11 (Strong), mode of inheritance: AR
lethal congenital contracture syndrome 11 (Strong), mode of inheritance: AR
lethal congenital contracture syndrome 11 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lethal congenital contracture syndrome 11	AR	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	Neurologic; Musculoskeletal	27616481

ClinVar

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

Inborn_genetic_diseases (82 variants)
Lethal_congenital_contracture_syndrome_11 (31 variants)
not_provided (25 variants)
GLDN-related_disorder (19 variants)
Fetal_akinesia_deformation_sequence_1 (3 variants)
Polyhydramnios (3 variants)
Multiple_joint_contractures (2 variants)
Arthrogryposis_multiplex_congenita (2 variants)
Breathing_dysregulation (1 variants)
Aromatase_deficiency (1 variants)
not_specified (1 variants)
Congenital_contracture (1 variants)
Flexion_contracture (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLDN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000181789.4. 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				9 clinvar	2 clinvar	11
missense		11 clinvar	83 clinvar	12 clinvar	2 clinvar	108
nonsense	1 clinvar	3 clinvar				4
start loss						0
frameshift	3 clinvar	5 clinvar				8
splice donor/acceptor (+/-2bp)	1 clinvar	4 clinvar	2 clinvar	1 clinvar		8
Total	5	23	85	22	4

Highest pathogenic variant AF is 0.0000718668

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLDN	protein_coding	protein_coding	ENST00000335449	10	66385

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.58e-13	0.0699	125675	0	73	125748	0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.130	303	297	1.02	0.0000145	3529
Missense in Polyphen		95	100.63	0.94405		1204
Synonymous	-1.07	133	118	1.13	0.00000654	1109
Loss of Function	0.525	21	23.8	0.884	0.00000124	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000346	0.000332
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000323	0.000316
Middle Eastern	0.000544	0.000544
South Asian	0.000530	0.000523
Other	0.000516	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Ligand for NRCAM and NFASC/neurofascin that plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Mediates interaction between Schwann cell microvilli and axons via its interactions with NRCAM and NFASC. Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters. Required, together with NRCAM, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier. {ECO:0000250|UniProtKB:Q8BMF8}.;
Disease: DISEASE: Lethal congenital contracture syndrome 11 (LCCS11) [MIM:617194]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. {ECO:0000269|PubMed:27616481}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.101

Intolerance Scores

loftool: 0.263
rvis_EVS: 1.42
rvis_percentile_EVS: 94.92

Haploinsufficiency Scores

pHI: 0.222
hipred: N
hipred_score: 0.287
ghis: 0.404

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.110

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Gldn
Phenotype: 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: microvillus organization;heterotypic cell-cell adhesion;clustering of voltage-gated sodium channels
Cellular component: collagen trimer;extracellular space;plasma membrane;integral component of membrane;axon
Molecular function: protein binding involved in heterotypic cell-cell adhesion