GLDN

Protein identityUniProt · HPA

UniProt accession

Q6ZMI3

Gene

GLDN

Ensembl

ENSG00000186417

Chromosome

15

Canonical length

551 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Vesicles,Plasma membrane

Secretome location

Secreted to extracellular matrix

Quaternary structure

Homotrimer

OverviewNCBI Gene

This gene encodes a protein that contains olfactomedin-like and collagen-like domains. The encoded protein, which exists in both transmembrane and secreted forms, promotes formation of the nodes of Ranvier in the peripheral nervous system. Mutations in this gene cause a form of lethal congenital contracture syndrome in human patients. Autoantibodies to the encoded protein have been identified in sera form patients with multifocal motor neuropathy. [provided by RefSeq, May 2017]

Canonical amino-acid sequenceUniProt

551 residues, UniProt reviewed canonical sequence.

>Q6ZMI3|GLDN
     1  MARGAEGGRG DAGWGLRGAL AAVALLSALN AAGTVFALCQ WRGLSSALRA LEAQRGREQR
    61  EDSALRSFLA ELSRAPRGAS APPQDPASSA RNKRSHSGEP APHIRAESHD MLMMMTYSMV
   121  PIRVMVDLCN STKGICLTGP SGPPGPPGAG GLPGHNGLDG QPGPQGPKGE KGANGKRGKM
   181  GIPGAAGNPG ERGEKGDHGE LGLQGNEGPP GQKGEKGDKG DVSNDVLLAG AKGDQGPPGP
   241  PGPPGPPGPP GPPGSRRAKG PRQPSMFNGQ CPGETCAIPN DDTLVGKADE KASEHHSPQA
   301  ESMITSIGNP VQVLKVTETF GTWIRESANK SDDRIWVTEH FSGIMVKEFK DQPSLLNGSY
   361  TFIHLPYYFH GCGHVVYNNS LYYHKGGSNT LVRFEFGQET SQTLKLENAL YFDRKYLFAN
   421  SKTYFNLAVD EKGLWIIYAS SVDGSSILVA QLDERTFSVV QHVNTTYPKS KAGNAFIARG
   481  ILYVTDTKDM RVTFAFDLLG GKQINANFDL RTSQSVLAML AYNMRDQHLY SWEDGHLMLY
   541  PVQFLSTTLN Q

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GLDN can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

44 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GLDN.

Disease | AllUniProt

Conditions GLDN is implicated in, by any mechanism.

• Lethal congenital contracture syndrome 11 (LCCS11) MIM:617194

Disease | GeneticClinVar

27 pathogenic / likely-pathogenic of 188 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Lethal congenital contracture syndrome 11
• Polyhydramnios
• Multiple joint contractures
• Fetal akinesia deformation sequence 1
• GLDN-related disorder

ReferencesPubMed · IEDB

Publications for GLDN from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.27

gnomAD pLI

0

gnomAD missense Z

-0.13

DepMap mean gene effect

-0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• clustering of voltage-gated sodium channels
• microvillus organization
• signal transduction

Molecular functions

• protein binding involved in heterotypic cell-cell adhesion

Cellular components

• axon
• cell surface
• collagen trimer
• extracellular space
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Olfactomedin-like domain
• Collagen triple helix repeat
• Olfactomedin-like domain-containing protein
• Collagen triple helix repeat (20 copies)
• Olfactomedin-like domain

KeywordsUniProt

• Cell membrane
• Cell projection
• Collagen
• Developmental protein
• Differentiation
• Extracellular matrix
• Glycoprotein
• Membrane
• Neurogenesis
• Repeat
• Secreted
• Signal-anchor
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of GLDN in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MYOC
• NRCAM