GCM2

Protein identityUniProt · HPA

UniProt accession

O75603

Gene

GCM2

Ensembl

ENSG00000124827

Chromosome

6

Canonical length

506 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

OverviewNCBI Gene

This gene is a homolog of the Drosophila glial cells missing gene, which is thought to act as a binary switch between neuronal and glial cell determination. The protein encoded by this gene contains a conserved N-terminal GCM motif that has DNA-binding activity. The protein is a transcription factor that acts as a master regulator of parathyroid development. It has been suggested that this transcription factor might mediate the effect of calcium on parathyroid hormone expression and secretion in parathyroid cells. Mutations in this gene are associated with hypoparathyroidism. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

506 residues, UniProt reviewed canonical sequence.

>O75603|GCM2
     1  MPAAAVQEAV GVCSYGMQLS WDINDPQMPQ ELALFDQFRE WPDGYVRFIY SSDEKKAQRH
    61  LSGWAMRNTN NHNGHILKKS CLGVVVCTQA CTLPDGSRLQ LRPAICDKAR LKQQKKACPN
   121  CHSALELIPC RGHSGYPVTN FWRLDGNAIF FQAKGVHDHP RPESKSETEA RRSAIKRQMA
   181  SFYQPQKKRI RESEAEENQD SSGHFSNIPP LENPEDFDIV TETSFPIPGQ PCPSFPKSDV
   241  YKATCDLATF QGDKMPPFQK YSSPRIYLPR PPCSYELANP GYTNSSPYPT LYKDSTSIPN
   301  DTDWVHLNTL QCNVNSYSSY ERSFDFTNKQ HGWKPALGKP SLVERTNHGQ FQAMATRPYY
   361  NPELPCRYLT TPPPGAPALQ TVITTTTKVS YQAYQPPAMK YSDSVREVKS LSSCNYAPED
   421  TGMSVYPEPW GPPVTVTRAA SPSGPPPMKI AGDCRAIRPT VAIPHEPVSS RTDEAETWDV
   481  CLSGLGSAVS YSDRVGPFFT YNNEDF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GCM2 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.59

Highest tissue expression

247 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GCM2.

Disease | AllUniProt

Conditions GCM2 is implicated in, by any mechanism.

• Hypoparathyroidism, familial isolated, 2 (FIH2) MIM:618883
• Hyperparathyroidism 4 (HRPT4) MIM:617343

Disease | GeneticClinVar

22 pathogenic / likely-pathogenic of 297 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypoparathyroidism, familial isolated, 2
• Hyperparathyroidism 4
• Familial hypoparathyroidism
• GCM2-related disorder

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)

0.8

gnomAD pLI

0

gnomAD missense Z

0.68

DepMap mean gene effect

-0.01

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• gliogenesis
• intracellular calcium ion homeostasis
• intracellular phosphate ion homeostasis
• parathyroid gland development
• regulation of transcription by RNA polymerase II
• transcription by RNA polymerase II

Molecular functions

• DNA binding
• DNA-binding transcription activator activity, RNA polymerase II-specific
• DNA-binding transcription factor activity, RNA polymerase II-specific
• metal ion binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific DNA binding
• sequence-specific double-stranded DNA binding

Cellular components

• chromatin
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Transcription regulator GCM domain
• GCM domain superfamily
• Chorion-specific transcription factor GCM
• GCM domain, large subdomain
• GCM, small domain
• GCM motif protein

KeywordsUniProt

• Developmental protein
• DNA-binding
• Metal-binding
• Nucleus
• Transcription
• Transcription regulation
• Zinc

InteractionsUniProt · HPA

Protein binding partners of GCM2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CRX
• FHL3
• HSFY1
• RBPMS