GCM2 (glial cells missing transcription factor 2)

Gene

• Entrez ID: 9247
• Gene name: Glial cells missing transcription factor 2
• Gene symbol: GCM2
• Synonyms (NCBI Gene): FIH2, GCMB, HRPT4, hGCMb
• Chromosome: 6
• Chromosome location: 6p24.2
• Summary: 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 ac

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104893959	C>A,T	Pathogenic	Coding sequence variant, missense variant
rs104893960	C>T	Pathogenic	Coding sequence variant, missense variant
rs142287570	T>G	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs533942394	T>C,G	Likely-pathogenic	Missense variant, coding sequence variant
rs759190203	->A	Pathogenic	Splice donor variant
rs886037646	A>-	Pathogenic	Frameshift variant, coding sequence variant
rs1057519581	G>C	Pathogenic	Coding sequence variant, missense variant
rs1057519582	A>T	Pathogenic	Coding sequence variant, missense variant
rs1554103179	G>T	Pathogenic	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT497339	hsa-miR-548b-3p	PAR-CLIP	22291592
MIRT497338	hsa-miR-4511	PAR-CLIP	22291592
MIRT497337	hsa-miR-500a-5p	PAR-CLIP	22291592
MIRT497336	hsa-miR-362-5p	PAR-CLIP	22291592
MIRT497335	hsa-miR-500b-5p	PAR-CLIP	22291592
MIRT497334	hsa-miR-617	PAR-CLIP	22291592
MIRT497333	hsa-miR-6505-3p	PAR-CLIP	22291592
MIRT497339	hsa-miR-548b-3p	PAR-CLIP	22291592
MIRT497338	hsa-miR-4511	PAR-CLIP	22291592
MIRT497337	hsa-miR-500a-5p	PAR-CLIP	22291592
MIRT497336	hsa-miR-362-5p	PAR-CLIP	22291592
MIRT497335	hsa-miR-500b-5p	PAR-CLIP	22291592
MIRT497334	hsa-miR-617	PAR-CLIP	22291592
MIRT497333	hsa-miR-6505-3p	PAR-CLIP	22291592

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IMP	20190276, 27745835
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0003677	Function	DNA binding	IEA
GO:0003677	Function	DNA binding	TAS	10343099
GO:0005515	Function	Protein binding	IPI	25416956, 25910212, 29892012, 31515488, 32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	20190276
GO:0005634	Component	Nucleus	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006366	Process	Transcription by RNA polymerase II	IEA
GO:0006366	Process	Transcription by RNA polymerase II	IMP	20190276, 27745835
GO:0006874	Process	Intracellular calcium ion homeostasis	IMP	15728199
GO:0030643	Process	Intracellular phosphate ion homeostasis	IMP	15728199
GO:0042063	Process	Gliogenesis	IBA
GO:0043565	Function	Sequence-specific DNA binding	IDA	15863676
GO:0043565	Function	Sequence-specific DNA binding	IMP	20190276
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0060017	Process	Parathyroid gland development	IMP	15728199, 27745835
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 603716
• HGNC: 4198
• e!Ensembl: ENSG00000124827

Protein

• UniProt ID: O75603
• Protein name: Chorion-specific transcription factor GCMb (hGCMb) (GCM motif protein 2) (Glial cells missing homolog 2)
• Protein function: Transcription factor that binds specific sequences on gene promoters and activate their transcription. Through the regulation of gene transcription, may play a role in parathyroid gland development. {ECO:0000269|PubMed:20190276, ECO:0000269|PubM
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03615	GCM	35 → 172	GCM motif protein	Family

• Sequence:

  MPAAAVQEAVGVCSYGMQLSWDINDPQMPQELALFDQFREWPDGYVRFIYSSDEKKAQRH
  LSGWAMRNTNNHNGHILKKSCLGVVVCTQACTLPDGSRLQLRPAICDKARLKQQKKACPN
  CHSALELIPCRGHSGYPVTNFWRLDGNAIFFQAKGVHDHPRPESKSETEARRSAIKRQMA
  SFYQPQKKRIRESEAEENQDSSGHFSNIPPLENPEDFDIVTETSFPIPGQPCPSFPKSDV
  YKATCDLATFQGDKMPPFQKYSSPRIYLPRPPCSYELANPGYTNSSPYPTLYKDSTSIPN
  DTDWVHLNTLQCNVNSYSSYERSFDFTNKQHGWKPALGKPSLVERTNHGQFQAMATRPYY
  NPELPCRYLTTPPPGAPALQTVITTTTKVSYQAYQPPAMKYSDSVREVKSLSSCNYAPED
  TGMSVYPEPWGPPVTVTRAASPSGPPPMKIAGDCRAIRPTVAIPHEPVSSRTDEAETWDV
  CLSGLGSAVSYSDRVGPFFTYNNEDF

• Sequence length: 506

Pathways

KEGG:

Parathyroid hormone synthesis, secretion and action

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Familial hypoparathyroidism	Likely pathogenic; Pathogenic	rs1779961435, rs748513242, rs1554103179	RCV003479434 RCV003486503 RCV000498316	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
GCM2-related disorder	Likely pathogenic	rs532834782	RCV003932060	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hyperparathyroidism 4	Likely pathogenic; Pathogenic	rs2113257238, rs2113243235, rs200283922, rs532834782	RCV001729986 RCV001834555 RCV003984247 RCV005040614	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypoparathyroidism, familial isolated, 2	Pathogenic; Likely pathogenic	rs2113242469, rs2113242520, rs2113243235, rs200283922, rs104893959, rs2532749281, rs532834782, rs886037646	RCV001375923 RCV001375924 RCV001834555 RCV005042784 RCV000006464 RCV003152937 RCV005040614 RCV003991819 RCV000054809	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EYE DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial hyperparathyroidism or Hypocalciuric hypercalcaemia	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL ISOLATED HYPERPARATHYROIDISM	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL ISOLATED HYPOPARATHYROIDISM DUE TO AGENESIS OF PARATHYROID GLAND	—	Disgenet, Orphanet Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERPARATHYROIDISM	—	Disgenet, GWAS catalog Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VISION DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenoma	Adenoma	BEFREE	12354132, 14715818, 15657585		★☆☆☆☆ Found in Text Mining only
Barakat syndrome	Hypoparathyroidism-deafness-renal disease syndrome	BEFREE	25917456		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	29897580		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	37628841, 40691650	Associate	★☆☆☆☆ Found in Text Mining only
Calcium Metabolism Disorders	Calcium metabolism disorders	Pubtator	33536578	Associate	★☆☆☆☆ Found in Text Mining only
Calcium pyrophosphate deposition disease	Chondrocalcinosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	28609842	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital absence of parathyroid gland	Parathyroid agenesis	ORPHANET_DG	11602629		★☆☆☆☆ Found in Text Mining only
Congenital absence of parathyroid gland	Parathyroid agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoparathyroidism	Congenital hypoparathyroidism	BEFREE	23155703		★☆☆☆☆ Found in Text Mining only
Congenital hypoparathyroidism	Congenital hypoparathyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial Isolated Hyperparathyroidism	Hyperparathyroidism	BEFREE	27745835, 29108698, 30848815, 31486992		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial Isolated Hyperparathyroidism	Hyperparathyroidism	ORPHANET_DG	27745835		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial isolated hyperparathyroidism	Hyperparathyroidism	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial isolated hypoparathyroidism due to agenesis of parathyroid gland	Hypoparathyroidism	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Generalized osteoporosis	Osteoporosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypercalcemia	Hypercalcemia	BEFREE	30848815		★☆☆☆☆ Found in Text Mining only
Hypercalcemia	Hypercalcemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperparathyroidism	Hyperparathyroidism	BEFREE	15657585, 28609842		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperparathyroidism	Hyperparathyroidism	LHGDN	15657585		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperparathyroidism	Hyperparathyroidism	Pubtator	28609842, 36055286	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperparathyroidism 1	Hyperparathyroidism	Pubtator	27745835, 29108698, 38130397	Associate	★☆☆☆☆ Found in Text Mining only
HYPERPARATHYROIDISM 4	Hyperparathyroidism	UNIPROT_DG	27745835		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPERPARATHYROIDISM 4	Hyperparathyroidism	GENOMICS_ENGLAND_DG	29199197		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPERPARATHYROIDISM 4	Hyperparathyroidism	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hyperparathyroidism Primary	Hyperparathyroidism	Pubtator	29108698, 29408534, 33536578, 38130397	Associate	★☆☆☆☆ Found in Text Mining only
Hyperparathyroidism, Primary	Hyperparathyroidism	BEFREE	12354132, 21642377, 25279501, 29108698, 30624640		★☆☆☆☆ Found in Text Mining only
Hyperparathyroidism, Primary	Hyperparathyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperphosphatemia (disorder)	Hyperphosphatemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypocalcemia	Hypocalcemia	Pubtator	33536578	Associate	★☆☆☆☆ Found in Text Mining only
Hypocalcemic seizures	Hypocalcemic seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypocalciuric hypercalcemia familial type 1	Hypocalciuric hypercalcemia	Pubtator	38130397	Associate	★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism	Hypoparathyroidism	BEFREE	11602629, 15728199, 16697534, 18182452, 18712808, 19940031, 20190276, 21642377, 23155703, 28422826		★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism	Hypoparathyroidism	LHGDN	18182452, 18583467		★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism	Hypoparathyroidism	Pubtator	21642377, 23155703, 31433868, 33536578, 36055286	Associate	★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism	Hypoparathyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism	Hypoparathyroidism	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism - autosomal dominant	Hypoparathyroidism	BEFREE	18712808, 20463099, 24823460		★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism - X-linked	Hypoparathyroidism	ORPHANET_DG	11602629		★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism familial isolated	Hypoparathyroidism	BEFREE	15728199, 28938448		★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism familial isolated	Hypoparathyroidism	UNIPROT_DG	15728199, 15863676, 20190276, 20463099, 23155703		★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism familial isolated	Hypoparathyroidism	GENOMICS_ENGLAND_DG	20190276, 29199197		★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism familial isolated	Hypoparathyroidism	CLINVAR_DG	23155703		★☆☆☆☆ Found in Text Mining only
Hypoparathyroidism familial isolated	Hypoparathyroidism	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
insulinoma	Insulinoma	BEFREE	29897580		★☆☆☆☆ Found in Text Mining only
Islet Cell Tumor	Islet Cell Tumor	BEFREE	29897580		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	29897580		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	15657585		★☆☆☆☆ Found in Text Mining only
Multiple Endocrine Neoplasia Type 1	Multiple Endocrine Neoplasia	BEFREE	29897580		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	14715818		★☆☆☆☆ Found in Text Mining only
Nephrocalcinosis	Nephrocalcinosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neuroendocrine Tumors	Neuroendocrine Tumors	BEFREE	31671402		★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Parathyroid Adenoma	Parathyroid Adenoma	BEFREE	12354132, 15657585, 21642377, 30624640		★☆☆☆☆ Found in Text Mining only
Parathyroid Adenoma	Parathyroid Adenoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Parathyroid Gland Adenocarcinoma	Parathyroid Gland Adenocarcinoma	BEFREE	29108698		★☆☆☆☆ Found in Text Mining only
Parathyroid Neoplasms	Parathyroid neoplasm	Pubtator	21642377, 28609842, 29108698, 29408534, 34054720	Associate	★☆☆☆☆ Found in Text Mining only
Parathyroid Neoplasms	Parathyroid Neoplasms	BEFREE	30848815		★☆☆☆☆ Found in Text Mining only
Parathyroid Neoplasms	Parathyroid neoplasm	Pubtator	34077544	Inhibit	★☆☆☆☆ Found in Text Mining only
Phosphate Diabetes	Phosphate Diabetes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal Insufficiency	Renal Insufficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Uremia	Uremia	BEFREE	12354132		★☆☆☆☆ Found in Text Mining only