GCM2

glial cells missing transcription factor 2

Basic information

Region (hg38): 6:10873223-10882041

Previous symbols: [ "GCMB" ]

Links

ENSG00000124827 ∙ NCBI:9247 ∙ OMIM:603716 ∙ HGNC:4198 ∙ Uniprot:O75603 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial isolated hypoparathyroidism due to agenesis of parathyroid gland (Supportive), mode of inheritance: AR
• familial isolated hyperparathyroidism (Supportive), mode of inheritance: AD
• hyperparathyroidism 4 (Limited), mode of inheritance: Unknown
• hypoparathyroidism, familial isolated, 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypoparathyroidism, familial isolated, 2; Hyperparathyroidism 4	AD/AR	Endocrine; Oncologic	In Hypoparathyroidism, familial isolated, early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae; In Hyperparathyroidism 4, individuals have been described with multiple parathyroid tumors (as well as other neoplasms), and awareness may allow early diagnosis and management of these tumors and sequelae	Endocrine; Oncologic	15863676; 18583467; 19940031; 20190276; 20463099; 22066718; 23155703; 27745835

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GCM2 gene.

• not provided (3 variants)
• Familial hypoparathyroidism (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GCM2 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			3	21	3	27
missense		7	41	10	3	61
nonsense	3		1			4
start loss		1				1
frameshift		1	2			3
inframe indel			1	1	1	3
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1	1		2
non coding			15	4	27	46
Total	4	10	63	36	34

Highest pathogenic variant AF is 0.00000657

Variants in GCM2

This is a list of pathogenic ClinVar variants found in the GCM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-10873249-T-C		Familial hypoparathyroidism	Uncertain significance (Jan 12, 2018)
6-10873268-G-GA		Familial hypoparathyroidism	Uncertain significance (Jun 14, 2016)
6-10873278-G-A		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
6-10873346-A-G		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
6-10873352-T-A		Familial hypoparathyroidism	Likely benign (Jan 13, 2018)
6-10873356-G-A		Familial hypoparathyroidism	Uncertain significance (Apr 27, 2017)
6-10873361-G-A		Familial hypoparathyroidism	Benign (Jan 13, 2018)
6-10873365-A-T		Familial hypoparathyroidism	Uncertain significance (Jan 12, 2018)
6-10873384-A-G		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
6-10873388-T-C		Familial hypoparathyroidism	Uncertain significance (Jan 12, 2018)
6-10873407-T-C		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
6-10873474-G-A		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
6-10873474-G-T		Familial hypoparathyroidism	Benign (Jan 13, 2018)
6-10873778-A-T		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
6-10873945-C-T		Familial hypoparathyroidism	Uncertain significance (Jan 13, 2018)
6-10874007-A-G		GCM2-related disorder	Likely benign (Sep 28, 2024)
6-10874012-T-C			Likely pathogenic (Jan 18, 2016)
6-10874012-T-G		Familial hypoparathyroidism • Hyperparathyroidism 4;Hypoparathyroidism, familial isolated, 2	Uncertain significance (Nov 12, 2021)
6-10874028-A-G			Likely benign (Dec 05, 2022)
6-10874032-A-G		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
6-10874054-C-A		Inborn genetic diseases	Uncertain significance (Aug 23, 2021)
6-10874085-A-T		Familial hypoparathyroidism	Uncertain significance (Jan 12, 2018)
6-10874107-GA-G			Uncertain significance (Mar 20, 2022)
6-10874113-ACTGG-A			Uncertain significance (Jun 24, 2022)
6-10874115-TG-T		Hypoparathyroidism, familial isolated, 2	Pathogenic (Apr 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GCM2	protein_coding	protein_coding	ENST00000379491	5	8719

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000911	0.987	125730	0	17	125747	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.676	246	278	0.886	0.0000159	3330
Missense in Polyphen		57	80.814	0.70532		925
Synonymous	0.345	103	108	0.958	0.00000676	986
Loss of Function	2.21	8	18.1	0.441	0.00000103	201

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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|PubMed:27745835, ECO:0000269|PubMed:9928992}.
• Disease: DISEASE: Hypoparathyroidism, familial isolated (FIH) [MIM:146200]: A disorder characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Clinical features include seizures, tetany and cramps. {ECO:0000269|PubMed:15728199, ECO:0000269|PubMed:15863676, ECO:0000269|PubMed:20190276, ECO:0000269|PubMed:20463099, ECO:0000269|PubMed:23155703, ECO:0000269|Ref.3}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hyperparathyroidism 4 (HRPT4) [MIM:617343]: A form of familial primary hyperparathyroidism, an hypercalcemic disorder caused by inappropriate oversecretion of parathyroid hormone due to parathyroid hyperplasia or neoplasms. Clinical features include hypercalcemia, phosphaturia, and increased bone resorption. HRPT4 inheritance is autosomal dominant. {ECO:0000269|PubMed:27745835}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.589
• rvis_EVS: 1.16
• rvis_percentile_EVS: 92.59

Haploinsufficiency Scores

• pHI: 0.269
• hipred: N
• hipred_score: 0.223

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gcm2
• Phenotype: endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; normal phenotype; 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); embryo phenotype; renal/urinary system phenotype; skeleton 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)

Zebrafish Information Network

• Gene name: gcm2
• Affected structure: neuromast hair cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: transcription by RNA polymerase II;cellular calcium ion homeostasis;multicellular organism development;cellular phosphate ion homeostasis;positive regulation of transcription by RNA polymerase II;parathyroid gland development
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding;sequence-specific DNA binding;metal ion binding