Hyperparathyroidism 4
diseaseOn this page
Also known as familial isolated hyperparathyroidism caused by mutation in GCM2GCM2 familial isolated hyperparathyroidismHRPT4hyperparathyroidism type 4
Summary
Hyperparathyroidism 4 (MONDO:0024570) is a disease caused by GCM2 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: GCM2 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 83
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hyperparathyroidism 4 |
| Mondo ID | MONDO:0024570 |
| OMIM | 617343 |
| UMLS | C4479229 |
| MedGen | 1386327 |
| GARD | 0018256 |
| Is cancer (heuristic) | no |
Also known as: familial isolated hyperparathyroidism caused by mutation in GCM2 · GCM2 familial isolated hyperparathyroidism · HRPT4 · hyperparathyroidism 4 · hyperparathyroidism type 4
Data availability: 83 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › familial isolated hyperparathyroidism › hyperparathyroidism 4
Related subtypes (2): hyperparathyroidism 1, hyperparathyroidism 3
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
83 retrieved; paginated sample, class counts are floors:
63 uncertain significance, 6 likely pathogenic, 6 conflicting classifications of pathogenicity, 4 benign/likely benign, 3 likely benign, 1 pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 375590 | NM_004752.3(GCM2):c.[1136T>A;751C>G] | Pathogenic | no assertion criteria provided | |
| 1299514 | NM_004752.4(GCM2):c.1A>G (p.Met1Val) | GCM2 | Likely pathogenic | criteria provided, single submitter |
| 1341348 | NM_004752.4(GCM2):c.1148T>C (p.Ile383Thr) | GCM2 | Likely pathogenic | criteria provided, single submitter |
| 3041710 | NM_004752.4(GCM2):c.199C>T (p.Arg67Cys) | GCM2 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3592949 | NM_004752.4(GCM2):c.1216C>T (p.Arg406Ter) | GCM2 | Likely pathogenic | criteria provided, single submitter |
| 3592955 | NM_004752.4(GCM2):c.1100_1103del (p.Arg367fs) | GCM2 | Likely pathogenic | criteria provided, single submitter |
| 3592958 | NM_004752.4(GCM2):c.1048C>T (p.Gln350Ter) | GCM2 | Likely pathogenic | criteria provided, single submitter |
| 1324460 | NM_004752.4(GCM2):c.1109C>T (p.Thr370Met) | GCM2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1707105 | NM_004752.4(GCM2):c.139C>T (p.Arg47Cys) | GCM2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2394494 | NM_004752.4(GCM2):c.22G>A (p.Glu8Lys) | GCM2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 355008 | NM_004752.4(GCM2):c.1181A>C (p.Tyr394Ser) | GCM2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 6092 | NM_004752.4(GCM2):c.187G>A (p.Gly63Ser) | GCM2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 904503 | NM_004752.4(GCM2):c.1342A>G (p.Met448Val) | GCM2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1698744 | NM_004752.4(GCM2):c.1398G>C (p.Glu466Asp) | GCM2 | Uncertain significance | criteria provided, single submitter |
| 1992365 | NM_004752.4(GCM2):c.1166T>C (p.Val389Ala) | GCM2 | Uncertain significance | criteria provided, single submitter |
| 1992385 | NM_004752.4(GCM2):c.523A>T (p.Ile175Phe) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1999959 | NM_004752.4(GCM2):c.1352C>T (p.Ala451Val) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2285256 | NM_004752.4(GCM2):c.1343T>A (p.Met448Lys) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2286665 | NM_004752.4(GCM2):c.1484T>C (p.Val495Ala) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2324309 | NM_004752.4(GCM2):c.443C>T (p.Ala148Val) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2734824 | NM_004752.4(GCM2):c.175C>T (p.Arg59Cys) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3028916 | NM_004752.4(GCM2):c.1003C>T (p.Pro335Ser) | GCM2 | Uncertain significance | no assertion criteria provided |
| 3099047 | NM_004752.4(GCM2):c.547T>C (p.Tyr183His) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 355007 | NM_004752.4(GCM2):c.1364G>A (p.Arg455Gln) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 355018 | NM_004752.4(GCM2):c.265C>G (p.Gln89Glu) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 355021 | NM_004752.4(GCM2):c.116G>A (p.Arg39Gln) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3592934 | NM_004752.4(GCM2):c.1505A>T (p.Asn502Ile) | GCM2 | Uncertain significance | criteria provided, single submitter |
| 3592935 | NM_004752.4(GCM2):c.1469G>T (p.Ser490Ile) | GCM2 | Uncertain significance | criteria provided, single submitter |
| 3592936 | NM_004752.4(GCM2):c.1462G>A (p.Ala488Thr) | GCM2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3592937 | NM_004752.4(GCM2):c.1435G>A (p.Asp479Asn) | GCM2 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| GCM2 | Strong | Autosomal dominant | hyperparathyroidism 4 | 5 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| GCM2 | Orphanet:2239 | Familial isolated hypoparathyroidism due to agenesis of parathyroid gland |
| GCM2 | Orphanet:99879 | Familial isolated hyperparathyroidism |
Cohort genes → proteins
1 cohort genes, 1 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 1 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| GCM2 | HGNC:4198 | ENSG00000124827 | O75603 | Chorion-specific transcription factor GCMb | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| GCM2 | Chorion-specific transcription factor GCMb | Transcription factor that binds specific sequences on gene promoters and activate their transcription. |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Other/Unknown | 1 | 1.8× | 0.558 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| GCM2 | Other/Unknown | no | Tscrpt_reg_GCM, GCM_dom_sf, GCM |
Expression context
Cohort genes with no expression data: 0.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 1 |
| broad (>20) | 0 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| ileal mucosa | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| pancreatic ductal cell | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| GCM2 | 9 | tissue_specific | yes | male germ line stem cell (sensu Vertebrata) in testis, pancreatic ductal cell, ileal mucosa |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| GCM2 | 892 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| GCM2 | O75603 | 58.78 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| gliogenesis | 1 | 2808.7× | 0.001 | GCM2 |
| parathyroid gland development | 1 | 2407.4× | 0.001 | GCM2 |
| intracellular phosphate ion homeostasis | 1 | 1532.0× | 0.001 | GCM2 |
| intracellular calcium ion homeostasis | 1 | 145.3× | 0.010 | GCM2 |
| transcription by RNA polymerase II | 1 | 70.5× | 0.017 | GCM2 |
| regulation of transcription by RNA polymerase II | 1 | 11.7× | 0.086 | GCM2 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| GCM2 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 0 | |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 0 | |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 1 | GCM2 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| GCM2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: GCM2