Familial isolated hypoparathyroidism due to agenesis of parathyroid gland

Summary

Familial isolated hypoparathyroidism due to agenesis of parathyroid gland (MONDO:0010618) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 8

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

8 HPO clinical features (Orphanet curated; top 8 by frequency):

HPO ID	Term	Frequency
HP:0002901	Hypocalcemia	Obligate (100%)
HP:0008198	Congenital hypoparathyroidism	Obligate (100%)
HP:0008211	Parathyroid agenesis	Obligate (100%)
HP:0002150	Hypercalciuria	Very frequent (80-99%)
HP:0002199	Hypocalcemic seizures	Very frequent (80-99%)
HP:0002905	Hyperphosphatemia	Very frequent (80-99%)
HP:0003251	Male infertility	Frequent (30-79%)
HP:0002917	Hypomagnesemia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	familial isolated hypoparathyroidism due to agenesis of parathyroid gland
Mondo ID	MONDO:0010618
MeSH	C563238
OMIM	307700
Orphanet	2239
DOID	DOID:0111388
ICD-11	1282942432
NCIT	C131079
UMLS	C0342344
MedGen	87437
GARD	0016589
Is cancer (heuristic)	no

Also known as: hypoparathyroidism, X-linked · HYPX · X-linked hypoparathyroidism

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › parathyroid gland disorder › hypoparathyroidism › hereditary hypoparathyroidism › familial hypoparathyroidism › hypoparathyroidism, familial isolated 1 › familial isolated hypoparathyroidism due to agenesis of parathyroid gland

Related subtypes (1): familial isolated hypoparathyroidism due to impaired PTH secretion

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

No tiered GWAS variants or ClinVar records for this disease.

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 recessive	hypoparathyroidism, familial isolated, 2	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

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.