familial isolated hypoparathyroidism due to impaired PTH secretion

Summary

familial isolated hypoparathyroidism due to impaired PTH secretion (MONDO:0016000) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	familial isolated hypoparathyroidism due to impaired PTH secretion
Mondo ID	MONDO:0016000
Orphanet	189466
UMLS	C5680524
MedGen	1843283
GARD	0017088
Is cancer (heuristic)	no

Data availability: 2 GenCC gene-disease records.

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 impaired PTH secretion

Related subtypes (1): familial isolated hypoparathyroidism due to agenesis of parathyroid gland

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: 14 · Orphanet: 3 · 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
PTH	Strong	Autosomal dominant	hypoparathyroidism, familial isolated 1	5
AIRE	Supportive	Autosomal dominant	familial isolated hypoparathyroidism due to impaired PTH secretion	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AIRE	Orphanet:189466	Familial isolated hypoparathyroidism due to impaired PTH secretion
AIRE	Orphanet:3453	Autoimmune polyendocrinopathy type 1
PTH	Orphanet:189466	Familial isolated hypoparathyroidism due to impaired PTH secretion

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AIRE	HGNC:360	ENSG00000160224	O43918	Autoimmune regulator	gencc
PTH	HGNC:9606	ENSG00000152266	P01270	Parathyroid hormone	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AIRE	Autoimmune regulator	Transcription factor playing an essential role to promote self-tolerance in the thymus by regulating the expression of a wide array of self-antigens that have the commonality of being tissue-restricted in their expression pattern in the pe…
PTH	Parathyroid hormone	Parathyroid hormone elevates calcium level by dissolving the salts in bone and preventing their renal excretion.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AIRE	Transcription factor	no		SAND_dom, Znf_PHD, HSR_dom
PTH	Other/Unknown	no		PTH/PTH-rel, PTH

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
diaphragm	1
gluteal muscle	1
triceps brachii	1
endometrium epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AIRE	105	tissue_specific	marker	triceps brachii, diaphragm, gluteal muscle
PTH	94	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, endometrium epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
AIRE	3,001
PTH	1,967

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTH	P01270	26
AIRE	O43918	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Class B/2 (Secretin family receptors)	1	190.3×	0.011	PTH
G alpha (s) signalling events	1	73.2×	0.014	PTH

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peripheral T cell tolerance induction	1	8426.0×	0.001	AIRE
central tolerance induction to self antigen	1	8426.0×	0.001	AIRE
macromolecule biosynthetic process	1	8426.0×	0.001	PTH
regulation of thymocyte migration	1	8426.0×	0.001	AIRE
thymus epithelium morphogenesis	1	4213.0×	0.002	AIRE
adenylate cyclase-activating G protein-coupled cAMP receptor signaling pathway	1	4213.0×	0.002	PTH
transcription by RNA polymerase II	2	70.5×	0.002	AIRE, PTH
negative regulation of apoptotic process in bone marrow cell	1	2808.7×	0.002	PTH
cAMP metabolic process	1	2106.5×	0.002	PTH
response to parathyroid hormone	1	2106.5×	0.002	PTH
positive regulation of cell proliferation in bone marrow	1	2106.5×	0.002	PTH
positive regulation of osteoclast proliferation	1	2106.5×	0.002	PTH
negative regulation of bone mineralization involved in bone maturation	1	2106.5×	0.002	PTH
hormone-mediated apoptotic signaling pathway	1	1685.2×	0.002	PTH
positive regulation of inositol phosphate biosynthetic process	1	1203.7×	0.003	PTH
response to fibroblast growth factor	1	1053.2×	0.003	PTH
magnesium ion homeostasis	1	936.2×	0.003	PTH
negative thymic T cell selection	1	702.2×	0.004	AIRE
positive regulation of signal transduction	1	648.1×	0.004	PTH
phosphate ion homeostasis	1	526.6×	0.004	PTH
positive regulation of glycogen biosynthetic process	1	495.6×	0.005	PTH
response to lead ion	1	468.1×	0.005	PTH
response to vitamin D	1	401.2×	0.005	PTH
response to cadmium ion	1	366.4×	0.005	PTH
negative regulation of chondrocyte differentiation	1	337.0×	0.006	PTH
bone resorption	1	290.6×	0.006	PTH
positive regulation of D-glucose import across plasma membrane	1	227.7×	0.007	PTH
homeostasis of number of cells within a tissue	1	221.7×	0.007	PTH
positive regulation of transcription by RNA polymerase II	2	14.9×	0.007	AIRE, PTH
positive regulation of bone mineralization	1	195.9×	0.008	PTH

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
AIRE	0	0
PTH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	AIRE, PTH

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
AIRE	0	—
PTH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.