Hyperparathyroidism, transient neonatal

Summary

Hyperparathyroidism, transient neonatal (MONDO:0032591) is a disease caused by TRPV6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TRPV6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 22

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hyperparathyroidism, transient neonatal
Mondo ID	MONDO:0032591
OMIM	618188
UMLS	C1300287
MedGen	722059
GARD	0016304
Is cancer (heuristic)	no

Also known as: HRPTTN · hyperparathyroidism, transient neonatal

Data availability: 22 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › endocrine system disorder › parathyroid gland disorder › hyperparathyroidism › hereditary hyperparathyroidism › hyperparathyroidism, transient neonatal

Related subtypes (1): familial primary hyperparathyroidism

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

22 retrieved; paginated sample, class counts are floors:

9 likely pathogenic, 7 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
590765	NM_018646.6(TRPV6):c.530_533dup (p.Arg179fs)	TRPV6	Pathogenic	criteria provided, multiple submitters, no conflicts
590769	NM_018646.6(TRPV6):c.978_979del (p.Gly327_Asp328insTer)	TRPV6	Pathogenic	no assertion criteria provided
590770	NM_018646.6(TRPV6):c.607+5G>A	TRPV6	Pathogenic	no assertion criteria provided
2572618	NM_018646.6(TRPV6):c.715_724del (p.Val239fs)	TRPV6	Likely pathogenic	criteria provided, single submitter
2692409	NM_018646.6(TRPV6):c.254G>A (p.Trp85Ter)	TRPV6	Likely pathogenic	criteria provided, single submitter
4077708	NM_018646.6(TRPV6):c.1657C>T (p.Gln553Ter)	TRPV6	Likely pathogenic	criteria provided, single submitter
4294456	NM_018646.6(TRPV6):c.1570A>T (p.Lys524Ter)	TRPV6	Likely pathogenic	criteria provided, single submitter
590767	NM_018646.6(TRPV6):c.1274G>A (p.Arg425Gln)	TRPV6	Likely pathogenic	criteria provided, single submitter
590768	NM_018646.6(TRPV6):c.1352G>A (p.Gly451Glu)	TRPV6	Likely pathogenic	criteria provided, multiple submitters, no conflicts
692130	NM_018646.6(TRPV6):c.635G>A (p.Cys212Tyr)	TRPV6	Likely pathogenic	criteria provided, single submitter
692132	NM_018646.6(TRPV6):c.1447C>T (p.Arg483Trp)	TRPV6	Likely pathogenic	criteria provided, single submitter
932914	NM_018646.6(TRPV6):c.1646A>G (p.Tyr549Cys)	TRPV6	Likely pathogenic	criteria provided, single submitter
590766	NM_018646.6(TRPV6):c.668T>C (p.Ile223Thr)	TRPV6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
692131	NM_018646.6(TRPV6):c.1282G>A (p.Gly428Arg)	TRPV6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028603	NM_018646.6(TRPV6):c.524C>T (p.Ala175Val)	TRPV6	Uncertain significance	criteria provided, single submitter
1028604	NM_018646.6(TRPV6):c.713C>G (p.Thr238Arg)	TRPV6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2384630	NM_018646.6(TRPV6):c.614A>G (p.His205Arg)	TRPV6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2437349	NM_018646.6(TRPV6):c.970G>A (p.Asp324Asn)	TRPV6	Uncertain significance	criteria provided, single submitter
2692410	NM_018646.6(TRPV6):c.1969G>A (p.Gly657Arg)	TRPV6	Uncertain significance	criteria provided, multiple submitters, no conflicts
4080608	NM_018646.6(TRPV6):c.958C>T (p.Leu320Phe)	TRPV6	Uncertain significance	criteria provided, single submitter
992367	NM_018646.6(TRPV6):c.1744G>A (p.Asp582Asn)	TRPV6	Uncertain significance	criteria provided, single submitter
768209	NM_018646.6(TRPV6):c.1092C>T (p.Tyr364=)	TRPV6	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
TRPV6	Strong	Autosomal recessive	hyperparathyroidism, transient neonatal	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRPV6	Orphanet:417	Neonatal severe primary hyperparathyroidism
TRPV6	Orphanet:676	Autosomal dominant hereditary chronic pancreatitis

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
TRPV6	HGNC:14006	ENSG00000165125	Q9H1D0	Transient receptor potential cation channel subfamily V member 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRPV6	Transient receptor potential cation channel subfamily V member 6	Calcium selective cation channel that mediates Ca(2+) uptake in various tissues, including the intestine.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRPV6	Ion channel	yes		Ankyrin_rpt, Ion_trans_dom, TRPV5/TRPV6

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	1
duodenum	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRPV6	125	tissue_specific	marker	body of pancreas, pancreas, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRPV6	1,197

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TRPV6	Q9H1D0	24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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
TRP channels	1	407.9×	0.002	TRPV6

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
parathyroid hormone secretion	1	8426.0×	8e-04	TRPV6
regulation of calcium ion-dependent exocytosis	1	936.2×	0.004	TRPV6
calcium ion import across plasma membrane	1	543.6×	0.004	TRPV6
calcium ion homeostasis	1	443.5×	0.004	TRPV6
response to calcium ion	1	318.0×	0.004	TRPV6
calcium ion transmembrane transport	1	210.7×	0.006	TRPV6
calcium ion transport	1	181.2×	0.006	TRPV6

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TRPV6	ECONAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TRPV6	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ECONAZOLE	4	TRPV6
TETRAHYDROCANNABIVARIN	2	TRPV6
SOR-C13	1	TRPV6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
TRPV6	32	Binding:32

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
ECONAZOLE	4	TRPV6
TETRAHYDROCANNABIVARIN	2	TRPV6
SOR-C13	1	TRPV6

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TRPV6
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.