Isolated anhidrosis with normal sweat glands

Summary

Isolated anhidrosis with normal sweat glands (MONDO:0007118) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated anhidrosis with normal sweat glands
Mondo ID	MONDO:0007118
OMIM	106190
Orphanet	468666
DOID	DOID:0060603
UMLS	C5568836
MedGen	1800259
GARD	0017843
Is cancer (heuristic)	no

Also known as: ANHD · anhidrosis caused by mutation in ITPR2 · anhidrosis, isolated, with normal sweat glands · Dann-Epstein-Sohar syndrome · isolated generalised anhidrosis with normal sweat glands · ITPR2 anhidrosis

Data availability: 13 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › sweat gland disorder › anhidrosis › isolated anhidrosis with normal sweat glands

Related subtypes (1): anhidrosis, familial generalized, with abnormal or absent sweat glands

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

13 retrieved; paginated sample, class counts are floors:

7 benign, 4 uncertain significance, 1 pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
189316	NM_002223.4(ITPR2):c.7492G>A (p.Gly2498Ser)	ITPR2	Pathogenic	no assertion criteria provided
2579735	NM_002223.4(ITPR2):c.3655C>A (p.Leu1219Ile)	ITPR2	Uncertain significance	criteria provided, single submitter
3891420	NM_002223.4(ITPR2):c.1894G>T (p.Asp632Tyr)	ITPR2	Uncertain significance	criteria provided, single submitter
3891421	NM_002223.4(ITPR2):c.2017A>G (p.Met673Val)	ITPR2	Uncertain significance	criteria provided, single submitter
4079025	NM_002223.4(ITPR2):c.3517A>G (p.Ser1173Gly)	ITPR2	Uncertain significance	criteria provided, single submitter
1300046	NM_002223.4(ITPR2):c.4407A>G (p.Lys1469=)	ITPR2	Benign	criteria provided, multiple submitters, no conflicts
1300047	NM_002223.4(ITPR2):c.4239C>T (p.Asp1413=)	ITPR2	Benign	criteria provided, multiple submitters, no conflicts
1300048	NM_002223.4(ITPR2):c.3801+23G>A	ITPR2	Benign	criteria provided, multiple submitters, no conflicts
1300049	NM_002223.4(ITPR2):c.2883C>T (p.His961=)	ITPR2	Benign	criteria provided, multiple submitters, no conflicts
1300050	NM_002223.4(ITPR2):c.2055A>G (p.Ser685=)	ITPR2	Benign	criteria provided, multiple submitters, no conflicts
1300051	NM_002223.4(ITPR2):c.765A>G (p.Glu255=)	ITPR2	Benign	criteria provided, multiple submitters, no conflicts
1300052	NM_002223.4(ITPR2):c.93-10T>A	ITPR2	Benign	criteria provided, multiple submitters, no conflicts
770228	NM_002223.4(ITPR2):c.6551C>G (p.Thr2184Ser)	ITPR2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · 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
ITPR2	Supportive	Autosomal recessive	isolated anhidrosis with normal sweat glands	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ITPR2	Orphanet:468666	Isolated generalized anhidrosis with normal sweat glands

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
ITPR2	HGNC:6181	ENSG00000123104	Q14571	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITPR2	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR2	Inositol 1,4,5-trisphosphate-gated calcium channel that upon inositol 1,4,5-trisphosphate binding transports calcium from the endoplasmic reticulum lumen to cytoplasm.

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)
ITPR2	Ion channel	yes		InsP3_rcpt, RIH_dom, Ion_trans_dom

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
adrenal tissue	1
calcaneal tendon	1
germinal epithelium of ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITPR2	273	ubiquitous	marker	calcaneal tendon, adrenal tissue, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITPR2	1,815

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ITPR2	Q14571

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. 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
CLEC7A (Dectin-1) induces NFAT activation	1	1038.2×	0.009	ITPR2
Elevation of cytosolic Ca2+ levels	1	713.8×	0.009	ITPR2
Platelet calcium homeostasis	1	713.8×	0.009	ITPR2
VEGFR2 mediated cell proliferation	1	571.0×	0.009	ITPR2
Effects of PIP2 hydrolysis	1	456.8×	0.009	ITPR2
Role of phospholipids in phagocytosis	1	456.8×	0.009	ITPR2
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.009	ITPR2
Leishmania parasite growth and survival	1	393.8×	0.009	ITPR2
FCERI mediated Ca+2 mobilization	1	356.9×	0.009	ITPR2
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.009	ITPR2
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.009	ITPR2
G-protein mediated events	1	326.3×	0.009	ITPR2
DAG and IP3 signaling	1	317.2×	0.009	ITPR2
Beta-catenin independent WNT signaling	1	292.8×	0.009	ITPR2
FCGR3A-mediated IL10 synthesis	1	292.8×	0.009	ITPR2
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.009	ITPR2
Platelet homeostasis	1	278.5×	0.009	ITPR2
Fc epsilon receptor (FCERI) signaling	1	271.9×	0.009	ITPR2
Opioid Signalling	1	265.6×	0.009	ITPR2
PLC beta mediated events	1	265.6×	0.009	ITPR2
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.009	ITPR2
C-type lectin receptors (CLRs)	1	237.9×	0.009	ITPR2
Signaling by VEGF	1	219.6×	0.009	ITPR2
Regulation of insulin secretion	1	219.6×	0.009	ITPR2
Ion homeostasis	1	203.9×	0.010	ITPR2
Ca2+ pathway	1	178.4×	0.010	ITPR2
Integration of energy metabolism	1	175.7×	0.010	ITPR2
Leishmania infection	1	163.1×	0.010	ITPR2
Parasitic Infection Pathways	1	163.1×	0.010	ITPR2
CLEC7A (Dectin-1) signaling	1	142.8×	0.011	ITPR2

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
cellular response to ethanol	1	1053.2×	0.005	ITPR2
release of sequestered calcium ion into cytosol	1	343.9×	0.006	ITPR2
cellular response to cAMP	1	290.6×	0.006	ITPR2
response to hypoxia	1	95.8×	0.013	ITPR2
signal transduction	1	16.1×	0.062	ITPR2

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITPR2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
ITPR2	8	Binding:7, Functional:1

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	1	ITPR2
E	Difficult family or no structure, no drug	0

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)
ITPR2	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.