Hypertrophic cardiomyopathy 19

Summary

Hypertrophic cardiomyopathy 19 (MONDO:0013476) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 339

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	hypertrophic cardiomyopathy 19
Mondo ID	MONDO:0013476
OMIM	613875
DOID	DOID:0110325
GARD	0024931
Is cancer (heuristic)	no

Also known as: CALR3 hypertrophic cardiomyopathy · cardiomyopathy familial hypertrophic 19 · cardiomyopathy, familial hypertrophic, 19 · cardiomyopathy, familial hypertrophic, type 19 · CMH19 · hypertrophic cardiomyopathy caused by mutation in CALR3 · hypertrophic cardiomyopathy type 19

Data availability: 339 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › cardiomyopathy › intrinsic cardiomyopathy › hypertrophic cardiomyopathy › familial hypertrophic cardiomyopathy › hypertrophic cardiomyopathy 19

Related subtypes (39): hypertrophic cardiomyopathy 2, hypertrophic cardiomyopathy 3, hypertrophic cardiomyopathy 4, Beckwith-Wiedemann syndrome, myotonic dystrophy type 1, hypertrophic cardiomyopathy 1, very long chain acyl-CoA dehydrogenase deficiency, multiple acyl-CoA dehydrogenase deficiency, 46,XY complete gonadal dysgenesis, hypertrophic cardiomyopathy 6, dilated cardiomyopathy 1C, hypertrophic cardiomyopathy 25, hypertrophic cardiomyopathy 8, hypertrophic cardiomyopathy 10, long chain 3-hydroxyacyl-CoA dehydrogenase deficiency, cardiomyopathy-hypotonia-lactic acidosis syndrome, hypertrophic cardiomyopathy 11, hypertrophic cardiomyopathy 12, hypertrophic cardiomyopathy 13, hypertrophic cardiomyopathy 14, hypertrophic cardiomyopathy 15, hypertrophic cardiomyopathy 7, hypertrophic cardiomyopathy 9, hypertrophic cardiomyopathy 16, hypertrophic cardiomyopathy 17, hypertrophic cardiomyopathy 18, hypertrophic cardiomyopathy 20, hypertrophic cardiomyopathy 21, dilated cardiomyopathy 1KK, hypertrophic cardiomyopathy 26, Noonan syndrome and Noonan-related syndrome, long chain acyl-CoA dehydrogenase deficiency, cardiomyopathy, familial hypertrophic, 28, cardiomyopathy, familial hypertrophic 27, cardiomyopathy, familial hypertrophic, 23, with or without ventricular noncompaction, cardiomyopathy, familial restrictive, 5, cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies, cardiomyopathy, familial hypertrophic, 30, atrial, cardiomyopathy, familial hypertrophic, 31

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

339 retrieved; paginated sample, class counts are floors:

198 uncertain significance, 108 likely benign, 18 benign, 9 conflicting classifications of pathogenicity, 6 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
191613	NM_145046.5(CALR3):c.215G>A (p.Gly72Asp)	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30907	NM_145046.5(CALR3):c.245A>G (p.Lys82Arg)	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
410619	NM_145046.5(CALR3):c.403G>A (p.Asp135Asn)	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
416239	NM_145046.5(CALR3):c.848C>T (p.Thr283Ile)	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
518292	NM_145046.5(CALR3):c.564del (p.Gln189fs)	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
539147	NM_145046.5(CALR3):c.1114G>C (p.Glu372Gln)	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
619268	NM_145046.5(CALR3):c.217C>G (p.Arg73Gly)	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
659042	NM_145046.5(CALR3):c.724G>A (p.Asp242Asn)	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
691735	NM_145046.5(CALR3):c.679-3dup	CALR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1000567	NM_145046.5(CALR3):c.377C>T (p.Ser126Leu)	CALR3	Uncertain significance	criteria provided, single submitter
1000661	NM_145046.5(CALR3):c.452A>G (p.Lys151Arg)	CALR3	Uncertain significance	criteria provided, single submitter
1009504	NM_145046.5(CALR3):c.941A>T (p.Asp314Val)	CALR3	Uncertain significance	criteria provided, single submitter
1016368	NM_145046.5(CALR3):c.476A>C (p.Lys159Thr)	CALR3	Uncertain significance	criteria provided, single submitter
1039014	NM_145046.5(CALR3):c.21G>C (p.Gln7His)	CALR3	Uncertain significance	criteria provided, single submitter
1044297	NM_145046.5(CALR3):c.600G>C (p.Trp200Cys)	CALR3	Uncertain significance	criteria provided, single submitter
1046730	NM_145046.5(CALR3):c.1147G>A (p.Glu383Lys)	CALR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1046936	NM_145046.5(CALR3):c.31A>G (p.Ile11Val)	CALR3	Uncertain significance	criteria provided, single submitter
1174672	NM_145046.5(CALR3):c.520C>A (p.Leu174Ile)	CALR3	Uncertain significance	criteria provided, single submitter
1343388	NM_145046.5(CALR3):c.961G>A (p.Asp321Asn)	CALR3	Uncertain significance	criteria provided, single submitter
1367008	NM_145046.5(CALR3):c.632C>T (p.Pro211Leu)	CALR3	Uncertain significance	criteria provided, single submitter
1374638	NM_145046.5(CALR3):c.224A>T (p.Tyr75Phe)	CALR3	Uncertain significance	criteria provided, single submitter
1377060	NM_145046.5(CALR3):c.384C>G (p.Tyr128Ter)	CALR3	Uncertain significance	criteria provided, single submitter
1377831	NM_145046.5(CALR3):c.535G>T (p.Asp179Tyr)	CALR3	Uncertain significance	criteria provided, single submitter
1386119	NM_145046.5(CALR3):c.923G>A (p.Arg308Lys)	CALR3	Uncertain significance	criteria provided, single submitter
1390603	NM_145046.5(CALR3):c.97T>C (p.Trp33Arg)	CALR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1393524	NM_145046.5(CALR3):c.520_527del (p.Leu174fs)	CALR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1396078	NM_145046.5(CALR3):c.139G>C (p.Gly47Arg)	CALR3	Uncertain significance	criteria provided, single submitter
1400864	NM_145046.5(CALR3):c.545A>G (p.Tyr182Cys)	CALR3	Uncertain significance	criteria provided, single submitter
1403444	NM_145046.5(CALR3):c.500G>A (p.Gly167Asp)	CALR3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1404174	NM_145046.5(CALR3):c.703G>A (p.Ala235Thr)	CALR3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 0 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
CALR3	HGNC:20407	ENSG00000269058	Q96L12	Calreticulin-3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CALR3	Calreticulin-3	During spermatogenesis, may act as a lectin-independent chaperone for specific client proteins such as ADAM3.

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)
CALR3	Other/Unknown	no		Calret/calnex, Calreticulin/calnexin_P_dom_sf, Calreticulin

Expression context

Cohort genes with no expression data: 0.

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
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CALR3	57	broad	yes	right testis, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CALR3	2,168

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CALR3	Q96L12	77.43

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
ERAD pathway	1	181.2×	0.019	CALR3
protein folding	1	103.4×	0.019	CALR3
spermatogenesis	1	35.2×	0.034	CALR3
cell differentiation	1	29.1×	0.034	CALR3

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
CALR3	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	CALR3

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)
CALR3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.