Endocardial fibroelastosis

Summary

Endocardial fibroelastosis (MONDO:0009169) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide)
• Cohort genes: 2
• ClinVar variants: 20
• Phenotypes (HPO): 16

Clinical features

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000358	Posteriorly rotated ears	Very frequent (80-99%)
HP:0000174	Abnormal palate morphology	Very frequent (80-99%)
HP:0000347	Micrognathia	Very frequent (80-99%)
HP:0000506	Telecanthus	Very frequent (80-99%)
HP:0001635	Congestive heart failure	Very frequent (80-99%)
HP:0001723	Restrictive cardiomyopathy	Very frequent (80-99%)
HP:0001852	Sandal gap	Very frequent (80-99%)
HP:0001943	Hypoglycemia	Very frequent (80-99%)
HP:0011039	Abnormality of the helix	Very frequent (80-99%)
HP:0030680	Abnormal cardiovascular system morphology	Very frequent (80-99%)
HP:0100543	Cognitive impairment	Very frequent (80-99%)
HP:0000028	Cryptorchidism	Frequent (30-79%)
HP:0000830	Anterior hypopituitarism	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0008736	Hypoplasia of penis	Frequent (30-79%)
HP:0001706	Endocardial fibroelastosis	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	endocardial fibroelastosis
Mondo ID	MONDO:0009169
EFO	EFO:0007251
MeSH	D004695
OMIM	226000
Orphanet	2022
DOID	DOID:12929
ICD-10-CM	I42.4
ICD-11	1971033419
NCIT	C98922
SNOMED CT	65457005
UMLS	C0014117
MedGen	4041
GARD	0006336
MedDRA	10014663
NORD	1090
Is cancer (heuristic)	no

Also known as: EFE · Elastomyofibrosis · endocardial fibroelastosis

Data availability: 20 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › endocardium disorder › endocardial fibroelastosis

Related subtypes (2): endocarditis, neoplasm of endocardium

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

20 retrieved; paginated sample, class counts are floors:

8 uncertain significance, 7 benign/likely benign, 4 conflicting classifications of pathogenicity, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
368087	NM_000116.5(TAFAZZIN):c.504G>A (p.Lys168=)	TAFAZZIN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
451312	NM_000116.5(TAFAZZIN):c.761C>T (p.Ala254Val)	TAFAZZIN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
914160	NM_000116.5(TAFAZZIN):c.270G>A (p.Leu90=)	TAFAZZIN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
914161	NM_000116.5(TAFAZZIN):c.351G>A (p.Lys117=)	TAFAZZIN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
913761	NM_000116.5(TAFAZZIN):c.49T>C (p.Trp17Arg)	DNASE1L1	Uncertain significance	criteria provided, single submitter
368089	NM_000116.5(TAFAZZIN):c.*387C>T	TAFAZZIN	Uncertain significance	criteria provided, single submitter
42261	NM_000116.5(TAFAZZIN):c.535C>G (p.Pro179Ala)	TAFAZZIN	Uncertain significance	criteria provided, multiple submitters, no conflicts
912700	NM_000116.5(TAFAZZIN):c.647-6C>T	TAFAZZIN	Uncertain significance	criteria provided, single submitter
913108	NM_000116.5(TAFAZZIN):c.*618A>G	TAFAZZIN	Uncertain significance	criteria provided, single submitter
913109	NM_000116.5(TAFAZZIN):c.*648A>C	TAFAZZIN	Uncertain significance	criteria provided, single submitter
913803	NM_000116.5(TAFAZZIN):c.*33G>A	TAFAZZIN	Uncertain significance	criteria provided, single submitter
914208	NM_000116.5(TAFAZZIN):c.*165T>A	TAFAZZIN	Uncertain significance	criteria provided, single submitter
368086	NM_000116.5(TAFAZZIN):c.-88G>C	DNASE1L1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
139390	NM_000116.5(TAFAZZIN):c.646+14C>T	TAFAZZIN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
368088	NM_000116.5(TAFAZZIN):c.675G>A (p.Pro225=)	TAFAZZIN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
368090	NM_000116.5(TAFAZZIN):c.*396C>T	TAFAZZIN	Benign/Likely benign	criteria provided, single submitter
368091	NM_000116.5(TAFAZZIN):c.*470=	TAFAZZIN	Benign	criteria provided, multiple submitters, no conflicts
368092	NM_000116.5(TAFAZZIN):c.*560G>A	TAFAZZIN	Benign/Likely benign	criteria provided, single submitter
42259	NM_000116.5(TAFAZZIN):c.383T>C (p.Phe128Ser)	TAFAZZIN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
42270	NM_000116.5(TAFAZZIN):c.873G>A (p.Gly291=)	TAFAZZIN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TAFAZZIN	Orphanet:111	Barth syndrome
TAFAZZIN	Orphanet:154	Familial isolated dilated cardiomyopathy

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
TAFAZZIN	HGNC:11577	ENSG00000102125	Q16635	Tafazzin	clinvar
DNASE1L1	HGNC:2957	ENSG00000013563	P49184	Deoxyribonuclease-1-like 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TAFAZZIN	Tafazzin	Acyltransferase required to remodel newly synthesized phospholipid cardiolipin (1’,3’-bis-[1,2-diacyl-sn-glycero-3-phospho]-glycerol or CL), a key component of the mitochondrial inner membrane, with tissue specific acyl chains necessary fo…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Phosphatase	1	42.0×	0.047
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TAFAZZIN	Other/Unknown	no		Tafazzin, Plipid/glycerol_acylTrfase
DNASE1L1	Phosphatase	yes		Endo/exonuclease/phosphatase, DNase_I, Deoxyribonuclease-1_AS

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
apex of heart	1
granulocyte	1
lower esophagus mucosa	1
gastrocnemius	1
gluteal muscle	1
hindlimb stylopod muscle	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TAFAZZIN	238	ubiquitous	marker	apex of heart, granulocyte, lower esophagus mucosa
DNASE1L1	283	ubiquitous	marker	hindlimb stylopod muscle, gastrocnemius, gluteal muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TAFAZZIN	1,754
DNASE1L1	1,012

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TAFAZZIN	Q16635	94.87
DNASE1L1	P49184	90.83

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Acyl chain remodeling of CL	1	951.7×	0.008	TAFAZZIN
Glycerophospholipid biosynthesis	1	167.9×	0.019	TAFAZZIN
Phospholipid metabolism	1	100.2×	0.019	TAFAZZIN
Protein localization	1	95.2×	0.019	TAFAZZIN
Mitochondrial protein import	1	84.0×	0.019	TAFAZZIN
Metabolism of lipids	1	15.8×	0.083	TAFAZZIN
Neutrophil degranulation	1	11.5×	0.097	DNASE1L1
Metabolism	1	5.8×	0.165	TAFAZZIN

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
positive regulation of cardiolipin metabolic process	1	4213.0×	0.002	TAFAZZIN
cardiolipin acyl-chain remodeling	1	2106.5×	0.002	TAFAZZIN
positive regulation of ATP biosynthetic process	1	601.9×	0.002	TAFAZZIN
DNA metabolic process	1	526.6×	0.002	DNASE1L1
cristae formation	1	526.6×	0.002	TAFAZZIN
DNA catabolic process	1	468.1×	0.002	DNASE1L1
inner mitochondrial membrane organization	1	421.3×	0.002	TAFAZZIN

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TAFAZZIN	0	0
DNASE1L1	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
TAFAZZIN	1	Binding:1

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	1	DNASE1L1
E	Difficult family or no structure, no drug	1	TAFAZZIN

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)
TAFAZZIN	1	—
DNASE1L1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.