Dilated Cardiomyopathy 2B

1. Disease Information

Overview. Dilated Cardiomyopathy 2B (CMD2B) is a rare autosomal recessive form of familial dilated cardiomyopathy caused by biallelic mutation of GATAD1 (GATA zinc-finger domain-containing protein 1). Like other DCMs it is defined by left-ventricular (LV) dilation and systolic dysfunction (reduced ejection fraction) not explained by abnormal loading conditions or coronary disease, presenting clinically as heart failure and predisposing to arrhythmia. CMD2B is distinguished from the far more common autosomal-dominant DCMs by its recessive transmission with clinically silent heterozygous carriers [human clinical, PMID 21965549].

Key identifiers. | Resource | ID | |---|---| | Mondo | MONDO:0013848 (dilated cardiomyopathy 2B) | | OMIM (phenotype) | 614672 — CARDIOMYOPATHY, DILATED, 2B; CMD2B | | OMIM (gene) | 614518 — GATAD1 | | HGNC | HGNC:29941 (GATAD1) | | NCBI Gene | 57798 | | Ensembl | ENSG00000157014 | | UniProt | Q8WUU5 (GATD1_HUMAN) | | RefSeq | NM_021167.5 / NP_066990.3 (GATAD1, 249 aa); LRG_746 | | Founder variant | NM_021167.5:c.304T>C (p.Ser102Pro); ClinVar VCV31656; rs387907188 | | ICD-10 | I42.0 (Dilated cardiomyopathy) | | ICD-11 | BC43.0 (Dilated cardiomyopathy) | | MeSH | D002311 (Cardiomyopathy, Dilated) | | Orphanet | within ORPHA:154 (Familial isolated dilated cardiomyopathy) — no distinct subtype code |

Synonyms / alternative names. CMD2B; Cardiomyopathy, dilated, 2B; GATAD1-related/GATAD1-associated dilated cardiomyopathy; autosomal recessive dilated cardiomyopathy (GATAD1 type).

Data source type. Disease-level aggregated resources (OMIM/Mondo) plus individual-patient data from one published family; no EHR/registry-scale cohort exists for this specific subtype.

2. Etiology

Primary causal factor — genetic. CMD2B is a monogenic, biallelic disorder. Disease requires two loss-/alteration-of-function alleles of GATAD1. In the index family a homozygous missense mutation altering the conserved serine-102 residue (reported as p.Ser102Pro) segregated with recessive DCM; it was absent from HapMap, 1000 Genomes and 474 ethnically matched controls [human clinical, PMID 21965549].

"altered a conserved residue of GATAD1 … Thirteen relatives were heterozygous mutation carriers with no evidence of myocardial disease, even at advanced ages." (PMID 21965549)

Genetic risk factors. - Causal variant: homozygous GATAD1 p.Ser102Pro (7q21.2). Because unaffected heterozygotes exist, a single allele is insufficient (recessive). - Consanguinity is a major predisposing structural factor — the founding couple were first cousins, and homozygosity mapping exploited runs of homozygosity [human clinical, PMID 21965549]. - Modifier genes: none specifically identified for CMD2B (data unavailable).

Environmental / lifestyle risk factors. No CMD2B-specific environmental trigger is established. For DCM broadly, alcohol, cardiotoxic chemotherapy (anthracyclines), myocarditis/viral infection, peripartum state, thyroid disease and tachyarrhythmia are recognized acquired causes/"second hits"; these may act as gene–environment modifiers superimposed on genetic susceptibility [DCM-class; PMID 42537484 notes "second-hit" genetic contributions]. Not demonstrated for GATAD1 specifically.

Protective factors. No genetic or environmental protective factor is described for CMD2B (data unavailable). By inference, absence of a second pathogenic allele is "protective" (heterozygotes unaffected).

Gene–environment interactions. Mouse data suggest GATAD1 becomes functionally important under stress: cardiac Gatad1 loss worsens ischemia–reperfusion injury and abolishes sphingosylphosphorylcholine cardioprotection [model organism, PMID 39626862], implying environmental/metabolic stressors may unmask or aggravate GATAD1-deficient myocardium — inferred, not shown in patients.

3. Phenotypes

All descriptions derive from the single reported kindred [human clinical, PMID 21965549] plus generic DCM knowledge.

Phenotype characteristics. Age of onset: adult-onset (HP:0003581) with age-dependent penetrance; the affected sisters were adults, and a brother had milder "idiopathic LV enlargement," illustrating variable expressivity (HP:0003828). Severity ranges from isolated LV dilatation to overt DCM/heart failure. Course: chronic, progressive.

Quality-of-life impact. No CMD2B-specific QoL data. For symptomatic DCM/heart failure generally, health-related QoL is substantially reduced (dyspnea, exertional limitation, hospitalizations); disease-specific instruments include the Kansas City Cardiomyopathy Questionnaire and Minnesota Living with Heart Failure Questionnaire (data unavailable for this subtype).

4. Genetic / Molecular Information

Causal gene. GATAD1 — GATA zinc-finger domain-containing protein 1; 7q21.2; HGNC:29941; NCBI Gene 57798; OMIM 614518; UniProt Q8WUU5. Encodes a nuclear protein containing a GATA-type zinc finger that functions as a reader of H3K4me3 and a subunit of a histone-modifying chromatin complex [in vitro, PMID 26841866; 39641830].

Pathogenic variant (founder allele of the index family). - HGVS: GATAD1 NM_021167.5:c.304T>C, protein p.Ser102Pro (LRG_746; UniProt Q8WUU5:p.Ser102Pro); genomic chr7:g.92078120T>C (GRCh38) [database-verified, ClinVar]. - Identifiers: ClinVar Variation ID 31656; dbSNP rs387907188. - Type/class: single-nucleotide missense; germline; homozygous in affected individuals [human clinical, PMID 21965549]. - Classification: Pathogenic in ClinVar for "Dilated cardiomyopathy 2B" (review status: no assertion criteria provided — 1-star). Ser102 is N-terminal to the GATA-type zinc finger, within the intrinsically disordered region bearing the 14-3-3 phospho-motif. In-silico: CADD 21.8, PolyPhen-2 probably damaging; SIFT tolerated (mildly discordant). - Allele frequency: absent from gnomAD (genomes and exomes) and absent from HapMap, 1000 Genomes and 474 matched controls [PMID 21965549] — private/ ultra-rare. - Broader GATAD1 landscape: most GATAD1 ClinVar entries are VUS or likely benign; only rare truncating variants are (likely) pathogenic. GATAD1 is frequently reported as VUS on cardiomyopathy panels (PMID 38664609, 40200748) — caution for novel variants. - Functional consequence: the mutation destroys a phospho-serine 14-3-3 docking site, altering GATAD1 nucleocytoplasmic transport and producing aberrant subcellular localization and abnormal nuclear morphology [in vitro, PMID 38605029; human IHC, PMID 21965549]. Mechanistically this is not a simple null (see §6): a cardiomyocyte Gatad1 knockout mouse is healthy [PMID 39641830], suggesting an aberrant-function/mislocalization effect rather than pure loss-of-function.

Modifier genes / epigenetic / chromosomal. No CMD2B-specific modifier genes, constitutional epigenetic marks, or chromosomal abnormalities reported (data unavailable). Note GATAD1 itself acts within an epigenetic (histone-modifying) complex — see §6.

5. Environmental Information

No environmental factor, occupational exposure, toxin, or infectious agent is implicated in the causation of CMD2B specifically (it is a monogenic disease; data unavailable). Generic DCM environmental contributors (alcohol, anthracyclines, viral myocarditis, peripartum state) may act as aggravating second hits on a genetically susceptible myocardium but are unproven for GATAD1. No infectious agent applies.

6. Mechanism / Pathophysiology

Ordered causal chain (initiating lesion → clinical manifestation)

1. Homozygous GATAD1 p.Ser102Pro substitutes proline for a serine phosphorylation site → abolishes a phospho-Ser 14-3-3 docking motif [in vitro, PMID 38605029].
2. Loss of 14-3-3 binding → dysregulated masking of a nuclear localization signal → altered nucleocytoplasmic transport / mislocalization of GATAD1 [in vitro, PMID 38605029]; observed as aberrant subcellular localization and abnormal nuclear morphology in patient LV myocytes [human clinical, PMID 21965549].
3. Mislocalized/altered GATAD1 → disrupted incorporation/function within the EMSY–KDM5A(H3K4me3 demethylase)–SIN3B/HDAC histone-modifying complex [in vitro, PMID 26841866] → altered H3K4me3-linked transcriptional regulation at target promoters [inferred].
4. Branch A (transcriptional/chromatin): dysregulated cardiac gene expression programs → impaired maintenance of normal cardiomyocyte structure/function → contractile dysfunction [inferred from PMID 21965549, 26841866].
5. Branch B (metabolic): as a transcription factor GATAD1 normally represses fatty-acid-oxidation genes (Acaa2, Acadm) and promotes glucose oxidation; its dysfunction shifts myocardial substrate metabolism and lowers stress tolerance (larger infarcts / worse function under ischemia–reperfusion) [model organism, PMID 39626862].
6. Converging branches → cardiomyocyte dysfunction → LV chamber dilation and systolic dysfunction (reduced EF) [human clinical, PMID 21965549].
7. → congestive heart failure, and (DCM-class) predisposition to ventricular arrhythmia / sudden cardiac death → end-stage disease potentially requiring transplantation.

Steps 1–2 are experimentally demonstrated; step 3 (complex membership) is demonstrated biochemically but not in heart tissue; steps 4–7 are inferred from correlative human pathology and model-organism data. A key unresolved point: cardiomyocyte-specific Gatad1 deletion does not cause disease in mouse (PMID 39641830), so the pathogenic mechanism likely involves an aberrant/ dominant-negative-like effect of the mislocalized mutant and/or non-cell- autonomous or developmental requirements — not simple loss-of-function.

Detail by category

• Molecular pathways: chromatin/epigenetic regulation via H3K4me3 reading/demethylation (KDM5A) and Sin3/HDAC deacetylation; 14-3-3 signaling. GO: GO:0006325 (chromatin organization), GO:0034968 (histone lysine methylation), GO:0032452 (histone demethylase activity), GO:0000122 (negative regulation of transcription).
• Cellular processes: transcriptional regulation, nucleocytoplasmic transport (GO:0006913), cardiac muscle contraction; metabolic gene regulation.
• Protein dysfunction: loss of a regulatory phosphosite → altered protein–protein interaction (14-3-3) and mislocalization; GATAD1 is intrinsically disordered in the relevant region [in vitro, PMID 38605029].
• Metabolic changes: dysregulated balance of fatty-acid oxidation (GO:0019395) vs glucose oxidation [model organism, PMID 39626862].
• Immune involvement: none established (non-inflammatory genetic cardiomyopathy).
• Tissue-damage mechanisms: DCM-class remodeling — cardiomyocyte dysfunction, interstitial/replacement fibrosis, chamber dilation; increased ischemic vulnerability [inferred/model].
• Epigenetic changes: GATAD1 is itself part of the epigenetic machinery (H3K4me3 reader). Disease-associated global methylation changes: data unavailable.
• Cell types: cardiac muscle cell / cardiomyocyte — CL:0000746 (ventricular cardiomyocyte CL:0002131).

7. Anatomical Structures Affected

• Organ (primary): heart — UBERON:0000948; specifically left ventricular myocardium / heart left ventricle — UBERON:0002084 (myocardium UBERON:0002349).
• Secondary/systemic: cardiovascular system (UBERON:0004535); congestive heart failure secondarily affects lungs (pulmonary congestion), kidneys, liver (congestion). Body system: cardiovascular.
• Tissue/cell: striated cardiac muscle tissue; cardiomyocytes (CL:0000746 / ventricular CL:0002131) are the primary affected cell population.
• Subcellular: nucleus (GO:0005634) — GATAD1 is nuclear; the defect centers on nuclear import/nuclear morphology. Chromatin (GO:0000785). A metabolic arm implicates mitochondrial fatty-acid oxidation machinery indirectly (GO:0005739) [inferred].
• Localization / laterality: predominantly left ventricular; DCM is typically global/bilateral ventricular involvement rather than focal.

8. Temporal Development

• Onset: adult-onset (HP:0003581), insidious/chronic; age-dependent penetrance (an explicit rationale for building an adult zebrafish model, PMID 28955713). No neonatal/pediatric CMD2B cases reported.
• Progression: chronic and progressive; ranges from isolated LV enlargement (intermediate phenotype) to overt DCM with systolic dysfunction and heart failure [human clinical, PMID 21965549]. DCM-class staging: early (asymptomatic LV dilation) → symptomatic HF → advanced/end-stage.
• Course pattern: progressive, lifelong (chronic). No spontaneous remission documented for CMD2B; DCM broadly can show reverse remodeling with guideline-directed therapy.
• Critical periods: adulthood is the window of clinical expression; the pre-symptomatic phase is the opportunity for surveillance/early therapy in at-risk homozygotes.

9. Inheritance and Population

• Inheritance: autosomal recessive (a defining, unusual feature — most DCM is autosomal dominant). Heterozygous carriers are unaffected even at advanced age [human clinical, PMID 21965549].
• Penetrance: appears high in homozygotes but age-dependent; carriers non-penetrant.
• Expressivity: variable (isolated LV enlargement → overt DCM within one family).
• Consanguinity: central — index family descended from first cousins; homozygosity mapping was the discovery strategy [PMID 21965549].
• Founder effect / geographic variant distribution / anticipation / germline mosaicism: none reported (data unavailable). No repeat expansion (no anticipation expected).
• Carrier frequency: not established; the specific allele is private/ultra-rare (absent from population databases).
• Epidemiology: No prevalence/incidence figures exist for CMD2B specifically — it is exceedingly rare (essentially one published kindred). For context, DCM overall has an estimated prevalence on the order of ~1 in 250–500 and a monogenic cause is identifiable in ~30–40% of familial cases (PMID 39855353); GATAD1 accounts for only a tiny fraction. Sex ratio: DCM overall is male-predominant; both sexes affected in the CMD2B family (the two fully affected probands were female). Age distribution: adults.

10. Diagnostics

Cardiac phenotyping (DCM-class, applied to CMD2B). - Imaging: transthoracic echocardiography (LV dilation, reduced LVEF) — first-line; cardiac MRI (chamber volumes, function, late-gadolinium fibrosis) [DCM-class; stress echo relevance PMID 18579481]. LOINC/RadLex apply. - ECG / Holter: arrhythmia and conduction assessment. - Biomarkers: NT-proBNP/BNP (heart-failure severity); troponin as adjunct (non-specific). No CMD2B-specific circulating biomarker. - Endomyocardial biopsy: not routine; in the proband it revealed aberrant cardiomyocyte nuclear morphology / GATAD1 mislocalization [PMID 21965549].

Genetic testing (definitive for subtype). - Recommended approach: NGS cardiomyopathy multigene panel (GATAD1 is included on modern panels, PMID 38664609) or whole-exome/genome sequencing; the original diagnosis used homozygosity mapping + exome sequencing in a consanguineous pedigree [PMID 21965549]. - Confirm biallelic GATAD1 variants (homozygous or compound heterozygous) with segregation; classify per ACMG/AMP (many GATAD1 variants are currently VUS). - CMA/karyotype/FISH/mtDNA/repeat-expansion testing: not indicated for this single-gene point-mutation disorder.

Clinical criteria / differential diagnosis. Diagnose DCM by LV dilation + systolic dysfunction after excluding ischemic, valvular, hypertensive, toxic (alcohol/anthracycline), infiltrative, peripartum and myocarditic causes. Differential: other genetic DCMs (TTN, LMNA, RBM20, FLNC, DES, MYH7), arrhythmogenic and hypertrophic cardiomyopathies. The recessive pattern + consanguinity + GATAD1 genotype distinguishes CMD2B.

Screening. Cascade genetic testing of relatives and echocardiographic surveillance of at-risk biallelic individuals (see §13). Family screening yields ~10% at baseline and ~10% more over 5 years in DCM generally (PMID 39833651).

11. Outcome / Prognosis

• CMD2B-specific outcome data are essentially absent beyond the index family (adult-onset DCM/heart failure). No survival, mortality or QoL statistics exist for this subtype.
• By DCM class: prognosis depends on LVEF and remodeling. In a large registry, patients presenting with mid-range EF (40–49%) had markedly better outcomes than reduced-EF (<40%) patients — death/transplant 9% vs 36% and SCD/major ventricular arrhythmia 4.5% vs 15% over ~10 years (PMID 31431100); ~17% of mid-range progressed to reduced EF.
• Complications: progressive heart failure, ventricular arrhythmia/sudden cardiac death, atrial fibrillation, thromboembolism, and end-stage disease requiring heart transplantation (genetic DCMs are enriched among transplant recipients, PMID 42537484).
• Recovery: reverse remodeling possible with guideline-directed therapy in DCM broadly; not documented specifically for CMD2B.
• Prognostic factors: LVEF, LV size, fibrosis on MRI, arrhythmia burden, NT-proBNP (DCM-class). No validated CMD2B-specific prognostic biomarker.

12. Treatment

No gene-specific or curative therapy exists for CMD2B. Management follows guideline-directed medical therapy (GDMT) for DCM/heart failure with reduced ejection fraction:

• Pharmacotherapy (NCIT terms in brackets):
• ACE inhibitors / ARBs / ARNI (sacubitril–valsartan) — afterload/neurohormonal.
• Beta-blockers (carvedilol, metoprolol succinate, bisoprolol).
• Mineralocorticoid-receptor antagonists (spironolactone, eplerenone).
• SGLT2 inhibitors (dapagliflozin, empagliflozin).
• Diuretics for congestion; anticoagulation if AF/thrombus.
• NCIT: ACE Inhibitor, Beta-Adrenergic Blocker, Diuretic, Aldosterone Antagonist.
• Pharmacogenomics: no GATAD1-specific PGx. General HF PGx (e.g., warfarin CYP2C9/VKORC1) applies only if those drugs are used.
• Device / interventional: ICD for sudden-death prevention and CRT for conduction delay per EF/QRS criteria; mitral intervention as indicated.
• Advanced / surgical: mechanical circulatory support (LVAD) and heart transplantation for end-stage disease.
• Advanced therapeutics (gene/cell/RNA/targeted/immunotherapy): none approved or in trials for GATAD1-DCM (data unavailable). Gene-directed strategies are conceptual only.
• Supportive/rehabilitative: cardiac rehabilitation, sodium/fluid guidance, exercise counseling, HF self-management.
• Experimental / trials: no CMD2B-specific registered trials identified.
• Personalized approach: genotype confirmation guides family screening and reproductive counseling rather than drug selection at present.

13. Prevention

• Primary prevention: not possible for the genetic cause; preconception/ reproductive genetic counseling in consanguineous or carrier families is the main lever. Options: carrier testing of partners, prenatal diagnosis or preimplantation genetic testing (PGT-M) for known biallelic risk.
• Secondary prevention: cascade genetic testing of relatives and serial echocardiographic surveillance of biallelic (homozygous/compound-het) at-risk individuals to detect subclinical LV dysfunction early; genotype-guided screening is efficient because non-carriers of the familial variant do not develop disease (PMID 39833651). ACMG/HFSA recommend genetic evaluation + family screening in familial DCM.
• Tertiary prevention: GDMT, ICD for arrhythmic death, HF-hospitalization avoidance, management of AF/thromboembolism.
• Behavioral: avoid alcohol excess and cardiotoxins; standard cardiovascular risk-factor control (may mitigate "second-hit" aggravation — inferred).
• Counseling: autosomal-recessive counseling — 25% recurrence risk for future sibs of an affected child; offspring of an affected person are obligate carriers (affected only if partner is also a carrier). Immunization/public-health and environmental interventions: not applicable.

14. Other Species / Natural Disease

• Taxonomy / orthologs: GATAD1 is evolutionarily conserved.
• Human GATAD1 — NCBI Gene 57798, HGNC:29941, 7q21.2 (Homo sapiens, Taxon 9606).
• Mouse Gatad1 — NCBI Gene 67210 (Mus musculus, NCBI Taxon 10090; chr5 A1).
• Zebrafish gatad1 — NCBI Gene 678617 (Danio rerio, NCBI Taxon 7955).
• Natural disease in other species: No naturally occurring GATAD1 cardiomyopathy in companion animals or wildlife is catalogued (no OMIA entry identified; data unavailable). Note: naturally occurring DCM is common in dogs (e.g., Doberman Pinscher, Great Dane) but is genetically distinct (not GATAD1).
• Comparative biology / conservation: the H3K4me3-reader/chromatin-complex function and the Ser102/14-3-3 regulatory motif are conserved, enabling cross-species modeling; however, phenotypic conservation is incomplete — zebrafish reproduce DCM whereas mouse cardiomyocyte knockout does not (§15).
• Transmission / zoonosis: not applicable (non-communicable genetic disease).

15. Model Organisms

Zebrafish (Danio rerio, Taxon 7955) — supportive positive model. Yang, Shah, Olson & Xu 2016 (PMID 28955713) generated an adult zebrafish model of the gatad1 homologue specifically to overcome age-dependent penetrance and validate GATAD1 as a bona fide DCM gene in a higher-throughput vertebrate.

"we generated an adult zebrafish model, which is a simpler vertebrate model with higher throughput than rodents." (PMID 28955713) - Model type: genetic vertebrate; application: validating causality, studying adult-onset cardiomyopathy mechanisms.

Mouse (Mus musculus, Taxon 10090) — informative negative / limitation. Pang et al. 2024 (PMID 39641830) made a cardiomyocyte-specific Gatad1 knockout (cKO). It showed normal cardiac function to 18 months, normal nuclear shape (unlike patients), and normal response to pressure overload (TAC).

"deletion of Gatad1 in cardiomyocytes does not induce cardiomyopathy during aging or affect the response to pressure-overload stress in mice." (PMID 39641830) - Interpretation/limitation: pure cardiomyocyte loss-of-function is insufficient in mouse → argues the human p.Ser102Pro acts via aberrant function/mislocalization or non-cardiomyocyte/developmental requirements; a knock-in of the p.Ser102Pro allele would be the more faithful (still-needed) model.

Additional mouse model (metabolic). A myocardium-specific Gatad1 cKO was used to show GATAD1 controls the fatty-acid/glucose oxidation balance and modulates ischemia–reperfusion injury (PMID 39626862).

In vitro / cellular systems. Peptide-interaction proteomics and structural studies of the Ser102 phosphosite–14-3-3 interaction (PMID 38605029); biochemical characterization of the EMSY/KDM5A/SIN3B complex (PMID 26841866). No iPSC- cardiomyocyte CMD2B model is yet reported (opportunity/gap).

Resources: MGI (mouse Gatad1), ZFIN (zebrafish gatad1), Alliance of Genome Resources.

Summary of Supported vs. Refuted / Open Hypotheses

• Supported: CMD2B = autosomal-recessive DCM caused by biallelic GATAD1 (p.Ser102Pro); GATAD1 is a nuclear H3K4me3-reader/chromatin-complex subunit; the mutation disrupts a Ser102 phospho-14-3-3 motif and GATAD1 nuclear localization; GATAD1 regulates cardiac substrate metabolism; zebrafish recapitulate DCM.
• Refuted / qualified: "simple cardiomyocyte loss-of-function causes the disease" — refuted in mouse cKO (PMID 39641830); mechanism is more likely aberrant-function/mislocalization.
• Resolved this review: founder allele nomenclature and status — GATAD1 NM_021167.5:c.304T>C (p.Ser102Pro), ClinVar VCV31656/rs387907188, Pathogenic, absent from gnomAD.
• Open / data-unavailable: population carrier frequency; CMD2B-specific penetrance %, survival, QoL; modifier genes; existence of additional families beyond the index kindred; iPSC and knock-in (p.Ser102Pro) models.

Limitations

Human evidence rests on one consanguineous kindred; mechanism is pieced together from in-vitro and cross-species models with a notable mouse/zebrafish discordance. Epidemiologic, prognostic, and treatment-response data specific to CMD2B do not exist and were substituted with clearly-labeled DCM-class information.

Key References (PMIDs)

• 21965549 — Theis et al. 2011: discovery of GATAD1 in AR-DCM [human clinical].
• 38605029 — Rrustemi et al. 2024: Ser102/14-3-3, nucleocytoplasmic transport [in vitro].
• 26841866 — Varier et al. 2016: EMSY/KDM5A/SIN3B complex, GATAD1 subunit [in vitro].
• 28955713 — Yang et al. 2016: adult zebrafish gatad1 DCM model [model organism].
• 39641830 — Pang et al. 2024: cardiomyocyte Gatad1 cKO — no cardiomyopathy [model organism].
• 39626862 — Cai et al. 2025: GATAD1 controls FAO/glucose oxidation, I/R injury [model organism].
• 38664609 / 40200748 / 39833651 / 39855353 — DCM genetic testing & family screening context.
• 31431100 — DCM natural history by EF stratum [human clinical, DCM-class].

Artifacts

• OpenScientist final report
• OpenScientist final report

Reference Validation

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All extracted references resolved successfully.

Term Validation

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Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

• HP:0001644 (1 mention) - the report calls it "clinical/imaging sign"; HP calls it Dilated cardiomyopathy
• HP:0001635 (2 mentions) - the report calls it "symptoms"; HP calls it Congestive heart failure

Obsolete terms

These terms are real but deprecated. Citing one is not a fabrication; it does mean the report is naming something the ontology has retired:

• GO:0034968 (obsolete histone lysine methylation) (1 mention)

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

• UBERON:0004535 (1 mention) - the report calls it "Secondary/systemic: cardiovascular system"; UBERON calls it cardiovascular system**
• GO:0005634 (1 mention) - the report calls it "Subcellular: nucleus"; GO calls it nucleus, and lists "cell nucleus" among its other names

Terms named inconsistently

The report gives these identifiers more than one name of its own:

• HP:0003581 - called "adult-onset", "Onset: adult-onset"

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: ORPHA.