Tyrosinemia

Summary

Tyrosinemia (MONDO:0004741) is a disease with 1 cohort gene and 6 clinical trials.

At a glance

• Cohort genes: 1
• ClinVar variants: 3
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tyrosinemia
Mondo ID	MONDO:0004741
MeSH	D020176
OMIM	276700
DOID	DOID:9275
ICD-10-CM	E70.21
NCIT	C98640
SNOMED CT	190694001
UMLS	C0268486
MedGen	541332
GARD	0024099
Is cancer (heuristic)	no

Data availability: 3 ClinVar variants.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn disorder of amino acid and other organic acid metabolism › inborn disorder of amino acid metabolism › inborn disorder of phenylalanine and tyrosine metabolism › disorder of tyrosine metabolism › tyrosinemia

Related subtypes (4): hawkinsinuria, alkaptonuria, TH-deficient dopa-responsive dystonia, oculocutaneous albinism type 1

Subtypes (4): tyrosinemia type II, tyrosinemia type I, tyrosinemia type III, transient tyrosinemia of the newborn

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

3 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic, 1 pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
11870	NM_000137.4(FAH):c.1062+5G>A	FAH	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
372766	NM_000137.4(FAH):c.1A>G (p.Met1Val)	FAH	Pathogenic	criteria provided, multiple submitters, no conflicts
828087	NM_000137.4(FAH):c.554-16del	FAH	Benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FAH	Orphanet:882	Tyrosinemia type 1

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
FAH	HGNC:3579	ENSG00000103876	P16930	Fumarylacetoacetase	clinvar

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FAH	Enzyme (other)	yes	3.7.1.2	Fumarylacetoacetase, Fumarylacetoacetase-like_C, Fumarylacetoacetase_N

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
liver	1
right adrenal gland	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FAH	255	ubiquitous	marker	right lobe of liver, liver, right adrenal gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FAH	1,872

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FAH	P16930	8

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
Tyrosine catabolism	1	2284.0×	4e-04	FAH

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
homogentisate catabolic process	1	16852.0×	3e-04	FAH
L-arginine catabolic process	1	2808.7×	6e-04	FAH
L-tyrosine catabolic process	1	2808.7×	6e-04	FAH
L-phenylalanine catabolic process	1	2106.5×	6e-04	FAH
lipid metabolic process	1	91.6×	0.011	FAH

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Nitisinone	Approved (phase 4)

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
FAH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FAH	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FAH	3.7.1.2	fumarylacetoacetase

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	1	FAH
D	Druggable family + AlphaFold only, no drug	0
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)
FAH	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	6

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06941532	Not specified	RECRUITING	GMP Powdered Substitutes in PKU and TYR
NCT04196959	Not specified	COMPLETED	Evaluation of TYR Sphere
NCT04761588	Not specified	COMPLETED	Evaluation of TYR Sphere in France
NCT05051657	Not specified	COMPLETED	Evaluation of the Express Plus Range
NCT05062226	Not specified	COMPLETED	GMP Case Studies of Tolerance, Safety and Acceptability in PKU and TYR
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan