Inborn disorder of lysine and hydroxylysine metabolism

Summary

Inborn disorder of lysine and hydroxylysine metabolism (MONDO:0017351) is a disease (an umbrella term covering 5 Mondo subtypes) with 2 cohort genes.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inborn disorder of lysine and hydroxylysine metabolism
Mondo ID	MONDO:0017351
Orphanet	289832
ICD-10-CM	E72.3
ICD-11	367868681
SNOMED CT	237929000
UMLS	C0268552
MedGen	541359
GARD	0021155
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 5 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 lysine and hydroxylysine metabolism

Related subtypes (12): inborn disorder of amino acid metabolism, pyruvate metabolism disorder, disorder of glutamine metabolism, disorder of beta and omega amino acid metabolism, disorder of melanin metabolism, inborn disorder of bile acid synthesis, inborn disorder of methionine cycle and sulfur amino acid metabolism, inborn disorder of ornithine or proline metabolism, inborn disorder of serine family metabolism, inborn disorder of the gamma-glutamyl cycle, inborn error of biotin metabolism, inherited fatty acid metabolism disorder

Subtypes (5): 2-aminoadipic 2-oxoadipic aciduria, seizures-intellectual disability due to hydroxylysinuria syndrome, hyperlysinemia, saccharopinuria, inborn disorder of lysine, hydroxylysine, and tryptophan metabolism

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

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
39564	NM_018706.7(DHTKD1):c.2185G>A (p.Gly729Arg)	DHTKD1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 2 · 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
HYKK	Limited	Autosomal recessive	inborn disorder of lysine and hydroxylysine metabolism

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DHTKD1	Orphanet:329258	Autosomal dominant Charcot-Marie-Tooth disease type 2Q
DHTKD1	Orphanet:79154	2-aminoadipic 2-oxoadipic aciduria

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
HYKK	HGNC:34403	ENSG00000188266	A2RU49	Hydroxylysine kinase	gencc
DHTKD1	HGNC:23537	ENSG00000181192	Q96HY7	2-oxoadipate dehydrogenase complex component E1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HYKK	Hydroxylysine kinase	Catalyzes the GTP-dependent phosphorylation of 5-hydroxy-L-lysine.
DHTKD1	2-oxoadipate dehydrogenase complex component E1	2-oxoadipate dehydrogenase (E1a) component of the 2-oxoadipate dehydrogenase complex (OADHC).

Protein-family classification

Druggable: 2 · 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
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HYKK	Kinase	yes	2.7.1.81	Aminoglycoside_PTrfase, Kinase-like_dom_sf, Pseudomonas-type_ThrB
DHTKD1	Enzyme (other)	yes	1.2.1.105	DH_E1, Transketolase-like_Pyr-bd, 2oxoglutarate_DH_E1

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
calcaneal tendon	1
ileal mucosa	1
olfactory segment of nasal mucosa	1
liver	1
right lobe of liver	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HYKK	170	ubiquitous	marker	olfactory segment of nasal mucosa, calcaneal tendon, ileal mucosa
DHTKD1	270	ubiquitous	marker	liver, right lobe of liver, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DHTKD1	2,099
HYKK	1,592

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DHTKD1	Q96HY7	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HYKK	A2RU49	93.89

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
OADH complex synthesizes glutaryl-CoA from 2-OA	1	1903.3×	0.001	DHTKD1
Lysine catabolism	1	571.0×	0.002	HYKK

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
obsolete lysine catabolic process	1	1203.7×	0.003	HYKK
glycolytic process	1	191.5×	0.008	DHTKD1
generation of precursor metabolites and energy	1	172.0×	0.008	DHTKD1
hematopoietic progenitor cell differentiation	1	118.7×	0.008	DHTKD1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
HYKK	0	0
DHTKD1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HYKK	2.7.1.81	hydroxylysine kinase
DHTKD1	1.2.1.105	2-oxoglutarate dehydrogenase system

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	1	DHTKD1
D	Druggable family + AlphaFold only, no drug	1	HYKK
E	Difficult family or no structure, no drug	0

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)
HYKK	0	—
DHTKD1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.