Amyloidosis, hereditary systemic 5

Summary

Amyloidosis, hereditary systemic 5 (MONDO:0971009) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	amyloidosis, hereditary systemic 5
Mondo ID	MONDO:0971009
OMIM	620658
UMLS	C5935572
MedGen	1859086
GARD	0027102
Is cancer (heuristic)	no

Data availability: 26 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › hereditary amyloidosis › familial amyloid neuropathy › amyloidosis, hereditary systemic 5

Related subtypes (3): amyloidosis, hereditary systemic 1, amyloidosis, hereditary systemic 3, amyloidosis, hereditary systemic 6

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

26 retrieved; paginated sample, class counts are floors:

18 uncertain significance, 4 conflicting classifications of pathogenicity, 2 pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
14374	NM_000239.3(LYZ):c.221T>C (p.Ile74Thr)	LYZ	Pathogenic	no assertion criteria provided
14377	NM_000239.3(LYZ):c.223T>A (p.Phe75Ile)	LYZ	Pathogenic	no assertion criteria provided
2142972	NM_000239.3(LYZ):c.230T>C (p.Ile77Thr)	LYZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2319596	NM_000239.3(LYZ):c.40G>T (p.Val14Phe)	LYZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3575258	NM_000239.3(LYZ):c.322G>A (p.Ala108Thr)	LYZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
882899	NM_000239.3(LYZ):c.151A>T (p.Lys51Ter)	LYZ	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1338132	NM_000239.3(LYZ):c.175C>T (p.Arg59Ter)	LYZ	Uncertain significance	criteria provided, multiple submitters, no conflicts
14375	NM_000239.3(LYZ):c.199G>C (p.Asp67His)	LYZ	Uncertain significance	criteria provided, single submitter
3575246	NM_000239.3(LYZ):c.5A>G (p.Lys2Arg)	LYZ	Uncertain significance	criteria provided, single submitter
3575247	NM_000239.3(LYZ):c.10C>T (p.Leu4Phe)	LYZ	Uncertain significance	criteria provided, single submitter
3575249	NM_000239.3(LYZ):c.44_45delinsTT (p.Thr15Ile)	LYZ	Uncertain significance	criteria provided, single submitter
3575250	NM_000239.3(LYZ):c.107A>G (p.Asp36Gly)	LYZ	Uncertain significance	criteria provided, single submitter
3575251	NM_000239.3(LYZ):c.156G>T (p.Trp52Cys)	LYZ	Uncertain significance	criteria provided, single submitter
3575252	NM_000239.3(LYZ):c.176G>A (p.Arg59Gln)	LYZ	Uncertain significance	criteria provided, multiple submitters, no conflicts
3575253	NM_000239.3(LYZ):c.228G>A (p.Gln76=)	LYZ	Uncertain significance	criteria provided, single submitter
3575254	NM_000239.3(LYZ):c.238C>T (p.Arg80Cys)	LYZ	Uncertain significance	criteria provided, single submitter
3575256	NM_000239.3(LYZ):c.281C>G (p.Ala94Gly)	LYZ	Uncertain significance	criteria provided, single submitter
3575257	NM_000239.3(LYZ):c.302-7_302-5dup	LYZ	Uncertain significance	criteria provided, single submitter
3575259	NM_000239.3(LYZ):c.381-2A>T	LYZ	Uncertain significance	criteria provided, single submitter
3575260	NM_000239.3(LYZ):c.381-1G>A	LYZ	Uncertain significance	criteria provided, single submitter
3575261	NM_000239.3(LYZ):c.416T>C (p.Val139Ala)	LYZ	Uncertain significance	criteria provided, single submitter
3575262	NM_000239.3(LYZ):c.442G>A (p.Val148Met)	LYZ	Uncertain significance	criteria provided, single submitter
3891608	NM_000239.3(LYZ):c.64G>T (p.Glu22Ter)	LYZ	Uncertain significance	criteria provided, single submitter
4086044	NM_000239.3(LYZ):c.268G>C (p.Gly90Arg)	LYZ	Uncertain significance	criteria provided, single submitter
3541465	NM_000239.3(LYZ):c.398G>A (p.Arg133His)	LYZ	Likely benign	criteria provided, multiple submitters, no conflicts
3575255	NM_000239.3(LYZ):c.239G>A (p.Arg80His)	LYZ	Likely benign	criteria provided, multiple submitters, no conflicts

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
LYZ	Orphanet:93561	ALys amyloidosis

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
LYZ	HGNC:6740	ENSG00000090382	P61626	Lysozyme C	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LYZ	Lysozyme C	Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents.

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)
LYZ	Enzyme (other)	yes	3.2.1.17	Glyco_hydro_22_lys, Glyco_hydro_22, Glyco_hydro_22_CS

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LYZ	270	broad	marker	monocyte, leukocyte, mononuclear cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LYZ	258

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LYZ	P61626	215

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Antimicrobial peptides	1	223.9×	0.027	LYZ
Amyloid fiber formation	1	102.9×	0.029	LYZ
Innate Immune System	1	25.5×	0.065	LYZ
Neutrophil degranulation	1	23.1×	0.065	LYZ
Immune System	1	13.0×	0.081	LYZ
Metabolism of proteins	1	12.4×	0.081	LYZ

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
antimicrobial humoral response	1	1532.0×	0.004	LYZ
killing of cells of another organism	1	271.8×	0.011	LYZ
defense response to Gram-negative bacterium	1	168.5×	0.011	LYZ
defense response to Gram-positive bacterium	1	127.7×	0.011	LYZ
defense response to bacterium	1	108.0×	0.011	LYZ
inflammatory response	1	37.7×	0.027	LYZ

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
LYZ	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
LYZ	3.2.1.17	lysozyme

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	LYZ
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)
LYZ	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.