peroxisome biogenesis disorder, complementation group K

Summary

peroxisome biogenesis disorder, complementation group K (MONDO:0800365) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 460

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	peroxisome biogenesis disorder, complementation group K
Mondo ID	MONDO:0800365
UMLS	C1866257
MedGen	356487
GARD	0026524
Is cancer (heuristic)	no

Also known as: CGK

Data availability: 460 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › Zellweger spectrum disorders › peroxisome biogenesis disorder due to PEX14 defect › peroxisome biogenesis disorder, complementation group K

Related subtypes (1): peroxisome biogenesis disorder 13A (Zellweger)

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

460 retrieved; paginated sample, class counts are floors:

201 likely benign, 182 uncertain significance, 47 conflicting classifications of pathogenicity, 12 benign, 8 benign/likely benign, 6 pathogenic, 4 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1453475	NC_000001.10:g.(?10535024)(10596374_?)del	PEX14	Pathogenic	criteria provided, single submitter
2425163	NC_000001.10:g.(?10535024)(10535079_?)del	PEX14	Pathogenic	criteria provided, single submitter
2425165	NC_000001.10:g.(?10535024)(10687440_?)del	PEX14	Pathogenic	criteria provided, single submitter
2753909	NM_004565.3(PEX14):c.109C>T (p.Gln37Ter)	PEX14	Pathogenic	criteria provided, single submitter
3247784	NC_000001.10:g.(?10596250)(10596374_?)del	PEX14	Pathogenic	criteria provided, single submitter
3663959	NC_000001.11:g.10599291_10599292insTAAAGCAGCAATAAACTCAAGGATAAATTAAGGAAATTGAATGAGCCACATTTGGAAGCAGTGTTGAGGCTAATATTCTGTCGCTTAAGGTTAAATTGCAACTGAGAGAGGTTCCGGAGAATCTGAAATCGGGGAGGCAACTTACTAGGATGCGAGGCATTCTGTGGCTGTAAAGGTCTTTGCTCAGTGAAGATTCTGTTGCAGCTATGGACACTGACAAAAGGTACTCACCTGCAATGATGTCCTCTTCTCCCCAGGGCTGACAGATGAAGAGATTGATATGGCCTTCCAGCAGTCGGGCACTGCTGCCG	PEX14	Pathogenic	criteria provided, single submitter
2709504	NM_004565.3(PEX14):c.204_298+125delinsTATTCCTT	PEX14	Likely pathogenic	criteria provided, single submitter
2769432	NM_004565.3(PEX14):c.299-5_306del	PEX14	Likely pathogenic	criteria provided, single submitter
2967272	NM_004565.3(PEX14):c.298+1G>C	PEX14	Likely pathogenic	criteria provided, single submitter
862190	NM_004565.3(PEX14):c.36+1G>T	PEX14	Likely pathogenic	criteria provided, single submitter
198515	NM_004565.3(PEX14):c.575C>G (p.Ala192Gly)	LOC126805616	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291192	NM_004565.3(PEX14):c.567C>T (p.His189=)	LOC126805616	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
595402	NM_004565.3(PEX14):c.543G>A (p.Gln181=)	LOC126805616	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
598254	NM_004565.3(PEX14):c.516C>T (p.Ser172=)	LOC126805616	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
876453	NM_004565.3(PEX14):c.488-14C>T	LOC126805616	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
167451	NM_004565.3(PEX14):c.824C>T (p.Ser275Leu)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
199100	NM_004565.3(PEX14):c.1013_1014inv (p.Asp338Gly)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
259436	NM_004565.3(PEX14):c.36+8G>A	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285256	NM_004565.3(PEX14):c.474C>T (p.Ser158=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285505	NM_004565.3(PEX14):c.451G>A (p.Gly151Ser)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286053	NM_004565.3(PEX14):c.795A>G (p.Ser265=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286703	NM_004565.3(PEX14):c.825G>A (p.Ser275=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288364	NM_004565.3(PEX14):c.299-8G>A	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291674	NM_004565.3(PEX14):c.297C>T (p.Tyr99=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291675	NM_004565.3(PEX14):c.381C>T (p.Tyr127=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291679	NM_004565.3(PEX14):c.855C>G (p.Gly285=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
291682	NM_004565.3(PEX14):c.993T>G (p.Asp331Glu)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
497626	NM_004565.3(PEX14):c.897C>T (p.Gly299=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
498110	NM_004565.3(PEX14):c.1116C>T (p.Asn372=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
498151	NM_004565.3(PEX14):c.1107C>T (p.Gly369=)	PEX14	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CASZ1	Orphanet:1606	1p36 deletion syndrome
PEX14	Orphanet:44	Neonatal adrenoleukodystrophy
PEX14	Orphanet:772	Infantile Refsum disease
PEX14	Orphanet:912	Zellweger syndrome

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
CASZ1	HGNC:26002	ENSG00000130940	Q86V15	Zinc finger protein castor homolog 1	clinvar
PEX14	HGNC:8856	ENSG00000142655	O75381	Peroxisomal membrane protein PEX14	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CASZ1	Zinc finger protein castor homolog 1	Transcriptional activator.
PEX14	Peroxisomal membrane protein PEX14	Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CASZ1	Transcription factor	no		Znf_C2H2_type, CASZ1
PEX14	Other/Unknown	no		Pex14_N, PEX14, WH-like_DNA-bd_sf

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
skin of abdomen	1
skin of leg	1
zone of skin	1
bronchial epithelial cell	1
bronchus	1
epithelium of bronchus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CASZ1	241	ubiquitous	marker	skin of leg, skin of abdomen, zone of skin
PEX14	286	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PEX14	1,273
CASZ1	926

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PEX14	O75381	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CASZ1	Q86V15	53.66

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
Class I peroxisomal membrane protein import	1	519.1×	0.006	PEX14
E3 ubiquitin ligases ubiquitinate target proteins	1	193.6×	0.006	PEX14
Peroxisomal protein import	1	173.0×	0.006	PEX14

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
peroxisome transport along microtubule	1	8426.0×	0.002	PEX14
protein import into peroxisome matrix, docking	1	2106.5×	0.002	PEX14
protein import into peroxisome matrix, translocation	1	2106.5×	0.002	PEX14
protein import into peroxisome matrix, substrate release	1	1685.2×	0.002	PEX14
protein import into peroxisome matrix	1	702.2×	0.004	PEX14
microtubule anchoring	1	648.1×	0.004	PEX14
peroxisome organization	1	401.2×	0.005	PEX14
obsolete negative regulation of DNA-binding transcription factor activity	1	366.4×	0.005	PEX14
regulation of neuron differentiation	1	366.4×	0.005	CASZ1
negative regulation of protein binding	1	312.1×	0.005	PEX14
cellular response to reactive oxygen species	1	205.5×	0.007	PEX14
protein-containing complex assembly	1	56.9×	0.022	PEX14
negative regulation of DNA-templated transcription	1	15.8×	0.072	PEX14
positive regulation of DNA-templated transcription	1	14.0×	0.075	CASZ1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.130	CASZ1

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
CASZ1	0	0
PEX14	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
PEX14	1	ADMET: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	0
E	Difficult family or no structure, no drug	2	CASZ1, PEX14

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)
CASZ1	0	—
PEX14	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.