Tubulointerstitial kidney disease, autosomal dominant 6

Summary

Tubulointerstitial kidney disease, autosomal dominant 6 (MONDO:0976234) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tubulointerstitial kidney disease, autosomal dominant 6
Mondo ID	MONDO:0976234
OMIM	621106
DOID	DOID:0061121
UMLS	C6012701
MedGen	1876482
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited kidney disorder › familial juvenile hyperuricemic nephropathy › tubulointerstitial kidney disease, autosomal dominant 6

Related subtypes (5): familial juvenile hyperuricemic nephropathy type 1, familial juvenile hyperuricemic nephropathy type 2, hyperuricemic nephropathy, familial juvenile type 3, hyperuricemic nephropathy, familial juvenile type 4, tubulointerstitial kidney disease, autosomal dominant, 2

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3764740	NM_000482.4(APOA4):c.196C>G (p.Leu66Val)	APOA4	Pathogenic	no assertion criteria provided
3764741	NM_000482.4(APOA4):c.97G>A (p.Asp33Asn)	APOA4	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
APOA4	HGNC:602	ENSG00000110244	P06727	Apolipoprotein A-IV	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
APOA4	Apolipoprotein A-IV	May have a role in chylomicrons and VLDL secretion and catabolism.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
APOA4	Other/Unknown	no		ApoA_E, Apolipoprotein_A1/A4/E

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
duodenum	1
ileal mucosa	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
APOA4	122	tissue_specific	marker	jejunal mucosa, ileal mucosa, duodenum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
APOA4	1,268

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
APOA4	P06727	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Chylomicron assembly	1	1142.0×	0.006	APOA4
Chylomicron remodeling	1	1142.0×	0.006	APOA4
Plasma lipoprotein assembly	1	713.8×	0.006	APOA4
Assembly of active LPL and LIPC lipase complexes	1	601.0×	0.006	APOA4
Plasma lipoprotein remodeling	1	475.8×	0.006	APOA4
Metabolism of fat-soluble vitamins	1	380.7×	0.007	APOA4
Visual phototransduction	1	259.6×	0.007	APOA4
Retinoid metabolism and transport	1	248.3×	0.007	APOA4
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.007	APOA4
Metabolism of vitamins and cofactors	1	116.5×	0.013	APOA4
Amyloid fiber formation	1	102.9×	0.013	APOA4
Sensory Perception	1	95.2×	0.013	APOA4
Transport of small molecules	1	25.1×	0.046	APOA4
Metabolism of proteins	1	12.4×	0.086	APOA4
Metabolism	1	11.6×	0.086	APOA4

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
protein-lipid complex assembly	1	16852.0×	9e-04	APOA4
response to lipid hydroperoxide	1	8426.0×	9e-04	APOA4
response to triglyceride	1	8426.0×	9e-04	APOA4
negative regulation of plasma lipoprotein oxidation	1	8426.0×	9e-04	APOA4
regulation of intestinal cholesterol absorption	1	4213.0×	1e-03	APOA4
chylomicron remodeling	1	4213.0×	1e-03	APOA4
chylomicron assembly	1	4213.0×	1e-03	APOA4
acylglycerol homeostasis	1	3370.4×	0.001	APOA4
response to stilbenoid	1	2808.7×	0.001	APOA4
regulation of cholesterol transport	1	2407.4×	0.001	APOA4
positive regulation of triglyceride catabolic process	1	2106.5×	0.001	APOA4
peripheral nervous system axon regeneration	1	2106.5×	0.001	APOA4
very-low-density lipoprotein particle remodeling	1	2106.5×	0.001	APOA4
positive regulation of fatty acid biosynthetic process	1	1296.3×	0.002	APOA4
phospholipid efflux	1	1123.5×	0.002	APOA4
removal of superoxide radicals	1	1053.2×	0.002	APOA4
lipoprotein metabolic process	1	936.2×	0.002	APOA4
reverse cholesterol transport	1	936.2×	0.002	APOA4
high-density lipoprotein particle remodeling	1	802.5×	0.002	APOA4
phosphatidylcholine metabolic process	1	802.5×	0.002	APOA4
innate immune response in mucosa	1	674.1×	0.002	APOA4
hydrogen peroxide catabolic process	1	674.1×	0.002	APOA4
cholesterol efflux	1	526.6×	0.002	APOA4
leukocyte cell-cell adhesion	1	468.1×	0.003	APOA4
lipid homeostasis	1	337.0×	0.003	APOA4
lipid transport	1	263.3×	0.004	APOA4
lipid catabolic process	1	244.2×	0.004	APOA4
cholesterol metabolic process	1	195.9×	0.005	APOA4
cholesterol homeostasis	1	156.0×	0.006	APOA4

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
APOA4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	APOA4

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)
APOA4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.