Polycystic kidney disease 5

Summary

Polycystic kidney disease 5 (MONDO:0033281) is a disease caused by DZIP1L (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DZIP1L (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	polycystic kidney disease 5
Mondo ID	MONDO:0033281
OMIM	617610
DOID	DOID:0080273
UMLS	C4539903
MedGen	1624679
GARD	0016242
Is cancer (heuristic)	no

Also known as: DZIP1L polycystic kidney disease · PKD5 · polycystic kidney disease 5 · polycystic kidney disease caused by mutation in DZIP1L

Data availability: 17 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive polycystic kidney disease › polycystic kidney disease 5

Related subtypes (1): polycystic kidney disease 4

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

17 retrieved; paginated sample, class counts are floors:

4 benign, 4 uncertain significance, 4 pathogenic, 3 likely pathogenic, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
431431	NM_173543.3(DZIP1L):c.269C>T (p.Ala90Val)	DZIP1L	Pathogenic	no assertion criteria provided
431432	NM_173543.3(DZIP1L):c.273G>C (p.Gln91His)	DZIP1L	Pathogenic	no assertion criteria provided
431433	NM_173543.3(DZIP1L):c.463C>T (p.Gln155Ter)	DZIP1L	Pathogenic	criteria provided, single submitter
431434	NM_173543.3(DZIP1L):c.1061_1062del (p.Glu354fs)	DZIP1L	Pathogenic	no assertion criteria provided
1030323	NM_173543.3(DZIP1L):c.727C>T (p.Gln243Ter)	DZIP1L	Likely pathogenic	criteria provided, single submitter
3065597	NM_173543.3(DZIP1L):c.2014C>T (p.Gln672Ter)	DZIP1L	Likely pathogenic	criteria provided, single submitter
3254571	NM_173543.3(DZIP1L):c.1570C>T (p.Gln524Ter)	DZIP1L	Likely pathogenic	criteria provided, single submitter
1313849	NM_173543.3(DZIP1L):c.256G>T (p.Val86Leu)	DZIP1L	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2409670	NM_173543.3(DZIP1L):c.1825G>A (p.Gly609Arg)	DZIP1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2584786	NM_173543.3(DZIP1L):c.1000-4T>C	DZIP1L	Uncertain significance	criteria provided, single submitter
3588610	NM_173543.3(DZIP1L):c.1681G>A (p.Ala561Thr)	DZIP1L	Uncertain significance	criteria provided, single submitter
3588611	NM_173543.3(DZIP1L):c.1289-6C>G	DZIP1L	Uncertain significance	criteria provided, single submitter
1250792	NM_173543.3(DZIP1L):c.1778G>A (p.Arg593His)	DZIP1L	Benign	criteria provided, multiple submitters, no conflicts
1255184	NM_173543.3(DZIP1L):c.1933A>G (p.Lys645Glu)	DZIP1L	Benign	criteria provided, multiple submitters, no conflicts
1255363	NM_173543.3(DZIP1L):c.1633A>G (p.Thr545Ala)	DZIP1L	Benign	criteria provided, multiple submitters, no conflicts
1255364	NM_173543.3(DZIP1L):c.961C>T (p.Arg321Trp)	DZIP1L	Benign	criteria provided, multiple submitters, no conflicts
721269	NM_173543.3(DZIP1L):c.1017A>G (p.Arg339=)	DZIP1L	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · 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
DZIP1L	Strong	Autosomal recessive	polycystic kidney disease 5	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DZIP1L	Orphanet:731	Autosomal recessive polycystic kidney disease

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
DZIP1L	HGNC:26551	ENSG00000158163	Q8IYY4	Cilium assembly protein DZIP1L	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DZIP1L	Cilium assembly protein DZIP1L	Involved in primary cilium formation.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DZIP1L	Transcription factor	no		Znf_C2H2_type, DZIP1_N, DZIP_RILPL

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
bronchial epithelial cell	1
right uterine tube	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DZIP1L	215	ubiquitous	marker	right uterine tube, sural nerve, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DZIP1L	914

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DZIP1L	Q8IYY4	70.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
ciliary transition zone assembly	1	5617.3×	1e-03	DZIP1L
neural tube patterning	1	2808.7×	1e-03	DZIP1L
floor plate development	1	2407.4×	1e-03	DZIP1L
protein localization to cilium	1	401.2×	0.004	DZIP1L
regulation of protein localization	1	205.5×	0.006	DZIP1L
smoothened signaling pathway	1	181.2×	0.006	DZIP1L
cilium assembly	1	73.6×	0.014	DZIP1L

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
DZIP1L	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	DZIP1L

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)
DZIP1L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.