DZIP1L

Chr 3AR

DAZ interacting zinc finger protein 1 like

Also known as: DZIP2, PKD5

NCBI Gene: 199221 ENSG00000158163 UniProt: Q8IYY4 OMIM: 617570

Predicted to enable zinc ion binding activity. Involved in cilium assembly and regulation of protein localization. Located in several cellular components, including intercellular bridge; microtubule cytoskeleton; and nucleoplasm. Implicated in polycystic kidney disease 5. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.301 OMIM phenotype

Clinical Summary— DZIP1L

🧬

Gene-Disease Validity (ClinGen)

autosomal recessive polycystic kidney disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

18 unique Pathogenic / Likely Pathogenic· 157 VUS of 327 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.30LOEUF

pLI 0.000

Z-score 0.06

OE 0.99 (0.76–1.30)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.10Z-score

OE missense 0.99 (0.91–1.07)

430 obs / 435.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.99 (0.76–1.30)

0≤0.351.4

Missense OE?0.99 (0.91–1.07)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 38 / 38.4Missense obs/exp: 430 / 435.9Syn Z: 0.39

This gene — mechanism propensity

0.6357th %ile

GOF

0.6540th %ile

LOF

0.3939th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

327 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11

Likely Pathogenic7

VUS157

Likely Benign90

Benign39

Conflicting5

Pathogenic

Likely Pathogenic

157

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	9	1	1	0	11
Likely Pathogenic	6	1	0	0	7
VUS	4	145	8	0	157
Likely Benign	0	12	35	43	90
Benign	0	14	21	4	39
Conflicting	—				5
Total	19	173	65	47	309

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap DZIP1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →