PDZK1IP1

Chr 1

PDZK1 interacting protein 1

Also known as: DD96, MAP17, SPAP

NCBI Gene: 10158ENSG00000162366UniProt: Q13113OMIM: 607178

The protein serves as an auxiliary component essential for the activity of the sodium-glucose cotransporter SGLT2 and also associates with SGLT1. Mutations cause renal glucosuria with autosomal recessive inheritance, characterized by glucose loss in the urine due to impaired renal glucose reabsorption. The gene shows low constraint against loss-of-function variants, consistent with the recessive inheritance pattern of the associated kidney phenotype.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.60
Clinical Summary— PDZK1IP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 unique Pathogenic / Likely Pathogenic· 21 VUS of 34 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
1.60LOEUF
pLI 0.001
Z-score 0.48
OE 0.79 (0.41–1.60)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.42Z-score
OE missense 0.86 (0.69–1.06)
59 obs / 68.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.79 (0.41–1.60)
0≤0.351.4
Missense OE0.86 (0.69–1.06)
0≤0.61.4
Synonymous OE1.21
0≤1.21.6
LoF obs/exp: 5 / 6.3Missense obs/exp: 59 / 68.9Syn Z: -0.92
DN
0.74top 25%
GOF
0.84top 5%
LOF
0.2386th %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

34 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS21
Likely Benign2
5
Pathogenic
3
Likely Pathogenic
21
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
3
0
3
VUS
0
20
1
0
21
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total02110031

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

View in ClinVar →

Protein Context — Lollipop Plot

PDZK1IP1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients