PKD1L1

Chr 7AR

polycystin 1 like 1, transient receptor potential channel interacting

Also known as: HTX8, PRO19563

NCBI Gene: 168507ENSG00000158683UniProt: Q8TDX9

This gene encodes a member of the polycystin protein family containing 11 transmembrane domains, a receptor for egg jelly (REJ) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. The encoded protein may play a role in the male reproductive system. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Heterotaxy, visceral, 8, autosomalMIM #617205
AR
582
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PKD1L1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 343 VUS of 582 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.73LOEUF
pLI 0.000
Z-score 4.29
OE 0.61 (0.52–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.33Z-score
OE missense 0.98 (0.94–1.02)
1512 obs / 1549.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.61 (0.52–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.94–1.02)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 88 / 143.5Missense obs/exp: 1512 / 1549.1Syn Z: -0.59

ClinVar Variant Classifications

582 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic16
VUS343
Likely Benign205
Benign9
Conflicting1
8
Pathogenic
16
Likely Pathogenic
343
VUS
205
Likely Benign
9
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
2
0
8
Likely Pathogenic
11
0
5
0
16
VUS
4
324
11
4
343
Likely Benign
0
27
56
122
205
Benign
0
3
5
1
9
Conflicting
—1
Total2135479127582

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

View in ClinVar →

Protein Context — Lollipop Plot

PKD1L1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

PKD1L1-related laterality defects

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Heterotaxy, visceral, 8, autosomal

MIM #617205

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
PKD1L1 Is Involved in Congenital Chylothorax.
Whitchurch JB et al.·Cells
2024
A novel nonsense PKD1L1 variant cause heterotaxy syndrome with congenital asplenia in a Han Chinese patient.
Gu H et al.·J Hum Genet
2022
Whole-exome sequencing reveals a monogenic cause in 56% of individuals with laterality disorders and associated congenital heart defects.
Bolkier Y et al.·J Med Genet
2022
Hydrops fetalis in PKD1L1-related heterotaxy: Report of two foetuses and expanding the phenotypic and molecular spectrum.
Correa ARE et al.·Ann Hum Genet
2021Case report
Exome sequencing in individuals with cardiovascular laterality defects identifies potential candidate genes.
Breuer K et al.·Eur J Hum Genet
2022
Genetic findings of children with congenital heart diseases using chromosomal microarray and trio-based whole exome sequencing.
Guo R et al.·Sci Rep
2025
Compound heterozygous Pkd1l1 variants in a family with two fetuses affected by heterotaxy and complex Chd.
Le Fevre A et al.·Eur J Med Genet
2020Case report
The prevalence of laterality defects in patients with congenital heart disease.
Xie XH et al.·J Hum Genet
2025Cohort
Identification of susceptibility gene mutations associated with the pathogenesis of familial nonmedullary thyroid cancer.
Zhu J et al.·Mol Genet Genomic Med
2019
Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing.
Alzahrani OR et al.·Medicina (Kaunas)
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools