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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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PKD1L1
polycystin 1 like 1, transient receptor potential channel interacting
Chromosome 7 Β· 7p12.3
NCBI Gene: 168507Ensembl: ENSG00000158683.10HGNC: HGNC:18053UniProt: Q8TDX9
22PubMed Papers
21Diseases
0Drugs
60Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
non-motile ciliumprotein bindingcalcium channel complexciliary membraneHeterotaxiavisceral heterotaxySitus inversus totalissitus inversus
✦AI Summary

PKD1L1 encodes polycystin-1L1, a ciliary protein essential for left-right axis specification during embryonic development. The protein functions as a component of calcium-permeant ion channels in primary cilia, where it controls cilium calcium concentration and regulates sonic hedgehog signaling 1. PKD1L1 forms mechanosensitive and temperature-sensitive channel complexes with PKD2L1, facilitating flow detection in left-right patterning 1. The protein contains multiple domains including Ig-like PKD, REJ, GPS, and transmembrane domains, with G-protein-coupled receptor signatures 1. PKD1L1 is expressed in testis, heart, and specifically in Leydig cells 1. Loss-of-function mutations cause heterotaxy syndrome with congenital heart defects, visceral malformations, and situs abnormalities 234. Additional phenotypes include biliary atresia with bile duct dysmorphogenesis and ciliopathy when deleted in liver tissue 5, congenital chylothorax with fetal hydrops 6, and congenital asplenia 3. The gene represents part of a vertebrate-specific genetic module controlling left-right asymmetry 7. Clinical significance includes its role as a monogenic cause identified in 56% of laterality disorder cases through whole-exome sequencing 2.

Sources cited
1
PKD1L1 encodes polycystin-1L1 with multiple domains, GPCR signatures, and expression in testis and heart
PMID: 11863367
2
PKD1L1 mutations cause heterotaxy and are found in 56% of laterality disorder cases
PMID: 34215651
3
PKD1L1 variants cause heterotaxy syndrome with congenital asplenia
PMID: 35691949
4
PKD1L1 mutations cause heterotaxy with hydrops fetalis and congenital heart disease
PMID: 33655537
5
Liver-specific PKD1L1 deletion causes biliary atresia and ciliopathy
PMID: 36645229
6
PKD1L1 variants are implicated in congenital chylothorax and fetal hydrops
PMID: 38247840
7
PKD1L1 is part of a vertebrate-specific genetic module for left-right patterning
PMID: 39753129
Disease Associationsβ“˜21
HeterotaxiaOpen Targets
0.77Strong
visceral heterotaxyOpen Targets
0.63Moderate
Situs inversus totalisOpen Targets
0.53Moderate
situs inversusOpen Targets
0.44Moderate
genetic disorderOpen Targets
0.34Weak
HeterotaxyOpen Targets
0.26Weak
IGA glomerulonephritisOpen Targets
0.26Weak
idiopathic pulmonary fibrosisOpen Targets
0.25Weak
ovarian neoplasmOpen Targets
0.23Weak
benign prostatic hyperplasiaOpen Targets
0.23Weak
Precordial painOpen Targets
0.23Weak
tympanic membrane perforationOpen Targets
0.22Weak
toxic encephalopathyOpen Targets
0.22Weak
tympanic membrane diseaseOpen Targets
0.22Weak
congenital chylothoraxOpen Targets
0.16Weak
autismOpen Targets
0.11Weak
endometriosisOpen Targets
0.08Suggestive
heart diseaseOpen Targets
0.04Suggestive
Abnormality of refractionOpen Targets
0.04Suggestive
biliary atresiaOpen Targets
0.04Suggestive
Heterotaxy, visceral, 8, autosomalUniProt
Pathogenic Variants60
NM_138295.5(PKD1L1):c.2332del (p.Gln778fs)Pathogenic
not provided|Heterotaxy, visceral, 8, autosomal
β˜…β˜…β˜†β˜†2025β†’ Residue 778
NM_138295.5(PKD1L1):c.7663C>T (p.Arg2555Ter)Pathogenic
not provided|PKD1L1-related disorder|Heterotaxy, visceral, 8, autosomal
β˜…β˜…β˜†β˜†2025β†’ Residue 2555
NM_138295.5(PKD1L1):c.7937C>G (p.Ser2646Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 2646
NM_138295.5(PKD1L1):c.6473+2_6473+3delPathogenic
Situs inversus|Heterotaxy, visceral, 8, autosomal|PKD1L1-related disorder|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025
NM_138295.5(PKD1L1):c.3412C>T (p.Arg1138Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1138
NM_138295.5(PKD1L1):c.1058_1059del (p.Lys353fs)Pathogenic
PKD1L1-related disorder|Heterotaxy, visceral, 8, autosomal|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 353
NM_138295.5(PKD1L1):c.6748C>T (p.Arg2250Ter)Likely pathogenic
Heterotaxy, visceral, 8, autosomal
β˜…β˜…β˜†β˜†2024β†’ Residue 2250
NM_138295.5(PKD1L1):c.3601C>T (p.Gln1201Ter)Pathogenic
Heterotaxy, visceral, 8, autosomal|not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 1201
NM_138295.5(PKD1L1):c.1691+2T>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_138295.5(PKD1L1):c.5813dup (p.Trp1939fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1939
NM_138295.5(PKD1L1):c.6587G>A (p.Trp2196Ter)Pathogenic
PKD1L1-related disorder|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 2196
NM_138295.5(PKD1L1):c.8005C>T (p.Arg2669Ter)Pathogenic
Heterotaxy, visceral, 8, autosomal|not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 2669
NM_138295.5(PKD1L1):c.1079T>G (p.Leu360Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 360
NM_138295.5(PKD1L1):c.4581dup (p.Pro1528fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1528
NM_138295.5(PKD1L1):c.7316del (p.Glu2439fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 2439
NM_138295.5(PKD1L1):c.4798_4799del (p.Gln1600fs)Pathogenic
not provided|Heterotaxy, visceral, 8, autosomal
β˜…β˜†β˜†β˜†2024β†’ Residue 1600
NM_138295.5(PKD1L1):c.1279G>T (p.Glu427Ter)Pathogenic
PKD1L1-related disorder|Heterotaxy, visceral, 8, autosomal
β˜…β˜†β˜†β˜†2024β†’ Residue 427
NM_138295.5(PKD1L1):c.520-2A>CLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_138295.5(PKD1L1):c.1229-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_138295.5(PKD1L1):c.3011del (p.Ala1004fs)Pathogenic
Heterotaxy, visceral, 8, autosomal
β˜…β˜†β˜†β˜†2024β†’ Residue 1004
View on ClinVar β†—
Related Genes
PKD2L1Protein interaction98%PRKD1Protein interaction73%PKD2L2Shared pathway50%PKD1L2Shared pathway50%PKDREJShared pathway40%PKD1L3Shared pathway25%
Tissue Expression6 tissues
Heart
100%
Lung
16%
Bone Marrow
8%
Liver
7%
Ovary
7%
Brain
6%
Gene Interaction Network
Click a node to explore
PKD1L1PKD2L1PRKD1PKD2L2PKD1L2PKDREJPKD1L3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q8TDX9
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.79LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.71 [0.63–0.79]
RankingsWhere PKD1L1 stands among ~20K protein-coding genes
  • #13,717of 20,598
    Most Researched22
  • #1,177of 5,498
    Most Pathogenic Variants60 Β· top quartile
  • #6,557of 17,882
    Most Constrained (LOEUF)0.79
Genes detectedPKD1L1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Liver-restricted deletion of the biliary atresia candidate gene Pkd1l1 causes bile duct dysmorphogenesis and ciliopathy.
PMID: 36645229
Hepatology Β· 2023
1.00
2
Human Genetics of Defects of Situs.
PMID: 38884744
Adv Exp Med Biol Β· 2024
0.90
3
The sequence, expression, and chromosomal localization of a novel polycystic kidney disease 1-like gene, PKD1L1, in human.
PMID: 11863367
Genomics Β· 2002
0.80
4
CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.
PMID: 39753129
Am J Hum Genet Β· 2025
0.70
5
PMID: 38247840
Cells Β· 2024
0.60