PKD1L1

protein-coding

polycystin 1 like 1, transient receptor potential channel interacting

Gene summary

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]

MANE transcript

NM_138295.5

Inheritance

AR, AD

ClinVar variants

P:92U:629B:363

Top phenotype

Heterotaxy, visceral, 8, autosomal

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr7:47,740,202-47,948,466

External References & Databases

Ensembl (ENSG00000158683)

Transcript & Mutation Effects

hg38 • Region Span ~208.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

heterotaxy, visceral, 8, autosomalSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014967

Submitter: Labcorp Genetics (formerly Invitae)

heterotaxy, visceral, 8, autosomalDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014967

Submitter: Ambry Genetics

situs inversusSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0010029

Submitter: Orphanet

heterotaxy, visceral, 8, autosomalDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014967

Submitter: G2P

heterotaxy, visceral, 8, autosomalMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014967

Submitter: Ambry Genetics

heterotaxy, visceral, 8, autosomalSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014967

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Heterotaxy, visceral, 8, autosomalAR

Manifestation: Cardiovascular; Gastrointestinal; Renal

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Comments: The ocndition can include multiple congenital anomalies

Refs: 27616478

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PKD1L1 variants in ClinVar

14 Conditions Cataloged

PKD1L1-related disorderTotal: 515

Inborn genetic diseasesTotal: 484

not providedTotal: 467

not specifiedTotal: 84

Heterotaxy, visceral, 8, autosomalTotal: 83

Situs inversusTotal: 3

Congenital chylothoraxTotal: 3

Fetal anomalies with a likely genetic causeTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138295.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			14 clinvar	245 clinvar	15 clinvar	274
missense		2 clinvar	606 clinvar	82 clinvar	21 clinvar	711
nonsense	10 clinvar	22 clinvar				32
start loss						0
frameshift	12 clinvar	27 clinvar	2 clinvar			41
splice donor/acceptor (+/-2bp)	1 clinvar	18 clinvar	7 clinvar			26
Total	23	69	629	327	36	1084

Highest pathogenic variant AF is 0.0008607999

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138295.5	RefSeq	NP_612152.1	57	MANE Select
ENST00000289672.7	Ensembl	ENSP00000289672.2	57	MANE Select
ENST00000433506.2	Ensembl	ENSP00000393466.2	6	Standard
ENST00000648482.1	Ensembl	ENSP00000496786.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

detection of nodal flow
detection of mechanical stimulus
calcium ion transmembrane transport
left/right axis specification
cell-cell adhesion

Molecular Function

calcium channel activity
protein binding

Cellular Component

cilium
membrane
calcium channel complex
ciliary membrane
non-motile cilium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000289672
Coding exons: 57
Length: 173839
Individuals with no LoFs: 125359
Homozygous LoFs: 0
Heterozygous LoFs: 389
Defined: 125748
p: 0.00155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.335	1512	1.55e+3	0.976	0.0000847	18505
Missense (PolyPhen)		267	326.23	0.81845		4326
Synonymous	-0.585	637	618	1.03	0.0000364	5730
Loss of Function	4.29	88	144	0.613	0.00000741	1636

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0014	0.0014	notable
Latino/Admixed American	0.0014	0.0014	notable
Ashkenazi Jewish	0.00081	0.00079	rare
East Asian	0.00094	0.00092	rare
Finnish	0.00098	0.00097	rare
European (Non-Finnish)	0.0020	0.0019	notable
South Asian	0.0015	0.0014	notable
Other	0.0015	0.0015	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD2L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. Does not constitute the pore-forming subunit. Also involved in left/right axis specification downstream of nodal flow: forms a complex with PKD2 in cilia to facilitate flow detection in left/right patterning. {ECO:0000269|PubMed:24336289}.;

Intolerance Scores

LoFtool: 0.921
RVIS EVS: 2.17
RVIS percentile EVS: 98.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.159

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium