PKD2L1

protein-coding

polycystin 2 like 1, transient receptor potential cation channel, the group of Transient receptor potential cation channels

Gene summary

This gene encodes a member of the polycystin protein family. The encoded protein contains multiple transmembrane domains, and cytoplasmic N- and C-termini. The protein may be an integral membrane protein involved in cell-cell/matrix interactions. This protein functions as a calcium-regulated nonselective cation channel. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Previous symbols:

PKD2L
PKDL

MANE transcript

NM_016112.3

Inheritance

—

ClinVar variants

U:113B:20

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr10:100,288,149-100,330,264

External References & Databases

Ensembl (ENSG00000107593)

Transcript & Mutation Effects

hg38 • Region Span ~42.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PKD2L1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 120

not providedTotal: 15

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016112.3. 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					6 clinvar	6
missense			113 clinvar	11 clinvar	3 clinvar	127
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	113	11	9	133

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016112.3	RefSeq	NP_057196.2	16	MANE Select
ENST00000318222.4	Ensembl	ENSP00000325296.3	16	MANE Select
NM_001253837.2	RefSeq	NP_001240766.1	16	Standard
ENST00000465680.2	Ensembl	ENSP00000434019.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
pkd2l1	Danio rerio	Structure: Kolmer-Agduhr neuron Quality: decreased process quality abnormal

Gene / Model

Organism

Observed Phenotype

pkd2l1

Danio rerio

Structure: Kolmer-Agduhr neuron

Quality: decreased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Taste transduction - Homo sapiens (human)

Biological Process

detection of chemical stimulus involved in sensory perception of sour taste
cation transport
smoothened signaling pathway
response to water
sodium ion transmembrane transport

Molecular Function

calcium activated cation channel activity
cation channel activity
calcium channel activity
sodium channel activity
calcium ion binding

Cellular Component

endoplasmic reticulum
plasma membrane
integral component of plasma membrane
cell surface
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318222
Coding exons: 16
Length: 42341
Individuals with no LoFs: 122437
Homozygous LoFs: 230
Heterozygous LoFs: 3081
Defined: 125748
p: 0.0133

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0696	450	454	0.991	0.0000252	5255
Missense (PolyPhen)		167	167.73	0.99566		2080
Synonymous	-0.855	199	184	1.08	0.0000105	1571
Loss of Function	0.213	42	43.5	0.965	0.00000238	457

Population LoF Frequency

Population	CAF	p-value	Status
African	0.18	0.17	notable
Latino/Admixed American	0.012	0.011	notable
Ashkenazi Jewish	0.0023	0.0023	notable
East Asian	0.0016	0.0016	notable
Finnish	0.00042	0.00042	rare
European (Non-Finnish)	0.0016	0.0016	notable
South Asian	0.0018	0.0017	notable
Other	0.0099	0.0092	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Pore-forming subunit of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD1L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. May act as a sour taste receptor by forming a calcium channel with PKD1L3 in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect. {ECO:0000269|PubMed:10517637, ECO:0000269|PubMed:19812697, ECO:0000269|PubMed:23212381, ECO:0000269|PubMed:24336289}.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.632
RVIS EVS: 1.01
RVIS percentile EVS: 90.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.575

Gene Damage Prediction

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