PKD1L1

polycystin 1 like 1, transient receptor potential channel interacting

Basic information

Region (hg38): 7:47740201-47948466

Links

ENSG00000158683 ∙ NCBI:168507 ∙ OMIM:609721 ∙ HGNC:18053 ∙ Uniprot:Q8TDX9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• heterotaxy, visceral, 8, autosomal (Strong), mode of inheritance: AR
• heterotaxy, visceral, 8, autosomal (Moderate), mode of inheritance: AR
• heterotaxy, visceral, 8, autosomal (Strong), mode of inheritance: AR
• situs inversus (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Heterotaxy, visceral, 8, autosomal	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Gastrointestinal; Renal	27616478
The ocndition can include multiple congenital anomalies

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PKD1L1 gene.

• not provided (384 variants)
• Inborn genetic diseases (138 variants)
• Heterotaxy, visceral, 8, autosomal (62 variants)
• PKD1L1-related condition (33 variants)
• not specified (6 variants)
• Situs inversus (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PKD1L1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	39	31	75
missense		1	194	26	33	254
nonsense	8	4				12
start loss						0
frameshift	5	6	1			12
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1	6				7
splice region			4	8	10	22
non coding			2	9	149	160
Total	14	17	203	74	213

Highest pathogenic variant AF is 0.000499

Variants in PKD1L1

This is a list of pathogenic ClinVar variants found in the PKD1L1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-47774931-G-A			Benign (Jun 19, 2021)
7-47775331-T-C			Benign (Nov 12, 2018)
7-47792656-C-T		Inborn genetic diseases	Uncertain significance (Jun 27, 2022)
7-47792664-C-T		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
7-47792693-G-A		PKD1L1-related disorder	Likely benign (Oct 05, 2023)
7-47792700-G-GT			Uncertain significance (Feb 21, 2022)
7-47792715-G-A		Heterotaxy, visceral, 8, autosomal	Uncertain significance (Nov 17, 2020)
7-47792717-G-T			Likely benign (Jul 26, 2018)
7-47792724-A-C			Uncertain significance (Aug 07, 2022)
7-47792732-G-A		PKD1L1-related disorder	Likely benign (Apr 16, 2021)
7-47792740-C-G			Uncertain significance (Aug 22, 2022)
7-47792779-A-G			Benign (Jun 24, 2022)
7-47795989-G-A			Uncertain significance (Jan 22, 2024)
7-47796002-A-G		PKD1L1-related disorder	Uncertain significance (Sep 08, 2022)
7-47796019-C-A		Inborn genetic diseases	Uncertain significance (Jul 20, 2021)
7-47796098-T-G		Inborn genetic diseases	Uncertain significance (Jul 26, 2021)
7-47796135-T-C		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
7-47796153-A-G		PKD1L1-related disorder	Likely benign (Dec 04, 2021)
7-47796216-G-A			Benign (Jun 19, 2021)
7-47800486-C-T			Benign (Nov 12, 2018)
7-47800503-G-A			Benign (Jun 20, 2021)
7-47800698-C-A		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
7-47800704-A-G		Inborn genetic diseases	Uncertain significance (Oct 24, 2023)
7-47800709-C-A		PKD1L1-related disorder	Likely benign (Feb 04, 2022)
7-47800710-C-T		PKD1L1-related disorder	Uncertain significance (Feb 08, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PKD1L1	protein_coding	protein_coding	ENST00000289672	57	173839

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.09e-40	1.00	125359	0	389	125748	0.00155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.335	1512	1.55e+3	0.976	0.0000847	18505
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00282	0.00275
Ashkenazi Jewish	0.000809	0.000794
East Asian	0.000939	0.000925
Finnish	0.000975	0.000971
European (Non-Finnish)	0.00200	0.00194
Middle Eastern	0.000939	0.000925
South Asian	0.00146	0.00144
Other	0.00149	0.00147

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.0712
• hipred: N
• hipred_score: 0.233

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.159

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pkd1l1
• Phenotype: normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; respiratory system phenotype; digestive/alimentary phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: detection of nodal flow;detection of mechanical stimulus;calcium ion transmembrane transport;left/right axis specification;cell-cell adhesion
• Cellular component: cilium;membrane;calcium channel complex;ciliary membrane;non-motile cilium
• Molecular function: calcium channel activity;protein binding