PKD2L2

Summary

PKD2L2 (polycystin 2 like 2, transient receptor potential cation channel, HGNC:9012) is a protein-coding gene on chromosome 5q31.2, encoding Polycystin-2-like protein 2 (Q9NZM6). Exhibits a lower single conductance but no spontaneous channel activity.

Predicted to enable calcium channel activity. Predicted to be involved in detection of mechanical stimulus. Predicted to be active in membrane.

Source: NCBI Gene 27039 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 89 total
• MANE Select transcript: NM_001300921

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9012
Approved symbol	PKD2L2
Name	polycystin 2 like 2, transient receptor potential cation channel
Location	5q31.2
Locus type	gene with protein product
Status	Approved
Aliases	TRPP5
Ensembl gene	ENSG00000078795
Ensembl biotype	protein_coding
OMIM	604669
Entrez	27039

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000290431, ENST00000414094, ENST00000502810, ENST00000503015, ENST00000508638, ENST00000508883, ENST00000511176

RefSeq mRNA: 4 — MANE Select: NM_001300921 NM_001258448, NM_001258449, NM_001300921, NM_014386

CCDS: CCDS43367, CCDS58971, CCDS58972, CCDS78062

Canonical transcript exons

ENST00000508883 — 15 exons

Exon	Start	End
ENSE00000453155	137906206	137906434
ENSE00000453156	137907742	137907912
ENSE00000764038	137892480	137892613
ENSE00000764043	137908765	137908946
ENSE00000764044	137921636	137921756
ENSE00000764046	137925040	137925104
ENSE00000764047	137925875	137925929
ENSE00000817407	137935797	137935909
ENSE00001196083	137923420	137923521
ENSE00002048655	137936320	137936427
ENSE00002074575	137889457	137889522
ENSE00002083568	137942384	137942747
ENSE00003627511	137894353	137894609
ENSE00003635142	137899516	137899737
ENSE00003687014	137890481	137890582

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 86.23.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2095 / max 33.8314, expressed in 79 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
58741	0.1364	44
58742	0.0731	15

Top tissues by expression

275 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	86.23	silver quality
buccal mucosa cell	CL:0002336	85.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.46	gold quality
left testis	UBERON:0004533	76.65	gold quality
right testis	UBERON:0004534	75.70	gold quality
testis	UBERON:0000473	75.15	gold quality
tendon	UBERON:0000043	73.33	gold quality
sperm	CL:0000019	72.80	gold quality
medial globus pallidus	UBERON:0002477	72.02	gold quality
male germ cell	CL:0000015	71.69	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.15	gold quality
globus pallidus	UBERON:0001875	66.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	66.13	gold quality
calcaneal tendon	UBERON:0003701	66.06	gold quality
muscle of leg	UBERON:0001383	64.02	gold quality
gastrocnemius	UBERON:0001388	63.70	gold quality
adrenal tissue	UBERON:0018303	60.95	gold quality
monocyte	CL:0000576	60.78	gold quality
mononuclear cell	CL:0000842	60.59	gold quality
bone marrow cell	CL:0002092	60.42	gold quality
muscle organ	UBERON:0001630	60.29	gold quality
leukocyte	CL:0000738	59.31	gold quality
heart left ventricle	UBERON:0002084	57.84	gold quality
left adrenal gland cortex	UBERON:0035825	57.81	gold quality
colonic epithelium	UBERON:0000397	57.76	silver quality
left adrenal gland	UBERON:0001234	57.64	gold quality
cardiac ventricle	UBERON:0002082	57.26	gold quality
right adrenal gland	UBERON:0001233	57.08	gold quality
adrenal gland	UBERON:0002369	57.05	gold quality
right adrenal gland cortex	UBERON:0035827	56.73	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7316	no	304.01
E-ANND-3	no	5.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting PKD2L2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-12116	97.94	68.91	595
HSA-MIR-203B-3P	97.82	66.27	979
HSA-MIR-127-5P	97.78	67.64	869
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-10397-5P	97.31	69.06	710
HSA-MIR-517-5P	97.13	68.43	781
HSA-MIR-4689	96.97	65.79	1209
HSA-MIR-6858-5P	96.05	64.59	1020

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	pkd1a	ENSDARG00000030417
danio_rerio	pkd1l2b	ENSDARG00000088121
danio_rerio	pkd1l2b	ENSDARG00000101214
danio_rerio	pkd1l2a	ENSDARG00000105344
mus_musculus	Pkd2l2	ENSMUSG00000014503
rattus_norvegicus	Pkd2l2	ENSRNOG00000025489
drosophila_melanogaster	Pkd2	FBGN0041195
caenorhabditis_elegans		WBGENE00004035

Paralogs (10): PKD1 (ENSG00000008710), PKD2L1 (ENSG00000107593), PKD2 (ENSG00000118762), PKDREJ (ENSG00000130943), PKD1L1 (ENSG00000158683), PKD1L2 (ENSG00000166473), LOXHD1 (ENSG00000167210), DENND5B (ENSG00000170456), DENND5A (ENSG00000184014), PKD1L3 (ENSG00000277481)

Protein

Protein identifiers

Polycystin-2-like protein 2 — Q9NZM6 (reviewed: Q9NZM6)

Alternative names: Polycystic kidney disease 2-like 2 protein, Polycystin-L2

All UniProt accessions (3): Q9NZM6, D6RBX8, D6RF71

UniProt curated annotations — full annotation on UniProt →

Function. Exhibits a lower single conductance but no spontaneous channel activity. May function as a regulator of calcium channels or a channel component involving Ca2(+) homeostasis.

Subunit / interactions. Interacts with TRPC1 and TRPC5.

Subcellular location. Membrane.

Tissue specificity. Expressed only in testis. Expressed also in brain and kidney. Expressed only in transformed lymphoblasts.

Similarity. Belongs to the polycystin family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9NZM6-1	1	yes
Q9NZM6-2	2, PKD2L2b
Q9NZM6-3	3, PKD2L2a
Q9NZM6-4	4, PKD2L2c
Q9NZM6-5	5
Q9NZM6-6	6
Q9NZM6-7	7

RefSeq proteins (4): NP_001245377, NP_001245378, NP_001287850, NP_055201 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003915	PKD_2	Family
IPR013122	PKD1_2_channel	Domain
IPR046791	Polycystin_dom	Domain
IPR051223	Polycystin	Family

Pfam: PF08016, PF20519

UniProt features (29 total): splice variant 9, topological domain 7, transmembrane region 6, glycosylation site 2, sequence variant 2, chain 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZM6-F1	81.39	0.47

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (2): 115, 138

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 89 (showing top): GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, GGGCATT_MIR365, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, AACTTT_UNKNOWN, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, POU3F2_02, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_MECHANICAL_STIMULUS, chr5q31, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (4): detection of mechanical stimulus (GO:0050982), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (2): calcium channel activity (GO:0005262), calcium ion binding (GO:0005509)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
detection of external stimulus	1
detection of abiotic stimulus	1
response to mechanical stimulus	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
metal ion binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

696 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PKD2L2	MCOLN1	Q9GZU1	619
PKD2L2	TRPM2	O94759	612
PKD2L2	TRPA1	O75762	603
PKD2L2	PKD1L3	Q7Z443	590
PKD2L2	TRPC1	P48995	588
PKD2L2	PKD1L1	Q8TDX9	587
PKD2L2	FAM13B	Q9NYF5	541
PKD2L2	TRPM5	Q9NZQ8	537
PKD2L2	TRPM4	Q8TD43	537
PKD2L2	TRPM7	Q96QT4	537
PKD2L2	TRPM3	Q9HCF6	530
PKD2L2	TRPV5	Q9NQA5	519
PKD2L2	TRPV1	Q8NER1	519
PKD2L2	TRPM8	Q7Z2W7	513
PKD2L2	TRPV2	Q9Y5S1	513

IntAct

6 interactions, top by confidence:

A	B	Type	Score
PKD2L2	PKD2	psi-mi:“MI:0914”(association)	0.530
PKD2L2	SERPINB3	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
PKD2L2	SEMG1	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): PKD2 (Affinity Capture-MS), SERPINB4 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), SERPINB3 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), GRAMD1A (Affinity Capture-MS), ITPR3 (Affinity Capture-MS), TRPM4 (Affinity Capture-MS), TRPM7 (Affinity Capture-MS), DNAJB9 (Affinity Capture-MS), PKD2 (Affinity Capture-MS), SEMG1 (Affinity Capture-MS), PKD2L2 (Cross-Linking-MS (XL-MS)), PKD2L2 (Protein-peptide), PKD2L2 (Affinity Capture-RNA)

ESM2 similar proteins: A1A5B4, A2A259, A2AIR5, E9PTA2, F6RG56, H2Q5A1, O35245, O62826, O70212, O94759, P02715, P04758, P09690, P11230, P13536, P23979, P25109, P35563, P37088, Q04671, Q13507, Q13563, Q4GZT3, Q60HE8, Q6IVV8, Q7Z403, Q86V40, Q8BWC0, Q8MIQ9, Q8R4F0, Q8TCT7, Q8TCU5, Q8TDD5, Q91YD4, Q96BD0, Q99J21, Q9EQJ0, Q9GZU1, Q9HA82, Q9JJH7

Diamond homologs: A2A259, H2LRU7, O35245, Q13563, Q4GZT3, Q6IVV8, Q9HCX4, Q9JLG4, Q9NZM6, Q9P0L9, Q9U1S7, Q9WVC5, Q7TN88, Q9JMI9, Q9QZC1, Q13507

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

89 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2574 predictions. Top by Δscore:

Variant	Effect	Δscore
5:137890540:G:GT	donor_gain	1.0000
5:137892543:T:TA	acceptor_gain	1.0000
5:137892544:G:A	acceptor_gain	1.0000
5:137894348:T:TA	acceptor_gain	1.0000
5:137894349:G:A	acceptor_gain	1.0000
5:137894608:GA:G	donor_gain	1.0000
5:137894610:G:GG	donor_gain	1.0000
5:137899672:G:T	donor_gain	1.0000
5:137925028:A:G	acceptor_gain	1.0000
5:137925927:AATG:A	donor_loss	1.0000
5:137925928:AT:A	donor_gain	1.0000
5:137925929:TGT:T	donor_loss	1.0000
5:137925930:G:GC	donor_loss	1.0000
5:137925930:G:GG	donor_gain	1.0000
5:137925931:T:G	donor_loss	1.0000
5:137935910:G:GG	donor_gain	1.0000
5:137941922:A:AC	donor_gain	1.0000
5:137941923:A:C	donor_gain	1.0000
5:137941939:CAAA:C	donor_loss	1.0000
5:137941940:AAACC:A	donor_loss	1.0000
5:137941941:AACCT:A	donor_loss	1.0000
5:137941942:ACC:A	donor_loss	1.0000
5:137941946:T:TA	donor_gain	1.0000
5:137942041:CAGGC:C	acceptor_gain	1.0000
5:137942042:AGGCC:A	acceptor_loss	1.0000
5:137942044:GCC:G	acceptor_loss	1.0000
5:137942045:CCT:C	acceptor_loss	1.0000
5:137942046:C:CC	acceptor_gain	1.0000
5:137942046:CTAGA:C	acceptor_loss	1.0000
5:137942047:T:C	acceptor_loss	1.0000

AlphaMissense

4145 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:137894480:G:C	R132P	0.996
5:137899722:T:C	L244P	0.990
5:137899658:T:A	W223R	0.989
5:137899658:T:C	W223R	0.989
5:137908846:T:C	F410L	0.988
5:137908848:T:A	F410L	0.988
5:137908848:T:G	F410L	0.988
5:137907904:T:A	W380R	0.987
5:137907904:T:C	W380R	0.987
5:137921650:G:C	R448P	0.984
5:137894486:T:C	L134P	0.983
5:137899708:T:A	N239K	0.982
5:137899708:T:G	N239K	0.982
5:137907884:C:A	A373D	0.982
5:137923433:C:A	A488E	0.982
5:137894477:T:A	V131D	0.980
5:137908891:G:A	G425R	0.979
5:137908891:G:C	G425R	0.979
5:137908924:T:C	F436L	0.979
5:137908926:T:A	F436L	0.979
5:137908926:T:G	F436L	0.979
5:137908825:T:C	C403R	0.978
5:137908883:C:A	A422D	0.978
5:137908892:G:A	G425E	0.978
5:137894483:A:C	Q133P	0.975
5:137908882:G:C	A422P	0.975
5:137908805:T:C	L396P	0.974
5:137894454:T:A	N123K	0.973
5:137894454:T:G	N123K	0.973
5:137908903:T:C	F429L	0.973

dbSNP variants (sampled 300 via entrez): RS1000047072 (5:137924694 T>G), RS1000118186 (5:137914518 T>G), RS1000374652 (5:137928237 T>C), RS1000427200 (5:137928572 C>T), RS1000546275 (5:137905363 C>G), RS1000659920 (5:137942325 G>A), RS1000693958 (5:137917948 T>C), RS1000703164 (5:137921658 C>A), RS1000720070 (5:137942648 C>A), RS1000756336 (5:137919828 G>A,T), RS1000817927 (5:137892795 C>T), RS1000830598 (5:137900438 A>C), RS1000887764 (5:137898549 T>C,G), RS1000940129 (5:137935836 A>C,G), RS1001082221 (5:137907514 A>G)

Disease associations

OMIM: gene MIM:604669 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004297_4	Atrial fibrillation	1.000000e-08
GCST004521_66	Autism spectrum disorder or schizophrenia	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Transient Receptor Potential channels (TRP)

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects acetylation, affects methylation, decreases expression	2
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
monomethylarsonous acid	affects acetylation, affects methylation	1
perfluorohexanesulfonic acid	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Lead	increases expression	1
Valproic Acid	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_YA76	IDG-HEK293T-PKD2L2-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.