PDCL2

Summary

PDCL2 (phosducin like 2, HGNC:29524) is a protein-coding gene on chromosome 4q12, encoding Phosducin-like protein 2 (Q8N4E4). Essential for male fertility, spermiogenesis and acrosome formation.

This gene encodes a member of the phosducin-like protein family and is a putative modulator of heterotrimeric G proteins. The protein shares extensive amino acid sequence homology with phosducin. Members of the phosducin-like protein family have been shown to bind to the beta-gamma subunits of G proteins.

Source: NCBI Gene 132954 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 24 total — 1 pathogenic
• MANE Select transcript: NM_152401

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29524
Approved symbol	PDCL2
Name	phosducin like 2
Location	4q12
Locus type	gene with protein product
Status	Approved
Aliases	GCPHLP
Ensembl gene	ENSG00000163440
Ensembl biotype	protein_coding
OMIM	611676
Entrez	132954

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000295645, ENST00000929200

RefSeq mRNA: 1 — MANE Select: NM_152401 NM_152401

CCDS: CCDS47059

Canonical transcript exons

ENST00000295645 — 6 exons

Exon	Start	End
ENSE00001074563	55562404	55562612
ENSE00001074565	55582117	55582237
ENSE00001074566	55569718	55569861
ENSE00001074569	55580821	55580911
ENSE00001714031	55592104	55592245
ENSE00002072831	55556519	55556711

Expression profiles

Bgee: expression breadth broad, 45 present calls, max score 94.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1147 / max 75.3312, expressed in 20 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52171	0.0511	4
52169	0.0342	14
52170	0.0161	4
52172	0.0087	3
52173	0.0047	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.97	gold quality
left testis	UBERON:0004533	94.92	gold quality
testis	UBERON:0000473	92.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.45	gold quality
sperm	CL:0000019	90.94	gold quality
adult organism	UBERON:0007023	84.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.62	gold quality
lower esophagus mucosa	UBERON:0035834	57.99	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
epithelial cell of pancreas	CL:0000083	52.81	gold quality
esophagus mucosa	UBERON:0002469	51.99	gold quality
lower lobe of lung	UBERON:0008949	50.39	silver quality
myocardium	UBERON:0002349	50.25	gold quality
cerebellar vermis	UBERON:0004720	48.32	gold quality
deltoid	UBERON:0001476	48.09	gold quality
tibialis anterior	UBERON:0001385	47.85	silver quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
quadriceps femoris	UBERON:0001377	46.89	gold quality
vastus lateralis	UBERON:0001379	45.40	gold quality
ventricular zone	UBERON:0003053	45.21	gold quality
ileal mucosa	UBERON:0000331	44.93	silver quality
pancreatic ductal cell	CL:0002079	44.81	silver quality
ganglionic eminence	UBERON:0004023	44.13	gold quality
upper leg skin	UBERON:0004262	43.81	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.45

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• The X-ray crystal structure of the thioredoxin (Trx)-fold domain of PDCL2 has been solved and resembles the Trx-fold domain of rat; the presence of two molecules in an asymmetric unit is suggested. (PMID:19193988)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pdcl2	ENSMUSG00000029235
rattus_norvegicus	Pdcl2	ENSRNOG00000002169
drosophila_melanogaster	viaf	FBGN0036237
drosophila_melanogaster	CG7650	FBGN0036519
caenorhabditis_elegans		WBGENE00003142

Paralogs (4): TXNDC9 (ENSG00000115514), PDCL3 (ENSG00000115539), PDC (ENSG00000116703), PDCL (ENSG00000136940)

Protein

Protein identifiers

Phosducin-like protein 2 — Q8N4E4 (reviewed: Q8N4E4)

All UniProt accessions (1): Q8N4E4

UniProt curated annotations — full annotation on UniProt →

Function. Essential for male fertility, spermiogenesis and acrosome formation.

Subunit / interactions. Interacts with the CCT chaperonin complex and actin.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Testis-specific.

Similarity. Belongs to the phosducin family.

RefSeq proteins (1): NP_689614* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR024253	Phosducin_thioredoxin-like_dom	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR051498	Phosducin-like_chap/apop_reg	Family

Pfam: PF02114

UniProt features (17 total): helix 6, strand 4, turn 3, chain 1, domain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3EVI	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4E4-F1	80.82	0.45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): GOBP_VESICLE_ORGANIZATION, GOBP_MALE_GAMETE_GENERATION, EFC_Q6, GOBP_PROTEIN_MATURATION, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ACROSOME_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_PROTEIN_FOLDING, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_MICROTUBULE_BUNDLE_FORMATION

GO Biological Process (8): acrosome assembly (GO:0001675), protein folding (GO:0006457), spermatid development (GO:0007286), sperm axoneme assembly (GO:0007288), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), flagellated sperm motility (GO:0030317), sperm flagellum assembly (GO:0120316)

GO Molecular Function (0):

GO Cellular Component (2): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	4
spermatid development	2
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
cellular process	1
protein maturation	1
germ cell development	1
spermatid differentiation	1
axoneme assembly	1
sperm flagellum assembly	1
male gamete generation	1
cellular developmental process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
flagellated sperm motility	1
motile cilium assembly	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

516 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDCL2	PLP2	Q04941	894
PDCL2	REST	Q13127	512
PDCL2	C11orf42	Q8N5U0	507
PDCL2	SRD5A3	Q9H8P0	491
PDCL2	SPATA3	Q8NHX4	491
PDCL2	LRRC66	Q68CR7	480
PDCL2	TMEM165	Q9HC07	480
PDCL2	SHCBP1L	Q9BZQ2	476
PDCL2	LRRN4CL	Q8ND94	453
PDCL2	PDC	P20941	448
PDCL2	ARL9	Q6T311	435
PDCL2	RPS13	P19116	425
PDCL2	BEND4	Q6ZU67	424
PDCL2	TMEM45B	Q96B21	415
PDCL2	RPS18	P25232	408
PDCL2	RBM19	Q9Y4C8	408

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ACTBL2	POTEF	psi-mi:“MI:0914”(association)	0.530
PDCL3	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): PDCL2 (Two-hybrid), PDCL2 (Two-hybrid), PDCL2 (Two-hybrid), PDCL2 (Affinity Capture-MS), PDCL2 (Two-hybrid), PDCL2 (Two-hybrid), UNC13B (Two-hybrid), PDCL2 (Affinity Capture-MS), PDCL2 (Affinity Capture-MS)

ESM2 similar proteins: O01757, O14530, O18883, O64628, O94267, P87115, Q04004, Q0VA16, Q11183, Q13371, Q2HJA9, Q32LB0, Q32LN3, Q3TWF6, Q4HYB8, Q5E9R3, Q5EB92, Q5RBP4, Q63737, Q641Z6, Q6GPP0, Q6NPL9, Q71A37, Q71A38, Q78Y63, Q8IRG6, Q8K581, Q8LCV1, Q8MR62, Q8N4E4, Q8R491, Q8VWG7, Q920B9, Q9CQ79, Q9DBX2, Q9EQP2, Q9H223, Q9H4M9, Q9M2Q4, Q9NW82

Diamond homologs: C9K7C5, O14095, O14530, O18883, O64628, P37395, Q04004, Q11183, Q32LN3, Q42403, Q6NPL9, Q71A37, Q71A38, Q78Y63, Q8K581, Q8LCV1, Q8N4E4, Q9CQ79, Q9VGV8, P19632, P20941, P41686, Q0VCW8, Q12017, Q4KLJ8, Q5RB77, Q6P268, Q71A39, Q8BVF2, Q8MR62, Q9H2J4, Q9QW08, Q9Y7L1, Q9XS39, Q13371, Q2HJA9, Q63737, Q9DBX2, P20942

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2672266	NM_152401.3(PDCL2):c.128-1G>A	Pathogenic

SpliceAI

1100 predictions. Top by Δscore:

Variant	Effect	Δscore
4:55569713:ATTAC:A	donor_loss	1.0000
4:55569714:TTA:T	donor_loss	1.0000
4:55569715:TA:T	donor_loss	1.0000
4:55569716:A:AG	donor_loss	1.0000
4:55569862:C:CC	acceptor_gain	1.0000
4:55569866:T:TC	acceptor_gain	1.0000
4:55569873:A:C	acceptor_gain	1.0000
4:55580819:A:AG	donor_loss	1.0000
4:55580824:T:C	donor_gain	1.0000
4:55580907:TTTCA:T	acceptor_gain	1.0000
4:55580908:TTCA:T	acceptor_gain	1.0000
4:55580909:TCA:T	acceptor_gain	1.0000
4:55580910:CA:C	acceptor_gain	1.0000
4:55580910:CAC:C	acceptor_gain	1.0000
4:55580911:AC:A	acceptor_loss	1.0000
4:55580912:C:CC	acceptor_gain	1.0000
4:55580913:T:C	acceptor_loss	1.0000
4:55582111:CCATA:C	donor_loss	1.0000
4:55582112:CATAC:C	donor_loss	1.0000
4:55582113:ATACC:A	donor_loss	1.0000
4:55582114:TACCC:T	donor_loss	1.0000
4:55582115:A:AC	donor_gain	1.0000
4:55582115:AC:A	donor_gain	1.0000
4:55582115:ACCC:A	donor_loss	1.0000
4:55582116:C:CC	donor_gain	1.0000
4:55582116:CC:C	donor_gain	1.0000
4:55582125:T:TA	donor_gain	1.0000
4:55582139:TAAA:T	donor_gain	1.0000
4:55582140:AAAA:A	donor_gain	1.0000
4:55582140:AAAAC:A	donor_gain	1.0000

AlphaMissense

1632 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:55562580:A:G	L132P	0.995
4:55562602:A:G	C125R	0.993
4:55569853:C:G	R76P	0.993
4:55582214:C:A	W10C	0.993
4:55582214:C:G	W10C	0.993
4:55562490:G:T	P162Q	0.992
4:55562600:A:C	C125W	0.992
4:55562490:G:C	P162R	0.991
4:55569769:A:T	V104D	0.991
4:55582216:A:G	W10R	0.991
4:55582216:A:T	W10R	0.991
4:55562569:C:G	A136P	0.990
4:55569813:A:C	F89L	0.990
4:55569813:A:T	F89L	0.990
4:55569815:A:G	F89L	0.990
4:55556696:A:G	L196P	0.989
4:55556708:A:G	L192P	0.989
4:55562478:A:T	V166E	0.989
4:55562558:A:C	F139L	0.989
4:55562558:A:T	F139L	0.989
4:55562560:A:G	F139L	0.989
4:55582203:A:G	L14S	0.989
4:55562491:G:A	P162S	0.988
4:55562543:A:C	F144L	0.988
4:55562543:A:T	F144L	0.988
4:55562545:A:G	F144L	0.988
4:55562592:A:T	V128D	0.987
4:55562536:C:G	A147P	0.986
4:55562568:G:T	A136E	0.986
4:55569734:G:C	H116D	0.986

dbSNP variants (sampled 300 via entrez): RS1000011201 (4:55557727 A>G), RS1000012047 (4:55563834 T>A,G), RS1000076306 (4:55564844 T>A), RS1000123770 (4:55556792 C>G,T), RS1000216975 (4:55581767 G>A,T), RS1000244951 (4:55557091 G>C), RS1000258554 (4:55592304 A>G), RS1000369079 (4:55585335 C>T), RS1000410757 (4:55588088 G>C), RS1000411814 (4:55572663 A>G), RS1000480864 (4:55589785 G>A,C,T), RS1000615362 (4:55559265 T>A), RS1000741482 (4:55589413 A>G), RS1000777554 (4:55584925 G>A), RS1000782960 (4:55580127 A>G)

Disease associations

OMIM: gene MIM:611676 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST003518_83	Daytime sleep phenotypes	6.000000e-06
GCST005962_39	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06
GCST008839_540	Height	6.000000e-11
GCST009391_993	Metabolite levels	7.000000e-06
GCST010396_145	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-06
GCST010699_101	Brain morphology (min-P)	1.000000e-11
GCST010701_29	Cortical surface area (MOSTest)	2.000000e-31
GCST010702_108	Subcortical volume (MOSTest)	1.000000e-09
GCST010703_345	Brain morphology (MOSTest)	4.000000e-10
GCST90020024_700	A body shape index	8.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0010475	deoxycholate measurement
EFO:0007874	gut microbiome measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenite	increases expression	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia