PDZRN4

Summary

PDZRN4 (PDZ domain containing ring finger 4, HGNC:30552) is a protein-coding gene on chromosome 12q12, encoding PDZ domain-containing RING finger protein 4 (Q6ZMN7).

Predicted to enable zinc ion binding activity.

Source: NCBI Gene 29951 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 162 total
• MANE Select transcript: NM_001164595

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30552
Approved symbol	PDZRN4
Name	PDZ domain containing ring finger 4
Location	12q12
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434B0417, LNX4, FLJ33777, IMAGE5767589
Ensembl gene	ENSG00000165966
Ensembl biotype	protein_coding
OMIM	609730
Entrez	29951

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000298919, ENST00000402685, ENST00000539469, ENST00000548316, ENST00000649474

RefSeq mRNA: 2 — MANE Select: NM_001164595 NM_001164595, NM_013377

CCDS: CCDS53777, CCDS8739

Canonical transcript exons

ENST00000402685 — 10 exons

Exon	Start	End
ENSE00001366765	41506456	41506712
ENSE00001376251	41509811	41509913
ENSE00001552457	41188320	41189103
ENSE00001552944	41194081	41194188
ENSE00001559215	41191458	41191544
ENSE00001561946	41572364	41574745
ENSE00003464609	41567783	41567899
ENSE00003465876	41563548	41563649
ENSE00003599144	41552656	41552754
ENSE00003681280	41555698	41555760

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 93.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4240 / max 71.7681, expressed in 159 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125101	0.1805	60
125099	0.1093	57
125100	0.1022	49
125102	0.0320	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	93.56	gold quality
blood vessel layer	UBERON:0004797	93.05	gold quality
popliteal artery	UBERON:0002250	89.41	gold quality
tibial artery	UBERON:0007610	89.39	gold quality
seminal vesicle	UBERON:0000998	88.98	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.53	gold quality
calcaneal tendon	UBERON:0003701	88.42	gold quality
saphenous vein	UBERON:0007318	87.89	gold quality
tibial nerve	UBERON:0001323	86.74	gold quality
penis	UBERON:0000989	86.73	gold quality
urethra	UBERON:0000057	86.68	gold quality
sural nerve	UBERON:0015488	86.55	gold quality
mucosa of stomach	UBERON:0001199	85.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	84.54	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.46	gold quality
lower esophagus	UBERON:0013473	84.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.48	gold quality
aorta	UBERON:0000947	82.44	gold quality
left coronary artery	UBERON:0001626	78.16	gold quality
right coronary artery	UBERON:0001625	78.14	gold quality
dorsal root ganglion	UBERON:0000044	77.30	gold quality
descending thoracic aorta	UBERON:0002345	77.21	gold quality
caput epididymis	UBERON:0004358	77.12	gold quality
prostate gland	UBERON:0002367	76.74	gold quality
coronary artery	UBERON:0001621	76.53	gold quality
ganglionic eminence	UBERON:0004023	76.43	gold quality
corpus epididymis	UBERON:0004359	75.95	gold quality
left uterine tube	UBERON:0001303	75.88	gold quality
ventricular zone	UBERON:0003053	75.76	gold quality
urinary bladder	UBERON:0001255	74.77	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	951.06
E-GEOD-93593	yes	639.10
E-CURD-119	yes	12.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting PDZRN4, 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-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 1)

• Results showed that PDZRN4 might be a potential tumour suppressor gene and had anti-proliferative effect on hepatocellular carcinoma cell proliferation. (PMID:26486104)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pdzrn4	ENSDARG00000045687
mus_musculus	Pdzrn4	ENSMUSG00000036218
rattus_norvegicus	Pdzrn4	ENSRNOG00000022844
drosophila_melanogaster	Slip1	FBGN0024728
caenorhabditis_elegans		WBGENE00016846

Paralogs (2): PDZD4 (ENSG00000067840), PDZRN3 (ENSG00000121440)

Protein

Protein identifiers

PDZ domain-containing RING finger protein 4 — Q6ZMN7 (reviewed: Q6ZMN7)

Alternative names: Ligand of Numb protein X 4, SEMACAP3-like protein

All UniProt accessions (2): A0A3B3ISS2, Q6ZMN7

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZMN7-1	1	yes
Q6ZMN7-2	2, PDZRN4S
Q6ZMN7-4	4

RefSeq proteins (2): NP_001158067, NP_037509 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR017907	Znf_RING_CS	Conserved_site
IPR036034	PDZ_sf	Homologous_superfamily
IPR051971	E3_ubiquitin-PDZ_ligase	Family

Pfam: PF00595, PF13923

UniProt features (21 total): compositionally biased region 6, splice variant 4, region of interest 3, domain 2, sequence variant 2, chain 1, sequence conflict 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMN7-F1	60.14	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, WALLACE_PROSTATE_CANCER_RACE_UP, PAX4_01, NKX25_02, CMYB_01, chr12q12, HNF1_Q6, LHX3_01, CHX10_01, AAAYRNCTG_UNKNOWN, CHANDRAN_METASTASIS_DN, EFC_Q6, NFKB_Q6, NKX61_01, YGACNNYACAR_UNKNOWN

GO Biological Process (0):

GO Molecular Function (3): zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion binding	1
binding	1
cation binding	1

Protein interactions and networks

STRING

1181 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PDZRN4	LONRF2	Q1L5Z9	464
PDZRN4	BEX5	Q5H9J7	459
PDZRN4	LNX2	Q8N448	442
PDZRN4	LNX1	Q8TBB1	438
PDZRN4	CTXN1	P60606	436
PDZRN4	OR5K3	A6NET4	434
PDZRN4	GNAO1	P09471	425
PDZRN4	HOXD3	P31249	414
PDZRN4	FZD7	O75084	407
PDZRN4	SPNS2	Q8IVW8	406
PDZRN4	FZD4	Q9ULV1	403
PDZRN4	FZD1	Q9UP38	399
PDZRN4	GRHL3	Q8TE85	398
PDZRN4	CCDC184	Q52MB2	398
PDZRN4	CA7	P43166	398

IntAct

523 interactions, top by confidence:

A	B	Type	Score
E6	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
PDZRN4	E6	psi-mi:“MI:0407”(direct interaction)	0.610
PDZRN4	RPS6KA1	psi-mi:“MI:0407”(direct interaction)	0.610
PDZRN4	SLC15A5	psi-mi:“MI:0407”(direct interaction)	0.610
PDZRN4	SLC15A5	psi-mi:“MI:0915”(physical association)	0.610
PDZRN4	FZD7	psi-mi:“MI:0407”(direct interaction)	0.610
Tax	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
PDZRN4	Tax	psi-mi:“MI:0915”(physical association)	0.610
PDZRN4	E6	psi-mi:“MI:0915”(physical association)	0.610
ATP2B4	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
DGKZ	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
FRMPD4	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
RASSF6	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
FZD7	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
ORF putative E6	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
NET1	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610
CYSLTR2	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.610

BioGRID (8): PDZRN4 (PCA), PDZRN4 (Affinity Capture-Western), PDZRN4 (Protein-peptide), PDZRN4 (Protein-peptide), PDZRN4 (Cross-Linking-MS (XL-MS)), PDZRN4 (Two-hybrid), PDZRN4 (Two-hybrid), PDZRN4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JUG7, A1L390, E9Q0S6, O08774, O14924, O15085, O43182, O54834, O54960, O60307, O75052, P57095, Q13009, Q3U1V8, Q3U214, Q3UHC7, Q4VAC9, Q5DU25, Q5JU85, Q5RBI7, Q5SXA9, Q5VWQ8, Q60610, Q64512, Q6AX33, Q6DN90, Q6NXJ0, Q6P0Q8, Q6P1I6, Q6ZMN7, Q76G19, Q76LL6, Q76M68, Q7T2V3, Q810W7, Q8CGE9, Q8IX03, Q8R0S2, Q8R4H2, Q8WYP3

Diamond homologs: A7XUJ6, B5DF45, B6CJY4, B6CJY5, D3YY23, O13033, O70263, P15919, P39428, P43254, P68907, P70196, P93471, Q02084, Q13077, Q17RB8, Q1L5Z9, Q28DL4, Q3MV19, Q3UWA4, Q3ZCC3, Q6CTZ8, Q6DJN2, Q6IWL4, Q6J2U6, Q6MFY8, Q6Q0C0, Q6ZMN7, Q865W2, Q8TBB1, Q91187, Q922B6, Q9D4H7, Q9D9R0, Q9ET26, Q9FNI6, Q9Y4K3, P15918, P39429, Q1XHT8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	PDZRN4	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Unblocking of NMDA receptors, glutamate binding and activation	7	37.3×	6e-08
Negative regulation of NMDA receptor-mediated neuronal transmission	7	37.3×	6e-08
Ras activation upon Ca2+ influx through NMDA receptor	6	33.6×	1e-06
Long-term potentiation	7	32.7×	1e-07
Synaptic adhesion-like molecules	6	32.0×	2e-06
Neurexins and neuroligins	12	23.2×	5e-11
Assembly and cell surface presentation of NMDA receptors	9	22.4×	5e-08
Ca2+ pathway	6	10.5×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to synapse	5	27.8×	3e-04
positive regulation of excitatory postsynaptic potential	6	22.9×	9e-05
establishment or maintenance of epithelial cell apical/basal polarity	5	21.1×	6e-04
establishment of protein localization	5	15.7×	2e-03
chemical synaptic transmission	14	7.8×	2e-06
cell-cell adhesion	10	7.4×	3e-04
transmembrane transport	6	7.3×	9e-03
protein-containing complex assembly	8	6.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	154
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3304 predictions. Top by Δscore:

Variant	Effect	Δscore
12:41189099:GCAGG:G	donor_gain	1.0000
12:41189100:CAGGG:C	donor_loss	1.0000
12:41189101:AGGG:A	donor_loss	1.0000
12:41189102:GG:G	donor_gain	1.0000
12:41189103:GG:G	donor_gain	1.0000
12:41189104:G:GA	donor_loss	1.0000
12:41189104:G:GG	donor_gain	1.0000
12:41189105:T:A	donor_loss	1.0000
12:41191452:TTCTA:T	acceptor_loss	1.0000
12:41191453:TCTAG:T	acceptor_loss	1.0000
12:41191454:CTA:C	acceptor_loss	1.0000
12:41191455:TA:T	acceptor_loss	1.0000
12:41194186:GAGGT:G	donor_loss	1.0000
12:41194187:AGG:A	donor_loss	1.0000
12:41194189:GTA:G	donor_loss	1.0000
12:41194190:T:G	donor_loss	1.0000
12:41506452:GTAGG:G	acceptor_loss	1.0000
12:41506453:TAG:T	acceptor_loss	1.0000
12:41506454:AGG:A	acceptor_loss	1.0000
12:41506455:G:GC	acceptor_loss	1.0000
12:41506708:GACAG:G	donor_gain	1.0000
12:41509809:A:AG	acceptor_gain	1.0000
12:41509810:G:GG	acceptor_gain	1.0000
12:41509810:GCT:G	acceptor_gain	1.0000
12:41552645:T:A	acceptor_gain	1.0000
12:41552652:TCAG:T	acceptor_loss	1.0000
12:41552652:TCAGG:T	acceptor_gain	1.0000
12:41552653:CAGG:C	acceptor_gain	1.0000
12:41552654:A:AG	acceptor_gain	1.0000
12:41552654:A:C	acceptor_loss	1.0000

AlphaMissense

6864 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:41573444:T:A	W889R	1.000
12:41573444:T:C	W889R	1.000
12:41573519:C:A	R914S	1.000
12:41573617:A:C	R946S	1.000
12:41573617:A:T	R946S	1.000
12:41573798:T:A	W1007R	1.000
12:41573798:T:C	W1007R	1.000
12:41573817:T:C	L1013P	1.000
12:41191516:T:C	F236S	0.999
12:41552699:T:C	L416P	0.999
12:41552747:T:A	V432D	0.999
12:41555717:C:A	A441D	0.999
12:41555753:T:C	I453T	0.999
12:41572797:T:C	L673P	0.999
12:41572988:A:C	S737R	0.999
12:41572990:T:A	S737R	0.999
12:41572990:T:G	S737R	0.999
12:41572994:T:C	Y739H	0.999
12:41572999:C:A	N740K	0.999
12:41572999:C:G	N740K	0.999
12:41573009:A:C	S744R	0.999
12:41573011:C:A	S744R	0.999
12:41573011:C:G	S744R	0.999
12:41573445:G:C	W889S	0.999
12:41573446:G:C	W889C	0.999
12:41573446:G:T	W889C	0.999
12:41573453:A:G	K892E	0.999
12:41573455:A:C	K892N	0.999
12:41573455:A:T	K892N	0.999
12:41573488:G:C	K903N	0.999

dbSNP variants (sampled 300 via entrez): RS1000004020 (12:41464212 A>G), RS1000005777 (12:41318934 T>C), RS1000010179 (12:41194161 C>G), RS1000018633 (12:41489013 G>T), RS1000035691 (12:41351003 A>G), RS1000036925 (12:41567662 G>A,C), RS1000038831 (12:41450893 A>C), RS1000044816 (12:41239212 G>A,T), RS1000046155 (12:41441079 C>A,T), RS1000055239 (12:41513232 C>G,T), RS1000069996 (12:41522272 C>T), RS1000079674 (12:41399287 A>G), RS1000083042 (12:41303536 C>G), RS1000098083 (12:41289133 C>T), RS1000098189 (12:41239389 G>A,T)

Disease associations

OMIM: gene MIM:609730 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000189_25	Protein quantitative trait loci	1.000000e-10
GCST000269_1	Multiple sclerosis	2.000000e-06
GCST002515_3	Pneumoconiosis in silica exposure	5.000000e-06
GCST002783_187	Body mass index	6.000000e-07
GCST002783_341	Body mass index	7.000000e-07
GCST002783_588	Body mass index	7.000000e-06
GCST002829_29	Urate levels in overweight individuals	3.000000e-06
GCST006956_2	Erectile dysfunction	5.000000e-06
GCST007821_3	Facial attractiveness (female raters)	6.000000e-07
GCST008158_115	Body mass index	3.000000e-06
GCST008338_1	Blood cell traits (multivariate analysis)	2.000000e-09
GCST009159_2	Blood protein levels	3.000000e-08
GCST009239_1	Change in serum metabolite levels (CMS)	9.000000e-06
GCST009241_1	Change in serum metabolite levels	3.000000e-08
GCST010988_490	Adult body size	1.000000e-11
GCST012322_46	Triglyceride levels x SSRI defined daily dose interaction in schizophrenia or bipolar disorder	4.000000e-09
GCST90000047_180	Age at first sexual intercourse	3.000000e-11

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0009892	facial attractiveness measurement
EFO:0004305	erythrocyte count
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0004747	protein measurement
EFO:0004530	triglyceride measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression	1
bisphenol A	increases methylation	1
ethyl-p-hydroxybenzoate	increases expression	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1
CGP 52608	increases reaction, affects binding	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
Arsenic Trioxide	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Nickel	decreases expression	1
Phthalic Acids	increases methylation	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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