PNMA3

Summary

PNMA3 (PNMA family member 3, HGNC:18742) is a protein-coding gene on chromosome Xq28, encoding Paraneoplastic antigen Ma3 (Q9UL41).

The protein encoded by this gene belongs to the paraneoplastic antigen MA (PNMA) family, which shares homology with retroviral Gag proteins. The PNMA antigens are highly expressed in the brain and also in a range of tumors associated with serious neurological phenotypes. PMID:16407312 reports the presence of a functional -1 ribosomal frameshift signal (consisting of a heptanucleotide shift motif followed 3’ by a pseudoknot structure) in this gene, however, the frame-shifted product has not been characterized. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 29944 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_013364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18742
Approved symbol	PNMA3
Name	PNMA family member 3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	MA5, MA3, MGC132756, MGC132758
Ensembl gene	ENSG00000183837
Ensembl biotype	protein_coding
OMIM	300675
Entrez	29944

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000424805, ENST00000593810, ENST00000619635

RefSeq mRNA: 2 — MANE Select: NM_013364 NM_001282535, NM_013364

CCDS: CCDS35435, CCDS65344

Canonical transcript exons

ENST00000593810 — 2 exons

Exon	Start	End
ENSE00003025156	153056950	153060462
ENSE00003916854	153056470	153056638

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 92.43.

FANTOM5 (CAGE): breadth broad, TPM avg 1.7780 / max 71.7681, expressed in 298 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198025	0.7741	216
198024	0.5610	233
198026	0.4428	108

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	92.43	gold quality
primary visual cortex	UBERON:0002436	91.05	gold quality
middle temporal gyrus	UBERON:0002771	90.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.22	gold quality
superior frontal gyrus	UBERON:0002661	89.98	gold quality
anterior cingulate cortex	UBERON:0009835	89.97	gold quality
cingulate cortex	UBERON:0003027	89.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.84	gold quality
frontal cortex	UBERON:0001870	89.82	gold quality
prefrontal cortex	UBERON:0000451	89.60	gold quality
occipital lobe	UBERON:0002021	89.53	gold quality
neocortex	UBERON:0001950	89.46	gold quality
postcentral gyrus	UBERON:0002581	89.43	gold quality
parietal lobe	UBERON:0001872	89.37	gold quality
pons	UBERON:0000988	88.30	gold quality
parotid gland	UBERON:0001831	87.96	gold quality
cerebral cortex	UBERON:0000956	87.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.28	gold quality
superior vestibular nucleus	UBERON:0007227	86.66	gold quality
entorhinal cortex	UBERON:0002728	86.04	gold quality
hypothalamus	UBERON:0001898	85.94	gold quality
substantia nigra pars compacta	UBERON:0001965	85.70	gold quality
telencephalon	UBERON:0001893	85.60	gold quality
forebrain	UBERON:0001890	85.10	gold quality
temporal lobe	UBERON:0001871	84.94	gold quality
corpus epididymis	UBERON:0004359	84.94	gold quality
brain	UBERON:0000955	84.32	gold quality
amygdala	UBERON:0001876	83.99	gold quality
Ammon’s horn	UBERON:0001954	83.73	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.49	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting PNMA3, 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-4283	100.00	66.42	2097
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6749-3P	99.00	65.73	1443

Literature-anchored findings (GeneRIF, showing 1)

• analysis of a ribosomal frameshift signal in the human paraneoplastic Ma3 gene (PMID:16407312)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pnma3	ENSMUSG00000046287
rattus_norvegicus	Pnma3	ENSRNOG00000052022

Paralogs (13): MOAP1 (ENSG00000165943), ZCCHC18 (ENSG00000166707), CCDC8 (ENSG00000169515), ZCCHC12 (ENSG00000174460), PNMA1 (ENSG00000176903), PNMA8A (ENSG00000182013), PNMA5 (ENSG00000198883), PNMA8B (ENSG00000204851), PNMA6E (ENSG00000214897), PNMA6F (ENSG00000225110), PNMA6A (ENSG00000235961), PNMA2 (ENSG00000240694), PNMA8C (ENSG00000277531)

Protein

Protein identifiers

Paraneoplastic antigen Ma3 — Q9UL41 (reviewed: Q9UL41)

All UniProt accessions (1): Q9UL41

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Expressed at high levels in the brain and testis. Expressed at lower levels in the heart, trachea and kidney.

Miscellaneous. Antibodies against PNMA3 are present in sera from patients suffering of paraneoplastic neurological disorders.

Similarity. Belongs to the PNMA family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UL41-1	1	yes
Q9UL41-2	2

RefSeq proteins (2): NP_001269464, NP_037496* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001878	Znf_CCHC	Domain
IPR026523	PNMA	Family
IPR036875	Znf_CCHC_sf	Homologous_superfamily
IPR048270	PNMA_C	Domain
IPR048271	PNMA_N	Domain

Pfam: PF14893, PF20846

UniProt features (9 total): region of interest 2, sequence variant 2, chain 1, zinc finger region 1, compositionally biased region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL41-F1	75.33	0.34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): ATF_B, CREBP1_Q2, CREB_Q4, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, E4F1_Q6, ATF3_Q6, CREB_Q2_01, ATF4_Q2, ATF_01, CREBP1CJUN_01, CREB_01, GOCC_NUCLEOLUS, TGACGTCA_ATF3_Q6, CREB_Q2, YGCANTGCR_UNKNOWN

GO Biological Process (1): positive regulation of apoptotic process (GO:0043065)

GO Molecular Function (4): nucleic acid binding (GO:0003676), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleolus (GO:0005730), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
transition metal ion binding	1
cation binding	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNMA3	GAPDH	P00354	675
PNMA3	ACTB	P02570	664
PNMA3	PXDN	Q92626	584
PNMA3	PXDNL	A1KZ92	584
PNMA3	ALB	P02768	545
PNMA3	SLCO6A1	Q86UG4	502
PNMA3	NUBP2	Q9Y5Y2	483
PNMA3	CASP3	P42574	473
PNMA3	NT5E	P21589	464
PNMA3	PRDX3	P30048	443
PNMA3	PECAM1	P16284	421
PNMA3	ZNF251	Q9BRH9	403
PNMA3	CDH1	P12830	400
PNMA3	MUC1	P13931	391
PNMA3	TNNT2	P45379	391

IntAct

37 interactions, top by confidence:

A	B	Type	Score
UBQLN2	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
APTX	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
PRPF31	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
C19orf25	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
PNMA3	RPH3AL	psi-mi:“MI:0915”(physical association)	0.560
LNX1	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
ZBTB47	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
TIGD3	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
MGC50722	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
SMG9	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
CNNM3	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
SLC25A37	PNMA3	psi-mi:“MI:0915”(physical association)	0.560
PNMA3	UBQLN2	psi-mi:“MI:0915”(physical association)	0.000
APTX	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
PRPF31	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
TIGD3	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
C19orf25	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
RPH3AL	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
LNX1	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
ZBTB47	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
MGC50722	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
SLC25A37	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
SMG9	PNMA3	psi-mi:“MI:0915”(physical association)	0.000
CNNM3	PNMA3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (22): PNMA3 (Affinity Capture-MS), PNMA3 (Affinity Capture-MS), PNMA3 (Affinity Capture-MS), PNMA3 (Affinity Capture-MS), PNMA3 (Affinity Capture-MS), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid), PNMA3 (Two-hybrid)

ESM2 similar proteins: A0A0J9YX94, A0A0J9YXQ4, A0A0J9YY54, A0A494C1R9, A5D7L8, A6NDY0, A6NKD2, A7E321, E9PGG2, F6SZT2, O14771, O19110, O75807, O88852, P0CV98, P0CV99, P0CW00, P0CW01, P0CW24, P17564, P78358, Q01534, Q0P5N2, Q15735, Q2KI51, Q2M329, Q587J8, Q5DTT8, Q5R5G8, Q5R6R8, Q5SV97, Q60465, Q62881, Q69ZB3, Q6P752, Q86V59, Q8BSI6, Q8IWY8, Q8N3D4, Q8VD63

Diamond homologs: A0A0J9YX94, A0A0J9YXQ4, A0A1B0GUJ8, A6QLK5, A7E321, P0CG32, P0CW24, Q08DL1, Q2KIT6, Q5HZA3, Q5R6R8, Q6PEW1, Q80VM8, Q86V59, Q8JZW8, Q8ND90, Q8VD24, Q8VHZ4, Q9CZA5, Q9UL41, Q9ULN7, D3YZV8, P62521, Q5DTT8, Q5R486, Q8BHK0, Q8C1C8, Q95KI4, Q96BY2, Q96PV4, Q9ERH6, Q9GMU3, Q9H0W5, Q9UL42

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

310 predictions. Top by Δscore:

Variant	Effect	Δscore
X:153057176:G:GT	donor_gain	1.0000
X:153057152:GA:G	donor_gain	0.9900
X:153057188:C:T	donor_gain	0.9700
X:153057153:A:G	donor_gain	0.9600
X:153057187:GCACC:G	donor_gain	0.9600
X:153057217:G:GT	donor_gain	0.9600
X:153057296:G:T	donor_gain	0.9400
X:153057109:G:GT	donor_gain	0.9000
X:153057209:A:AG	donor_gain	0.9000
X:153057270:A:G	donor_gain	0.8800
X:153057210:T:G	donor_gain	0.8600
X:153057199:A:G	donor_gain	0.8000
X:153057277:C:G	donor_gain	0.8000
X:153057164:G:GT	donor_gain	0.7900
X:153057296:G:GT	donor_gain	0.7900
X:153057204:GG:G	donor_gain	0.7300
X:153057205:GG:G	donor_gain	0.7300
X:153057275:GAC:G	donor_gain	0.7300
X:153057295:GGAAA:G	donor_gain	0.7000
X:153057151:GGA:G	donor_gain	0.6900
X:153057277:C:CG	donor_gain	0.6800
X:153057307:A:T	donor_gain	0.6800
X:153057140:G:GT	donor_gain	0.6700
X:153057149:GAGGA:G	donor_gain	0.6700
X:153057203:AG:A	donor_gain	0.6500
X:153057153:A:AG	donor_gain	0.6200
X:153057368:A:AG	acceptor_gain	0.6200
X:153057369:G:GG	acceptor_gain	0.6200
X:153057148:C:T	donor_gain	0.6100
X:153057180:C:T	donor_gain	0.6100

AlphaMissense

2990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:153057554:T:C	F167L	0.991
X:153057556:T:A	F167L	0.991
X:153057556:T:G	F167L	0.991
X:153057854:T:C	F267L	0.989
X:153057856:T:A	F267L	0.989
X:153057856:T:G	F267L	0.989
X:153057221:T:C	F56L	0.986
X:153057223:T:A	F56L	0.986
X:153057223:T:G	F56L	0.986
X:153057773:T:C	F240L	0.986
X:153057775:C:A	F240L	0.986
X:153057775:C:G	F240L	0.986
X:153057945:T:A	V297D	0.980
X:153057555:T:C	F167S	0.974
X:153057602:T:A	W183R	0.974
X:153057602:T:C	W183R	0.974
X:153058022:T:C	F323L	0.974
X:153058024:C:A	F323L	0.974
X:153058024:C:G	F323L	0.974
X:153057320:T:A	W89R	0.973
X:153057320:T:C	W89R	0.973
X:153057359:T:C	F102L	0.972
X:153057361:T:A	F102L	0.972
X:153057361:T:G	F102L	0.972
X:153057593:T:C	F180L	0.972
X:153057595:T:A	F180L	0.972
X:153057595:T:G	F180L	0.972
X:153057987:T:A	L311H	0.970
X:153058023:T:C	F323S	0.970
X:153057762:T:C	L236S	0.967

dbSNP variants (sampled 300 via entrez): RS1000739102 (X:153055485 C>T), RS1001845136 (X:153055981 C>T), RS1002382412 (X:153056332 C>A,G,T), RS1002460498 (X:153059950 T>C), RS1003600104 (X:153058807 C>T), RS1004922545 (X:153054831 C>T), RS1005517845 (X:153059149 A>G), RS1005863500 (X:153058917 G>A), RS1006453249 (X:153056588 C>G,T), RS1007240127 (X:153059904 A>G), RS1008108385 (X:153057853 C>T), RS1008498691 (X:153060919 T>C), RS1011400001 (X:153060059 C>A), RS1012496640 (X:153060142 G>A,C), RS1012960609 (X:153060292 G>A)

Disease associations

OMIM: gene MIM:300675 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	2
Aflatoxin B1	decreases methylation, decreases expression	2
FR900359	increases phosphorylation	1
ethyl-p-hydroxybenzoate	decreases expression	1
2-palmitoylglycerol	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Lead	affects expression	1
Phthalic Acids	decreases methylation	1
Valproic Acid	increases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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