PNMA2

Summary

PNMA2 (PNMA family member 2, HGNC:9159) is a protein-coding gene on chromosome 8p21.2, encoding Paraneoplastic antigen Ma2 (Q9UL42).

Predicted to be involved in positive regulation of apoptotic process. Predicted to be located in nucleolus.

Source: NCBI Gene 10687 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_007257

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9159
Approved symbol	PNMA2
Name	PNMA family member 2
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	MA2, RGAG2
Ensembl gene	ENSG00000240694
Ensembl biotype	protein_coding
OMIM	603970
Entrez	10687

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding_CDS_not_defined, 5 protein_coding, 1 retained_intron

ENST00000518212, ENST00000521740, ENST00000521875, ENST00000522362, ENST00000522450, ENST00000522764, ENST00000523244, ENST00000523616, ENST00000854209, ENST00000854210, ENST00000939502, ENST00000968519

RefSeq mRNA: 1 — MANE Select: NM_007257 NM_007257

CCDS: CCDS34868

Canonical transcript exons

ENST00000522362 — 3 exons

Exon	Start	End
ENSE00002101878	26504701	26509243
ENSE00002124348	26513816	26513872
ENSE00002135724	26509548	26509677

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.4491 / max 775.0952, expressed in 927 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92418	12.4114	927
205130	0.0377	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
orbitofrontal cortex	UBERON:0004167	99.37	gold quality
middle temporal gyrus	UBERON:0002771	99.28	gold quality
postcentral gyrus	UBERON:0002581	99.26	gold quality
superior frontal gyrus	UBERON:0002661	99.24	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.14	gold quality
parietal lobe	UBERON:0001872	99.08	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.05	gold quality
superior vestibular nucleus	UBERON:0007227	98.86	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.83	gold quality
pons	UBERON:0000988	98.82	gold quality
endothelial cell	CL:0000115	98.74	gold quality
CA1 field of hippocampus	UBERON:0003881	98.49	gold quality
frontal pole	UBERON:0002795	98.36	gold quality
substantia nigra pars compacta	UBERON:0001965	98.33	gold quality
entorhinal cortex	UBERON:0002728	98.31	gold quality
occipital lobe	UBERON:0002021	98.18	gold quality
lateral globus pallidus	UBERON:0002476	98.04	gold quality
primary visual cortex	UBERON:0002436	98.01	gold quality
prefrontal cortex	UBERON:0000451	97.72	gold quality
medulla oblongata	UBERON:0001896	97.69	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.60	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.24	gold quality
frontal cortex	UBERON:0001870	97.16	gold quality
cerebral cortex	UBERON:0000956	97.15	gold quality
neocortex	UBERON:0001950	97.01	gold quality
cortical plate	UBERON:0005343	96.99	gold quality
hypothalamus	UBERON:0001898	96.93	gold quality
temporal lobe	UBERON:0001871	96.76	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.71	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	9.33
E-ANND-3	yes	8.06
E-GEOD-84465	yes	7.02
E-MTAB-7249	no	113.78
E-MTAB-6911	no	96.57

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting PNMA2, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-3529-3P	99.90	73.55	3045

Literature-anchored findings (GeneRIF, showing 4)

• Ma2 may have a role in early recurrence of small intestine neuroendocrine tumors (PMID:21209860)
• Immunohistochemical analysis of MA2/D2-40 combined with p16(INK4A) may have a significant implication in clinical practice for better identifying the grade of cervical intraepithelial neoplasia. (PMID:21729305)
• PNMA2 functions as antagonist of MOAP-1 and PNMA1 through heterodimeric interaction (PMID:27003254)
• Human paraneoplastic antigen Ma2 (PNMA2) forms icosahedral capsids that can be engineered for mRNA delivery. (PMID:38437549)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pnma2	ENSMUSG00000046204
rattus_norvegicus	Pnma2	ENSRNOG00000009815

Paralogs (13): MOAP1 (ENSG00000165943), ZCCHC18 (ENSG00000166707), CCDC8 (ENSG00000169515), ZCCHC12 (ENSG00000174460), PNMA1 (ENSG00000176903), PNMA8A (ENSG00000182013), PNMA3 (ENSG00000183837), PNMA5 (ENSG00000198883), PNMA8B (ENSG00000204851), PNMA6E (ENSG00000214897), PNMA6F (ENSG00000225110), PNMA6A (ENSG00000235961), PNMA8C (ENSG00000277531)

Protein

Protein identifiers

Paraneoplastic antigen Ma2 — Q9UL42 (reviewed: Q9UL42)

Alternative names: 40 kDa neuronal protein, Onconeuronal antigen Ma2, Paraneoplastic neuronal antigen MM2

All UniProt accessions (1): Q9UL42

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Brain-specific. In some cancer patients, specifically expressed by testicular tumor cells.

Miscellaneous. Antibodies against PNMA2 are present in sera from patients suffering of paraneoplastic neurological disorders.

Similarity. Belongs to the PNMA family.

RefSeq proteins (1): NP_009188* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026523	PNMA	Family
IPR048270	PNMA_C	Domain
IPR048271	PNMA_N	Domain

Pfam: PF14893, PF20846

UniProt features (11 total): sequence conflict 4, compositionally biased region 2, initiator methionine 1, chain 1, region of interest 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8UYO	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UL42-F1	81.31	0.39

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 110 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, BILD_HRAS_ONCOGENIC_SIGNATURE, chr8p21, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN, ONDER_CDH1_TARGETS_2_UP, SENESE_HDAC3_TARGETS_DN, GOCC_NUCLEOLUS, BLALOCK_ALZHEIMERS_DISEASE_DN, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, BILBAN_B_CLL_LPL_UP, HUTTMANN_B_CLL_POOR_SURVIVAL_UP, KIM_BIPOLAR_DISORDER_OLIGODENDROCYTE_DENSITY_CORR_UP, KIM_ALL_DISORDERS_CALB1_CORR_UP, JOHNSTONE_PARVB_TARGETS_3_UP

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

GO Molecular Function (1): protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

1198 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PNMA2	AMPH	P49418	888
PNMA2	DPYSL5	Q9BPU6	881
PNMA2	LGI1	O95970	877
PNMA2	BIN1	O00499	851
PNMA2	ZIC4	Q8N9L1	813
PNMA2	CNTNAP2	Q9UHC6	799
PNMA2	IGLON5	A6NGN9	791
PNMA2	DPP10	Q8N608	788
PNMA2	DPP6	P42658	773
PNMA2	RCVRN	P35243	735
PNMA2	DNER	Q8NFT8	727
PNMA2	GAD2	Q05329	721
PNMA2	SOX1	O00570	720
PNMA2	TTN	Q8WZ42	591
PNMA2	GRM5	P41594	553

IntAct

210 interactions, top by confidence:

A	B	Type	Score
PNMA2	ENKD1	psi-mi:“MI:0915”(physical association)	0.870
ENKD1	PNMA2	psi-mi:“MI:0915”(physical association)	0.870
SDCBP	PNMA2	psi-mi:“MI:0915”(physical association)	0.780
PNMA2	RNF8	psi-mi:“MI:0915”(physical association)	0.780
BYSL	PNMA2	psi-mi:“MI:0915”(physical association)	0.780
PNMA2	SDCBP	psi-mi:“MI:0915”(physical association)	0.780
RNF8	PNMA2	psi-mi:“MI:0915”(physical association)	0.780
FAM161A	PNMA2	psi-mi:“MI:0915”(physical association)	0.740
PNMA2	PRPF31	psi-mi:“MI:0915”(physical association)	0.720
RPL9	PNMA2	psi-mi:“MI:0915”(physical association)	0.720
PNMA2	ZNF587	psi-mi:“MI:0915”(physical association)	0.720
PNMA2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
PNMA2	RPL9	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (297): PNMA2 (Two-hybrid), PNMA2 (Two-hybrid), PNMA2 (Two-hybrid), PNMA2 (Two-hybrid), PNMA2 (Two-hybrid), PNMA2 (Two-hybrid), PNMA2 (Two-hybrid), PNMA2 (Two-hybrid), PRPF31 (Two-hybrid), CBX8 (Two-hybrid), SCNM1 (Two-hybrid), CCDC33 (Two-hybrid), ENKD1 (Two-hybrid), FAM161A (Two-hybrid), ZNF587 (Two-hybrid)

ESM2 similar proteins: A0A1B0GUJ8, A1Z651, A6QLK5, G1SRW8, P03330, P03334, P03336, P03340, P03359, P0CG32, P0CW24, P10262, P11227, P11269, P21414, P21416, P26805, P26806, P26807, P27460, P31622, P31623, P31625, P32594, Q08DL1, Q27ID9, Q2F7I9, Q2F7J0, Q2F7J2, Q2F7J3, Q2KIT6, Q5HZA3, Q5R486, Q6PEW1, Q7SVK7, Q8BHK0, Q8C1C8, Q8JZW8, Q8ND90, Q8VD24

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 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
FCGR3A-mediated phagocytosis	6	12.9×	3e-03
Regulation of actin dynamics for phagocytic cup formation	6	12.7×	3e-03
Post NMDA receptor activation events	5	11.7×	6e-03
Leishmania infection	6	11.2×	3e-03
Parasitic Infection Pathways	6	11.2×	3e-03
Activation of NMDA receptors and postsynaptic events	5	10.6×	6e-03
Loss of Nlp from mitotic centrosomes	5	9.1×	8e-03
Loss of proteins required for interphase microtubule organization from the centrosome	5	9.1×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment of cell polarity	6	19.8×	2e-04
protein targeting to membrane	5	12.7×	6e-03
protein phosphorylation	16	9.4×	1e-08
intracellular signal transduction	16	5.3×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

402 predictions. Top by Δscore:

Variant	Effect	Δscore
8:26513811:CTTA:C	donor_loss	0.9900
8:26513812:TTAC:T	donor_loss	0.9900
8:26513813:TAC:T	donor_loss	0.9900
8:26513814:A:AC	donor_gain	0.9900
8:26513814:AC:A	donor_gain	0.9900
8:26513814:ACC:A	donor_gain	0.9900
8:26513815:C:A	donor_loss	0.9900
8:26513815:C:CC	donor_gain	0.9900
8:26513815:CC:C	donor_gain	0.9900
8:26513815:CCC:C	donor_gain	0.9900
8:26513815:CCCA:C	donor_gain	0.9900
8:26513815:CCCAG:C	donor_gain	0.9900
8:26513810:ACTT:A	donor_loss	0.9800
8:26513999:C:A	donor_gain	0.9800
8:26509687:A:C	acceptor_gain	0.9700
8:26514002:T:TA	donor_gain	0.9200
8:26514006:C:CA	donor_gain	0.9000
8:26512639:C:CA	acceptor_gain	0.8700
8:26512968:ACTC:A	donor_gain	0.8500
8:26512969:CTCC:C	donor_gain	0.8500
8:26513176:T:A	donor_gain	0.8100
8:26512968:A:AC	donor_gain	0.8000
8:26512969:C:CC	donor_gain	0.8000
8:26509016:C:T	donor_gain	0.7900
8:26509087:G:T	donor_gain	0.7900
8:26509241:CCC:C	acceptor_gain	0.7900
8:26509242:CCC:C	acceptor_gain	0.7900
8:26513808:ATACT:A	donor_loss	0.7800
8:26513809:TACTT:T	donor_loss	0.7800
8:26509673:CTGCT:C	acceptor_gain	0.7700

AlphaMissense

2359 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:26508033:A:C	F241L	0.988
8:26508033:A:T	F241L	0.988
8:26508035:A:G	F241L	0.988
8:26508252:G:C	F168L	0.987
8:26508252:G:T	F168L	0.987
8:26508254:A:G	F168L	0.987
8:26507863:A:T	V298D	0.973
8:26508253:A:G	F168S	0.973
8:26507776:A:G	L327P	0.971
8:26507954:A:C	Y268D	0.971
8:26507876:G:T	R294S	0.969
8:26508206:A:G	W184R	0.968
8:26508206:A:T	W184R	0.968
8:26508194:C:G	A188P	0.967
8:26507938:T:A	E273V	0.965
8:26507996:A:C	Y254D	0.959
8:26508247:C:T	G170E	0.959
8:26507764:A:T	I331K	0.957
8:26508035:A:T	F241I	0.955
8:26507921:C:G	A279P	0.953
8:26508559:A:G	L66S	0.953
8:26508688:A:T	V23D	0.953
8:26507875:C:G	R294P	0.952
8:26507902:A:G	I285T	0.951
8:26507944:C:G	R271P	0.951
8:26507954:A:T	Y268N	0.951
8:26507784:G:C	F324L	0.950
8:26507784:G:T	F324L	0.950
8:26507786:A:G	F324L	0.950
8:26507785:A:G	F324S	0.948

dbSNP variants (sampled 300 via entrez): RS1000312413 (8:26509640 G>C,T), RS1000427036 (8:26509300 A>C,G), RS1000619883 (8:26515013 C>G,T), RS1000702926 (8:26509222 C>G,T), RS1001064340 (8:26515004 A>C), RS1001555326 (8:26509276 C>T), RS1001587815 (8:26509805 T>G), RS1002225542 (8:26515520 T>C), RS1002624606 (8:26514049 G>A), RS1002676441 (8:26505905 G>A), RS1003230519 (8:26510872 G>A,T), RS1003677148 (8:26504667 G>A), RS1003777016 (8:26506427 C>A,T), RS1004431249 (8:26506981 C>T), RS1004659084 (8:26512885 T>G)

Disease associations

OMIM: gene MIM:603970 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003075_132	Cognitive decline rate in late mild cognitive impairment	4.000000e-07
GCST003075_90	Cognitive decline rate in late mild cognitive impairment	3.000000e-07
GCST010703_188	Brain morphology (MOSTest)	7.000000e-11
GCST90000047_151	Age at first sexual intercourse	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007710	cognitive decline measurement
EFO:0004346	neuroimaging measurement
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

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	8
sodium arsenite	increases abundance, affects cotreatment, increases expression, decreases expression	4
trichostatin A	increases expression, affects cotreatment, decreases expression	3
belinostat	decreases expression, affects cotreatment	2
Decitabine	affects expression, decreases expression, decreases reaction	2
Benzo(a)pyrene	affects methylation, increases expression	2
Smoke	decreases reaction, decreases expression	2
Tretinoin	affects cotreatment, increases expression, decreases expression	2
Particulate Matter	increases abundance, affects cotreatment, decreases expression	2
GSK-J4	increases expression	1
methyleugenol	increases expression	1
2-amino-9H-pyrido(2,3-b)indole	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Allergens	decreases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	affects expression	1
Copper	affects binding, increases expression	1
Diethylnitrosamine	increases expression	1
Disulfiram	affects binding, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Fluorouracil	affects response to substance	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Methotrexate	affects response to substance	1

Clinical trials (associated diseases)

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