PRIMA1

Summary

PRIMA1 (proline rich membrane anchor 1, HGNC:18319) is a protein-coding gene on chromosome 14q32.12, encoding Proline-rich membrane anchor 1 (Q86XR5). Required to anchor acetylcholinesterase (ACHE) to the basal lamina of the neuromuscular junction and to the membrane of neuronal synapses in brain.

The product of this gene functions to organize acetylcholinesterase (AChE) into tetramers, and to anchor AChE at neural cell membranes.

Source: NCBI Gene 145270 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 170 total — 4 pathogenic
• MANE Select transcript: NM_178013

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18319
Approved symbol	PRIMA1
Name	proline rich membrane anchor 1
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Aliases	PRIMA
Ensembl gene	ENSG00000175785
Ensembl biotype	protein_coding
OMIM	613851
Entrez	145270

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000316227, ENST00000393140, ENST00000393143, ENST00000477603, ENST00000907899, ENST00000907900

RefSeq mRNA: 1 — MANE Select: NM_178013 NM_178013

CCDS: CCDS9912

Canonical transcript exons

ENST00000393140 — 5 exons

Exon	Start	End
ENSE00001235932	93737241	93737370
ENSE00001235946	93779176	93779311
ENSE00001514273	93788410	93788485
ENSE00001514275	93718298	93721546
ENSE00002201679	93787626	93787749

Expression profiles

Bgee: expression breadth ubiquitous, 127 present calls, max score 96.34.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1395 / max 80.0419, expressed in 262 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144643	0.6807	184
144642	0.4588	174

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	96.34	gold quality
sural nerve	UBERON:0015488	93.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.73	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.86	gold quality
lower esophagus	UBERON:0013473	91.84	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.97	gold quality
left uterine tube	UBERON:0001303	89.09	gold quality
mucosa of stomach	UBERON:0001199	85.47	gold quality
colon	UBERON:0001155	85.36	gold quality
smooth muscle tissue	UBERON:0001135	85.19	gold quality
lower esophagus mucosa	UBERON:0035834	84.77	gold quality
fundus of stomach	UBERON:0001160	84.25	gold quality
esophagus	UBERON:0001043	84.01	gold quality
intestine	UBERON:0000160	83.39	gold quality
fallopian tube	UBERON:0003889	83.18	gold quality
substantia nigra	UBERON:0002038	82.98	gold quality
body of uterus	UBERON:0009853	82.52	gold quality
endocervix	UBERON:0000458	82.47	gold quality
ectocervix	UBERON:0012249	82.36	gold quality
transverse colon	UBERON:0001157	82.05	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.00	gold quality
prostate gland	UBERON:0002367	81.90	gold quality
body of stomach	UBERON:0001161	81.69	gold quality
colonic epithelium	UBERON:0000397	81.60	gold quality
corpus callosum	UBERON:0002336	81.58	gold quality
vagina	UBERON:0000996	80.75	gold quality
myometrium	UBERON:0001296	80.58	gold quality
small intestine	UBERON:0002108	80.46	gold quality
putamen	UBERON:0001874	80.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	16.03
E-ANND-3	no	0.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53

miRNA regulators (miRDB)

130 targeting PRIMA1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-605-3P	99.88	69.22	1833
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4779	99.86	66.50	1583
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442

Literature-anchored findings (GeneRIF, showing 12)

• PRiMA-Luc promotor-driven luciferase activity was increased during cell differentiation (PMID:16429581)
• These results suggested that a MAP kinase signaling pathway served as one of the transcriptional regulators in controlling PRiMA gene expression during the neuronal differentiation process. (PMID:19368807)
• PRiMA in neurons has a role in targeting acetylcholinesterase to membrane rafts (PMID:20147288)
• A strong association of AChE with PRiMA at the plasma membrane is therefore a feature specific to principal cholinergic neurons that innervate the central nervous system. (PMID:20471375)
• By using site-directed mutagenesis, the asparagine-43 was identified to be the N-linked glycosylation site of PRiMA. Abolishing glycosylation on mouse PRiMA appeared not to affect its assembly with AChE(T). (PMID:22750213)
• The autophagic potential of PRIMA-1 could be modulated in a different way by the presence of wild type or mutant p53. (PMID:23545415)
• Hypermethylation of the selected markers (MAL, PRIMA1, PTGDR and SFRP1) can result in reduced gene expression and may contribute to the formation of colorectal cancer. (PMID:26482433)
• Silencing of CD24 enhanced restoration of PRIMA-1-induced mutant p53 in endogenous TP53(P223L/V274F) DU145 cells. (PMID:26712693)
• The results suggest that aberrant methylation of rDNA and PRIMA1 is associated with the pathogenesis of Borderline Personality Disorder. (PMID:26742039)
• PRIMA-1 could cause the demethylation of TP73, through DNMT1 depletion, to subsequently enhance the unfolded protein response (PMID:27533450)
• Methylation of SFRP1, SFRP2, SDC2, and PRIMA1 promoter sequences was observed in 85.1%, 72.3%, 89.4%, and 80.9% of plasma samples from patients with Colorectal cancer and 89.2%, 83.8%, 81.1% and 70.3% from adenoma patients, respectively. (PMID:28753106)
• PRIMA-1 can rescue amyloid-state p53 mutants (PMID:30602570)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prima1	ENSDARG00000077377
mus_musculus	Prima1	ENSMUSG00000041669
rattus_norvegicus	Prima1	ENSRNOG00000008915

Protein

Protein identifiers

Proline-rich membrane anchor 1 — Q86XR5 (reviewed: Q86XR5)

All UniProt accessions (1): Q86XR5

UniProt curated annotations — full annotation on UniProt →

Function. Required to anchor acetylcholinesterase (ACHE) to the basal lamina of the neuromuscular junction and to the membrane of neuronal synapses in brain. Also able to organize ACHE into tetramers.

Subunit / interactions. Interacts with ACHE, probably through disulfide bonds.

Subcellular location. Cell membrane. Cell junction. Synapse.

Domain organisation. The proline-rich attachment domain (PRAD) binds the AChE catalytic subunits.

Induction. By RAF1.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86XR5-1	1, Variant I	yes
Q86XR5-2	2, Variant II

RefSeq proteins (1): NP_821092* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029659	PRIMA1	Family

Pfam: PF16101

UniProt features (12 total): splice variant 2, topological domain 2, signal peptide 1, chain 1, sequence variant 1, transmembrane region 1, domain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86XR5-F1	63.74	0.00

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 (1): 79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 83 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, TGCGCANK_UNKNOWN, FOXD3_01, NKX62_Q2, AAACCAC_MIR140, HFH8_01, AACTTT_UNKNOWN, GFI1_01, VDR_Q3, SABATES_COLORECTAL_ADENOMA_DN, YY1_01, VECCHI_GASTRIC_CANCER_EARLY_DN, chr14q32, GOCC_SYNAPSE, GOCC_ANCHORING_JUNCTION

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (4): plasma membrane (GO:0005886), synapse (GO:0045202), anchoring junction (GO:0070161), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell junction	2
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRIMA1	COLQ	Q9Y215	809
PRIMA1	TP53	P04637	769
PRIMA1	BCHE	P06276	711
PRIMA1	ACHE	P22303	603
PRIMA1	MDM2	Q00987	602
PRIMA1	SDC2	P34741	552
PRIMA1	PMAIP1	Q13794	541
PRIMA1	SFRP1	Q8N474	506
PRIMA1	KCNS1	Q96KK3	492
PRIMA1	MDM4	O15151	423
PRIMA1	FAM181A	Q8N9Y4	412
PRIMA1	CABP2	Q9NPB3	390
PRIMA1	TXNRD1	Q16881	370
PRIMA1	STAT1	P42224	367
PRIMA1	NPRL2	Q8WTW4	357

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PRIMA1	TTC9	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): PRIMA1 (Negative Genetic), TTC9 (Affinity Capture-MS)

ESM2 similar proteins: A0A5F4BST2, A5PJC7, A8MWV9, D3ZZP4, O14836, P0CAN6, P11911, P11912, P14753, Q01114, Q07303, Q13113, Q2KI80, Q2KL21, Q3TS39, Q3URD2, Q4V9L6, Q5F267, Q5FVJ4, Q5FVQ7, Q5RA41, Q5T1S8, Q6P9G4, Q6UWJ8, Q6UX34, Q80VJ8, Q810F0, Q86XR5, Q8BRJ3, Q8BX43, Q8K064, Q8K5A9, Q8N112, Q8N4K4, Q8N6L0, Q8NBR0, Q8NC24, Q8QZT4, Q8R138, Q923S2

Diamond homologs: D3ZZP4, Q810F0, Q86XR5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	75
Likely benign	79
Benign	6

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1496815	NM_178013.4(PRIMA1):c.270G>A (p.Trp90Ter)	Pathogenic
2913433	NM_178013.4(PRIMA1):c.80G>A (p.Trp27Ter)	Pathogenic
3244043	NC_000014.8:g.(?94187790)(94254064_?)del	Pathogenic
3244044	NC_000014.8:g.(?94245502)(94245677_?)del	Pathogenic

SpliceAI

979 predictions. Top by Δscore:

Variant	Effect	Δscore
14:93737236:CTCA:C	donor_loss	0.9900
14:93737237:TCA:T	donor_loss	0.9900
14:93737238:CAC:C	donor_loss	0.9900
14:93737240:C:CG	donor_loss	0.9900
14:93778961:A:C	donor_gain	0.9900
14:93778976:T:TA	donor_gain	0.9900
14:93779335:C:T	acceptor_gain	0.9900
14:93787623:CA:C	donor_loss	0.9900
14:93787624:A:AG	donor_loss	0.9900
14:93787625:CCTG:C	donor_loss	0.9900
14:93737235:ACTC:A	donor_loss	0.9800
14:93779330:G:C	acceptor_gain	0.9800
14:93779424:T:A	donor_gain	0.9800
14:93778953:T:C	donor_gain	0.9700
14:93721447:CACCA:C	donor_gain	0.9600
14:93737234:CACT:C	donor_loss	0.9600
14:93737368:GAGCT:G	acceptor_loss	0.9600
14:93737370:GCT:G	acceptor_loss	0.9600
14:93737371:C:CC	acceptor_gain	0.9600
14:93737371:CTGAA:C	acceptor_loss	0.9600
14:93737372:T:G	acceptor_loss	0.9600
14:93737373:G:C	acceptor_loss	0.9500
14:93737374:AAAAA:A	acceptor_loss	0.9500
14:93779051:C:A	donor_gain	0.9500
14:93779336:A:T	acceptor_gain	0.9500
14:93779419:T:TA	donor_gain	0.9500
14:93778932:T:C	donor_gain	0.9400
14:93779335:C:CT	acceptor_gain	0.9400
14:93787624:A:AC	donor_gain	0.9400
14:93787625:C:CC	donor_gain	0.9400

AlphaMissense

976 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:93737260:A:G	C114R	0.989
14:93737243:T:A	K119N	0.986
14:93737243:T:G	K119N	0.986
14:93737251:C:G	A117P	0.983
14:93737252:T:A	K116N	0.981
14:93737252:T:G	K116N	0.981
14:93721546:C:A	R120S	0.975
14:93721546:C:G	R120S	0.975
14:93737257:A:C	Y115D	0.974
14:93737253:T:A	K116I	0.972
14:93737299:A:G	C101R	0.970
14:93737244:T:A	K119I	0.968
14:93737241:C:G	R120T	0.966
14:93737302:A:G	C100R	0.966
14:93737241:C:A	R120M	0.962
14:93721543:T:A	K121N	0.958
14:93721543:T:G	K121N	0.958
14:93737245:T:C	K119E	0.957
14:93737247:A:T	I118K	0.957
14:93737280:A:C	L107R	0.954
14:93737254:T:C	K116E	0.947
14:93737307:G:T	A98D	0.945
14:93737250:G:T	A117D	0.944
14:93737258:G:C	C114W	0.943
14:93737247:A:G	I118T	0.942
14:93737259:C:T	C114Y	0.933
14:93779243:G:C	C54W	0.931
14:93721544:T:A	K121I	0.928
14:93737244:T:G	K119T	0.927
14:93721545:T:C	K121E	0.925

dbSNP variants (sampled 300 via entrez): RS1000048284 (14:93731481 G>T), RS1000073120 (14:93750355 T>C), RS1000130927 (14:93743216 C>A), RS1000140498 (14:93725248 G>A), RS1000144402 (14:93774041 G>A,C), RS1000149273 (14:93750112 C>T), RS1000167977 (14:93764790 A>AT), RS1000186389 (14:93738006 C>G), RS1000247444 (14:93743026 T>C,G), RS1000255850 (14:93746108 T>G), RS1000260404 (14:93770370 C>G), RS1000334473 (14:93770158 C>G), RS1000344555 (14:93733832 A>C), RS1000393823 (14:93745631 GCCA>G), RS1000394013 (14:93768941 G>T)

Disease associations

OMIM: gene MIM:613851 | disease phenotypes: MIM:600513

GenCC curated gene-disease

Disease	Classification	Inheritance
frontal lobe epilepsy	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
epilepsy	Limited	AR

Mondo (2): familial sleep-related hypermotor epilepsy (MONDO:0000030), frontal lobe epilepsy (MONDO:0002612)

Orphanet (1): Sleep-related hypermotor epilepsy (Orphanet:98784)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001586_9	Insomnia (caffeine-induced)	1.000000e-06
GCST003980_5	Sleep duration	1.000000e-07
GCST003980_6	Sleep duration	2.000000e-06
GCST005951_7	Body mass index	4.000000e-08
GCST006810_26	Self-reported risk-taking behaviour	5.000000e-08
GCST006811_2	Body mass index	5.000000e-14
GCST009524_193	Household income (MTAG)	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007876	insomnia measurement
EFO:0004340	body mass index
EFO:0008579	risk-taking behaviour
EFO:0009695	household income

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D017034	Epilepsy, Frontal Lobe	C10.228.140.490.360.270; C10.228.140.490.493.188
C579932	Autosomal Dominant Nocturnal Frontal Lobe Epilepsy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	3
Ethinyl Estradiol	affects expression, decreases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects expression	1
trichostatin A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
ferrous chloride	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Cadmium	decreases expression	1
Calcitriol	increases expression, affects cotreatment	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Testosterone	affects cotreatment, increases expression, decreases expression	1
Thimerosal	decreases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00382707	Not specified	TERMINATED	Transcranial Magnetic Stimulation and Anti-epileptic Effect: Optimization and Evaluation With Electrophysiology.
NCT02441478	Not specified	COMPLETED	Co-operative Behavior and Decision-making in Frontal Lobe Epilepsy
NCT06466681	Not specified	RECRUITING	Changes in Attentional Control After a Focal Seizure.