PRR14

Summary

PRR14 (proline rich 14, HGNC:28458) is a protein-coding gene on chromosome 16p11.2, encoding Proline-rich protein 14 (Q9BWN1). Functions in tethering peripheral heterochromatin to the nuclear lamina during interphase, possibly through the interaction with heterochromatin protein CBX5/HP1 alpha.

The protein encoded by this gene tethers heterochromatin to the nuclear laminar scaffold by binding heterochromatin protein 1 (HP1) and the nuclear lamina. The tether is broken during mitosis and reforms quickly after mitosis, with the encoded protein first binding HP1 and then attaching to the nuclear lamina. This protein also has been shown to promote MyoD activity and skeletal myogenesis. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 78994 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 99 total
• MANE Select transcript: NM_024031

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28458
Approved symbol	PRR14
Name	proline rich 14
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	MGC3121
Ensembl gene	ENSG00000156858
Ensembl biotype	protein_coding
OMIM	617423
Entrez	78994

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 retained_intron, 8 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000287463, ENST00000300835, ENST00000542965, ENST00000563211, ENST00000563399, ENST00000564946, ENST00000565410, ENST00000565977, ENST00000567322, ENST00000567989, ENST00000568754, ENST00000569864, ENST00000571654, ENST00000889797, ENST00000889798, ENST00000935503, ENST00000951012

RefSeq mRNA: 2 — MANE Select: NM_024031 NM_001320464, NM_024031

CCDS: CCDS10687

Canonical transcript exons

ENST00000300835 — 12 exons

Exon	Start	End
ENSE00001028730	30652914	30653103
ENSE00001362770	30650960	30651127
ENSE00003510017	30656032	30656413
ENSE00003510465	30655502	30655593
ENSE00003547187	30655351	30655420
ENSE00003555429	30653365	30653408
ENSE00003555456	30655868	30655939
ENSE00003568423	30651796	30651964
ENSE00003595554	30654629	30655214
ENSE00003637829	30654230	30654339
ENSE00003670933	30651596	30651668
ENSE00003784996	30652721	30652842

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 96.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7926 / max 134.3853, expressed in 1815 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153673	8.5504	1773
153671	5.4855	1637
153675	1.7531	914
153672	1.6345	1118
153669	1.0317	353
153670	0.9492	448
153674	0.3882	181

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.79	gold quality
cerebellar cortex	UBERON:0002129	95.58	gold quality
cerebellar hemisphere	UBERON:0002245	95.58	gold quality
lower esophagus mucosa	UBERON:0035834	95.34	gold quality
cerebellum	UBERON:0002037	95.13	gold quality
ganglionic eminence	UBERON:0004023	94.86	gold quality
mucosa of stomach	UBERON:0001199	94.53	gold quality
left uterine tube	UBERON:0001303	94.29	gold quality
spleen	UBERON:0002106	94.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.23	gold quality
lower esophagus	UBERON:0013473	94.14	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.14	gold quality
body of stomach	UBERON:0001161	94.01	gold quality
mucosa of transverse colon	UBERON:0004991	93.99	gold quality
body of uterus	UBERON:0009853	93.98	gold quality
fundus of stomach	UBERON:0001160	93.74	gold quality
metanephros cortex	UBERON:0010533	93.66	gold quality
thymus	UBERON:0002370	93.62	gold quality
right ovary	UBERON:0002118	93.46	gold quality
endocervix	UBERON:0000458	93.31	gold quality
right coronary artery	UBERON:0001625	93.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.26	gold quality
adenohypophysis	UBERON:0002196	93.16	gold quality
olfactory bulb	UBERON:0002264	93.06	gold quality
cortical plate	UBERON:0005343	93.02	gold quality
oocyte	CL:0000023	93.01	gold quality
right lobe of thyroid gland	UBERON:0001119	92.94	gold quality
ventricular zone	UBERON:0003053	92.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.02

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

12 targeting PRR14, 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-6744-5P	99.93	66.82	748
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-512-5P	97.47	66.48	591
HSA-MIR-6748-3P	97.20	65.66	836
HSA-MIR-3976	96.67	67.79	1187
HSA-MIR-28-3P	96.42	67.18	579

Literature-anchored findings (GeneRIF, showing 5)

• The stepwise reassembly of PRR14 suggests a function in the selection of heterochromatin protein 1-bound heterochromatin for reattachment to the nuclear lamina as cells exit mitosis. (PMID:24209742)
• The results altogether support a model in which PRR14 promotes skeletal myogenesis via supporting nuclear lamina structure and enhancing the activity of MyoD. (PMID:25906157)
• We show that increased PRR14 expression promoted and reduced PRR14 expression impeded lung cancer cell proliferation. Interestingly, PRR14 cells were markedly enlarged in size and exhibited an elevated activity of the PI3-kinase/Akt/mTOR pathway (PMID:27041574)
• PRR14 may promote the progression and metastasis of colon cancer, and may be a novel prognostic and therapeutic marker for the disease. (PMID:31596887)
• The PRR14 heterochromatin tether encodes modular domains that mediate and regulate nuclear lamina targeting. (PMID:32317397)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	prr14	ENSDARG00000089232
mus_musculus	Prr14	ENSMUSG00000030822
rattus_norvegicus	Prr14	ENSRNOG00000018518

Paralogs (1): PRR14L (ENSG00000183530)

Protein

Protein identifiers

Proline-rich protein 14 — Q9BWN1 (reviewed: Q9BWN1)

All UniProt accessions (3): Q9BWN1, H3BND2, H3BQL8

UniProt curated annotations — full annotation on UniProt →

Function. Functions in tethering peripheral heterochromatin to the nuclear lamina during interphase, possibly through the interaction with heterochromatin protein CBX5/HP1 alpha. Might play a role in reattaching heterochromatin to the nuclear lamina at mitotic exit. Promotes myoblast differentiation during skeletal myogenesis, possibly by stimulating transcription factor MyoD activity via binding to CBX5/HP1 alpha. Involved in the positive regulation of the PI3K-Akt-mTOR signaling pathway and in promoting cell proliferation, possibly via binding to GRB2.

Subunit / interactions. Interacts (via proline-rich region) with GRB2 (via SH3 domain 2). Interacts (via N-terminus) with CBX5.

Subcellular location. Chromosome. Nucleus. Nucleus lamina. Nucleoplasm.

RefSeq proteins (2): NP_001307393, NP_076936* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026320	PRR14	Family
IPR028149	Tantalus-like	Domain

Pfam: PF15386

UniProt features (21 total): region of interest 9, compositionally biased region 4, mutagenesis site 4, modified residue 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWN1-F1	55.62	0.02

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 (2): 1, 277

Mutagenesis-validated functional residues (4):

Position	Phenotype
54–55	loss of heterochromatin association. loss of interaction with cbx5.
54–55	loss of heterochromatin association during interphase and loss of chromatin association during anaphase.
101	increased binding to grb2 and enhanced cell proliferation.
566	increased binding to grb2 and enhanced cell proliferation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 125 (showing top): GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, chr16p11, HNF4_DR1_Q3, HNF4_01, ROSS_AML_WITH_PML_RARA_FUSION, CCCNNGGGAR_OLF1_01, GOCC_NUCLEAR_ENVELOPE, GOCC_NUCLEAR_PERIPHERY, GSE13887_HEALTHY_VS_LUPUS_RESTING_CD4_TCELL_UP, GOCC_ORGANELLE_ENVELOPE, WAKABAYASHI_ADIPOGENESIS_PPARG_BOUND_8D, GOCC_NUCLEAR_LAMINA, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_UP, ASH1L_TARGET_GENES, CIITA_TARGET_GENES

GO Biological Process (1): muscle organ development (GO:0007517)

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

GO Cellular Component (4): nuclear lamina (GO:0005652), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
animal organ development	1
muscle structure development	1
binding	1
nuclear envelope	1
nuclear periphery	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRR14	LBR	Q14739	688
PRR14	AHCTF1	Q8WYP5	520
PRR14	PRSS53	Q2L4Q9	503
PRR14	CBX5	P45973	499
PRR14	RRP1B	Q14684	454
PRR14	WIZ	O95785	447
PRR14	FBXL19	Q6PCT2	441
PRR14	ZNF774	Q6NX45	416
PRR14	EMD	P50402	414
PRR14	BANF2	Q9H503	403
PRR14	TMEM8B	A6NDV4	391
PRR14	MITD1	Q8WV92	383
PRR14	CDCA7L	Q96GN5	380
PRR14	SMCHD1	A6NHR9	378
PRR14	CAMKV	Q8NCB2	377

IntAct

49 interactions, top by confidence:

A	B	Type	Score
CBX5	PRR14	psi-mi:“MI:0915”(physical association)	0.920
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2CB	STRN	psi-mi:“MI:0914”(association)	0.790
PRR14	PPP2R1A	psi-mi:“MI:0914”(association)	0.790
CBX3	PRR14	psi-mi:“MI:0915”(physical association)	0.740
PPP2CB	CEP43	psi-mi:“MI:0914”(association)	0.730
PPP2R1A	PPFIA3	psi-mi:“MI:0914”(association)	0.670
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PPP2R1A	ENSA	psi-mi:“MI:0914”(association)	0.530
CBX1	ZNF292	psi-mi:“MI:0914”(association)	0.530
CRK	PRR14	psi-mi:“MI:0407”(direct interaction)	0.440
SH3GL2	PRR14	psi-mi:“MI:0915”(physical association)	0.370
Ppp2r1a	CCHCR1	psi-mi:“MI:0914”(association)	0.350
Cbx1		psi-mi:“MI:0914”(association)	0.350
PPP2R1A	INTS2	psi-mi:“MI:0914”(association)	0.350
C6orf141	KRBA1	psi-mi:“MI:0914”(association)	0.350
CELA1	KRBA1	psi-mi:“MI:0914”(association)	0.350
CTDSP2	TBC1D4	psi-mi:“MI:0914”(association)	0.350
LYPD4	DPYSL4	psi-mi:“MI:0914”(association)	0.350
CBX5	ZNF568	psi-mi:“MI:0914”(association)	0.350
CBX1	EXOC5	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT2	IFT56	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
PNMA2	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): PRR14 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), PRR14 (Two-hybrid), PRR14 (Reconstituted Complex), PRR14 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), PRR14 (Affinity Capture-MS), PPP2R5D (Affinity Capture-MS), PPP2R5A (Affinity Capture-MS), PPP2R5E (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVZ6, A0JNN6, A2A9F4, A6NDZ8, A6NE82, A6NJ08, A6NJB7, A7MB40, A8MQ03, D2HS03, O43151, O93343, O94850, O95886, P01099, P97838, Q00587, Q0VBZ8, Q2KJ10, Q2M2S6, Q3KP66, Q58CU6, Q5NCP0, Q5RBE4, Q64322, Q68DV7, Q6AY88, Q6PFD5, Q7TN12, Q80V38, Q86YN6, Q86YV5, Q8BFY7, Q8BG87, Q8NAX2, Q8NC06, Q8NHZ7, Q8TEF2, Q91XA5, Q96EL1

Diamond homologs: Q0VBZ8, Q5THK1, Q7TPN9, Q9BWN1

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	15.6×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	83
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1266 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30652717:CCA:C	acceptor_loss	1.0000
16:30652718:CAGGT:C	acceptor_loss	1.0000
16:30652719:A:AG	acceptor_gain	1.0000
16:30652719:AGGTC:A	acceptor_loss	1.0000
16:30652720:G:GT	acceptor_gain	1.0000
16:30652720:GGT:G	acceptor_gain	1.0000
16:30652720:GGTCC:G	acceptor_gain	1.0000
16:30652826:T:TA	donor_gain	1.0000
16:30652827:G:GA	donor_gain	1.0000
16:30653071:G:GT	donor_gain	1.0000
16:30653103:GG:G	donor_loss	1.0000
16:30653105:T:G	donor_loss	1.0000
16:30654223:A:AG	acceptor_gain	1.0000
16:30654228:A:AG	acceptor_gain	1.0000
16:30654229:G:GG	acceptor_gain	1.0000
16:30654229:GA:G	acceptor_gain	1.0000
16:30654229:GAGCT:G	acceptor_gain	1.0000
16:30655492:A:AG	acceptor_gain	1.0000
16:30655493:T:G	acceptor_gain	1.0000
16:30655499:CA:C	acceptor_loss	1.0000
16:30655500:A:AC	acceptor_loss	1.0000
16:30655500:A:AG	acceptor_gain	1.0000
16:30655501:G:GA	acceptor_gain	1.0000
16:30655501:GA:G	acceptor_gain	1.0000
16:30655501:GAC:G	acceptor_gain	1.0000
16:30655501:GACC:G	acceptor_gain	1.0000
16:30655501:GACCA:G	acceptor_gain	1.0000
16:30655591:CAGGT:C	donor_loss	1.0000
16:30655594:G:GA	donor_loss	1.0000
16:30655595:T:A	donor_loss	1.0000

AlphaMissense

3692 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30655884:T:C	F475L	0.998
16:30655886:C:A	F475L	0.998
16:30655886:C:G	F475L	0.998
16:30656120:T:C	F523L	0.998
16:30656121:T:C	F523S	0.998
16:30656122:T:A	F523L	0.998
16:30656122:T:G	F523L	0.998
16:30654749:T:C	F260S	0.997
16:30655885:T:C	F475S	0.997
16:30654748:T:C	F260L	0.996
16:30654750:T:A	F260L	0.996
16:30654750:T:G	F260L	0.996
16:30655900:T:G	I480S	0.996
16:30656048:T:C	F499L	0.996
16:30656050:T:A	F499L	0.996
16:30656050:T:G	F499L	0.996
16:30655900:T:C	I480T	0.995
16:30656121:T:G	F523C	0.995
16:30654738:G:C	K256N	0.994
16:30654738:G:T	K256N	0.994
16:30656046:T:A	I498N	0.994
16:30656049:T:C	F499S	0.994
16:30654728:T:A	V253D	0.993
16:30654749:T:G	F260C	0.993
16:30655910:C:A	N483K	0.993
16:30655910:C:G	N483K	0.993
16:30654740:T:C	L257P	0.992
16:30654761:T:C	F264S	0.992
16:30655885:T:G	F475C	0.992
16:30655900:T:A	I480N	0.992

dbSNP variants (sampled 300 via entrez): RS1000078125 (16:30648909 G>T), RS1000854182 (16:30651279 G>T), RS1001462760 (16:30652361 G>A), RS1003126405 (16:30653758 C>T), RS1003240061 (16:30648928 T>C), RS1003283848 (16:30653922 C>T), RS1003610894 (16:30654376 G>A), RS1003794969 (16:30653962 A>C,G), RS1003847031 (16:30653649 T>C), RS1004314950 (16:30654128 C>A,T), RS1005072531 (16:30649341 A>G,T), RS1005716335 (16:30650978 G>A,T), RS1005811420 (16:30656846 G>A), RS1005862870 (16:30656572 G>A,T), RS1005967940 (16:30650349 A>C)

Disease associations

OMIM: gene MIM:617423 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST004028_8	Immunoglobulin light chain (AL) amyloidosis	4.000000e-06
GCST006940_59	Neurociticism	3.000000e-10
GCST006941_13	Irritable mood	6.000000e-09
GCST012396_10	Multiple myeloma	6.000000e-06
GCST90002388_167	Lymphocyte count	1.000000e-16

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0009594	irritability measurement
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Zoledronic Acid	increases expression	1
Arsenic	increases expression, increases abundance	1
Benzo(a)pyrene	decreases methylation	1
Coumestrol	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Thiram	increases expression	1
Urethane	increases expression	1
Valproic Acid	affects expression	1
Vitamin E	increases expression	1
Cyclosporine	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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