PRM3

Summary

PRM3 (protamine 3, HGNC:13732) is a protein-coding gene on chromosome 16p13.13, encoding Protamine-3 (Q9NNZ6). Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis.

Predicted to enable DNA binding activity. Predicted to be involved in flagellated sperm motility. Predicted to be located in chromosome and nucleus. Predicted to be part of nucleosome. Predicted to be active in cytoplasm.

Source: NCBI Gene 58531 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_021247

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13732
Approved symbol	PRM3
Name	protamine 3
Location	16p13.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000178257
Ensembl biotype	protein_coding
Entrez	58531

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000327157

RefSeq mRNA: 1 — MANE Select: NM_021247 NM_021247

CCDS: CCDS76821

Canonical transcript exons

ENST00000327157 — 1 exons

Exon	Start	End
ENSE00001230959	11273199	11273629

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 96.05.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0665 / max 59.5432, expressed in 5 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156243	0.0572	5
207756	0.0061	3
156244	0.0032	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.05	gold quality
left testis	UBERON:0004533	94.20	gold quality
right testis	UBERON:0004534	93.88	gold quality
testis	UBERON:0000473	93.40	gold quality
sural nerve	UBERON:0015488	66.05	gold quality
cerebellar hemisphere	UBERON:0002245	58.50	gold quality
cerebellar cortex	UBERON:0002129	58.31	gold quality
right hemisphere of cerebellum	UBERON:0014890	58.11	gold quality
cerebellum	UBERON:0002037	57.72	gold quality
left uterine tube	UBERON:0001303	49.33	gold quality
bone marrow	UBERON:0002371	47.03	gold quality
right lung	UBERON:0002167	46.09	gold quality
stromal cell of endometrium	CL:0002255	43.50	gold quality
smooth muscle tissue	UBERON:0001135	43.10	gold quality
granulocyte	CL:0000094	42.74	silver quality
right uterine tube	UBERON:0001302	42.43	silver quality
duodenum	UBERON:0002114	42.37	gold quality
cortical plate	UBERON:0005343	41.42	gold quality
monocyte	CL:0000576	41.41	gold quality
rectum	UBERON:0001052	41.26	gold quality
endometrium	UBERON:0001295	41.19	gold quality
right ovary	UBERON:0002118	40.97	gold quality
myometrium	UBERON:0001296	40.95	gold quality
leukocyte	CL:0000738	40.94	gold quality
right frontal lobe	UBERON:0002810	40.05	gold quality
small intestine Peyer’s patch	UBERON:0003454	39.76	gold quality
fallopian tube	UBERON:0003889	39.60	gold quality
mucosa of stomach	UBERON:0001199	39.43	silver quality
bone marrow cell	CL:0002092	39.21	gold quality
Brodmann (1909) area 9	UBERON:0013540	38.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.34
E-ANND-3	no	0.32

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, DNMT1, ZHX2

Literature-anchored findings (GeneRIF, showing 1)

• Mutations in the protamine locus may be an infrequent cause of male infertility. (PMID:19602509)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prm3	ENSMUSG00000050058

Protein

Protein identifiers

Protamine-3 — Q9NNZ6 (reviewed: Q9NNZ6)

Alternative names: Sperm protamine P3

All UniProt accessions (1): Q9NNZ6

UniProt curated annotations — full annotation on UniProt →

Function. Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex.

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the protamine P3 family.

RefSeq proteins (1): NP_067070* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026077	PRMP3	Family

UniProt features (8 total): compositionally biased region 3, chain 1, region of interest 1, modified residue 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NNZ6-F1	58.43	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.

Post-translational modifications (1): 95

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 54 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_CHROMOSOME_ORGANIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_CHROMOSOME_CONDENSATION, YGACNNYACAR_UNKNOWN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_PROTEIN_DNA_COMPLEX, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_UP, ICHIBA_GRAFT_VERSUS_HOST_DISEASE_D7_DN, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, NRL_DN.V1_UP

GO Biological Process (4): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), chromosome condensation (GO:0030261), flagellated sperm motility (GO:0030317)

GO Molecular Function (1): DNA binding (GO:0003677)

GO Cellular Component (4): nucleosome (GO:0000786), nucleus (GO:0005634), cytoplasm (GO:0005737), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
chromosome organization	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
nucleic acid binding	1
chromatin	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRM3	PRM2	P04554	815
PRM3	TNP2	Q05952	808
PRM3	TNP1	P09430	681
PRM3	PRM1	P04553	541
PRM3	ROMO1	P60602	490
PRM3	BRDT	Q58F21	452
PRM3	TMEM225	Q6GV28	451
PRM3	HADHB	P55084	418
PRM3	TBXA2R	P21731	415
PRM3	IZUMO3	Q5VZ72	412
PRM3	TMEM225B	P0DP42	407
PRM3	SPACA3	Q8IXA5	404
PRM3	TSSK6	Q9BXA6	400
PRM3	SYCP1	Q15431	396
PRM3	SOX30	O94993	384

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PRM3	ARRB2	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A0U1RQG5, A1L429, A6NDE8, A6NER3, A6NGK3, E1AZ71, O08664, O60829, O75459, O76087, P0C2W7, P0CL80, P0CL81, P0CL82, P0DSO3, P0DTW1, P52651, P62521, P86478, P86479, P86480, P86481, P86496, Q13066, Q13069, Q13070, Q17QW4, Q28181, Q2T9P9, Q32PA2, Q4V321, Q4V326, Q5JQC4, Q5U2Y8, Q62100, Q63803, Q64256, Q6NT46, Q6X7S9, Q7Z2X7

Diamond homologs: Q32PA2, Q62100, Q64256, Q9NNZ6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

110 predictions. Top by Δscore:

Variant	Effect	Δscore
16:11273441:T:TA	donor_gain	0.8800
16:11273481:CA:C	donor_gain	0.8600
16:11273470:AT:A	donor_gain	0.7800
16:11273348:T:TA	donor_gain	0.7500
16:11273480:A:AC	donor_gain	0.7500
16:11273481:C:CC	donor_gain	0.7500
16:11273471:T:TA	donor_gain	0.7300
16:11273345:T:TA	donor_gain	0.6800
16:11273264:T:TA	donor_gain	0.6500
16:11273448:CCG:C	acceptor_gain	0.6500
16:11273449:CGC:C	acceptor_gain	0.6500
16:11273606:G:A	donor_gain	0.6500
16:11273447:CCCG:C	acceptor_gain	0.6400
16:11273448:CCGC:C	acceptor_gain	0.6400
16:11273380:G:A	donor_gain	0.6000
16:11273563:G:A	donor_gain	0.5900
16:11273451:C:CC	acceptor_gain	0.5800
16:11273333:T:TA	donor_gain	0.5700
16:11273449:CG:C	acceptor_gain	0.5600
16:11273602:CG:C	donor_gain	0.5400
16:11273449:C:T	acceptor_gain	0.5300
16:11273603:G:C	donor_gain	0.5200
16:11273449:CGCT:C	acceptor_loss	0.4900
16:11273450:GCTG:G	acceptor_loss	0.4900
16:11273451:CTGAT:C	acceptor_loss	0.4900
16:11273452:T:C	acceptor_loss	0.4900
16:11273481:CACAG:C	donor_gain	0.4900
16:11273446:G:A	donor_gain	0.4800
16:11273454:A:AC	acceptor_gain	0.4800
16:11273225:T:TA	donor_gain	0.4600

AlphaMissense

675 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:11273498:T:A	K33I	0.918
16:11273476:A:C	S40R	0.910
16:11273476:A:T	S40R	0.910
16:11273478:T:G	S40R	0.910
16:11273471:T:A	D42V	0.884
16:11273497:T:A	K33N	0.874
16:11273497:T:G	K33N	0.874
16:11273484:A:G	C38R	0.861
16:11273464:G:C	F44L	0.846
16:11273464:G:T	F44L	0.846
16:11273466:A:G	F44L	0.846
16:11273482:A:C	C38W	0.835
16:11273492:A:G	L35P	0.833
16:11273483:C:T	C38Y	0.822
16:11273472:C:G	D42H	0.818
16:11273471:T:G	D42A	0.808
16:11273483:C:G	C38S	0.799
16:11273484:A:T	C38S	0.799
16:11273375:A:G	L74P	0.797
16:11273583:A:G	C5R	0.786
16:11273581:A:C	C5W	0.779
16:11273372:A:G	L75P	0.771
16:11273498:T:G	K33T	0.766
16:11273459:A:G	L46S	0.760
16:11273582:C:G	C5S	0.758
16:11273583:A:T	C5S	0.758
16:11273492:A:T	L35H	0.757
16:11273375:A:T	L74Q	0.748
16:11273465:A:G	F44S	0.740
16:11273500:C:A	M32I	0.737

dbSNP variants (sampled 300 via entrez): RS1000007335 (16:11273201 C>A), RS1001674418 (16:11274026 C>T), RS1002046271 (16:11274712 G>T), RS1002111087 (16:11273880 A>G), RS1002416832 (16:11274926 C>G), RS1003890829 (16:11274886 T>C), RS1004532263 (16:11274706 T>A), RS1005190632 (16:11273950 G>A), RS1005468394 (16:11274168 T>C), RS1006370777 (16:11272733 T>C), RS1007867149 (16:11274304 C>T), RS1008097954 (16:11275083 C>T), RS1008374860 (16:11274429 C>A,T), RS1009984706 (16:11274081 C>A), RS1010415324 (16:11274280 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST000258_5	Type 1 diabetes	3.000000e-06
GCST001341_12	Multiple sclerosis	6.000000e-07
GCST001958_14	Bulimia nervosa	2.000000e-06
GCST003268_27	Psoriasis vulgaris	3.000000e-07
GCST004131_115	Inflammatory bowel disease	1.000000e-06
GCST004132_39	Crohn’s disease	1.000000e-07
GCST005527_32	Psoriasis	5.000000e-08
GCST009798_15	Asthma	2.000000e-33

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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