PRM1

Summary

PRM1 (protamine 1, HGNC:9447) is a protein-coding gene on chromosome 16p13.13, encoding Sperm protamine P1 (P04553). 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 chromosome organization and spermatogenesis. Predicted to act upstream of or within nucleus organization and spermatid development. Located in cytosol and nucleoplasm.

Source: NCBI Gene 5619 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_002761

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9447
Approved symbol	PRM1
Name	protamine 1
Location	16p13.13
Locus type	gene with protein product
Status	Approved
Aliases	CT94.1
Ensembl gene	ENSG00000175646
Ensembl biotype	protein_coding
OMIM	182880
Entrez	5619

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000312511

RefSeq mRNA: 1 — MANE Select: NM_002761 NM_002761

CCDS: CCDS10547

Canonical transcript exons

ENST00000312511 — 2 exons

Exon	Start	End
ENSE00001203456	11280841	11281035
ENSE00001203463	11281127	11281330

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 99.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 24.7274 / max 22407.1955, expressed in 18 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156261	24.4553	12
156262	0.0540	3
156260	0.0413	3
156258	0.0267	4
156263	0.0265	3
156259	0.0260	4
156255	0.0259	3
156257	0.0246	3
156251	0.0226	3
156254	0.0106	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.96	gold quality
right testis	UBERON:0004534	99.94	gold quality
adult organism	UBERON:0007023	99.94	gold quality
male germ cell	CL:0000015	99.89	gold quality
left testis	UBERON:0004533	99.41	gold quality
testis	UBERON:0000473	96.68	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.01	gold quality
caput epididymis	UBERON:0004358	84.44	gold quality
cauda epididymis	UBERON:0004360	84.19	gold quality
metanephros cortex	UBERON:0010533	78.03	gold quality
right coronary artery	UBERON:0001625	77.52	gold quality
corpus epididymis	UBERON:0004359	76.63	gold quality
ectocervix	UBERON:0012249	74.76	gold quality
endocervix	UBERON:0000458	74.63	gold quality
right uterine tube	UBERON:0001302	73.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	71.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.27	gold quality
vastus lateralis	UBERON:0001379	68.93	gold quality
adenohypophysis	UBERON:0002196	68.87	gold quality
right lobe of liver	UBERON:0001114	68.54	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.47	gold quality
right lung	UBERON:0002167	68.08	gold quality
diaphragm	UBERON:0001103	67.97	gold quality
quadriceps femoris	UBERON:0001377	66.97	gold quality
cerebellar vermis	UBERON:0004720	65.08	gold quality
coronary artery	UBERON:0001621	64.32	gold quality
metanephros	UBERON:0000081	63.60	gold quality
left coronary artery	UBERON:0001626	63.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	63.32	gold quality
lower esophagus mucosa	UBERON:0035834	63.16	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	143223.49
E-GEOD-124263	yes	60740.57
E-HCAD-38	yes	57315.01
E-ANND-3	no	0.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MBD2, NR6A1, SP1, TET1, WT1, YBX2, YBX3

miRNA regulators (miRDB)

24 targeting PRM1, 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-4692	100.00	67.32	2066
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-3688-5P	99.12	69.67	1091
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-4764-5P	98.88	65.53	894
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-4722-5P	98.46	66.34	1611
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-3165	96.18	66.22	473
HSA-MIR-1256	95.44	66.33	784

Literature-anchored findings (GeneRIF, showing 37)

• single nucleotide polymorphisms in this gene in fertile and infertile males (PMID:12569175)
• A number of SNPs are present in the testis-specific nuclear protein genes. (PMID:16989827)
• The P1/P2 ratio has a significant relationship to sperm fertilization ability. (PMID:17011555)
• Mutations in PRM1 gene were identified in males with oligozoospermia. (PMID:17494104)
• The PRM1 contributes not only to successful fertilization, but may has an important impact in development of preimplantation embryos. (PMID:18292840)
• A reduction in contents of PRM1 transcript in spermatozoa may be linked with asthenozoospermia. (PMID:18292846)
• Decreased pre-P2/P2 and P1/P2 ratios are related to a poor pregnancy outcome, but not with the proportion of embryos obtained after assisted reproduction. (PMID:18314125)
• Low-frequency protamine 1 gene transversions c.102G->T and c.-107G->C do not correlate with male infertility. (PMID:18381856)
• Histones localized to the posterior ring region (i.e. the sperm nuclear annulus), whereas PRM1 and PRM2 appeared to be dispersed throughout the entire nucleus. (PMID:18478156)
• The CCNA1, CCNB1, CCNB2, PRM1, and PRM2 messenger RNA transcript ratios were significantly decreased in patients with spermatogenic disorders. Transcript ratios in patients with successful sperm retrieval were higher than with failed sperm retrieval. (PMID:18692784)
• Mutations in the protamine locus may be an infrequent cause of male infertility. (PMID:19602509)
• identified and we report for the first time five novel rare haplotypes encompassing the protamine 1 and 2 genes (PMID:21029114)
• Data suggest that Casp4, Casp 6 and TNFSF10 are differentially expressed in potentially fertile and subfertile men and represent useful biomarkers for predicting male fertility in combination with P1 and P2. (PMID:21317160)
• Single nuclotide polymorphisms in PRM1 gene is associated with male infertility. (PMID:22104739)
• significant correlation has been found between protamine 1 and 2 transcripts/proteins and: sperm concentration, progressive sperm motility, sperm fertilization ability as well as embryo quality (PMID:22472940)
• The SNP of PRM1-190C- > A might be associated with teratozoospermia-induced male infertility in the Han Chinese. (PMID:22574365)
• genetic association study in Han population in China: Data suggest that an SNP in PRM1 (rs35576928; T allele; 34R>S) is associated with severe oligozoospermia and can play a protective role against this disease. (PMID:23079002)
• the quantity of PRM1, PRM2, and TNP2 transcripts and the PRM1/PRM2 mRNA ratio affect spermiogenesis, sperm morphology (PMID:25536093)
• The expressed human protamine1 in two fast-growing cell systems, E. coli and HeLa cells. The protamine 1 expression significantly attenuated cell proliferation when compared with control cells. (PMID:25649960)
• Studies indicate that ribonucleotide reductase M1 polypeptide (RRM1) expression is associated with the response rate and overall survival rate of advanced NSCLC patients treated with gemcitabine-based chemotherapy. (PMID:26092210)
• The KDM3A to PRM1 mRNA expression ratio can be used as a reliable marker of successful testicular sperm extraction in men with obstructive and non-obstructive azoospermia with 95% sensitivity. (PMID:27027467)
• Single nucleotide polymorphisms in the human PRM1 gene are associated with a genetic risk factor for idiopathic oligozoospermia. (PMID:27216534)
• Bacterial infections have significant negative effects on sperm chromatin condensation and protamine P1/P2 ratio. (PMID:28736810)
• Protamine-1 and protamine-2 mRNA levels as well as the protamine mRNA ratio and all routine semen parameters revealed significant differences between recurrent miscarriage couples and healthy volunteers. Values of protamine-1 and protamine-2 mRNAs were significantly higher and the protamine mRNA ratio was significantly lower in couples with recurrent miscarriage. (PMID:28854581)
• The expression level of PRM1 was significantly higher in colon cancer tissues and the staining degree of PRM1 in poorly-differentiated was stronger. (PMID:29140788)
• examinded the association between protamine gene alleles (PRM1 c.-190C>A, PRM1 c.197G>T, and PRM2 c.248C>T), and YBX2 (c.187T>C and c.1095 + 16A>G) and male infertility. We found that the AA and CA genotypes of the PRM1 c.-190C>A polymorphism had a significant association with infertility (p < 0.001) and the AA genotype was also highly significantly associated with high sperm DNA damage (p < 0.001). (PMID:29227750)
• Polymorphisms of sperm protamine genes and CMA3 staining in infertile men with varicocele. (PMID:30482464)
• Study revealed that CA and AA genotypes in PRM1 gene were associated significantly with low sperm concentration and decreased sperm motility. Cases carrying A allele had a 6.05-fold increased risk for idiopathic infertility than cases carrying the C allele in a sample of Egyptian men. (PMID:31286559)
• Evaluation of the association between polymorphisms of PRM1 and PRM2 and the risk of male infertility: a systematic review, meta-analysis, and meta-regression. (PMID:33057064)
• Identification of the PRM1 gene mutations in oligoasthenoteratozoospermic men. (PMID:33118225)
• Protamine 1/Protamine 2 mRNA ratio in nonobstructive azoospermic patients. (PMID:33427330)
• Tobacco smoking and its impact on the expression level of sperm nuclear protein genes: H2BFWT, TNP1, TNP2, PRM1 and PRM2. (PMID:33440036)
• Impact of tobacco smoking in association with H2BFWT, PRM1 and PRM2 genes variants on male infertility. (PMID:36217675)
• Protamine 1 as a secreted colorectal cancer-specific antigen facilitating G1/S phase transition under nutrient stress conditions. (PMID:36593375)
• Reversible promoter demethylation of PDGFD confers gemcitabine resistance through STAT3 activation and RRM1 upregulation. (PMID:37321532)
• Proteomic analysis of human sperm reveals changes in protamine 1 phosphorylation in men with infertility. (PMID:38065301)
• Molecular and Functional Characterization of Human Sex-Determining Region on the Y Chromosome Variants Using Protamine 1 Promoter. (PMID:38170186)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Sperm protamine P1 — P04553 (reviewed: P04553)

Alternative names: Cysteine-rich protamine

All UniProt accessions (2): P04553, Q3MN80

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.

Subunit / interactions. Cross-linked by interchain disulfide bonds around the DNA-helix.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Testis.

Post-translational modifications. Phosphorylated by SRPK1.

Similarity. Belongs to the protamine P1 family.

RefSeq proteins (1): NP_002752* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000221	Protamine_P1	Family

Pfam: PF00260

UniProt features (8 total): disulfide bond 3, compositionally biased region 2, initiator methionine 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04553-F1	54.01	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.

Disulfide bonds (3): 6, 39, 40–48

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9821993	Replacement of protamines by nucleosomes in the male pronucleus

MSigDB gene sets: 70 (showing top): GOBP_CHROMOSOME_ORGANIZATION, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_MALE_GAMETE_GENERATION, GOBP_CHROMOSOME_CONDENSATION, SRF_Q5_01, SRF_01, SRF_C, GOBP_NUCLEUS_ORGANIZATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GNF2_CCNA1, GOBP_SPERMATID_NUCLEUS_DIFFERENTIATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, KANG_IMMORTALIZED_BY_TERT_DN, YY1_01

GO Biological Process (5): spermatogenesis (GO:0007283), chromosome condensation (GO:0030261), sperm DNA condensation (GO:0035092), chromosome organization (GO:0051276), cell differentiation (GO:0030154)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): nucleosome (GO:0000786), nucleoplasm (GO:0005654), cytosol (GO:0005829), nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
developmental process involved in reproduction	1
male gamete generation	1
chromosome organization	1
chromatin organization	1
spermatid nucleus differentiation	1
organelle organization	1
cellular developmental process	1
nucleic acid binding	1
binding	1
chromatin	1
protein-DNA complex	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRM1	PRM2	P04554	980
PRM1	TNP1	P09430	959
PRM1	TNP2	Q05952	948
PRM1	NUPR1	O60356	869
PRM1	KDM3A	Q9Y4C1	866
PRM1	KLHL10	Q6JEL2	846
PRM1	TFAP4	Q01664	710
PRM1	STRBP	Q96SI9	563
PRM1	ACR	P10323	543
PRM1	PRM3	Q9NNZ6	541
PRM1	DAZL	Q92904	475
PRM1	SYCP3	Q8IZU3	473
PRM1	SMCP	P49901	447
PRM1	STRA8	Q7Z7C7	433
PRM1	YBX2	Q9Y2T7	419

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PRM1	CLK2	psi-mi:“MI:0915”(physical association)	0.560
CLK2	PRM1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (2): CLK2 (Two-hybrid), PRM1 (Biochemical Activity)

ESM2 similar proteins: O18746, O18747, O18748, P02318, P04101, P04553, P10119, P15341, P15342, P15343, P24713, P24714, P35302, P35303, P35304, P35306, P35308, P35309, P35310, P35312, P42148, P67833, P68038, Q28337, Q66QC7, Q7JHM8, Q7JHM9, Q7JIX8, Q7JIX9, Q7JIY0, Q8MHZ2, Q8MJS8, Q8MJT0, Q8WNY7, Q8WNZ0, Q8WNZ1, Q8WNZ2, Q8WNZ3, Q8WNZ4, Q8WNZ5

Diamond homologs: P04553, P35306, P35309, Q9GKQ5, P35308, Q8WNZ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

74 predictions. Top by Δscore:

Variant	Effect	Δscore
16:11281122:CTTA:C	donor_gain	1.0000
16:11281123:TTA:T	donor_loss	1.0000
16:11281124:TA:T	donor_loss	1.0000
16:11281125:A:AC	donor_gain	1.0000
16:11281125:A:C	donor_loss	1.0000
16:11281125:ACT:A	donor_gain	1.0000
16:11281126:C:CT	donor_gain	1.0000
16:11281126:CT:C	donor_gain	1.0000
16:11281126:CTC:C	donor_gain	1.0000
16:11281126:CTCA:C	donor_gain	1.0000
16:11281126:CTCAT:C	donor_gain	1.0000
16:11281136:T:A	donor_gain	1.0000
16:11281139:T:TA	donor_gain	1.0000
16:11281121:A:AC	donor_gain	0.9900
16:11281122:C:CC	donor_gain	0.9900
16:11281129:A:AC	donor_gain	0.9900
16:11281034:CC:C	acceptor_gain	0.9800
16:11281035:CC:C	acceptor_gain	0.9800
16:11281129:ATGG:A	donor_gain	0.9800
16:11281130:T:C	donor_gain	0.9800
16:11281036:C:CC	acceptor_gain	0.9700
16:11281034:CCCT:C	acceptor_loss	0.9600
16:11281036:C:CA	acceptor_loss	0.9600
16:11281037:T:A	acceptor_loss	0.9600
16:11281032:CACC:C	acceptor_gain	0.9500
16:11281123:T:C	donor_gain	0.9500
16:11281160:T:TA	donor_gain	0.9500
16:11281031:GCACC:G	acceptor_gain	0.9400
16:11281032:CACCC:C	acceptor_gain	0.9400
16:11281036:C:T	acceptor_gain	0.9400

AlphaMissense

324 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:11281212:G:C	S9R	0.771
16:11281212:G:T	S9R	0.771
16:11281214:T:G	S9R	0.771
16:11281206:G:C	S11R	0.765
16:11281206:G:T	S11R	0.765
16:11281208:T:G	S11R	0.765
16:11281221:G:C	C6W	0.737
16:11281200:G:C	S13R	0.727
16:11281200:G:T	S13R	0.727
16:11281202:T:G	S13R	0.727
16:11281218:A:C	C7W	0.723
16:11281223:A:G	C6R	0.712
16:11281138:C:A	R34M	0.710
16:11281182:T:A	R19S	0.690
16:11281182:T:G	R19S	0.690
16:11281231:C:A	R3M	0.670
16:11281213:C:A	S9I	0.661
16:11281201:C:A	S13I	0.654
16:11281159:C:A	R27M	0.652
16:11281020:C:A	R43M	0.650
16:11281190:G:T	R17S	0.643
16:11281207:C:A	S11I	0.643
16:11281220:A:G	C7R	0.635
16:11281197:T:A	R14S	0.630
16:11281197:T:G	R14S	0.630
16:11281137:C:A	R34S	0.629
16:11281137:C:G	R34S	0.629
16:11281219:C:G	C7S	0.609
16:11281220:A:T	C7S	0.609
16:11281035:C:A	R38M	0.606

dbSNP variants (sampled 300 via entrez): RS1000597076 (16:11281510 G>A), RS1001032733 (16:11281347 C>A,G,T), RS1001106297 (16:11281200 G>A), RS1001366235 (16:11282222 C>A,G), RS1002296372 (16:11280709 A>C,G), RS1003166517 (16:11282983 A>G,T), RS1003505499 (16:11283214 A>T), RS1003863607 (16:11282969 A>G), RS1004062961 (16:11283270 G>A), RS1005276043 (16:11282938 T>C), RS1005535156 (16:11281967 A>C,G), RS1006477149 (16:11280866 C>A,T), RS1006935414 (16:11280581 G>A,C,T), RS1007689638 (16:11281554 A>G), RS1007747410 (16:11281752 G>C)

Disease associations

OMIM: gene MIM:182880 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST001341_12	Multiple sclerosis	6.000000e-07
GCST001762_433	Obesity-related traits	8.000000e-07
GCST001762_437	Obesity-related traits	8.000000e-07
GCST001762_618	Obesity-related traits	1.000000e-06
GCST001958_14	Bulimia nervosa	2.000000e-06
GCST004131_115	Inflammatory bowel disease	1.000000e-06
GCST004132_39	Crohn’s disease	1.000000e-07
GCST005528_30	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	2.000000e-07
GCST005581_11	Primary biliary cirrhosis	7.000000e-15
GCST005581_12	Primary biliary cirrhosis	2.000000e-13
GCST005581_13	Primary biliary cirrhosis	3.000000e-08
GCST005581_35	Primary biliary cirrhosis	6.000000e-20
GCST005581_36	Primary biliary cirrhosis	2.000000e-23
GCST007120_2	Multiple sclerosis and type 2 diabetes (pleiotropy)	8.000000e-06
GCST009597_287	Multiple sclerosis	1.000000e-23
GCST009798_15	Asthma	2.000000e-33

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005106	body composition measurement

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
bisphenol A	decreases methylation	1
Tetrachlorodibenzodioxin	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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