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 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 28 total
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.14 (intermediate), LOEUF 1.91 (unconstrained)
• 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

MANE Select: ENST00000327157

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.

Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, testis, sural nerve, cerebellar hemisphere, cerebellar cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRM3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	2.2e-03	-0.12	16:11273620:G:A

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

showing 100 of 129 tissues 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
small intestine	UBERON:0002108	38.70	gold quality
hypothalamus	UBERON:0001898	38.65	gold quality
brain	UBERON:0000955	38.50	gold quality
ascending aorta	UBERON:0001496	38.44	gold quality
lymph node	UBERON:0000029	38.31	gold quality
upper lobe of left lung	UBERON:0008952	38.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	38.10	gold quality
tonsil	UBERON:0002372	38.04	silver quality
left coronary artery	UBERON:0001626	37.97	gold quality
thoracic aorta	UBERON:0001515	37.96	gold quality
anterior cingulate cortex	UBERON:0009835	37.79	gold quality
body of uterus	UBERON:0009853	37.63	gold quality
subcutaneous adipose tissue	UBERON:0002190	37.45	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
amygdala	UBERON:0001876	37.06	gold quality
placenta	UBERON:0001987	37.04	gold quality
tibial nerve	UBERON:0001323	37.01	gold quality
temporal lobe	UBERON:0001871	36.97	gold quality
putamen	UBERON:0001874	36.85	gold quality
muscle tissue	UBERON:0002385	36.79	gold quality
multicellular organism	UBERON:0000468	36.70	gold quality
ectocervix	UBERON:0012249	36.64	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
caudate nucleus	UBERON:0001873	36.37	gold quality
Ammon’s horn	UBERON:0001954	36.28	gold quality
cerebral cortex	UBERON:0000956	36.22	gold quality
nucleus accumbens	UBERON:0001882	36.15	gold quality
tibial artery	UBERON:0007610	36.08	gold quality
popliteal artery	UBERON:0002250	35.91	gold quality
lung	UBERON:0002048	35.60	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
metanephros cortex	UBERON:0010533	35.30	gold quality
skeletal muscle tissue	UBERON:0001134	35.20	gold quality
adipose tissue	UBERON:0001013	34.93	gold quality
superior frontal gyrus	UBERON:0002661	34.89	gold quality
vagina	UBERON:0000996	34.55	silver quality
uterine cervix	UBERON:0000002	34.51	gold quality
right coronary artery	UBERON:0001625	34.50	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	34.46	gold quality
ovary	UBERON:0000992	34.33	gold quality
frontal cortex	UBERON:0001870	34.28	gold quality
intestine	UBERON:0000160	34.23	silver quality
lower esophagus muscularis layer	UBERON:0035833	34.14	gold quality
lower esophagus	UBERON:0013473	34.12	gold quality
transverse colon	UBERON:0001157	34.05	silver quality
right lobe of thyroid gland	UBERON:0001119	33.96	silver quality
primary visual cortex	UBERON:0002436	33.89	silver quality
left ovary	UBERON:0002119	33.72	gold quality
blood	UBERON:0000178	33.52	gold quality
esophagus	UBERON:0001043	33.50	gold quality
saliva-secreting gland	UBERON:0001044	33.29	gold quality
thoracic mammary gland	UBERON:0005200	33.11	gold quality
spleen	UBERON:0002106	33.05	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	33.02	gold quality
esophagus mucosa	UBERON:0002469	32.91	silver quality
body of pancreas	UBERON:0001150	32.85	silver quality
left lobe of thyroid gland	UBERON:0001120	32.78	gold quality
colon	UBERON:0001155	32.76	silver quality
descending thoracic aorta	UBERON:0002345	32.73	silver quality
minor salivary gland	UBERON:0001830	32.70	gold quality
muscle of leg	UBERON:0001383	32.54	gold quality
endocervix	UBERON:0000458	32.49	silver quality
zone of skin	UBERON:0000014	32.43	gold quality
gastrocnemius	UBERON:0001388	32.42	gold quality
skin of abdomen	UBERON:0001416	32.42	gold quality
prostate gland	UBERON:0002367	32.38	gold quality
muscle layer of sigmoid colon	UBERON:0035805	32.38	gold quality
cortex of kidney	UBERON:0001225	32.19	gold quality
thyroid gland	UBERON:0002046	32.17	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	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

HPA expression

RNA tissue specificity: Tissue enriched

28 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Testis	tissue	20.2
Postcentral gyrus	tissue	4.7
Putamen	tissue	3.5
Bone marrow	tissue	2.5
Retrosplenial cortex	tissue	2.4
Nucleus accumbens	tissue	2.0
Hippocampus	tissue	1.8
Medulla oblongata	tissue	1.7
Spinal cord	tissue	1.4
Retina	tissue	1.2
Locus coeruleus	tissue	1.2
Substantia nigra	tissue	0.8
Choroid plexus	tissue	0.7
Skin 1	tissue	0.6
Lymph node	tissue	0.2
Salivary gland	tissue	0.2
Skeletal muscle	tissue	0.2
Spleen	tissue	0.2
Duodenum	tissue	0.2
Heart muscle	tissue	0.1
Cerebral cortex	tissue	0.1
Esophagus	tissue	0.1
Endometrium 1	tissue	0.1
Basal ganglia	tissue	0.1
Ventral forebrain	tissue	0.1
Caudate putamen	tissue	0.1
Somatosensory cortex	tissue	0.1
Occipital cortex	tissue	0.1

Brain sub-regions (HPA Brain Atlas): detected in 183; highest nTPM — Cerebellar cortex (7.5), Vermis (7.3), Flocculonodular lobe (7.2), Area parastriata, temporal (4.2), Posterior insular cortex (3.7).

Regulation

Is transcription factor: no

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

Functional genomics

gnomAD constraint: pLI 0.143, LOEUF 1.91, missense Z -1.48 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000327157 — one region, missense o/e 1.20.

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:106601) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal sperm motility	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Rattus norvegicus	Q64256	100.0%	Diamond
Bos taurus	Q32PA2	80.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR548H2	ncRNA	100313773
RMI2	protein-coding	116028
APOLTP	protein-coding	400499
PRM1	protein-coding	5619
PRM2	protein-coding	5620
TNP2	protein-coding	7142
SOCS1	protein-coding	8651
LITAF	protein-coding	9516

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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NNZ6-F1	58.43	0.00

Human Protein Atlas

Protein class: Predicted intracellular proteins, UniProt - Inferred from homology

Protein evidence: Evidence at protein level

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)

Type	Positions
Phosphoserine	95

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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

14 GO namespaces:

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

showing 15 of 340 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRM3	PRM2	P04554	799
PRM3	TNP1	P09430	731
PRM3	TNP2	Q05952	720
PRM3	TSSK6	Q9BXA6	633
PRM3	CATSPER3	Q86XQ3	580
PRM3	PRM1	P04553	570
PRM3	SPATA25	Q9BR10	569
PRM3	ACRV1	P26436	493
PRM3	SPACA3	Q8IXA5	487
PRM3	IZUMO2	Q6UXV1	460
PRM3	BRDT	Q58F21	443
PRM3	SYCP3	Q8IZU3	443
PRM3	STPG1	Q5TH74	429
PRM3	SPACA4	Q8TDM5	423
PRM3	CATSPER4	Q7RTX7	418

IntAct

Human interaction partners of PRM3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
ARRB2	association	0.350	1

Disease & clinical

Genetic variants

Variant evidence for PRM3: 28 ClinVar records (0 pathogenic / likely pathogenic); 8 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 15 predictions of 61):

Position(s)	Effect	Δscore	Sites
16:11273380	donor_gain	0.6400
16:11273606	donor_gain	0.6400
16:11273449	acceptor_gain	0.6000
16:11273563	donor_gain	0.5700
16:11273451–11273452	acceptor_loss	0.5500	6
16:11273446	donor_gain	0.5200
16:11273264	donor_gain	0.5000
16:11273453	acceptor_loss	0.5000
16:11273459	acceptor_loss	0.4900
16:11273603	donor_gain	0.4900

AlphaMissense

67 missense substitutions predicted likely pathogenic (of 675 scored), across 20 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C38	7	0.772	0.861
D42	6	0.752	0.884
S40	5	0.814	0.910
K33	5	0.801	0.918
F44	5	0.785	0.846
C5	5	0.747	0.786
K34	4	0.636	0.694
M32	3	0.737	0.737
L35	3	0.732	0.833
L74	3	0.732	0.797
K7	3	0.696	0.737
L76	3	0.645	0.726
K73	2	0.719	0.719
N43	2	0.701	0.701
L75	2	0.678	0.771
G2	2	0.675	0.736
L46	2	0.674	0.760
V39	2	0.617	0.665
G72	2	0.605	0.639
A37	1	0.679	0.679

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

8 associations:

Study	Trait	p-value
GCST009798_40	Asthma	2e-33
GCST005527_32	Psoriasis	5e-8
GCST004132_14	Crohn’s disease	1e-7
GCST003268_10	Psoriasis vulgaris	3e-7
GCST001341_12	Multiple sclerosis	6e-7
GCST004131_115	Inflammatory bowel disease	1e-6
GCST001958_23	Bulimia nervosa	2e-6
GCST000258_5	Type 1 diabetes	3e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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)

Via MONDO — disease-level, not drug-specific.