EDDM3A

Summary

EDDM3A (epididymal protein 3A, HGNC:16978) is a protein-coding gene on chromosome 14q11.2, encoding Epididymal secretory protein E3-alpha (Q14507). Possible function in sperm maturation.

Testicular sperm are morphologically differentiated but are not progressively motile nor able to fertilize an egg. Post-testicular maturation requires exposure of spermatozoa to the microenvironment of the epididymal lumen. Spermatozoa undergo extensive changes in the epididymis, including enzymatic modifications, loss of pre-existing components and addition of new glycoproteins from epididymal secretions. These modifying proteins and enzymes are synthesized by epithelial cells lining the epididymal duct and secreted apically into the lumen, where they come into contact with, and may be absorbed onto, the sperm membranes. The proteins encoded by the genes in this cluster are synthesized and secreted by epididymal epithelial cells.

Source: NCBI Gene 10876 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• MANE Select transcript: NM_006683

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16978
Approved symbol	EDDM3A
Name	epididymal protein 3A
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	HE3-ALPHA
Ensembl gene	ENSG00000181562
Ensembl biotype	protein_coding
OMIM	611580
Entrez	10876

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000326842

RefSeq mRNA: 1 — MANE Select: NM_006683 NM_006683

CCDS: CCDS9556

Canonical transcript exons

ENST00000326842 — 2 exons

Exon	Start	End
ENSE00001289156	20745887	20745992
ENSE00001320041	20747555	20748380

Expression profiles

Bgee: expression breadth broad, 27 present calls, max score 99.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1922 / max 153.4887, expressed in 9 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138457	0.1353	8
138456	0.0382	4
138458	0.0188	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.67	gold quality
cauda epididymis	UBERON:0004360	99.02	gold quality
seminal vesicle	UBERON:0000998	97.07	gold quality
sperm	CL:0000019	90.66	gold quality
male germ cell	CL:0000015	88.75	gold quality
caput epididymis	UBERON:0004358	66.54	gold quality
buccal mucosa cell	CL:0002336	58.39	gold quality
diaphragm	UBERON:0001103	57.53	gold quality
tibialis anterior	UBERON:0001385	57.18	silver quality
decidua	UBERON:0002450	56.55	gold quality
gluteal muscle	UBERON:0002000	56.07	gold quality
triceps brachii	UBERON:0001509	56.05	gold quality
left ventricle myocardium	UBERON:0006566	54.65	gold quality
deltoid	UBERON:0001476	54.27	gold quality
pancreatic ductal cell	CL:0002079	53.27	silver quality
nephron tubule	UBERON:0001231	52.43	silver quality
hair follicle	UBERON:0002073	52.43	gold quality
ileal mucosa	UBERON:0000331	51.55	silver quality
adult mammalian kidney	UBERON:0000082	51.16	gold quality
Brodmann (1909) area 46	UBERON:0006483	51.07	gold quality
quadriceps femoris	UBERON:0001377	50.73	gold quality
metanephros	UBERON:0000081	50.45	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
epithelial cell of pancreas	CL:0000083	50.03	gold quality
cranial nerve II	UBERON:0000941	49.97	silver quality
right testis	UBERON:0004534	49.53	gold quality
kidney epithelium	UBERON:0004819	49.47	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	1213.12
E-ANND-3	yes	5.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting EDDM3A, 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-1277-5P	100.00	73.95	5056
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-1197	99.70	67.75	1027
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-642A-3P	99.23	67.67	1258
HSA-MIR-642B-3P	99.23	67.67	1258
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-618	97.62	67.46	861
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-6730-3P	97.03	67.54	889
HSA-MIR-331-5P	96.59	67.94	705

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Eddm3b	ENSMUSG00000072575
rattus_norvegicus	Eddm3b	ENSRNOG00000030110
rattus_norvegicus	LOC103693823	ENSRNOG00000054022

Paralogs (1): EDDM3B (ENSG00000181552)

Protein

Protein identifiers

Epididymal secretory protein E3-alpha — Q14507 (reviewed: Q14507)

Alternative names: Human epididymis-specific protein 3-alpha

All UniProt accessions (2): Q14507, W0UTC5

UniProt curated annotations — full annotation on UniProt →

Function. Possible function in sperm maturation.

Subcellular location. Secreted.

Tissue specificity. Epididymis, with predominant expression in the corpus region. Moderately expressed in the vas deferens; only low levels are detectable in the caput and cauda regions.

RefSeq proteins (1): NP_006674* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR023412	RNaseA_domain	Domain
IPR036816	RNaseA-like_dom_sf	Homologous_superfamily
IPR042402	EDDM3A/EDDM3B	Family

Pfam: PF00074

UniProt features (3 total): signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14507-F1	91.64	0.79

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 36 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_BEHAVIOR, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_INSEMINATION, GOBP_REPRODUCTIVE_BEHAVIOR, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GOBP_COPULATION, MULLIGHAN_NPM1_MUTATED_SIGNATURE_1_UP, RATTENBACHER_BOUND_BY_CELF1, RAPA_EARLY_UP.V1_DN, JAK2_DN.V1_UP, GLI1_TARGET_GENES, MIR1277_5P, MIR3658, MIR6504_3P

GO Biological Process (1): sperm displacement (GO:0007321)

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

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sperm competition	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

232 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EDDM3A	PTGER3	P43115	580
EDDM3A	WFDC9	Q8NEX5	489
EDDM3A	GOLGA8CP	A6NN73	479
EDDM3A	PTGER4	P35408	476
EDDM3A	DEFB134	Q4QY38	465
EDDM3A	WFDC11	Q8NEX6	452
EDDM3A	PTGER1	P34995	448
EDDM3A	DEFB131A	P59861	414
EDDM3A	CRISP1	P54107	403
EDDM3A	DEFB132	Q7Z7B7	396
EDDM3A	DEFB127	Q9H1M4	394
EDDM3A	WFDC8	Q8IUA0	390
EDDM3A	A0A0G2JN59	A0A0G2JN59	373
EDDM3A	RNASE4	P34096	372
EDDM3A	TEDDM1	Q5T9Z0	366

IntAct

7 interactions, top by confidence:

A	B	Type	Score
EDDM3A	BTNL9	psi-mi:“MI:0915”(physical association)	0.560
TEX101	MAP4K4	psi-mi:“MI:0914”(association)	0.350
EDDM3A	PLXNA2	psi-mi:“MI:0914”(association)	0.350
EDDM3A	HS3ST1	psi-mi:“MI:0914”(association)	0.350
EDDM3A	BTNL9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): EDDM3A (Affinity Capture-MS), EDDM3A (Two-hybrid), EDDM3A (Positive Genetic), EDDM3A (Positive Genetic), TMEM2 (Affinity Capture-MS), PLXNA3 (Affinity Capture-MS), PLXNA2 (Affinity Capture-MS), GALNT6 (Affinity Capture-MS), TCTN1 (Affinity Capture-MS), SIAE (Affinity Capture-MS), CERCAM (Affinity Capture-MS), NLGN1 (Affinity Capture-MS), CD109 (Affinity Capture-MS), CACNA2D2 (Affinity Capture-MS), GPR98 (Affinity Capture-MS)

ESM2 similar proteins: A0A2B4SES9, A0A7H0DN79, A0Q402, A4ZCW3, A9BIE9, O57205, O71193, P03513, P04873, P08583, P0DSY9, P0DSZ0, P10297, P15190, P20496, P28915, P28975, P29888, P33004, P33544, P39257, P39317, P44171, P52536, P58213, P84786, P85101, P89522, Q00124, Q03240, Q03244, Q03705, Q07934, Q14507, Q28ZG0, Q45UF4, Q5WVK6, Q5X472, Q5ZUF4, Q6EH50

Diamond homologs: P56851, Q14507

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

133 predictions. Top by Δscore:

Variant	Effect	Δscore
14:20747553:A:AG	acceptor_gain	1.0000
14:20747554:G:GG	acceptor_gain	1.0000
14:20747554:GAC:G	acceptor_gain	1.0000
14:20745983:TCC:T	donor_gain	0.9900
14:20745988:GTAGG:G	donor_gain	0.9900
14:20747553:A:G	acceptor_loss	0.9900
14:20747554:GA:G	acceptor_gain	0.9900
14:20747554:GACAC:G	acceptor_gain	0.9900
14:20745991:GG:G	donor_gain	0.9800
14:20745992:GG:G	donor_gain	0.9800
14:20747554:GACA:G	acceptor_gain	0.9700
14:20747550:T:TA	acceptor_gain	0.9600
14:20747549:CTGTA:C	acceptor_gain	0.9500
14:20747550:TGTAG:T	acceptor_gain	0.9500
14:20747551:GTAGA:G	acceptor_gain	0.9500
14:20747552:TAGA:T	acceptor_gain	0.9500
14:20747553:AGA:A	acceptor_gain	0.9500
14:20745993:G:GC	donor_loss	0.9400
14:20745993:G:GG	donor_gain	0.9400
14:20745994:T:TT	donor_loss	0.9400
14:20747554:G:C	acceptor_gain	0.9400
14:20747271:ATTTT:A	donor_gain	0.9200
14:20747200:TTC:T	donor_gain	0.9100
14:20747260:C:G	donor_gain	0.9000
14:20745987:A:G	donor_gain	0.8600
14:20746121:T:A	donor_gain	0.7600
14:20745990:AG:A	donor_gain	0.7500
14:20745992:G:GT	donor_gain	0.7400
14:20745993:G:T	donor_gain	0.7400
14:20745997:G:C	donor_loss	0.7400

AlphaMissense

990 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:20747677:T:C	F33L	0.976
14:20747679:C:A	F33L	0.976
14:20747679:C:G	F33L	0.976
14:20747893:T:A	C105S	0.965
14:20747894:G:C	C105S	0.965
14:20747714:T:G	F45C	0.961
14:20747954:T:C	F125S	0.960
14:20747959:T:A	C127S	0.960
14:20747960:G:C	C127S	0.960
14:20747713:T:C	F45L	0.958
14:20747715:C:A	F45L	0.958
14:20747715:C:G	F45L	0.958
14:20747893:T:C	C105R	0.953
14:20747953:T:C	F125L	0.951
14:20747955:C:A	F125L	0.951
14:20747955:C:G	F125L	0.951
14:20747728:T:A	C50S	0.949
14:20747729:G:C	C50S	0.949
14:20747728:T:C	C50R	0.942
14:20747782:T:C	F68L	0.942
14:20747784:C:A	F68L	0.942
14:20747784:C:G	F68L	0.942
14:20747865:G:C	W95C	0.942
14:20747865:G:T	W95C	0.942
14:20747820:C:G	C80W	0.939
14:20747714:T:C	F45S	0.933
14:20747954:T:G	F125C	0.933
14:20747895:T:G	C105W	0.932
14:20747960:G:A	C127Y	0.932
14:20747818:T:A	C80S	0.929

dbSNP variants (sampled 300 via entrez): RS1000009175 (14:20738387 C>T), RS1000047766 (14:20738196 A>G), RS1000450696 (14:20743367 T>C), RS1000653709 (14:20747417 G>A), RS1000869225 (14:20739922 G>C), RS1001200716 (14:20748122 A>G), RS1001231785 (14:20747912 A>G,T), RS1001297406 (14:20741835 G>A), RS1001388397 (14:20744929 G>A), RS1001874332 (14:20741096 C>A,T), RS1001947765 (14:20740881 G>A), RS1002203117 (14:20747146 C>T), RS1002233944 (14:20746839 T>A), RS1002365273 (14:20741758 C>G), RS1002421072 (14:20745870 C>A)

Disease associations

OMIM: gene MIM:611580 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
CGP 52608	affects binding, increases reaction	1
Hydralazine	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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