EDDM3B

Summary

EDDM3B (epididymal protein 3B, HGNC:19223) is a protein-coding gene on chromosome 14q11.2, encoding Epididymal secretory protein E3-beta (P56851). 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 64184 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_022360

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19223
Approved symbol	EDDM3B
Name	epididymal protein 3B
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	HE3-BETA
Ensembl gene	ENSG00000181552
Ensembl biotype	protein_coding
OMIM	611582
Entrez	64184

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000326783

RefSeq mRNA: 1 — MANE Select: NM_022360 NM_022360

CCDS: CCDS9557

Canonical transcript exons

ENST00000326783 — 2 exons

Exon	Start	End
ENSE00001289108	20770133	20770948
ENSE00001401520	20768404	20768506

Expression profiles

Bgee: expression breadth broad, 15 present calls, max score 99.89.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3997 / max 634.2123, expressed in 8 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
138462	0.2486	6
138464	0.0634	3
138460	0.0404	4
138465	0.0241	3
138463	0.0127	3
138461	0.0078	2
138459	0.0027	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.89	gold quality
cauda epididymis	UBERON:0004360	99.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.06	gold quality
seminal vesicle	UBERON:0000998	65.85	gold quality
caput epididymis	UBERON:0004358	56.50	gold quality
male germ cell	CL:0000015	56.07	silver quality
sperm	CL:0000019	54.21	silver quality
left ventricle myocardium	UBERON:0006566	51.47	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
myocardium	UBERON:0002349	49.17	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
quadriceps femoris	UBERON:0001377	48.53	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
epithelial cell of pancreas	CL:0000083	48.06	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
metanephric glomerulus	UBERON:0004736	47.45	gold quality
thymus	UBERON:0002370	47.42	gold quality
kidney epithelium	UBERON:0004819	47.39	gold quality
nephron tubule	UBERON:0001231	47.30	gold quality
diaphragm	UBERON:0001103	47.05	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting EDDM3B, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-618	97.62	67.46	861
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-3117-3P	95.96	67.82	473

Cross-species orthologs

3 orthologs

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

Paralogs (1): EDDM3A (ENSG00000181562)

Protein

Protein identifiers

Epididymal secretory protein E3-beta — P56851 (reviewed: P56851)

Alternative names: Human epididymis-specific protein 3-beta

All UniProt accessions (2): P56851, W0UV31

UniProt curated annotations — full annotation on UniProt →

Function. Possible function in sperm maturation.

Subcellular location. Secreted.

Tissue specificity. Epididymis.

RefSeq proteins (1): NP_071755* (*=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-P56851-F1	90.55	0.72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 18 (showing top): ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MODULE_207, MODULE_49, MIR548L, MIR9500, MIR6509_5P, GSE12845_NAIVE_VS_DARKZONE_GC_TONSIL_BCELL_UP, GSE24081_CONTROLLER_VS_PROGRESSOR_HIV_SPECIFIC_CD8_TCELL_DN, CTTTGA_LEF1_Q2, GSE8515_IL1_VS_IL6_4H_STIM_MAC_UP, GSE1112_OT1_VS_HY_CD8AB_THYMOCYTE_RTOC_CULTURE_UP, MODULE_67, GSE26290_CTRL_VS_AKT_INHIBITOR_TREATED_ANTI_CD3_AND_IL2_STIM_CD8_TCELL_UP, chr14q11, GSE37534_GW1929_VS_ROSIGLITAZONE_TREATED_CD4_TCELL_PPARG1_FOXP3_TRANSDUCED_UP

GO Biological Process (0):

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

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

266 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EDDM3B	LRCOL1	A6NCL2	568
EDDM3B	WFDC8	Q8IUA0	517
EDDM3B	WFDC9	Q8NEX5	488
EDDM3B	FAM229B	Q4G0N7	476
EDDM3B	SPMIP4	Q8N865	475
EDDM3B	GOLGA8CP	A6NN73	473
EDDM3B	PTGER3	P43115	447
EDDM3B	WFDC11	Q8NEX6	443
EDDM3B	LTF	P02788	412
EDDM3B	FSCB	Q5H9T9	406
EDDM3B	DEFB129	Q9H1M3	398
EDDM3B	TMEM255B	Q8WV15	372
EDDM3B	CRISP1	P54107	370
EDDM3B	A0A0G2JN59	A0A0G2JN59	368
EDDM3B	TEDDM1	Q5T9Z0	349

IntAct

66 interactions, top by confidence:

A	B	Type	Score
EDDM3B	SYNE4	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	KIR3DL3	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
CD74	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	LRRC59	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	JPH1	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	TMEM106C	psi-mi:“MI:0915”(physical association)	0.560
MUC1	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	GPX8	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	GPR152	psi-mi:“MI:0915”(physical association)	0.560
KCNJ6	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
CLDN7	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
ICAM3	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	LRRC25	psi-mi:“MI:0915”(physical association)	0.560
FFAR2	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
COX8A	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
CD79A	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	FNDC9	psi-mi:“MI:0915”(physical association)	0.560
PVR	EDDM3B	psi-mi:“MI:0915”(physical association)	0.560
TEX101	MAP4K4	psi-mi:“MI:0914”(association)	0.350
EDDM3B	PLXNB2	psi-mi:“MI:0914”(association)	0.350
COX8A	EDDM3B	psi-mi:“MI:0915”(physical association)	0.000
EDDM3B	TMPRSS2	psi-mi:“MI:0915”(physical association)	0.000
EDDM3B	CD74	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (59): SYNE4 (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Affinity Capture-MS), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid), EDDM3B (Two-hybrid)

ESM2 similar proteins: A0A0R4I951, A0A125S9F9, A0A144LVM3, A0A218QXE6, A0A888, A0A8U0LTT9, A0A8U0LU66, A2IA78, A7X3V0, B3A0R5, B6V6L0, C0KJQ4, C5DVG0, C9E1S2, C9X4K8, D9U2B4, E3P6S4, F5HBX1, I6R1R9, I6S3A0, M5BGS2, M5BGY5, M5BHN0, O46200, P02816, P0CI45, P0CI87, P0DL36, P0DM16, P0DPV9, P0DPW8, P0DQC3, P0DQC7, P42579, P56851, P60987, P60988, P82628, P82632, P82640

Diamond homologs: P56851, Q14507

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

162 predictions. Top by Δscore:

Variant	Effect	Δscore
14:20770122:T:TA	acceptor_gain	1.0000
14:20768494:GAGTC:G	donor_gain	0.9900
14:20768502:GTAGG:G	donor_gain	0.9900
14:20768505:GG:G	donor_gain	0.9900
14:20768506:GG:G	donor_gain	0.9900
14:20770120:T:TA	acceptor_gain	0.9900
14:20770123:G:A	acceptor_gain	0.9900
14:20770128:C:G	acceptor_gain	0.9900
14:20770130:CAGGC:C	acceptor_loss	0.9800
14:20770131:A:AG	acceptor_gain	0.9800
14:20770131:A:G	acceptor_loss	0.9800
14:20770131:AGGC:A	acceptor_gain	0.9800
14:20770132:G:GG	acceptor_gain	0.9800
14:20770132:GGC:G	acceptor_gain	0.9800
14:20770132:GGCG:G	acceptor_gain	0.9800
14:20770127:AC:A	acceptor_gain	0.9700
14:20770131:AGGCG:A	acceptor_gain	0.9700
14:20770132:GGCGG:G	acceptor_gain	0.9700
14:20768501:A:AG	donor_gain	0.9600
14:20770128:C:CA	acceptor_gain	0.9500
14:20768503:TAGGG:T	donor_loss	0.9400
14:20768504:AGGG:A	donor_loss	0.9400
14:20768505:GGGT:G	donor_loss	0.9400
14:20768507:GTA:G	donor_loss	0.9400
14:20768508:TAA:T	donor_loss	0.9400
14:20770127:A:AG	acceptor_gain	0.9400
14:20768507:G:GG	donor_gain	0.9300
14:20768509:AA:A	donor_loss	0.9200
14:20770131:AG:A	acceptor_gain	0.9200
14:20770132:GG:G	acceptor_gain	0.9200

AlphaMissense

1000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:20770247:T:C	F33L	0.981
14:20770249:C:A	F33L	0.981
14:20770249:C:G	F33L	0.981
14:20770529:T:A	C127S	0.980
14:20770530:G:C	C127S	0.980
14:20770390:C:G	C80W	0.979
14:20770463:T:A	C105S	0.979
14:20770464:G:C	C105S	0.979
14:20770388:T:A	C80S	0.978
14:20770389:G:C	C80S	0.978
14:20770524:T:C	F125S	0.977
14:20770531:T:G	C127W	0.976
14:20770284:T:G	F45C	0.972
14:20770389:G:A	C80Y	0.972
14:20770248:T:C	F33S	0.970
14:20770530:G:A	C127Y	0.970
14:20770352:T:C	F68L	0.968
14:20770354:T:A	F68L	0.968
14:20770354:T:G	F68L	0.968
14:20770248:T:G	F33C	0.967
14:20770463:T:C	C105R	0.967
14:20770298:T:A	C50S	0.966
14:20770299:G:C	C50S	0.966
14:20770298:T:C	C50R	0.965
14:20770283:T:C	F45L	0.964
14:20770285:C:A	F45L	0.964
14:20770285:C:G	F45L	0.964
14:20770529:T:C	C127R	0.964
14:20770435:G:C	W95C	0.963
14:20770435:G:T	W95C	0.963

dbSNP variants (sampled 300 via entrez): RS1000038268 (14:20768283 T>C), RS1000177132 (14:20767829 G>T), RS1000991790 (14:20769742 C>A,T), RS1001042803 (14:20769459 A>G), RS1002499488 (14:20770836 A>G), RS1002600918 (14:20766446 C>A), RS1002940748 (14:20771165 A>T), RS1002960574 (14:20766770 C>T), RS1004034655 (14:20767675 G>A), RS1004470110 (14:20768180 C>A), RS1004613276 (14:20769163 C>G,T), RS1005454369 (14:20766543 T>C), RS1005609263 (14:20770277 C>A,G,T), RS1005934476 (14:20771111 G>A,T), RS1007553414 (14:20767251 T>C)

Disease associations

OMIM: gene MIM:611582 | 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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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