MOSPD3

Summary

MOSPD3 (motile sperm domain containing 3, HGNC:25078) is a protein-coding gene on chromosome 7q22.1, encoding Motile sperm domain-containing protein 3 (O75425).

This gene encodes a multi-pass membrane protein with a major sperm protein (MSP) domain. The deletion of a similar mouse gene is associated with defective cardiac development and neonatal lethality. Alternate transcriptional splice variants, encoding different isoforms, have been described.

Source: NCBI Gene 64598 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_023948

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25078
Approved symbol	MOSPD3
Name	motile sperm domain containing 3
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CDS3, NET30
Ensembl gene	ENSG00000106330
Ensembl biotype	protein_coding
OMIM	609125
Entrez	64598

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 18 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000223054, ENST00000379527, ENST00000393950, ENST00000424091, ENST00000462372, ENST00000490309, ENST00000493970, ENST00000497456, ENST00000902390, ENST00000902391, ENST00000902392, ENST00000902393, ENST00000902394, ENST00000902395, ENST00000902396, ENST00000902397, ENST00000902398, ENST00000902399, ENST00000921521, ENST00000921522, ENST00000921523

RefSeq mRNA: 6 — MANE Select: NM_023948 NM_001040097, NM_001040098, NM_001040099, NM_001363415, NM_001363416, NM_023948

CCDS: CCDS47662, CCDS5701

Canonical transcript exons

ENST00000393950 — 5 exons

Exon	Start	End
ENSE00001481420	100612540	100612996
ENSE00003468053	100613477	100613706
ENSE00003470984	100613194	100613269
ENSE00003561386	100614867	100615031
ENSE00003847303	100615152	100615377

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 94.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.8564 / max 102.1530, expressed in 1812 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80034	13.3029	1796
80031	4.8387	1662
80033	1.6418	944
80032	0.0730	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.94	gold quality
left testis	UBERON:0004533	94.84	gold quality
lower esophagus mucosa	UBERON:0035834	94.37	gold quality
testis	UBERON:0000473	92.69	gold quality
right adrenal gland cortex	UBERON:0035827	92.46	gold quality
right adrenal gland	UBERON:0001233	92.42	gold quality
left adrenal gland cortex	UBERON:0035825	92.15	gold quality
adrenal cortex	UBERON:0001235	91.96	gold quality
left adrenal gland	UBERON:0001234	91.86	gold quality
skin of leg	UBERON:0001511	91.73	gold quality
ganglionic eminence	UBERON:0004023	91.33	gold quality
sperm	CL:0000019	91.29	gold quality
right lobe of liver	UBERON:0001114	90.81	gold quality
male germ cell	CL:0000015	90.68	gold quality
cortical plate	UBERON:0005343	90.65	gold quality
skin of abdomen	UBERON:0001416	90.52	gold quality
adrenal gland	UBERON:0002369	90.04	gold quality
esophagus mucosa	UBERON:0002469	89.75	gold quality
ectocervix	UBERON:0012249	89.28	gold quality
zone of skin	UBERON:0000014	89.10	gold quality
upper arm skin	UBERON:0004263	89.05	gold quality
nipple	UBERON:0002030	88.82	gold quality
embryo	UBERON:0000922	88.81	gold quality
amygdala	UBERON:0001876	88.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.57	gold quality
pharyngeal mucosa	UBERON:0000355	88.35	gold quality
metanephros cortex	UBERON:0010533	88.28	gold quality
endocervix	UBERON:0000458	88.27	gold quality
trachea	UBERON:0003126	88.25	gold quality
right ovary	UBERON:0002118	88.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting MOSPD3, 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-4481	100.00	66.42	1669
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-609	99.82	64.26	505
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3612	99.45	66.02	1333
HSA-MIR-650	99.45	65.77	1309
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-4311	99.31	70.47	3041
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-890	97.47	68.67	982

Literature-anchored findings (GeneRIF, showing 2)

• Deletion fo the Mospd3 locus is mutagenic and breeding to homozygosity results in a characteristic right ventricle defect and neonatal lethality in 50% of mice. (PMID:15533722)
• Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs. (PMID:33296653)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Mospd3	ENSMUSG00000037221
rattus_norvegicus	Mospd3	ENSRNOG00000001396

Protein

Protein identifiers

Motile sperm domain-containing protein 3 — O75425 (reviewed: O75425)

All UniProt accessions (3): O75425, C9J3M4, F8WF07

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (4)

UniProt ID	Names	Canonical?
O75425-1	1	yes
O75425-2	2
O75425-3	3
O75425-4	4

RefSeq proteins (6): NP_001035186, NP_001035187, NP_001035188, NP_001350344, NP_001350345, NP_076438* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000535	MSP_dom	Domain
IPR008962	PapD-like_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR039283	MOSPD1/3	Family

Pfam: PF00635

UniProt features (11 total): splice variant 4, transmembrane region 2, region of interest 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75425-F1	75.30	0.38

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): RNGTGGGC_UNKNOWN, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, SCGGAAGY_ELK1_02, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_UP, DODD_NASOPHARYNGEAL_CARCINOMA_DN, COULOUARN_TEMPORAL_TGFB1_SIGNATURE_DN, WIERENGA_STAT5A_TARGETS_UP, WIERENGA_STAT5A_TARGETS_GROUP1, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, PEDRIOLI_MIR31_TARGETS_DN, ASH1L_TARGET_GENES, BARX1_TARGET_GENES, CEBPZ_TARGET_GENES, CIITA_TARGET_GENES

GO Biological Process (1): heart development (GO:0007507)

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

GO Cellular Component (2): cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
animal organ development	1
circulatory system development	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOSPD3	MOSPD2	Q8NHP6	641
MOSPD3	TBC1D22A	Q8WUA7	485
MOSPD3	VAPA	Q9P0L0	475
MOSPD3	ZFYVE27	Q5T4F4	452
MOSPD3	VAPB	O95292	409
MOSPD3	IL17D	Q8TAD2	400
MOSPD3	ERG28	Q9UKR5	385
MOSPD3	STARD3NL	O95772	377
MOSPD3	ZSWIM4	Q9H7M6	372
MOSPD3	ZNF688	P0C7X2	367
MOSPD3	ANO8	Q9HCE9	346
MOSPD3	TMEM120A	Q9BXJ8	338
MOSPD3	CEP85	Q6P2H3	334
MOSPD3	RMDN3	Q96TC7	332
MOSPD3	TBCK	Q8TEA7	328

IntAct

53 interactions, top by confidence:

A	B	Type	Score
MOSPD3	SAR1A	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3		psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	HSD17B13	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	IER3IP1	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	RETREG3	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	MFF	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	KASH5	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	FATE1	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	RILPL1	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	MOSPD3	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	GPR152	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	FNDC9	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	CD79A	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	REEP4	psi-mi:“MI:0915”(physical association)	0.560
	MOSPD3	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	MILR1	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	ATP5PF	psi-mi:“MI:0915”(physical association)	0.560
MOSPD3	TSN	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): MOSPD3 (Affinity Capture-RNA), MOSPD3 (Two-hybrid), MOSPD3 (Two-hybrid), IER3IP1 (Two-hybrid), FAM134C (Two-hybrid), FATE1 (Two-hybrid), ATP5J (Two-hybrid), CCDC155 (Two-hybrid), PSCA (Two-hybrid), REEP4 (Two-hybrid), MFF (Two-hybrid), ARL13B (Two-hybrid), HSD17B13 (Two-hybrid), FNDC9 (Two-hybrid), GPR152 (Two-hybrid)

ESM2 similar proteins: A5PJU7, A8MQ27, F1MLB4, F1MX48, F1SAM7, I3L5V6, O75425, O95382, P36916, Q08DG4, Q0MW30, Q14451, Q2YD98, Q32P44, Q3MIP1, Q3T033, Q3UPE3, Q3UV16, Q505F5, Q5EBM0, Q5U651, Q5ZM20, Q641Q3, Q6MG06, Q6SZW1, Q6ZTW0, Q7T0L4, Q8BGG6, Q8BH83, Q8C0R7, Q8K0Y7, Q8N9W5, Q8R2K4, Q8TE68, Q8VC03, Q96BM1, Q96E14, Q96EF6, Q96EY9, Q99JB7

Diamond homologs: O75425, Q2T9W7, Q3T033, Q5RCC7, Q5RJS6, Q8BGG6, Q8VEL0, Q9UJG1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

979 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100613270:G:GG	donor_gain	1.0000
7:100613464:ACCTT:A	acceptor_gain	1.0000
7:100613468:T:A	acceptor_gain	1.0000
7:100613702:GGAGC:G	donor_gain	1.0000
7:100613703:GAGC:G	donor_gain	1.0000
7:100613703:GAGCG:G	donor_gain	1.0000
7:100613705:GC:G	donor_gain	1.0000
7:100613707:G:GG	donor_gain	1.0000
7:100614865:A:AG	acceptor_gain	1.0000
7:100614866:G:GA	acceptor_gain	1.0000
7:100614866:G:GC	acceptor_loss	1.0000
7:100614866:GA:G	acceptor_gain	1.0000
7:100614866:GAC:G	acceptor_gain	1.0000
7:100612163:G:GT	donor_gain	0.9900
7:100612997:G:GA	donor_loss	0.9900
7:100613192:A:AG	acceptor_gain	0.9900
7:100613193:G:GG	acceptor_gain	0.9900
7:100613193:GTCCT:G	acceptor_gain	0.9900
7:100613265:GACAT:G	donor_gain	0.9900
7:100613389:AAG:A	acceptor_gain	0.9900
7:100613450:T:TA	acceptor_gain	0.9900
7:100613451:G:A	acceptor_gain	0.9900
7:100613464:A:AG	acceptor_gain	0.9900
7:100613465:C:G	acceptor_gain	0.9900
7:100613469:G:A	acceptor_gain	0.9900
7:100613475:A:AG	acceptor_gain	0.9900
7:100613476:G:GG	acceptor_gain	0.9900
7:100613476:GT:G	acceptor_gain	0.9900
7:100613704:A:T	donor_gain	0.9900
7:100614866:GACC:G	acceptor_gain	0.9900

AlphaMissense

1472 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100613530:T:C	F112S	0.999
7:100612990:T:C	F67L	0.998
7:100612991:T:C	F67S	0.998
7:100612992:C:A	F67L	0.998
7:100612992:C:G	F67L	0.998
7:100613218:A:C	Y77S	0.998
7:100613533:G:C	R113P	0.998
7:100612968:C:A	N59K	0.997
7:100612968:C:G	N59K	0.997
7:100613217:T:G	Y77D	0.997
7:100613482:T:A	I96N	0.997
7:100613536:T:A	I114N	0.997
7:100615031:G:C	G226R	0.997
7:100612919:T:C	F43S	0.996
7:100612918:T:C	F43L	0.995
7:100612920:C:A	F43L	0.995
7:100612920:C:G	F43L	0.995
7:100612961:T:A	L57H	0.995
7:100613217:T:C	Y77H	0.995
7:100613218:A:G	Y77C	0.995
7:100612955:T:C	L55P	0.994
7:100612963:T:G	Y58D	0.994
7:100613194:T:A	V69D	0.994
7:100613201:C:G	C71W	0.994
7:100613224:T:A	V79E	0.994
7:100613238:G:A	G84R	0.994
7:100613238:G:C	G84R	0.994
7:100613245:T:A	V86E	0.994
7:100613256:T:C	S90P	0.994
7:100613485:G:C	R97P	0.994

dbSNP variants (sampled 300 via entrez): RS1001512454 (7:100610368 A>G), RS1001616084 (7:100612764 C>G,T), RS1001962147 (7:100612453 C>T), RS1002209069 (7:100615738 C>T), RS1003022370 (7:100614028 A>G), RS1003614020 (7:100615553 C>A), RS1003737339 (7:100613361 A>G), RS1004214005 (7:100613093 G>A,T), RS1004736675 (7:100610867 A>G), RS1005193001 (7:100611151 G>A), RS1005754562 (7:100613520 C>T), RS1005767470 (7:100613768 G>A), RS1005789468 (7:100612382 G>A), RS1006151615 (7:100612242 G>A,C), RS1006735857 (7:100613535 A>G)

Disease associations

OMIM: gene MIM:609125 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004006_8	Mean corpuscular hemoglobin	6.000000e-08
GCST004332_1	Red blood cell count	1.000000e-08
GCST90002385_145	High light scatter reticulocyte count	4.000000e-15
GCST90002396_355	Mean reticulocyte volume	2.000000e-12

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, decreases expression, affects expression	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression, affects cotreatment	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Diuron	decreases expression	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Thiram	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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