SPEM1

Summary

SPEM1 (spermatid maturation 1, HGNC:32429) is a protein-coding gene on chromosome 17p13.1, encoding Spermatid maturation protein 1 (Q8N4L4). Required for proper cytoplasm removal during spermatogenesis.

Predicted to be involved in flagellated sperm motility and sperm individualization. Predicted to act upstream of or within spermatogenesis. Predicted to be located in membrane. Predicted to be active in cytoplasm.

Source: NCBI Gene 374768 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_199339

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32429
Approved symbol	SPEM1
Name	spermatid maturation 1
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40081
Ensembl gene	ENSG00000181323
Ensembl biotype	protein_coding
OMIM	615116
Entrez	374768

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000323675

RefSeq mRNA: 1 — MANE Select: NM_199339 NM_199339

CCDS: CCDS42254

Canonical transcript exons

ENST00000323675 — 3 exons

Exon	Start	End
ENSE00001264995	7420881	7421632
ENSE00001265344	7420324	7420528
ENSE00003687868	7420627	7420687

Expression profiles

Bgee: expression breadth broad, 24 present calls, max score 94.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1489 / max 160.5863, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159183	0.1489	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.00	gold quality
left testis	UBERON:0004533	93.97	gold quality
testis	UBERON:0000473	93.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.33	gold quality
colonic epithelium	UBERON:0000397	52.65	gold quality
lower esophagus mucosa	UBERON:0035834	38.92	gold quality
granulocyte	CL:0000094	37.15	gold quality
skeletal muscle tissue	UBERON:0001134	36.82	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	34.81	gold quality
uterine cervix	UBERON:0000002	33.90	silver quality
ectocervix	UBERON:0012249	33.73	silver quality
mucosa of stomach	UBERON:0001199	33.56	gold quality
duodenum	UBERON:0002114	33.32	silver quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
gall bladder	UBERON:0002110	31.85	silver quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle of leg	UBERON:0001383	31.15	gold quality
gastrocnemius	UBERON:0001388	31.08	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
descending thoracic aorta	UBERON:0002345	30.12	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
myometrium	UBERON:0001296	29.78	silver quality
lymph node	UBERON:0000029	28.94	gold quality
right ovary	UBERON:0002118	28.88	gold quality
tonsil	UBERON:0002372	28.58	gold quality
multicellular organism	UBERON:0000468	28.01	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• SPEM1 appears to have a significant clinical value for prediction of sperm retrieval in azoospermic men. (PMID:30054974)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spem1	ENSMUSG00000041165
rattus_norvegicus	Spem1	ENSRNOG00000015419

Protein

Protein identifiers

Spermatid maturation protein 1 — Q8N4L4 (reviewed: Q8N4L4)

All UniProt accessions (1): Q8N4L4

UniProt curated annotations — full annotation on UniProt →

Function. Required for proper cytoplasm removal during spermatogenesis.

Subcellular location. Membrane. Cytoplasm.

RefSeq proteins (1): NP_955371* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031368	SPEM1_N	Domain

Pfam: PF15670

UniProt features (4 total): chain 1, transmembrane region 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4L4-F1	53.85	0.09

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 42 (showing top): RNGTGGGC_UNKNOWN, GCANCTGNY_MYOD_Q6, TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, OSF2_Q6, MATZUK_SPERMATOZOA, SMAD_Q6, SREBP1_Q6, PR_Q2, TEF_Q6, BRUINS_UVC_RESPONSE_LATE

GO Biological Process (4): sperm individualization (GO:0007291), flagellated sperm motility (GO:0030317), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

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
developmental process involved in reproduction	2
cellular anatomical structure	2
spermatid development	1
cellularization	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
male gamete generation	1
cellular developmental process	1
binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPEM1	TNP1	P09430	743
SPEM1	PRM2	P04554	665
SPEM1	TNP2	Q05952	609
SPEM1	TSSK6	Q9BXA6	593
SPEM1	SPATA3	Q8NHX4	591
SPEM1	SPATA16	Q9BXB7	589
SPEM1	JUP	P14923	585
SPEM1	CBY2	Q8NA61	582
SPEM1	UBQLN1	Q9UMX0	543
SPEM1	SPATA45	Q537H7	540
SPEM1	SPMIP10	Q6ZNM6	527
SPEM1	ZMYND15	Q9H091	520
SPEM1	TEX35	Q5T0J7	518
SPEM1	CATSPER4	Q7RTX7	507
SPEM1	CATSPER3	Q86XQ3	486

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SPEM1	PPP1R1A	psi-mi:“MI:0915”(physical association)	0.560
SPEM1	PRG2	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): PPP1R1A (Affinity Capture-MS), PRG2 (Affinity Capture-MS), PPP1R1A (Affinity Capture-MS), PRG2 (Affinity Capture-MS), PPP1R1A (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8I316, A0A286YDK6, A2A8T7, A5WWA0, A6H7B4, A6NFA0, A6NFR6, A6NGY1, A6NKB5, A6QP24, A8MX80, B2RQL2, O93343, P0C6A0, Q0VD86, Q1EHW4, Q1RN00, Q2HR82, Q32LI3, Q32LN6, Q3B8N5, Q49AJ0, Q5BMD4, Q5DU28, Q5NCP0, Q5SSZ7, Q64ET8, Q66H53, Q68DV7, Q68US1, Q6P4J6, Q6PE65, Q6PG16, Q7SYV9, Q80U22, Q80VY2, Q80W69, Q8BII1, Q8K2F3, Q8N2Y8

Diamond homologs: A0A1B0GUW6, Q32LJ5, Q5F289, Q8N4L4, Q0P670, Q68FV4, Q8C5U4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

449 predictions. Top by Δscore:

Variant	Effect	Δscore
17:7420505:A:AG	donor_gain	0.9900
17:7420684:AAAGG:A	donor_loss	0.9900
17:7420685:AAGGT:A	donor_loss	0.9900
17:7420686:AGGT:A	donor_loss	0.9900
17:7420687:GGTAA:G	donor_loss	0.9900
17:7420688:GTAAG:G	donor_loss	0.9900
17:7420689:T:A	donor_loss	0.9900
17:7420454:GACC:G	donor_gain	0.9800
17:7420683:GAAAG:G	donor_gain	0.9800
17:7421138:G:GT	donor_gain	0.9800
17:7421138:G:T	donor_gain	0.9800
17:7420879:A:AG	acceptor_gain	0.9700
17:7420880:G:GG	acceptor_gain	0.9700
17:7420880:GAA:G	acceptor_gain	0.9700
17:7421235:A:T	donor_gain	0.9700
17:7420520:G:GG	donor_gain	0.9600
17:7420533:GG:G	donor_gain	0.9600
17:7420534:GG:G	donor_gain	0.9600
17:7421120:G:GT	donor_gain	0.9600
17:7421120:G:T	donor_gain	0.9600
17:7421253:GCA:G	donor_gain	0.9500
17:7420462:C:T	donor_gain	0.9300
17:7420519:A:AG	donor_gain	0.9300
17:7421091:A:AG	donor_gain	0.9300
17:7421092:G:GG	donor_gain	0.9300
17:7420524:C:G	donor_gain	0.9200
17:7421278:GGCC:G	donor_gain	0.9200
17:7420880:GA:G	acceptor_gain	0.9100
17:7420515:A:AG	donor_gain	0.9000
17:7420523:A:AG	donor_gain	0.9000

AlphaMissense

1994 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:7420508:A:C	S42R	0.975
17:7420510:C:A	S42R	0.975
17:7420510:C:G	S42R	0.975
17:7420496:T:C	C38R	0.942
17:7421216:T:C	F181L	0.941
17:7421218:C:A	F181L	0.941
17:7421218:C:G	F181L	0.941
17:7420504:C:A	N40K	0.939
17:7420504:C:G	N40K	0.939
17:7420516:T:A	N44K	0.920
17:7420516:T:G	N44K	0.920
17:7420663:T:C	F61L	0.885
17:7420665:C:A	F61L	0.885
17:7420665:C:G	F61L	0.885
17:7420484:G:C	G34R	0.883
17:7421217:T:C	F181S	0.882
17:7420630:T:A	W50R	0.841
17:7420630:T:C	W50R	0.841
17:7421262:C:T	S196F	0.830
17:7421217:T:G	F181C	0.822
17:7421578:G:C	W301C	0.818
17:7421578:G:T	W301C	0.818
17:7420494:T:A	I37N	0.815
17:7421211:T:C	I179T	0.812
17:7420958:T:C	C95R	0.801
17:7421299:C:A	N208K	0.798
17:7421299:C:G	N208K	0.798
17:7420470:T:A	V29D	0.790
17:7420632:G:C	W50C	0.766
17:7420632:G:T	W50C	0.766

dbSNP variants (sampled 300 via entrez): RS1001704697 (17:7420350 G>A), RS1002112171 (17:7418964 A>G), RS1002143249 (17:7418763 G>C,T), RS1002743713 (17:7418661 C>T), RS1002776235 (17:7418450 A>C,G), RS1003146365 (17:7420068 C>G,T), RS1004630709 (17:7421484 G>A,C), RS1005630390 (17:7420374 C>T), RS1006064477 (17:7418324 C>T), RS1006146413 (17:7419335 C>G), RS1006446175 (17:7418437 G>A,T), RS1006520743 (17:7419145 GC>G,GCC), RS1008402376 (17:7421999 C>T), RS1009063297 (17:7422030 T>C), RS1009891565 (17:7420737 T>C)

Disease associations

OMIM: gene MIM:615116 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_119	Refractive error	3.000000e-22

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
maleic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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