SPMIP8

Summary

SPMIP8 (sperm microtubule inner protein 8, HGNC:33745) is a protein-coding gene on chromosome 16q21, encoding Sperm microtubule inner protein 8 (Q6URK8). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme.

Predicted to be involved in flagellated sperm motility. Predicted to be located in cytoplasm; cytoskeleton; and motile cilium. Predicted to be active in axonemal A tubule inner sheath and sperm flagellum.

Source: NCBI Gene 374739 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_199456

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33745
Approved symbol	SPMIP8
Name	sperm microtubule inner protein 8
Location	16q21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159648
Ensembl biotype	protein_coding
OMIM	610264
Entrez	374739

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000290871, ENST00000441824, ENST00000562915, ENST00000569996

RefSeq mRNA: 2 — MANE Select: NM_199456 NM_199046, NM_199456

CCDS: CCDS10790, CCDS45496

Canonical transcript exons

ENST00000441824 — 8 exons

Exon	Start	End
ENSE00001364518	57977815	57978039
ENSE00003524101	57984303	57984364
ENSE00003525719	57985206	57985267
ENSE00003545710	57984636	57984810
ENSE00003551307	57985909	57985941
ENSE00003578593	57985482	57985546
ENSE00003917450	57976544	57976634
ENSE00003919490	57987396	57988116

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 82.03.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6984 / max 78.0377, expressed in 337 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154426	0.6294	334
154425	0.0689	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	82.03	gold quality
right testis	UBERON:0004534	81.52	gold quality
testis	UBERON:0000473	78.57	gold quality
left lobe of thyroid gland	UBERON:0001120	76.72	gold quality
right lobe of thyroid gland	UBERON:0001119	76.33	gold quality
thyroid gland	UBERON:0002046	74.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	72.02	gold quality
tibialis anterior	UBERON:0001385	66.73	silver quality
left ovary	UBERON:0002119	65.17	gold quality
tibial nerve	UBERON:0001323	63.96	gold quality
adult organism	UBERON:0007023	63.63	gold quality
pancreatic ductal cell	CL:0002079	63.42	silver quality
right lung	UBERON:0002167	63.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	62.19	gold quality
right ovary	UBERON:0002118	61.97	gold quality
lower esophagus mucosa	UBERON:0035834	61.70	gold quality
ectocervix	UBERON:0012249	61.62	gold quality
endocervix	UBERON:0000458	61.54	gold quality
sperm	CL:0000019	60.88	silver quality
ovary	UBERON:0000992	60.53	gold quality
uterine cervix	UBERON:0000002	59.96	gold quality
vagina	UBERON:0000996	59.37	gold quality
minor salivary gland	UBERON:0001830	59.35	gold quality
cortical plate	UBERON:0005343	59.24	gold quality
body of uterus	UBERON:0009853	59.23	gold quality
skin of hip	UBERON:0001554	58.60	silver quality
esophagus mucosa	UBERON:0002469	58.35	gold quality
urinary bladder	UBERON:0001255	58.23	gold quality
right uterine tube	UBERON:0001302	57.76	gold quality
left adrenal gland cortex	UBERON:0035825	57.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.11

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting SPMIP8, 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-3646	100.00	73.56	5283
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-12113	99.32	67.54	1072
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-5088-5P	97.97	64.28	487
HSA-MIR-3085-5P	97.72	65.43	544
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-6805-5P	95.79	64.86	670

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spmip8	ENSMUSG00000090206
rattus_norvegicus	Spmip8	ENSRNOG00000013465

Protein

Protein identifiers

Sperm microtubule inner protein 8 — Q6URK8 (reviewed: Q6URK8)

Alternative names: Testis, prostate and placenta-expressed protein

All UniProt accessions (1): Q6URK8

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme. May serve to reinforce and thus stabilize the microtubule structure in the sperm flagella.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules.

Subcellular location. Cytoplasm. Cytoskeleton. Flagellum axoneme.

Tissue specificity. Expressed in testis, prostate and placenta.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6URK8-1	1	yes
Q6URK8-2	2

RefSeq proteins (2): NP_950247, NP_955535* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR034584	SPMIP8	Family

Pfam: PF22574

UniProt features (4 total): chain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6URK8-F1	57.62	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, TGACATY_UNKNOWN, chr16q21, GOCC_CYTOPLASMIC_REGION, GOCC_MOTILE_CILIUM, GOCC_CYTOPLASMIC_MICROTUBULE, GOCC_CILIUM, YKACATTT_UNKNOWN, HEB_Q6, MIKKELSEN_ES_ICP_WITH_H3K4ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, GOCC_AXONEMAL_MICROTUBULE, GOCC_9PLUS2_MOTILE_CILIUM, GOCC_SUPRAMOLECULAR_COMPLEX

GO Biological Process (1): flagellated sperm motility (GO:0030317)

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

GO Cellular Component (7): sperm flagellum (GO:0036126), axonemal A tubule inner sheath (GO:0160111), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
binding	1
9+2 motile cilium	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cilium	1

Protein interactions and networks

STRING

126 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPMIP8	CRK	P46108	713
SPMIP8	MCHR1	Q99705	506
SPMIP8	AHNAK	Q09666	426
SPMIP8	SLC25A25	Q6KCM7	370
SPMIP8	SNX9	Q9Y5X1	353
SPMIP8	CRKL	P46109	349
SPMIP8	ODF4	Q2M2E3	323
SPMIP8	NIPBL	Q6KC79	306
SPMIP8	IFIT2	P09913	301
SPMIP8	VAV2	P52735	301
SPMIP8	SOS1	Q07889	296
SPMIP8	CAPRIN2	Q6IMN6	289
SPMIP8	BAHD1	Q8TBE0	279
SPMIP8	DOCK1	Q14185	268
SPMIP8	FNBP1	Q96RU3	266

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SPMIP8	HSPA5	psi-mi:“MI:0915”(physical association)	0.500
SPMIP8	HSPD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): HSPA5 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), NAGLU (Affinity Capture-MS), LONP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A023IWE2, A0A023IWE3, A0A023IWI4, A0A023IWK7, A0A067SLB9, A5GNA0, A6MMY5, A8W7M7, A8W7M9, A8W7N0, A8W7N2, A8W7N8, A8W7N9, A8W7P1, A9CB95, D6CFW3, H2E7Q6, O83435, O98453, P05443, P0CAP8, P0CU62, P20556, P24475, P24477, P55749, P76096, P83918, Q03QZ3, Q09G05, Q0G9H9, Q0I7V6, Q250M8, Q318W1, Q47272, Q49KV8, Q54R75, Q65133, Q6EW11, Q6R7I7

Diamond homologs: Q2YDM5, Q6IMG9, Q6IMH0, Q6URK8

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	50
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1463 predictions. Top by Δscore:

Variant	Effect	Δscore
16:57984803:G:GT	donor_gain	1.0000
16:57985470:T:A	acceptor_gain	1.0000
16:57985480:A:AG	acceptor_gain	1.0000
16:57985481:G:GG	acceptor_gain	1.0000
16:57985547:G:GG	donor_gain	1.0000
16:57987394:A:AG	acceptor_gain	1.0000
16:57987395:G:GG	acceptor_gain	1.0000
16:57987395:GTC:G	acceptor_gain	1.0000
16:57978037:AAGG:A	donor_loss	0.9900
16:57978038:AGGT:A	donor_loss	0.9900
16:57978039:GGTTA:G	donor_loss	0.9900
16:57978040:GTTAG:G	donor_loss	0.9900
16:57984301:A:AG	acceptor_gain	0.9900
16:57984302:G:GG	acceptor_gain	0.9900
16:57984361:TTTGG:T	donor_loss	0.9900
16:57984362:TTGGT:T	donor_loss	0.9900
16:57984363:TGGT:T	donor_loss	0.9900
16:57984365:G:GC	donor_loss	0.9900
16:57984365:G:GG	donor_gain	0.9900
16:57984366:TGAG:T	donor_loss	0.9900
16:57984367:GAGTG:G	donor_loss	0.9900
16:57984368:A:AT	donor_loss	0.9900
16:57984779:G:GT	donor_gain	0.9900
16:57984779:G:T	donor_gain	0.9900
16:57984806:GCGAG:G	donor_gain	0.9900
16:57984810:GG:G	donor_loss	0.9900
16:57984811:G:C	donor_loss	0.9900
16:57985467:T:TA	acceptor_gain	0.9900
16:57985474:C:CA	acceptor_gain	0.9900
16:57985481:GT:G	acceptor_gain	0.9900

AlphaMissense

1766 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:57977930:G:C	K93N	0.987
16:57977930:G:T	K93N	0.987
16:57984308:T:C	F132L	0.985
16:57984310:T:A	F132L	0.985
16:57984310:T:G	F132L	0.985
16:57985262:T:A	W228R	0.981
16:57985262:T:C	W228R	0.981
16:57984753:T:A	W190R	0.975
16:57984753:T:C	W190R	0.975
16:57985264:G:C	W228C	0.970
16:57985264:G:T	W228C	0.970
16:57985916:T:C	F254L	0.961
16:57985918:C:A	F254L	0.961
16:57985918:C:G	F254L	0.961
16:57984309:T:G	F132C	0.954
16:57977964:C:A	R105S	0.953
16:57977928:A:G	K93E	0.951
16:57977940:T:G	Y97D	0.951
16:57984309:T:C	F132S	0.948
16:57984755:G:C	W190C	0.946
16:57984755:G:T	W190C	0.946
16:57978011:C:A	H120Q	0.944
16:57978011:C:G	H120Q	0.944
16:57987418:T:A	W270R	0.940
16:57987418:T:C	W270R	0.940
16:57985925:T:C	F257L	0.936
16:57985927:C:A	F257L	0.936
16:57985927:C:G	F257L	0.936
16:57984323:T:C	F137L	0.935
16:57984325:T:A	F137L	0.935

dbSNP variants (sampled 300 via entrez): RS1000679874 (16:57983757 G>A), RS1000710622 (16:57983643 G>A), RS1001055620 (16:57979041 C>G,T), RS1001097762 (16:57977465 C>T), RS1001311227 (16:57977097 C>T), RS1001574514 (16:57976779 C>A,G,T), RS1001702735 (16:57978853 A>T), RS1001713032 (16:57985022 G>A), RS1002177353 (16:57978221 C>T), RS1002591245 (16:57980533 G>T), RS1002689879 (16:57986668 A>C), RS1002719234 (16:57986318 T>A), RS1003064521 (16:57981294 T>C), RS1003115559 (16:57980259 T>G), RS1004013485 (16:57974811 T>A)

Disease associations

OMIM: gene MIM:610264 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST003473_26	Aggressiveness in attention deficit hyperactivity disorder	3.000000e-06
GCST007692_77	Chronic obstructive pulmonary disease	1.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	7
ethyl-p-hydroxybenzoate	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Smoke	decreases expression	1
Triclosan	increases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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