SPMIP4

Summary

SPMIP4 (sperm microtubule inner protein 4, HGNC:21722) is a protein-coding gene on chromosome 7p15.3, encoding Sperm-associated microtubule inner protein 4 (Q8N865). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in flagellum axoneme.

Located in centrosome.

Source: NCBI Gene 136895 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_138811

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21722
Approved symbol	SPMIP4
Name	sperm microtubule inner protein 4
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000153790
Ensembl biotype	protein_coding
OMIM	616071
Entrez	136895

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000283905, ENST00000409280, ENST00000415598, ENST00000443822, ENST00000444434

RefSeq mRNA: 3 — MANE Select: NM_138811 NM_001371351, NM_001371352, NM_138811

CCDS: CCDS5394

Canonical transcript exons

ENST00000283905 — 10 exons

Exon	Start	End
ENSE00001012416	25142241	25142332
ENSE00001085020	25142640	25142814
ENSE00001285656	25151596	25151684
ENSE00001285664	25155011	25155192
ENSE00001285674	25158501	25158530
ENSE00001285683	25161189	25161260
ENSE00001285691	25168289	25168465
ENSE00001285698	25179662	25180354
ENSE00001285721	25179175	25179332
ENSE00001899891	25134692	25136793

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.2336 / max 216.5208, expressed in 1359 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
83160	4.8461	1346
83159	0.3660	73
204388	0.0214	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.62	gold quality
left testis	UBERON:0004533	92.01	gold quality
right testis	UBERON:0004534	91.69	gold quality
testis	UBERON:0000473	90.86	gold quality
adult organism	UBERON:0007023	86.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.51	gold quality
pigmented layer of retina	UBERON:0001782	82.73	gold quality
retina	UBERON:0000966	82.71	gold quality
monocyte	CL:0000576	79.19	gold quality
leukocyte	CL:0000738	79.11	gold quality
cartilage tissue	UBERON:0002418	77.95	gold quality
left adrenal gland	UBERON:0001234	77.88	gold quality
mucosa of transverse colon	UBERON:0004991	77.80	gold quality
left adrenal gland cortex	UBERON:0035825	77.71	gold quality
right adrenal gland cortex	UBERON:0035827	76.57	gold quality
right adrenal gland	UBERON:0001233	76.29	gold quality
adrenal cortex	UBERON:0001235	76.08	gold quality
bone marrow cell	CL:0002092	75.86	gold quality
adrenal gland	UBERON:0002369	75.48	gold quality
granulocyte	CL:0000094	75.02	gold quality
palpebral conjunctiva	UBERON:0001812	74.84	gold quality
transverse colon	UBERON:0001157	74.30	gold quality
colonic epithelium	UBERON:0000397	74.23	gold quality
rectum	UBERON:0001052	74.20	gold quality
buccal mucosa cell	CL:0002336	74.18	gold quality
popliteal artery	UBERON:0002250	73.20	gold quality
tibial artery	UBERON:0007610	73.18	gold quality
tibia	UBERON:0000979	72.99	gold quality
smooth muscle tissue	UBERON:0001135	72.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting SPMIP4, 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-4283	100.00	66.42	2097
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-7161-5P	99.68	68.92	1592
HSA-MIR-545-5P	99.66	70.18	2308

Literature-anchored findings (GeneRIF, showing 1)

• LINGO1 might be a positive primary glioblastoma prognostic gene and C7orf31 and VEGFA might be negative prognosticators. (PMID:30064229)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spmip4	ENSMUSG00000029828
rattus_norvegicus	Spmip4	ENSRNOG00000010594

Protein

Protein identifiers

Sperm-associated microtubule inner protein 4 — Q8N865 (reviewed: Q8N865)

All UniProt accessions (4): Q8N865, C9J431, C9JF06, C9JTB1

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.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Flagellum axoneme.

Tissue specificity. Predominantly expressed in the testes.

RefSeq proteins (3): NP_001358280, NP_001358281, NP_620166* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027886	SPMIP4	Family

Pfam: PF15093

UniProt features (19 total): sequence variant 10, modified residue 6, cross-link 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N865-F1	58.22	0.02

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (8): 219, 407, 422, 442, 485, 547, 427, 545

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 50 (showing top): ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOCC_CENTROSOME, NAKAMURA_METASTASIS, KRIGE_RESPONSE_TO_TOSEDOSTAT_24HR_UP, VANASSE_BCL2_TARGETS_DN, MEISSNER_NPC_HCP_WITH_H3K4ME2, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, TERAO_AOX4_TARGETS_SKIN_DN, SRPK2_TARGET_GENES, MIR153_5P, MIR4477A, MIR6508_5P, MIR545_5P, MIR7161_5P

GO Biological Process (0):

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

GO Cellular Component (6): centrosome (GO:0005813), 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	2
binding	1
centriole	1
microtubule organizing center	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

192 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPMIP4	LRCOL1	A6NCL2	705
SPMIP4	CFAP96	A7E2U8	668
SPMIP4	CFAP184	Q2M329	652
SPMIP4	FAM229B	Q4G0N7	614
SPMIP4	C10orf120	Q5SQS8	606
SPMIP4	CCDC38	Q502W7	584
SPMIP4	CCDC116	Q8IYX3	583
SPMIP4	C10orf53	Q8N6V4	571
SPMIP4	CFAP263	Q9H0I3	570
SPMIP4	CCDC146	Q8IYE0	545
SPMIP4	CABS1	Q96KC9	531
SPMIP4	FSCB	Q5H9T9	514
SPMIP4	C7orf57	Q8NEG2	506
SPMIP4	ZNF621	Q6ZSS3	505
SPMIP4	SPATA24	Q86W54	486

IntAct

65 interactions, top by confidence:

A	B	Type	Score
SPMIP4		psi-mi:“MI:0915”(physical association)	0.560
	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
OIP5	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
BCL6	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	TEKT5	psi-mi:“MI:0915”(physical association)	0.560
CLIC3	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
KCTD9	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
CLCNKA	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	PFDN5	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	APBB2	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	GRN	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	NEFL	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	PHYH	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	KIF1B	psi-mi:“MI:0915”(physical association)	0.560
SPMIP4	RNF11	psi-mi:“MI:0915”(physical association)	0.560
HTT	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560
ATXN3	SPMIP4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (18): C7orf31 (Two-hybrid), PGK2 (Affinity Capture-MS), GRK6 (Affinity Capture-MS), GDA (Affinity Capture-MS), C7orf31 (Two-hybrid), C7orf31 (Two-hybrid), C7orf31 (Two-hybrid), C7orf31 (Two-hybrid), C7orf31 (Two-hybrid), HSF2BP (Two-hybrid), CLIC3 (Two-hybrid), CLCNKA (Two-hybrid), CYSRT1 (Two-hybrid), GDA (Affinity Capture-MS), PGK2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTD5, A0A1B0GUX0, A0A3Q1MT14, A4D263, A6NL82, A6QQL5, A8QW39, B0UXH9, B5X5D0, B9EJX3, E1B9R1, F1MMV1, Q148A4, Q1JPL0, Q2T9T0, Q32KQ1, Q32L72, Q32L77, Q32P67, Q3V0J4, Q5BN46, Q5NC57, Q5NC83, Q5SPV6, Q5SS90, Q5SVJ3, Q5VTT2, Q5VZQ5, Q66HC0, Q66HR9, Q6AYM0, Q6NXP0, Q6P3G4, Q6ZVS7, Q80X60, Q8CDT5, Q8CDU5, Q8N5S3, Q8N7U6, Q8N865

Diamond homologs: E1B9R1, Q6AYM0, Q8N865, Q9D5Y0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1279 predictions. Top by Δscore:

Variant	Effect	Δscore
7:25136800:T:C	acceptor_gain	1.0000
7:25136800:T:TC	acceptor_gain	1.0000
7:25136807:A:C	acceptor_gain	1.0000
7:25142240:CCGG:C	donor_gain	1.0000
7:25151591:CTT:C	donor_loss	1.0000
7:25151593:TACA:T	donor_loss	1.0000
7:25151594:A:AC	donor_gain	1.0000
7:25151594:ACAT:A	donor_gain	1.0000
7:25151595:C:CC	donor_gain	1.0000
7:25151595:CA:C	donor_gain	1.0000
7:25151595:CAT:C	donor_gain	1.0000
7:25151595:CATC:C	donor_gain	1.0000
7:25155200:T:TC	acceptor_gain	1.0000
7:25155203:T:TC	acceptor_gain	1.0000
7:25161187:A:AC	donor_gain	1.0000
7:25161188:C:CT	donor_gain	1.0000
7:25161188:CA:C	donor_gain	1.0000
7:25161188:CAA:C	donor_gain	1.0000
7:25161257:CTTT:C	acceptor_gain	1.0000
7:25161260:TCT:T	acceptor_loss	1.0000
7:25161261:C:CA	acceptor_loss	1.0000
7:25161262:T:C	acceptor_loss	1.0000
7:25168288:C:CT	donor_loss	1.0000
7:25179169:TTTTA:T	donor_loss	1.0000
7:25179170:TTTA:T	donor_loss	1.0000
7:25179171:TTAC:T	donor_loss	1.0000
7:25179172:TA:T	donor_loss	1.0000
7:25179174:CCTG:C	donor_loss	1.0000
7:25179329:CAAC:C	acceptor_gain	1.0000
7:25179333:C:CA	acceptor_loss	1.0000

AlphaMissense

3891 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:25151622:A:G	W220R	0.982
7:25151622:A:T	W220R	0.982
7:25142644:A:C	F285L	0.973
7:25142644:A:T	F285L	0.973
7:25142646:A:G	F285L	0.973
7:25155163:T:C	H148R	0.969
7:25155018:C:A	K196N	0.966
7:25155018:C:G	K196N	0.966
7:25155117:G:C	F163L	0.962
7:25155117:G:T	F163L	0.962
7:25155119:A:G	F163L	0.962
7:25155162:G:C	H148Q	0.962
7:25155162:G:T	H148Q	0.962
7:25151671:T:A	R203S	0.961
7:25151671:T:G	R203S	0.961
7:25155126:G:C	F160L	0.961
7:25155126:G:T	F160L	0.961
7:25155128:A:G	F160L	0.961
7:25136005:G:C	F580L	0.951
7:25136005:G:T	F580L	0.951
7:25136007:A:G	F580L	0.951
7:25142779:G:C	F240L	0.948
7:25142779:G:T	F240L	0.948
7:25142781:A:G	F240L	0.948
7:25142778:A:C	Y241D	0.945
7:25142684:A:G	L272P	0.943
7:25142676:A:G	S275P	0.942
7:25136744:C:G	R334P	0.941
7:25151620:C:A	W220C	0.938
7:25151620:C:G	W220C	0.938

dbSNP variants (sampled 300 via entrez): RS1000072293 (7:25153837 T>A,G), RS1000079702 (7:25142410 T>C), RS1000253027 (7:25177793 A>C,G), RS1000263458 (7:25137449 A>G), RS1000350479 (7:25182008 A>C,G), RS1000353508 (7:25172413 G>A), RS1000381888 (7:25181696 A>G), RS1000383015 (7:25172102 T>C), RS1000429179 (7:25135394 T>G), RS1000438254 (7:25143862 G>A,C), RS1000481536 (7:25135075 C>T), RS1000493464 (7:25176721 A>G), RS1000533613 (7:25149561 T>C), RS1000569988 (7:25139277 A>G), RS1000577454 (7:25179569 C>A)

Disease associations

OMIM: gene MIM:616071 | 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
GCST008502_7	Low susceptibility to hepatitis C infection	8.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010101	decreased susceptibility to hepatitis C infection

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases abundance	2
Cadmium	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, increases reaction	1
nickel sulfate	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Dronabinol	increases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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