SPMIP6

Summary

SPMIP6 (sperm microtubule inner protein 6, HGNC:19919) is a protein-coding gene on chromosome 9p13.3, encoding Sperm microtubule inner protein 6 (Q8NCR6). May participate in intramanchette transport and midpiece formation of the sperm tail.

This gene encodes a nuclear- or perinuclear-localized protein with no predicted domains or similarity to other known proteins. Expression of this gene is induced during the differentiation of bronchial epithelial cells, and the encoded protein may play a role in ciliogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 84688 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 10 total
• MANE Select transcript: NM_032596

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19919
Approved symbol	SPMIP6
Name	sperm microtubule inner protein 6
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	bA573M23.4, NYD-SP22, MGC32921, MGC33614, CBE1, SMRP1
Ensembl gene	ENSG00000164972
Ensembl biotype	protein_coding
OMIM	619502
Entrez	84688

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297623, ENST00000379124, ENST00000379126, ENST00000379127, ENST00000379133, ENST00000444429, ENST00000481295, ENST00000692548

RefSeq mRNA: 5 — MANE Select: NM_032596 NM_001252195, NM_001410962, NM_032596, NM_147168, NM_147169

CCDS: CCDS59121, CCDS6553, CCDS6554, CCDS6555, CCDS94398

Canonical transcript exons

ENST00000297623 — 7 exons

Exon	Start	End
ENSE00001190410	34380902	34381131
ENSE00001610556	34382754	34382869
ENSE00001692334	34385637	34385781
ENSE00001823977	34397499	34397810
ENSE00003481096	34381369	34381444
ENSE00003514238	34379019	34379181
ENSE00003630246	34379646	34379732

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 99.82.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2027 / max 140.8282, expressed in 180 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100505	0.6101	139
100501	0.2701	94
100502	0.2192	103
100503	0.0357	18
100507	0.0286	3
100504	0.0285	11
100506	0.0105	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	99.82	gold quality
right uterine tube	UBERON:0001302	99.70	gold quality
bronchus	UBERON:0002185	99.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.36	gold quality
right testis	UBERON:0004534	96.72	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.52	gold quality
left testis	UBERON:0004533	96.49	gold quality
sperm	CL:0000019	94.86	gold quality
caudate nucleus	UBERON:0001873	94.85	gold quality
nucleus accumbens	UBERON:0001882	94.45	gold quality
testis	UBERON:0000473	93.63	gold quality
epithelium of nasopharynx	UBERON:0001951	93.00	gold quality
oviduct epithelium	UBERON:0004804	92.93	gold quality
putamen	UBERON:0001874	92.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.70	gold quality
anterior cingulate cortex	UBERON:0009835	92.48	gold quality
fallopian tube	UBERON:0003889	92.37	gold quality
right frontal lobe	UBERON:0002810	91.79	gold quality
adult organism	UBERON:0007023	91.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.38	gold quality
nasal cavity epithelium	UBERON:0005384	91.24	gold quality
hypothalamus	UBERON:0001898	91.12	gold quality
prefrontal cortex	UBERON:0000451	90.28	gold quality
amygdala	UBERON:0001876	90.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.92	gold quality
neocortex	UBERON:0001950	89.07	gold quality
ventricular zone	UBERON:0003053	88.96	gold quality
trachea	UBERON:0003126	88.91	gold quality
frontal cortex	UBERON:0001870	88.68	gold quality
forebrain	UBERON:0001890	88.20	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	3416.62
E-MTAB-6653	yes	2649.45
E-HCAD-1	yes	2515.24
E-CURD-126	yes	2495.65
E-CURD-114	yes	2492.75
E-MTAB-8221	yes	2290.66
E-MTAB-10283	yes	2237.14
E-GEOD-130148	yes	2206.06
E-MTAB-6308	yes	1539.63
E-MTAB-10287	yes	28.00
E-MTAB-9388	yes	6.76
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• CBE1 may play an important role in the differentiation and/or function of ciliated cells in human airways (PMID:15242845)
• Chronological regulation of CBE1/Cbe1 expression during pulmonary differentiation suggests involvement in ciliogenesis, with an additional role during early lung development. (PMID:19213785)
• Our data strongly suggest an influence of CBE1 in ciliogenesis in spermatids due to the localization at the microtubules of the elongating spermatids, indicating a role in the intramanchette and/or intraflagellar transport mechanism. (PMID:28601408)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spmip6	ENSMUSG00000028441
rattus_norvegicus	Spmip6	ENSRNOG00000013320

Protein

Protein identifiers

Sperm microtubule inner protein 6 — Q8NCR6 (reviewed: Q8NCR6)

Alternative names: Ciliated bronchial epithelial protein 1, Spermatid-specific manchette-related protein 1, Testis development protein NYD-SP22

All UniProt accessions (2): A0A8I5KRB0, Q8NCR6

UniProt curated annotations — full annotation on UniProt →

Function. May participate in intramanchette transport and midpiece formation of the sperm tail. May play a potential role in somatic cell proliferation.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with alpha-tubulin.

Subcellular location. Cytoplasm. Cytoskeleton. Nucleus. Mitochondrion. Flagellum axoneme.

Tissue specificity. Expressed in testis. Strongly expressed in ciliated epithelial cells with lower levels in goblet cells (at protein level).

Induction. Down-regulated by IL13.

Similarity. Belongs to the SPMIP6 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q8NCR6-1	1, NYD-SP22 v1	yes
Q8NCR6-2	2
Q8NCR6-3	3, NYD-SP22 v3
Q8NCR6-4	4, CBE1 ORF2
Q8NCR6-5	5, CBE1 ORF1, NYD-SP22 v2

RefSeq proteins (5): NP_001239124, NP_001397891, NP_115985, NP_671697, NP_671698 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028195	SPMIP6	Family

Pfam: PF15181

UniProt features (8 total): splice variant 4, chain 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NCR6-F1	53.91	0.00

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
223–224	predominantly cytoplasmic rather than nuclear localization.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, FOXD3_01, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, chr9p13, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, USF_02, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, CCCAGAG_MIR326, GATA1_02, TGACCTTG_SF1_Q6, TGGAAA_NFAT_Q4_01, GOCC_MOTILE_CILIUM, MEF2_03

GO Biological Process (4): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), flagellated sperm motility (GO:0030317), protein-containing complex assembly (GO:0065003)

GO Molecular Function (2): alpha-tubulin binding (GO:0043014), protein binding (GO:0005515)

GO Cellular Component (15): manchette (GO:0002177), nucleus (GO:0005634), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), axonemal A tubule inner sheath (GO:0160111), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), sperm flagellum (GO:0036126), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	9
cytoplasm	3
intracellular membrane-bounded organelle	2
sperm flagellum	2
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
cellular component assembly	1
protein-containing complex organization	1
tubulin binding	1
binding	1
microtubule cytoskeleton	1
nuclear lumen	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
9+2 motile cilium	1

Protein interactions and networks

STRING

1872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPMIP6	FAM219A	Q8IW50	563
SPMIP6	RPP25L	Q8N5L8	446
SPMIP6	CCDC160	A6NGH7	430
SPMIP6	TMCO5A	Q8N6Q1	417
SPMIP6	RIMBP3	Q9UFD9	396
SPMIP6	EQTN	Q9NQ60	395
SPMIP6	CXorf65	A6NEN9	393
SPMIP6	DCTN3	O75935	384
SPMIP6	CCDC187	A0A096LP49	379
SPMIP6	C20orf173	Q96LM9	379
SPMIP6	CIMAP1A	Q96PU9	378
SPMIP6	MYORG	Q6NSJ0	374
SPMIP6	TMCO2	Q7Z6W1	373
SPMIP6	GBA2	Q9HCG7	372
SPMIP6	SPATA31F1	Q6ZU69	370

IntAct

82 interactions, top by confidence:

A	B	Type	Score
RBPMS	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	SPG21	psi-mi:“MI:0915”(physical association)	0.560
UBASH3A	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
MEIS2	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
CLIC3	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
HGS	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-5	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
BCL6	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
CCDC57	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-6	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	A1CF	psi-mi:“MI:0915”(physical association)	0.560
CDR2L	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	AIRIM	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	TSSK3	psi-mi:“MI:0915”(physical association)	0.560
NOXA1	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
BCAS2	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	PIK3R3	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	CATSPER1	psi-mi:“MI:0915”(physical association)	0.560
PROP1	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	TEKT4	psi-mi:“MI:0915”(physical association)	0.560
KCTD9	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
COL8A1	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
HSF2BP	SPMIP6	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	CABP2	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	DCTN6	psi-mi:“MI:0914”(association)	0.530

BioGRID (46): C9orf24 (Two-hybrid), NIF3L1 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), MMADHC (Affinity Capture-MS), HECTD1 (Affinity Capture-MS), NAGK (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), ACTR10 (Affinity Capture-MS), PSMF1 (Affinity Capture-MS), MMADHC (Affinity Capture-MS), PSMF1 (Affinity Capture-MS), NIF3L1 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS), LONP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTD5, A0A1B0GTJ6, A0A1B0GUX0, A0A3Q1MT14, A0JNL1, A5PJD8, B9EJX3, E1B9R1, E1BNS6, F1MMV1, Q0P591, Q148A4, Q14BB9, Q1JPL0, Q2KJ10, Q2MH31, Q2T9T0, Q2TA11, Q32L72, Q32L77, Q3V0Q6, Q5BN46, Q5PQN4, Q5RBH3, Q5RHU7, Q5SPV6, Q5SVJ3, Q5VTT2, Q5VZQ5, Q66HR9, Q6AYM0, Q7Z5V6, Q8CDU5, Q8N5S3, Q8N865, Q8NA69, Q8NCR6, Q8NEG2, Q95LU0, Q96K30

Diamond homologs: Q2MH31, Q32KP0, Q8NCR6, Q95LU0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1009 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34380456:A:T	acceptor_gain	1.0000
9:34381163:C:T	acceptor_gain	1.0000
9:34385632:CTTAC:C	donor_loss	1.0000
9:34385633:TTA:T	donor_loss	1.0000
9:34385634:TAC:T	donor_loss	1.0000
9:34385635:A:AC	donor_gain	1.0000
9:34385635:A:C	donor_loss	1.0000
9:34385635:AC:A	donor_gain	1.0000
9:34385635:ACCTT:A	donor_gain	1.0000
9:34385636:C:CC	donor_gain	1.0000
9:34385636:CC:C	donor_gain	1.0000
9:34385636:CCTT:C	donor_gain	1.0000
9:34385636:CCTTC:C	donor_gain	1.0000
9:34385639:T:A	donor_gain	1.0000
9:34385777:AGACC:A	acceptor_gain	1.0000
9:34385778:GACC:G	acceptor_gain	1.0000
9:34385778:GACCC:G	acceptor_loss	1.0000
9:34385779:ACC:A	acceptor_gain	1.0000
9:34385780:CC:C	acceptor_gain	1.0000
9:34385780:CCC:C	acceptor_gain	1.0000
9:34385780:CCCT:C	acceptor_loss	1.0000
9:34385781:CC:C	acceptor_gain	1.0000
9:34385782:C:CC	acceptor_gain	1.0000
9:34385782:C:T	acceptor_gain	1.0000
9:34385782:CTGGG:C	acceptor_loss	1.0000
9:34385783:T:A	acceptor_loss	1.0000
9:34385787:C:CT	acceptor_gain	1.0000
9:34385788:A:T	acceptor_gain	1.0000
9:34397494:CTTA:C	donor_loss	1.0000
9:34397495:TTACC:T	donor_loss	1.0000

AlphaMissense

1694 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34397595:A:C	S13R	0.979
9:34397595:A:T	S13R	0.979
9:34397597:T:G	S13R	0.979
9:34397508:A:C	F42L	0.971
9:34397508:A:T	F42L	0.971
9:34397510:A:G	F42L	0.971
9:34397556:C:A	K26N	0.969
9:34397556:C:G	K26N	0.969
9:34397622:G:C	F4L	0.957
9:34397622:G:T	F4L	0.957
9:34397624:A:G	F4L	0.957
9:34397628:G:C	F2L	0.952
9:34397628:G:T	F2L	0.952
9:34397630:A:G	F2L	0.952
9:34397596:C:T	S13N	0.929
9:34381007:A:C	S199R	0.921
9:34381007:A:T	S199R	0.921
9:34381009:T:G	S199R	0.921
9:34397596:C:A	S13I	0.921
9:34397579:A:C	Y19D	0.903
9:34397523:C:A	W37C	0.901
9:34397523:C:G	W37C	0.901
9:34397525:A:G	W37R	0.893
9:34397525:A:T	W37R	0.893
9:34397629:A:G	F2S	0.891
9:34397591:A:G	Y15H	0.889
9:34397574:C:A	R20S	0.886
9:34397574:C:G	R20S	0.886
9:34397591:A:C	Y15D	0.877
9:34381131:T:A	E158V	0.863

dbSNP variants (sampled 300 via entrez): RS1000111534 (9:34387139 C>T), RS1000273298 (9:34380018 C>T), RS1000415643 (9:34386747 G>A), RS1000451584 (9:34390485 GTTT>G,GTT,GTTTT), RS1000616711 (9:34383510 C>A,T), RS1000661143 (9:34378749 G>A,C), RS1000675675 (9:34392768 C>G,T), RS1000724395 (9:34397380 A>C,T), RS1000768386 (9:34385407 C>G,T), RS1000798934 (9:34383792 G>A), RS1000889039 (9:34399792 G>A), RS1001128624 (9:34399512 G>A), RS1001226864 (9:34398307 C>T), RS1001360215 (9:34392322 C>T), RS1001465616 (9:34397895 G>A,C)

Disease associations

OMIM: gene MIM:619502 | 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
GCST010136_34	Fruit consumption	4.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression, affects expression	3
entinostat	increases expression, affects cotreatment	2
bisphenol S	decreases expression, affects cotreatment, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	increases expression, affects cotreatment	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
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Plant Oils	increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases methylation	1
Copper Sulfate	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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