ODF1

Summary

ODF1 (outer dense fiber of sperm tails 1, HGNC:8113) is a protein-coding gene on chromosome 8q22.3, encoding Outer dense fiber protein 1 (Q14990). Component of the outer dense fibers (ODF) of spermatozoa.

The outer dense fibers are cytoskeletal structures that surround the axoneme in the middle piece and principal piece of the sperm tail. The fibers function in maintaining the elastic structure and recoil of the sperm tail as well as in protecting the tail from shear forces during epididymal transport and ejaculation. Defects in the outer dense fibers lead to abnormal sperm morphology and infertility. The human outer dense fibers contains at least 10 major proteins and this gene encodes the main protein.

Source: NCBI Gene 4956 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_024410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8113
Approved symbol	ODF1
Name	outer dense fiber of sperm tails 1
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ODFPG, ODF27, RT7, HSPB10, CT133
Ensembl gene	ENSG00000155087
Ensembl biotype	protein_coding
OMIM	182878
Entrez	4956

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000285402, ENST00000518835

RefSeq mRNA: 1 — MANE Select: NM_024410 NM_024410

CCDS: CCDS6293

Canonical transcript exons

ENST00000285402 — 2 exons

Exon	Start	End
ENSE00001019107	102560452	102561018
ENSE00001019109	102551589	102552047

Expression profiles

Bgee: expression breadth ubiquitous, 130 present calls, max score 99.86.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1875 / max 172.3145, expressed in 4 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90052	0.0800	3
90049	0.0634	4
90051	0.0316	3
90048	0.0107	3
90050	0.0017	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.86	gold quality
male germ cell	CL:0000015	98.80	gold quality
right testis	UBERON:0004534	98.56	gold quality
left testis	UBERON:0004533	98.48	gold quality
adult organism	UBERON:0007023	96.75	gold quality
testis	UBERON:0000473	95.75	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.48	gold quality
tongue squamous epithelium	UBERON:0006919	64.23	gold quality
oocyte	CL:0000023	62.70	gold quality
pancreatic ductal cell	CL:0002079	60.34	silver quality
gingival epithelium	UBERON:0001949	60.13	gold quality
mucosa of paranasal sinus	UBERON:0005030	60.10	gold quality
Brodmann (1909) area 23	UBERON:0013554	59.95	gold quality
orbitofrontal cortex	UBERON:0004167	59.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	59.84	gold quality
periodontal ligament	UBERON:0008266	59.77	gold quality
gingiva	UBERON:0001828	58.97	gold quality
middle temporal gyrus	UBERON:0002771	58.83	gold quality
hair follicle	UBERON:0002073	58.76	gold quality
bronchial epithelial cell	CL:0002328	57.40	silver quality
epithelium of bronchus	UBERON:0002031	57.01	silver quality
bronchus	UBERON:0002185	56.81	silver quality
epithelium of nasopharynx	UBERON:0001951	56.78	gold quality
decidua	UBERON:0002450	56.55	gold quality
cervix epithelium	UBERON:0004801	56.48	gold quality
cranial nerve II	UBERON:0000941	55.96	silver quality
endometrium epithelium	UBERON:0004811	55.71	gold quality
thymus	UBERON:0002370	55.63	gold quality
superficial temporal artery	UBERON:0001614	54.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting ODF1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-558	97.50	67.16	977
HSA-MIR-630	97.50	66.38	921
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3116	97.07	65.78	1324

Literature-anchored findings (GeneRIF, showing 4)

• The expression of ODF1 was significantly decreased in the ejaculated spermatozoa of asthenozoospermic men. (PMID:20112736)
• Thiols of flagellar proteins, such as outer dense fibre protein 1 (ODF1), are oxidised to form disulfides during epididymal transit and the spermatozoa become motile. This study was designed to determine how oxidative changes in protein thiol status affect progressive motility in spermatozoa. (PMID:27363428)
• Study provides evidence that ODF1 down regulation is responsible for male infertility. (PMID:27770032)
• Overexpression of ODF1 in Gastrointestinal Tract Neuroendocrine Neoplasms: a Novel Potential Immunohistochemical Biomarker for Well-differentiated Neuroendocrine Tumors. (PMID:32869188)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Odf1	ENSMUSG00000061923
rattus_norvegicus	Odf1	ENSRNOG00000006578

Protein

Protein identifiers

Outer dense fiber protein 1 — Q14990 (reviewed: Q14990)

Alternative names: Heat shock protein beta-10, Heat shock protein family B member 10

All UniProt accessions (2): Q14990, E5RH17

UniProt curated annotations — full annotation on UniProt →

Function. Component of the outer dense fibers (ODF) of spermatozoa. ODF are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail.

Subunit / interactions. Interacts (via leucine zipper motif) with TCP11 isoform 2 and isoform 3. Interacts with SPAG4. Interacts with KLC3. Interacts with CCDC42.

Subcellular location. Cell projection. Cilium. Flagellum. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Tissue specificity. Testis.

Domain organisation. The C-terminal contains many C-X-P repeats.

RefSeq proteins (1): NP_077721* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002068	A-crystallin/Hsp20_dom	Domain
IPR008978	HSP20-like_chaperone	Homologous_superfamily
IPR037389	ODFP	Family
IPR037552	ODF1_ACD	Domain

Pfam: PF00011

UniProt features (19 total): modified residue 10, sequence variant 3, repeat 2, region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14990-F1	62.45	0.07

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 (10): 123, 151, 167, 189, 194, 5, 10, 64, 86, 122

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): MODULE_52, MODULE_45, TGACCTY_ERR1_Q2, GOBP_MALE_GAMETE_GENERATION, MODULE_16, GOCC_MICROTUBULE_ORGANIZING_CENTER, GCM_PRKCG, MODULE_118, CEBP_Q2, GCM_RING1, MODULE_379, GCM_DPF2, OUELLET_CULTURED_OVARIAN_CANCER_INVASIVE_VS_LMP_DN, GOCC_CENTROSOME, OCT1_06

GO Biological Process (2): spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

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

GO Cellular Component (11): outer dense fiber (GO:0001520), manchette (GO:0002177), nucleus (GO:0005634), centrosome (GO:0005813), sperm flagellum (GO:0036126), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), motile cilium (GO:0031514), cell projection (GO:0042995), polymeric cytoskeletal fiber (GO:0099513)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
binding	1
sperm flagellum	1
polymeric cytoskeletal fiber	1
microtubule cytoskeleton	1
intracellular membrane-bounded organelle	1
centriole	1
microtubule organizing center	1
9+2 motile cilium	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
cytoskeleton	1
supramolecular fiber	1

Protein interactions and networks

STRING

1206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ODF1	SPAG4	Q9NPE6	998
ODF1	ODF2	Q5BJF6	900
ODF1	SPATC1	Q76KD6	885
ODF1	CNTLN	Q9NXG0	778
ODF1	CCDC42	Q96M95	770
ODF1	OAZ3	Q9UMX2	744
ODF1	ODF4	Q2M2E3	741
ODF1	CEP128	Q6ZU80	735
ODF1	SUN5	Q8TC36	735
ODF1	HSPB9	Q9BQS6	720
ODF1	SPAG5	Q96R06	712
ODF1	SPATA6	Q9NWH7	707
ODF1	ART1	P52961	696
ODF1	CDC27	P30260	682
ODF1	CIMAP1A	Q96PU9	663

IntAct

34 interactions, top by confidence:

A	B	Type	Score
MTUS2	ODF1	psi-mi:“MI:0915”(physical association)	0.670
ODF1	MTUS2	psi-mi:“MI:0915”(physical association)	0.670
ODF1	KRTAP12-2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	ODF1	psi-mi:“MI:0915”(physical association)	0.560
ODF1	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
	ODF1	psi-mi:“MI:0915”(physical association)	0.560
ODF1	MDFI	psi-mi:“MI:0915”(physical association)	0.560
KRT86	ODF1	psi-mi:“MI:0915”(physical association)	0.560
HOXA1	ODF1	psi-mi:“MI:0915”(physical association)	0.560
BAG4	ODF1	psi-mi:“MI:0915”(physical association)	0.560
ODF1	LCE1C	psi-mi:“MI:0915”(physical association)	0.560
P4HB	ODF1	psi-mi:“MI:0915”(physical association)	0.560
ODF1	TCP1	psi-mi:“MI:0914”(association)	0.530
ODF1	PSMD11	psi-mi:“MI:0914”(association)	0.350
ODF1	MDFI	psi-mi:“MI:0915”(physical association)	0.000
ODF1	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
ODF1		psi-mi:“MI:0915”(physical association)	0.000
ODF1	KRT86	psi-mi:“MI:0915”(physical association)	0.000
BAG4	ODF1	psi-mi:“MI:0915”(physical association)	0.000
ODF1	HOXA1	psi-mi:“MI:0915”(physical association)	0.000
ODF1	LCE1C	psi-mi:“MI:0915”(physical association)	0.000
ODF1	P4HB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (39): MTUS2 (Two-hybrid), KRTAP12-2 (Two-hybrid), SPATA20 (Affinity Capture-MS), NIF3L1 (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), FAM175B (Affinity Capture-MS), CCT7 (Affinity Capture-MS), PSMD11 (Affinity Capture-MS), PDCL (Affinity Capture-MS), CCT6A (Affinity Capture-MS), TCP1 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT5 (Affinity Capture-MS)

ESM2 similar proteins: A2VD23, B3A0Q3, C7G0B5, D4APE0, H2A0N4, O31510, O31802, P05229, P06649, P06719, P07790, P07915, P08016, P09346, P12796, P13396, P13523, P13817, P15270, P15515, P19469, P19470, P21769, P34084, P38978, P39801, P40899, P80760, P83148, P86960, Q14990, Q29077, Q29438, Q3LHN1, Q54CY3, Q54LE8, Q58676, Q5UP44, Q5UPC9, Q5UR10

Diamond homologs: P04792, P21769, Q04757, Q14990, Q29077, Q29438, Q61999

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

270 predictions. Top by Δscore:

Variant	Effect	Δscore
8:102560450:A:AG	acceptor_gain	0.9900
8:102560451:G:GG	acceptor_gain	0.9900
8:102552048:G:GG	donor_gain	0.9800
8:102560251:C:G	donor_gain	0.9800
8:102560446:TTCCA:T	acceptor_loss	0.9800
8:102560447:TCCAG:T	acceptor_loss	0.9800
8:102560448:CCAGA:C	acceptor_loss	0.9800
8:102560449:CAGA:C	acceptor_loss	0.9800
8:102560450:A:AC	acceptor_loss	0.9800
8:102560451:G:A	acceptor_loss	0.9800
8:102560451:GACT:G	acceptor_gain	0.9700
8:102560250:GCTGT:G	donor_gain	0.9500
8:102560451:GAC:G	acceptor_gain	0.9500
8:102551606:G:GG	donor_gain	0.9300
8:102560451:GA:G	acceptor_gain	0.9300
8:102552043:GCCAA:G	donor_gain	0.9200
8:102556804:GGAT:G	donor_gain	0.8900
8:102560218:G:GT	donor_gain	0.8900
8:102560450:AGACT:A	acceptor_gain	0.8700
8:102560451:GACTG:G	acceptor_gain	0.8700
8:102552026:A:G	donor_gain	0.8600
8:102560444:A:AG	acceptor_gain	0.8600
8:102560445:A:G	acceptor_gain	0.8600
8:102560223:G:T	donor_gain	0.8400
8:102560445:ATTCC:A	acceptor_loss	0.8400
8:102560224:C:T	donor_gain	0.8200
8:102560227:G:GT	donor_gain	0.8200
8:102560286:G:GA	donor_gain	0.7800
8:102551604:AA:A	donor_gain	0.7600
8:102551602:TAAAG:T	donor_loss	0.7500

AlphaMissense

1640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:102560531:T:C	F134L	1.000
8:102560533:T:A	F134L	1.000
8:102560533:T:G	F134L	1.000
8:102560553:T:A	V141D	1.000
8:102560586:C:A	A152D	1.000
8:102560532:T:C	F134S	0.999
8:102560532:T:G	F134C	0.999
8:102560547:T:A	V139D	0.999
8:102560580:T:A	V150E	0.999
8:102560585:G:C	A152P	0.999
8:102560592:G:C	R154P	0.999
8:102560661:T:C	L177S	0.999
8:102560661:T:G	L177W	0.999
8:102560574:T:A	V148E	0.998
8:102560650:A:C	K173N	0.998
8:102560650:A:T	K173N	0.998
8:102560655:T:C	F175S	0.998
8:102560688:T:A	V186E	0.998
8:102560718:T:A	V196D	0.998
8:102551890:T:C	C55R	0.997
8:102560454:T:C	L108P	0.997
8:102560582:T:C	S151P	0.997
8:102560627:T:C	Y166H	0.997
8:102560627:T:G	Y166D	0.997
8:102560633:T:G	Y168D	0.997
8:102560649:A:T	K173I	0.997
8:102560654:T:C	F175L	0.997
8:102560656:C:A	F175L	0.997
8:102560656:C:G	F175L	0.997
8:102560724:T:A	I198N	0.997

dbSNP variants (sampled 300 via entrez): RS1000129823 (8:102559626 C>G), RS1000193711 (8:102551201 T>C), RS1000421436 (8:102557987 C>G), RS1000487219 (8:102555114 C>T), RS1000896792 (8:102558221 G>A), RS1001144361 (8:102561207 T>C), RS1001175656 (8:102559861 A>G), RS1001222752 (8:102561300 C>A,G), RS1001710084 (8:102560227 G>A), RS1001869744 (8:102550005 C>G,T), RS1001932934 (8:102550837 T>C), RS1001962514 (8:102551143 G>A,C), RS1002333822 (8:102555441 G>A), RS1002366311 (8:102550275 G>T), RS1002497139 (8:102556489 C>T)

Disease associations

OMIM: gene MIM:182878 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST002073_10	Chronic lymphocytic leukemia	5.000000e-08
GCST002943_4	IgA nephropathy	1.000000e-09
GCST003468_8	Chronic lymphocytic leukemia	2.000000e-07
GCST004125_7	Type 2 diabetes (age of onset)	2.000000e-06
GCST004146_36	Chronic lymphocytic leukemia	6.000000e-08
GCST008575_1	IgM levels	2.000000e-24

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Benzo(a)pyrene	decreases methylation	1
Formaldehyde	decreases expression	1

Clinical trials (associated diseases)

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