SPEF2 (sperm flagellar 2)

Gene

• Entrez ID: 79925
• Gene name: Sperm flagellar 2
• Gene symbol: SPEF2
• Synonyms (NCBI Gene): CT122, KPL2, SPGF43
• Chromosome: 5
• Chromosome location: 5p13.2

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1391102782	C>-	Pathogenic	Frameshift variant, non coding transcript variant, 5 prime UTR variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1383679	hsa-miR-4255	CLIP-seq
MIRT1383680	hsa-miR-4276	CLIP-seq
MIRT1383681	hsa-miR-4325	CLIP-seq
MIRT1383682	hsa-miR-450b-5p	CLIP-seq
MIRT1383683	hsa-miR-507	CLIP-seq
MIRT1383684	hsa-miR-557	CLIP-seq
MIRT2114832	hsa-miR-4445	CLIP-seq
MIRT2114833	hsa-miR-4477b	CLIP-seq
MIRT2114834	hsa-miR-500a	CLIP-seq
MIRT2114835	hsa-miR-554	CLIP-seq
MIRT2114836	hsa-miR-587	CLIP-seq
MIRT2114837	hsa-miR-885-5p	CLIP-seq
MIRT2631103	hsa-miR-548c-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002177	Component	Manchette	IBA
GO:0002177	Component	Manchette	ISS
GO:0003351	Process	Epithelial cilium movement involved in extracellular fluid movement	ISS
GO:0005576	Component	Extracellular region	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	ISS
GO:0005794	Component	Golgi apparatus	IEA
GO:0005794	Component	Golgi apparatus	ISS
GO:0005829	Component	Cytosol	IDA
GO:0005929	Component	Cilium	IDA
GO:0005929	Component	Cilium	IEA
GO:0007283	Process	Spermatogenesis	IEA
GO:0007283	Process	Spermatogenesis	ISS
GO:0007288	Process	Sperm axoneme assembly	IBA
GO:0007288	Process	Sperm axoneme assembly	IMP	31048344, 31151990
GO:0007288	Process	Sperm axoneme assembly	ISS
GO:0016604	Component	Nuclear body	IDA
GO:0030154	Process	Cell differentiation	IEA
GO:0031514	Component	Motile cilium	IEA
GO:0036126	Component	Sperm flagellum	IDA	31048344, 31151990, 31278745
GO:0042995	Component	Cell projection	IEA
GO:0048705	Process	Skeletal system morphogenesis	ISS
GO:0048854	Process	Brain morphogenesis	ISS
GO:0060541	Process	Respiratory system development	ISS
GO:0097225	Component	Sperm midpiece	IBA
GO:0097225	Component	Sperm midpiece	ISS

Other IDs

• MIM: 610172
• HGNC: 26293
• e!Ensembl: ENSG00000152582

Protein

• UniProt ID: Q9C093
• Protein name: Sperm flagellar protein 2 (Protein KPL2)
• Protein function: Required for correct axoneme development in spermatozoa. Important for normal development of the manchette and sperm head morphology. Essential for male fertility. Plays a role in localization of the intraflagellar transport protein IFT20 to the
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF06294	CH_2	5 → 102	CH-like domain in sperm protein	Domain
  PF00406	ADK	671 → 764		Domain

• Sequence:

  MSEILCQWLNKELKVSRTVSPKSFAKAFSSGYLLGEVLHKFELQDDFSEFLDSRVSSAKL
  NNFSRLEPTLNLLGVQFDQNVAHGIITEKPGVATKLLYQLYIALQKKKKSGLTGVEMQTM
  QRLTNLRLQNMKSDTFQERLRHMIPRQTDFNLMRITYRFQEKYKHVKEDLAHLHFEKLER
  FQKLKEEQRCFDIEKQYLNRRRQNEIMAKIQAAIIQIPKPASNRTLKALEAQKMMKKKKE
  AEDVADEIKKFEALIKKDLQAKESASKTSLDTAGQTTTDLLNTYSDDEYIKKIQKRLEED
  AFAREQREKRRRKLLMDQLIAHEAQEEAYREEQLINRLMRQSQQERRIAVQLMHVRHEKE
  VLWQNRIFREKQHEERRLKDFQDALDREAALAKQAKIDFEEQFLKEKRFHDQIAVERAQA
  RYEKHYSVCAEILDQIVDLSTKVADYRMLTNNLIPYKLMHDWKELFFNAKPIYEQASVKT
  LPANPSREQLTELEKRDLLDTNDYEEYKNMVGEWALPEEMVDNLPPSNNCILGHILHRLA
  EKSLPPRAESTTPELPSFAVKGCLLGKTLSGKTTILRSLQKDFPIQILSIDTLVQEAIQA
  FHDNEKVSEVLPIQKNDEEDALPVLQEEIKESQDPQHVFSAGPVSDEVLPETEGETMLSA
  NADKTPKAEEVKSSDSFLKLTTRAQLGAKSEQLLKKGKSIPDVLLVDIIVNAINEIPVNQ
  DCILDGFPMTLNQAQLLEEALTGCNRNLTEVERKKAQKSTLAIDPATSKEIPLPSPAFDF
  VILLDVSDTSSMSRMNDIIAEELSYKTAHEDISQRVAAENQDKDGDQNLRDQIQHRIIGF
  LDNWPLLEQWFSEPENILIKINAEIDKESLCEKVKEILTTEIAKKKNKVEKKLEEKEAEK
  KAAASLAELPLPTPPPAPPPEPEKEKEIHQSHVASKTPTAKGKPQSEAPHGKQESLQEGK
  GKKGETALKRKGSPKGKSSGGKVPVKKSPADSTDTSPVAIVPQPPKPGSEEWVYVNEPVP
  EEMPLFLVPYWELIENSYINTIKTVLRHLREDQHTVLAYLYEIRTSFQEFLKRPDHKQDF
  VAQWQADFNSLPDDLWDDEETKAELHQRVNDLRDRLWDICDARKEEAEQERLDIINESWL
  QDTLGMTMNHFFSLMQAELNRFQDTKRLLQDYYWGMESKIPVEDNKRFTRIPLVQLDSKD
  NSESQLRIPLVPRISISLETVTPKPKTKSVLKGKMDNSLENVESNFEADEKLVMDTWQQA
  SLAVSHMVAAEIHQRLMEEEKENQPADPKEKSPQMGANKKVKKEPPKKKQEDKKPKGKSP
  PMAEATPVIVTTEEIAEIKRKNELRVKIKEEHLAALQFEEIATQFRLELIKTKALALLED
  LVTKVVDVYKLMEKWLGERYLNEMASTEKLTDVARYHIETSTKIQNELYLSQEDFFINGN
  IKVFPDPPPSIRPPPVEKEEDGTLTIEQLDSLRDQFLDMAPKGIIGNKAFTDILIDLVTL
  NLGTNNFPSNWMHLTQPELQELTSLLTVNSEFVDWRKFLLVTSMPWPIPLEEELLETLQK
  FKAVDKEQLGTITFEQYMQAGLWFTGDEDIKIPENPLEPLPFNRQEHLIEFFFRLFADYE
  KDPPQLDYTQMLLYFACHPDTVEGVYRALSVAVGTHVFQQVKASIPSAEKTSSTDAGPAE
  EFPEPEENAAREERKLKDDTEKREQKDEEIPENANNEKMSMETLLKVFKGGSEAQDSNRF
  ASHLKIENIYAEGFIKTFQDLGAKNLEPIEVAVLLKHPFIQDLISNYSDYKFPDIKIILQ
  RSEHVQGSDGERSPSRHTEEKK

• Sequence length: 1822

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Primary ciliary dyskinesia	Pathogenic	rs1739374011	RCV001089640	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SPEF2-related disorder	Likely pathogenic	rs1239348737, rs1754689321	RCV003397824 RCV003903964	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Spermatogenic failure 43	Pathogenic	rs1391102782, rs1375975527, rs1230916222, rs1580704451, rs1580383744, rs1580783651, rs1580529760	RCV000993859 RCV000993860 RCV000993861 RCV000993862 RCV000993863 RCV000993864 RCV000993865	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Adrenocortical carcinoma, hereditary	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATOPIC ASTHMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATOPIC ECZEMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATROPHIC MACULAR DEGENERATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE THYROID DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BILIARY LIVER CIRRHOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC RHINOSINUSITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CILIARY MOTILITY DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL IMPAIRMENT OF SPERMATOZOA MOTILITY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DUCHENNE MUSCULAR DYSTROPHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MULTIPLE SCLEROSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NASAL CAVITY POLYP	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NASAL DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PRIMARY BILIARY CIRRHOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PSORIASIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
SEASONAL ALLERGIC RHINITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TONSILLITIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
WET MACULAR DEGENERATION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Asthenozoospermia	Asthenozoospermia	Pubtator	34755699	Associate	★☆☆☆☆ Found in Text Mining only
Ciliary Dyskinesia, Primary, 1, With Or Without Situs Inversus	Ciliary Dyskinesia	ORPHANET_DG	31545650		★☆☆☆☆ Found in Text Mining only
Ciliary Motility Disorders	Ciliary dyskinesia	Pubtator	38568462	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hydrocephalus	Hydrocephalus	BEFREE	29339787, 30190587		★☆☆☆☆ Found in Text Mining only
Infertility	Infertility	Pubtator	38568462	Associate	★☆☆☆☆ Found in Text Mining only
Infertility Male	Male infertility	Pubtator	38568462	Associate	★☆☆☆☆ Found in Text Mining only
Kartagener Syndrome	Kartagener Syndrome	BEFREE	29339787		★☆☆☆☆ Found in Text Mining only
Kartagener Syndrome	Kartagener Syndrome	ORPHANET_DG	31545650		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	Pubtator	37801226	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Macular Degeneration	Macular degeneration	Pubtator	32246154	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	GWASCAT_DG	21244703		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Multiple Sclerosis	Multiple Sclerosis	GWASDB_DG	21244703		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nasopharyngeal Carcinoma	Nasopharyngeal carcinoma	Pubtator	31770211	Associate	★☆☆☆☆ Found in Text Mining only
Non-syndromic male infertility due to sperm motility disorder	Non-Syndromic Male Infertility Due To Sperm Motility Disorder	Orphanet			★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	BEFREE	28574850		★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	Pubtator	28574850	Associate	★☆☆☆☆ Found in Text Mining only
Polynesian Bronchiectasis	Kartagener syndrome	ORPHANET_DG	31545650		★☆☆☆☆ Found in Text Mining only
Primary Ciliary Dyskinesia	Ciliary dyskinesia	BEFREE	29339787, 31545650		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary Ciliary Dyskinesia	Ciliary dyskinesia	ORPHANET_DG	31545650		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary ciliary dyskinesia	Ciliary dyskinesia	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thrombosis	Thrombosis	Pubtator	28574850	Associate	★☆☆☆☆ Found in Text Mining only