SPGF6
MCID: SPR041
MIFTS: 41

Spermatogenic Failure 6 (SPGF6)

Categories: Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Spermatogenic Failure 6

MalaCards integrated aliases for Spermatogenic Failure 6:

Name: Spermatogenic Failure 6 57 12 74
Globozoospermia 57 53 25 74 37 29 13 55 6
Acrosome Malformation of Spermatozoa 57 25 74
Round-Headed Spermatozoa 57 25 74
Spermatogenic Failure 9 53 25 72
Spgf6 57 12 74
Male Infertility Due to Round-Headed Spermatozoa 53 59
Male Infertility Due to Globozoospermia 53 59
Round-Headed Sperm Syndrome 53 59
Mae Infertility Due to Round-Headed Spermatozoa 53
Spermatogenic Failure, Type 6 40
Spermatozoa, Round-Headed 57
Globozoospermia, Complete 53
Globozoospermia, Total 53
Spgf9 53

Characteristics:

Orphanet epidemiological data:

59
male infertility due to globozoospermia
Inheritance: Autosomal recessive; Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
one ashkenazi jewish family with globozoospermia and spata16 mutation has been described (last curated april 2015)


HPO:

32
spermatogenic failure 6:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Rare infertility disorders


External Ids:

Disease Ontology 12 DOID:0070167
KEGG 37 H01208
MeSH 44 D007248
ICD10 via Orphanet 34 N46
Orphanet 59 ORPHA171709
MedGen 42 C0403825
UMLS 72 C3151407

Summaries for Spermatogenic Failure 6

NIH Rare Diseases : 53 Globozoospermia is a rare form of male infertility. Men affected by this condition have abnormal sperm with a round (rather than oval) head and no acrosome (a cap-like covering which contains enzymes that break down the outer membrane of an egg cell). As a result of these abnormalities, the sperm are unable to fertilize an egg cell, leading to male factor infertility. Approximately 70% of men with globozoospermia have changes (mutations) in the DPY19L2 gene, which are inherited in an autosomal recessive manner. In the remaining cases, the underlying cause of the condition is unknown; however, researchers suspect that mutations in other genes likely cause globozoospermia. Although there is currently no cure for the condition, certain assisted reproductive technologies (ICSI combined with assisted egg cell activation, specifically) can help men affected by the condition conceive children.

MalaCards based summary : Spermatogenic Failure 6, also known as globozoospermia, is related to spermatogenic failure 9 and male infertility with teratozoospermia due to single gene mutation. An important gene associated with Spermatogenic Failure 6 is SPATA16 (Spermatogenesis Associated 16). The drugs Calcium and Hormones have been mentioned in the context of this disorder. Affiliated tissues include Testis, bone and testes, and related phenotypes are infertility and globozoospermia

Disease Ontology : 12 A male infertility characterized by autosomal recessive inheritance of globozoospermia that has material basis in mutation in the SPATA16 gene on chromosome 3q26.

Genetics Home Reference : 25 Globozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility). Normal sperm cells have an oval-shaped head with a cap-like covering called the acrosome. The acrosome contains enzymes that break down the outer membrane of an egg cell, allowing the sperm to fertilize the egg. The sperm cells of males with globozoospermia, however, have a round head and no acrosome. The abnormal sperm are unable to fertilize an egg cell, leading to infertility.

OMIM : 57 Spermatogenic failure-6 is a form of male infertility with globozoospermia. The acrosome is a unique structure of the mature spermatozoon, which plays an important role at the site of sperm-zonapellucida binding during the fertilization process. Globozoospermia (also called round-headed spermatozoa) is a human infertility syndrome caused by spermatogenesis defects (Lalonde et al., 1988, Singh, 1992). The most prominent feature of globozoospermia is the malformation of the acrosome and, in the most severe cases, the acrosome is totally absent. Globozoospermia is also characterized by abnormal nuclear shape as well as abnormal arrangement of the mitochondria of the spermatozoon (Battaglia et al., 1997). For a discussion of phenotypic and genetic heterogeneity of spermatogenic failure, see SPGF1 (258150). (102530)

KEGG : 37
Globozoospermia is a rare form of teratozoospermia, mainly characterized by round-headed spermatozoa that lack an acrosome. Acrosome plays an important role at the site of sperm-zonapellucida binding during the fertilization process. It was suggested that a homozygous mutation in SPATA16 was associated with male infertility in human globozoospermia. It has also been reported that a recurrent deletion of DPY19L2 causes infertility in man by blocking sperm head elongation and acrosome formation.

UniProtKB/Swiss-Prot : 74 Spermatogenic failure 6: An infertility disorder caused by spermatogenesis defects. The most prominent feature is the malformation of the acrosome, which can be totally absent in most severe cases. Additional features are an abnormal nuclear shape and abnormal arrangement of the mitochondria of the spermatozoon.

Related Diseases for Spermatogenic Failure 6

Diseases in the Spermatogenic Failure 6 family:

Spermatogenic Failure 2 Spermatogenic Failure 5
Spermatogenic Failure 1 Spermatogenic Failure 4
Spermatogenic Failure 3 Spermatogenic Failure 7
Spermatogenic Failure 8 Spermatogenic Failure 9
Spermatogenic Failure 10 Spermatogenic Failure 11
Spermatogenic Failure 12 Spermatogenic Failure 13
Spermatogenic Failure 14 Spermatogenic Failure 15
Spermatogenic Failure 16 Spermatogenic Failure 17
Spermatogenic Failure 18 Spermatogenic Failure 19
Spermatogenic Failure 20 Spermatogenic Failure 21
Spermatogenic Failure 22 Spermatogenic Failure 23
Spermatogenic Failure 24 Spermatogenic Failure 25
Spermatogenic Failure 26 Spermatogenic Failure 27
Spermatogenic Failure 28 Spermatogenic Failure 29
Spermatogenic Failure 30 Spermatogenic Failure 31
Spermatogenic Failure 32 Spermatogenic Failure 33
Spermatogenic Failure 34 Spermatogenic Failure 35
Spermatogenic Failure 36 Spermatogenic Failure 37
Spermatogenic Failure 38

Diseases related to Spermatogenic Failure 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 13)
# Related Disease Score Top Affiliating Genes
1 spermatogenic failure 9 12.4
2 male infertility with teratozoospermia due to single gene mutation 11.2
3 male infertility 10.8
4 infertility 10.8
5 polykaryocytosis inducer 10.3
6 partial deletion of y 10.3
7 varicocele 10.1
8 azoospermia 10.1
9 oligospermia 10.1
10 chromosomal triplication 10.1
11 down syndrome 10.1
12 ring chromosome 2 10.1
13 spermatogenic failure 5 9.1 SPATA16 PICK1 DPY19L2

Graphical network of the top 20 diseases related to Spermatogenic Failure 6:



Diseases related to Spermatogenic Failure 6

Symptoms & Phenotypes for Spermatogenic Failure 6

Human phenotypes related to Spermatogenic Failure 6:

32
# Description HPO Frequency HPO Source Accession
1 infertility 32 HP:0000789
2 globozoospermia 32 HP:0012205

Symptoms via clinical synopsis from OMIM:

57
Genitourinary Internal Genitalia Male:
infertility
abnormal sperm morphology
oligoasthenoteratozoospermia
globozoospermia, total
reduced or absent acrosin in the acrosome

Clinical features from OMIM:

102530

MGI Mouse Phenotypes related to Spermatogenic Failure 6:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.35 CSNK2A2 DPY19L2 GOPC PICK1 SPATA16
2 reproductive system MP:0005389 9.1 ACR CSNK2A2 DPY19L2 GOPC PICK1 SPATA16

Drugs & Therapeutics for Spermatogenic Failure 6

Drugs for Spermatogenic Failure 6 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 8)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Calcium Approved, Nutraceutical 7440-70-2 271
2 Hormones
3 Pharmaceutical Solutions
4 Calcium, Dietary
5 Ionomycin
6 Ionophores
7 Bone Density Conservation Agents
8 Calcium Ionophores

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Effect of Calcium Ionophore Solution on Fertilization Rate During ICSI Cycles of Poor Ovarian Reserve Patients Unknown status NCT02045914
2 COMPARISON BETWEEN IMSI AND ICSI TECHNIQUES WITH DONATED EGGS Completed NCT01316705

Search NIH Clinical Center for Spermatogenic Failure 6

Genetic Tests for Spermatogenic Failure 6

Genetic tests related to Spermatogenic Failure 6:

# Genetic test Affiliating Genes
1 Globozoospermia 29 SPATA16

Anatomical Context for Spermatogenic Failure 6

MalaCards organs/tissues related to Spermatogenic Failure 6:

41
Bone, Testes, Testis
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Spermatogenic Failure 6:
# Tissue Anatomical CompartmentCell Relevance
1 Testis Seminiferous Tubules Elongated Spermatid Affected by disease

Publications for Spermatogenic Failure 6

Articles related to Spermatogenic Failure 6:

(show top 50) (show all 189)
# Title Authors PMID Year
1
Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. 38 8 71
17847006 2007
2
Evaluation and treatment of familial globozoospermia in five brothers. 38 8 71
15533374 2004
3
Globozoospermia is mainly due to DPY19L2 deletion via non-allelic homologous recombination involving two recombination hotspots. 38 71
22653751 2012
4
DPY19L2 deletion as a major cause of globozoospermia. 38 71
21397063 2011
5
A recurrent deletion of DPY19L2 causes infertility in man by blocking sperm head elongation and acrosome formation. 38 71
21397064 2011
6
Lack of acrosome formation in mice lacking a Golgi protein, GOPC. 38 8
12149515 2002
7
Failure of oocyte activation after intracytoplasmic sperm injection using round-headed sperm. 38 8
9207595 1997
8
Ultrastructural features of round-headed human spermatozoa. 8
1349598 1992
9
Male infertility associated with round-headed acrosomeless spermatozoa. 8
3338587 1988
10
Biochemical and genetic investigation of round-headed spermatozoa in infertile men including two brothers and their father. 8
6380341 1984
11
Acrosin and the acrosome in human spermatogenesis. 8
6357995 1983
12
[Absolute teratozoospermia in a family. Irregular microcephalic spermatozoa without acrosome]. 8
686404 1978
13
A possible haploid effect in acrosome malformations of human spermatozoa. 8
596658 1977
14
On round-headed human spermatozoa. 8
4383 1975
15
[Etiologic analysis of globozoospermia: a 1-case report]. 9 38
16833197 2006
16
Search for mutations involved in human globozoospermia. 9 38
15746197 2005
17
Searching for candidate genes for male infertility. 9 38
12778326 2003
18
Globozoospermia in mice lacking the casein kinase II alpha' catalytic subunit. 9 38
10471512 1999
19
Reduction of truncated Kit Expression in Men with Abnormal Semen Parameters, Globozoospermia and History of Low or Fertilization Failure. 38
31210438 2019
20
Proteomic Analysis of Dpy19l2-Deficient Human Globozoospermia Reveals Multiple Molecular Defects. 38
31424156 2019
21
Comparison of sperm morphology and nuclear sperm quality in SPATA16- and DPY19L2-mutated globozoospermic patients. 38
30912172 2019
22
New insights into sperm with total globozoospermia: Increased fatty acid oxidation and centrin1 alteration. 38
31204846 2019
23
Embryos derived from couples with consanguineous marriages with globozoospermia should be screened for gender or DPY19L2 deletion. 38
30584989 2019
24
Increase of germ cell nuclear factor expression in globozoospermic Gopc-/- knockout mice. 38
30786176 2019
25
A homozygous RNF220 mutation leads to male infertility with small-headed sperm. 38
30500349 2019
26
Assessment of sperm PAWP expression in infertile men. 38
30882161 2019
27
A successful healthy childbirth and an ongoing evolutive pregnancy in a case of partial globozoospermia by hyaluronic acid sperm selection. 38
30324675 2019
28
Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility. 38
30333325 2019
29
An Overview of The Globozoospermia as A Multigenic Identified Syndrome. 38
30291685 2019
30
Mouse DCUN1D1 (SCCRO) is required for spermatogenetic individualization. 38
30653527 2019
31
Artificial oocyte activation with calcium ionophore for frozen sperm cycles. 38
29620419 2018
32
Artificial oocyte activation with SrCl2 or calcimycin after ICSI improves clinical and embryological outcomes compared with ICSI alone: results of a randomized clinical trial. 38
30099496 2018
33
AU040320 deficiency leads to disruption of acrosome biogenesis and infertility in homozygous mutant mice. 38
29991750 2018
34
Obstetric and neonatal outcome following ICSI with assisted oocyte activation by calcium ionophore treatment. 38
29392515 2018
35
Prediction of male infertility by the World Health Organization laboratory manual for assessment of semen analysis: A systematic review. 38
29713540 2018
36
Expression of sperm PLCĪ¶ and clinical outcomes of ICSI-AOA in men affected by globozoospermia due to DPY19L2 deletion. 38
29339016 2018
37
Association between total globozoospermia and sperm chromatin defects. 38
28660655 2018
38
Sperm chromatin quality and DNA integrity in partial versus total globozoospermia. 38
28517043 2018
39
Intracytoplasmic Sperm Injection with Assisted Oocyte Activation Resulting in Successful Pregnancies and Live Birth in Couples with Globozoospermia: A Report of Two Cases. 38
29681719 2018
40
DNAH6 is a novel candidate gene associated with sperm head anomaly. 38
29356036 2018
41
Abnormal retention of nuclear lamina and disorganization of chromatin-related proteins in spermatozoa from DPY19L2-deleted globozoospermic patients. 38
28882431 2017
42
Human Globozoospermia-Related Gene Spata16 Is Required for Sperm Formation Revealed by CRISPR/Cas9-Mediated Mouse Models. 38
29065458 2017
43
[Mutation analysis and treatment of a case with globozoospermia]. 38
28981950 2017
44
Essential role for SUN5 in anchoring sperm head to the tail. 38
28945193 2017
45
Sperm morphology: assessment, pathophysiology, clinical relevance, and state of the art in 2017. 38
28692759 2017
46
Dynamic of contribution of UBPy-sorted cargo to acrosome biogenesis: effects of its derailment in a mouse model of globozoospermia, the infertile Vps54 (L967Q) mutant. 38
28299521 2017
47
Loss of the Na+/H+ exchanger NHE8 causes male infertility in mice by disrupting acrosome formation. 38
28476888 2017
48
Decreased fertilization seen in globozoospermia can be overcome with a modified ICSI technique in both IVF and IVM cycles. 38
28116890 2017
49
Genetic abnormalities leading to qualitative defects of sperm morphology or function. 38
27779748 2017
50
Sirt1 regulates acrosome biogenesis by modulating autophagic flux during spermiogenesis in mice. 38
28003215 2017

Variations for Spermatogenic Failure 6

ClinVar genetic disease variations for Spermatogenic Failure 6:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 SPATA16 NM_031955.6(SPATA16): c.1588-2A> G single nucleotide variant Uncertain significance 3:172607484-172607484 3:172889694-172889694
2 SPATA16 NM_031955.6(SPATA16): c.848G> A (p.Arg283Gln) single nucleotide variant Uncertain significance rs137853118 3:172737276-172737276 3:173019486-173019486

UniProtKB/Swiss-Prot genetic disease variations for Spermatogenic Failure 6:

74
# Symbol AA change Variation ID SNP ID
1 SPATA16 p.Arg283Gln VAR_038334 rs137853118

Expression for Spermatogenic Failure 6

Search GEO for disease gene expression data for Spermatogenic Failure 6.

Pathways for Spermatogenic Failure 6

GO Terms for Spermatogenic Failure 6

Cellular components related to Spermatogenic Failure 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 postsynaptic membrane GO:0045211 8.62 PICK1 GOPC

Biological processes related to Spermatogenic Failure 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 spermatogenesis GO:0007283 8.8 SPATA16 DPY19L2 CSNK2A2

Sources for Spermatogenic Failure 6

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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