Male infertility due to globozoospermia

Summary

Male infertility due to globozoospermia (MONDO:0015746) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	male infertility due to globozoospermia
Mondo ID	MONDO:0015746
Orphanet	171709
DOID	DOID:0112312
UMLS	C5679591
MedGen	1826006
GARD	0012502
Is cancer (heuristic)	no

Also known as: male infertility due to globozoospermia · Male infertility due to round-headed spermatozoa · male infertility due to round-headed spermatozoa · round-headed sperm syndrome

Data availability: 3 GenCC gene-disease records · 8 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › male reproductive system disorder › male infertility › male infertility with teratozoospermia due to single gene mutation › male infertility due to globozoospermia

Related subtypes (2): spermatogenic failure 5, spermatogenic failure 12

Subtypes (2): spermatogenic failure 6, spermatogenic failure 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DPY19L2	Supportive	Autosomal recessive	male infertility due to globozoospermia	4
PICK1	Supportive	Autosomal recessive	male infertility due to globozoospermia
SPATA16	Supportive	Autosomal recessive	male infertility due to globozoospermia	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DPY19L2	Orphanet:171709	Male infertility due to globozoospermia
SPATA16	Orphanet:171709	Male infertility due to globozoospermia
PICK1	Orphanet:171709	Male infertility due to globozoospermia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DPY19L2	HGNC:19414	ENSG00000177990	Q6NUT2	Probable C-mannosyltransferase DPY19L2	gencc
SPATA16	HGNC:29935	ENSG00000144962	Q9BXB7	Spermatogenesis-associated protein 16	gencc
PICK1	HGNC:9394	ENSG00000100151	Q9NRD5	PRKCA-binding protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DPY19L2	Probable C-mannosyltransferase DPY19L2	Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.
SPATA16	Spermatogenesis-associated protein 16	Essential for spermiogenesis and male fertility.
PICK1	PRKCA-binding protein	Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DPY19L2	Other/Unknown	no		Dpy-19/Dpy-19-like
SPATA16	Other/Unknown	no		TPR-like_helical_dom_sf, SPATA16
PICK1	Scaffold/PPI	no		PDZ, AH_dom, AH/BAR_dom_sf

Expression context

Cohort genes with no expression data: 0.

3 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
apex of heart	1
popliteal artery	1
tibial artery	1
left testis	1
right testis	1
sperm	1
adenohypophysis	1
right hemisphere of cerebellum	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DPY19L2	202	broad	marker	apex of heart, popliteal artery, tibial artery
SPATA16	30	tissue_specific	marker	sperm, left testis, right testis
PICK1	199	ubiquitous	marker	adenohypophysis, right hemisphere of cerebellum, right uterine tube

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PICK1	4,112
SPATA16	899
DPY19L2	671

Intra-cohort edges

A	B	Sources
DPY19L2	PICK1	string_interaction
DPY19L2	SPATA16	string_interaction
PICK1	SPATA16	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PICK1	Q9NRD5	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
DPY19L2	Q6NUT2	81.61
SPATA16	Q9BXB7	72.84

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 3 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Trafficking of GluR2-containing AMPA receptors	1	671.8×	0.003	PICK1
Cell surface interactions at the vascular wall	1	95.2×	0.011	PICK1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
spermatid development	2	96.8×	0.002	DPY19L2, SPATA16
glial cell development	1	1872.4×	0.002	PICK1
neuronal ion channel clustering	1	1872.4×	0.002	PICK1
cellular response to decreased oxygen levels	1	1404.3×	0.002	PICK1
dendritic spine organization	1	1404.3×	0.002	PICK1
negative regulation of Arp2/3 complex-mediated actin nucleation	1	802.5×	0.004	PICK1
dendritic spine maintenance	1	432.1×	0.005	PICK1
obsolete monoamine transport	1	401.2×	0.005	PICK1
regulation of Arp2/3 complex-mediated actin nucleation	1	351.1×	0.005	PICK1
long-term synaptic depression	1	295.6×	0.006	PICK1
positive regulation of receptor internalization	1	234.1×	0.007	PICK1
receptor clustering	1	208.1×	0.007	PICK1
regulation of insulin secretion	1	130.6×	0.010	PICK1
cellular response to glucose starvation	1	112.3×	0.011	PICK1
protein phosphorylation	1	22.6×	0.048	PICK1
intracellular protein transport	1	21.6×	0.048	PICK1
spermatogenesis	1	11.7×	0.083	SPATA16

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 0 of 3 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DPY19L2	0	0
SPATA16	0	0
PICK1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	DPY19L2, SPATA16, PICK1

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DPY19L2	0	—
SPATA16	0	—
PICK1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.