Oligoasthenoteratozoospermia

Summary

Oligoasthenoteratozoospermia (MONDO:0850098) is a disease with 4 cohort genes and 6 clinical trials.

At a glance

• Cohort genes: 4
• ClinVar variants: 6
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oligoasthenoteratozoospermia
Mondo ID	MONDO:0850098
DOID	DOID:0070311
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › male reproductive system disorder › male infertility › oligoasthenoteratozoospermia

Related subtypes (7): infertility due to extratesticular cause, oligospermia, spermatogenic failure, partial chromosome Y deletion, male infertility with teratozoospermia due to single gene mutation, male infertility due to acephalic spermatozoa, azoospermia

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

ClinVar germline variants

6 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2687797	NM_001379451.1(BCORL1):c.2615T>G (p.Val872Gly)	BCORL1	Pathogenic	no assertion criteria provided
2687871	NM_001379451.1(BCORL1):c.4171G>A (p.Gly1391Arg)	BCORL1	Pathogenic	no assertion criteria provided
3901150	NM_014641.3(MDC1):c.5644C>T (p.Arg1882Ter)	MDC1	Pathogenic	criteria provided, single submitter
3901151	NM_014641.3(MDC1):c.1A>T (p.Met1Leu)	MDC1	Pathogenic	criteria provided, single submitter
3901223	NM_014641.3(MDC1):c.5977C>T (p.Arg1993Ter)	MDC1	Pathogenic	criteria provided, single submitter
3773738	NM_006602.4(TCFL5):c.1207G>A (p.Glu403Lys)	TCFL5	Conflicting classifications of pathogenicity	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 1 · 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
DNAH12	Limited	Autosomal recessive	oligoasthenoteratozoospermia

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCORL1	Orphanet:528084	Non-specific syndromic intellectual disability

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNAH12	HGNC:2943	ENSG00000174844	Q6ZR08	Dynein axonemal heavy chain 12	gencc
TCFL5	HGNC:11646	ENSG00000101190	Q9UL49	Transcription factor-like 5 protein	clinvar
MDC1	HGNC:21163	ENSG00000137337	Q14676	Mediator of DNA damage checkpoint protein 1	clinvar
BCORL1	HGNC:25657	ENSG00000085185	Q5H9F3	BCL-6 corepressor-like protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAH12	Dynein axonemal heavy chain 12	Involved in spermiogenesis.
TCFL5	Transcription factor-like 5 protein	Putative transcription factor.
MDC1	Mediator of DNA damage checkpoint protein 1	Histone reader protein required for checkpoint-mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle.
BCORL1	BCL-6 corepressor-like protein 1	Transcriptional corepressor.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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	4.3×	0.605
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAH12	Other/Unknown	no		AAA+_ATPase, Dhc_D6_P-loop, Dhc_linker
TCFL5	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, TCFL5/SOLH1/2
MDC1	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
BCORL1	Scaffold/PPI	no		Ankyrin_rpt, PUFD, Ankyrin_rpt-contain_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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
bronchus	1
right uterine tube	1
adult organism	1
male germ cell	1
sperm	1
left testis	1
right testis	1
testis	1
cardia of stomach	1
cervix squamous epithelium	1
vena cava	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAH12	174	tissue_specific	marker	bronchial epithelial cell, bronchus, right uterine tube
TCFL5	272	ubiquitous	marker	sperm, adult organism, male germ cell
MDC1	134	ubiquitous	yes	right testis, left testis, testis
BCORL1	250	ubiquitous	marker	cervix squamous epithelium, cardia of stomach, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MDC1	3,633
BCORL1	1,513
DNAH12	1,268
TCFL5	506

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MDC1	Q14676	12
BCORL1	Q5H9F3	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TCFL5	Q9UL49	54.93
DNAH12	Q6ZR08

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 22. Enrichment computed across 4 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
DNA Double Strand Break Response	1	475.8×	0.015	MDC1
Homology Directed Repair	1	308.6×	0.015	MDC1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	308.6×	0.015	MDC1
DNA Double-Strand Break Repair	1	248.3×	0.015	MDC1
TP53 Regulates Transcription of DNA Repair Genes	1	181.3×	0.015	MDC1
SUMO E3 ligases SUMOylate target proteins	1	178.4×	0.015	MDC1
Nonhomologous End-Joining (NHEJ)	1	167.9×	0.015	MDC1
SUMOylation	1	163.1×	0.015	MDC1
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.015	MDC1
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	146.4×	0.015	MDC1
G2/M Checkpoints	1	134.3×	0.015	MDC1
G2/M DNA damage checkpoint	1	120.2×	0.015	MDC1
Processing of DNA double-strand break ends	1	114.2×	0.015	MDC1
DNA Repair	1	98.5×	0.016	MDC1
Cell Cycle Checkpoints	1	88.5×	0.017	MDC1
Transcriptional Regulation by TP53	1	62.1×	0.022	MDC1
Cell Cycle	1	36.0×	0.036	MDC1
RNA Polymerase II Transcription	1	22.5×	0.054	MDC1
Post-translational protein modification	1	19.2×	0.060	MDC1
Gene expression (Transcription)	1	17.8×	0.062	MDC1
Generic Transcription Pathway	1	15.1×	0.069	MDC1
Metabolism of proteins	1	12.4×	0.081	MDC1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
DNA replication checkpoint signaling	1	324.1×	0.017	MDC1
axonemal dynein complex assembly	1	263.3×	0.017	DNAH12
protein localization to site of double-strand break	1	263.3×	0.017	MDC1
mitotic intra-S DNA damage checkpoint signaling	1	234.1×	0.017	MDC1
sperm axoneme assembly	1	117.0×	0.025	DNAH12
regulation of cell differentiation	1	108.0×	0.025	TCFL5
negative regulation of transcription by RNA polymerase II	2	8.9×	0.040	TCFL5, BCORL1
spermatid development	1	36.3×	0.055	DNAH12
regulation of cell population proliferation	1	28.9×	0.061	TCFL5
chromatin organization	1	24.8×	0.064	BCORL1
transcription by RNA polymerase II	1	17.6×	0.081	TCFL5
DNA repair	1	16.0×	0.082	MDC1
DNA damage response	1	13.4×	0.089	MDC1
spermatogenesis	1	8.8×	0.125	TCFL5
regulation of DNA-templated transcription	1	7.9×	0.129	TCFL5
cell differentiation	1	7.3×	0.131	TCFL5

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MDC1	1	2
DNAH12	0	0
TCFL5	0	0
BCORL1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	MDC1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MDC1	6	Binding:6
DNAH12	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	MDC1

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	1	MDC1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	DNAH12, TCFL5, BCORL1

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)
DNAH12	1	—
TCFL5	0	—
BCORL1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07579858	PHASE3	COMPLETED	PRP Improves Blastocyst Formation in ICSI Cycles
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT07345455	Not specified	RECRUITING	Probiotics on Sperm Quality in Male Infertility Patients
NCT02752555	Not specified	UNKNOWN	Severe Male Factor Infertility Management
NCT06088693	Not specified	COMPLETED	The Role of Electroacupuncture With Standard Therapy on Sperm Analysis and SOD Levels in Oligozoospermia.
NCT07286279	Not specified	COMPLETED	Identifying Candidates for Limited Dissection at Microdissection TESE.