Oocyte maturation defect 2

disease

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Also known as inherited oocyte maturation defect caused by mutation in TUBB8OOMD2TUBB8 inherited oocyte maturation defect

Summary

Oocyte maturation defect 2 (MONDO:0021573) is a disease caused by TUBB8 (GenCC Definitive), with 1 cohort gene.

At a glance

Causal gene: TUBB8 (GenCC Definitive)
Cohort genes: 1
ClinVar variants: 69

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oocyte maturation defect 2
Mondo ID	MONDO:0021573
OMIM	616780
UMLS	C4225210
MedGen	903836
GARD	0018496
Is cancer (heuristic)	no

Also known as: inherited oocyte maturation defect caused by mutation in TUBB8 · oocyte maturation defect 2 · OOMD2 · TUBB8 inherited oocyte maturation defect

Data availability: 69 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited oocyte maturation defect › oocyte maturation defect 2

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

69 retrieved; paginated sample, class counts are floors:

31 likely pathogenic, 13 uncertain significance, 12 benign, 12 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
221268	NM_177987.3(TUBB8):c.686T>C (p.Val229Ala)	TUBB8	Pathogenic	criteria provided, single submitter
221269	NM_177987.3(TUBB8):c.1249G>A (p.Asp417Asn)	TUBB8	Pathogenic	criteria provided, single submitter
221270	NM_177987.3(TUBB8):c.5G>A (p.Arg2Lys)	TUBB8	Pathogenic	criteria provided, single submitter
223143	NM_177987.3(TUBB8):c.527C>T (p.Ser176Leu)	TUBB8	Pathogenic	criteria provided, single submitter
223144	NM_177987.3(TUBB8):c.785G>A (p.Arg262Gln)	TUBB8	Pathogenic	criteria provided, single submitter
223145	NM_177987.3(TUBB8):c.1088T>C (p.Met363Thr)	TUBB8	Pathogenic	criteria provided, single submitter
223146	NM_177987.3(TUBB8):c.900G>A (p.Met300Ile)	TUBB8	Pathogenic	criteria provided, single submitter
378059	NM_177987.3(TUBB8):c.713C>T (p.Thr238Met)	TUBB8	Pathogenic	no assertion criteria provided
378060	NM_177987.3(TUBB8):c.80_100del (p.Glu27_Ala33del)	TUBB8	Pathogenic	no assertion criteria provided
378061	NM_177987.3(TUBB8):c.426dup (p.Thr143fs)	TUBB8	Pathogenic	no assertion criteria provided
977667	NM_177987.3(TUBB8):c.1203_1204insCT (p.Gly402fs)	TUBB8	Pathogenic	no assertion criteria provided
977673	NM_177987.3(TUBB8):c.722G>A (p.Arg241His)	TUBB8	Pathogenic	no assertion criteria provided
444045	NM_001387263.1(PATL2):c.478C>T (p.Arg160Ter)	LOC130056977	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3382491	NM_177987.3(TUBB8):c.322G>A (p.Glu108Lys)	TUBB8	Likely pathogenic	criteria provided, single submitter
4686581	NM_177987.3(TUBB8):c.880T>C (p.Phe294Leu)	TUBB8	Likely pathogenic	criteria provided, single submitter
4686582	NM_177987.3(TUBB8):c.1030T>A (p.Trp344Arg)	TUBB8	Likely pathogenic	criteria provided, single submitter
4686583	NM_177987.3(TUBB8):c.404_405dup (p.Thr136Ter)	TUBB8	Likely pathogenic	criteria provided, single submitter
4845687	NM_177987.3(TUBB8):c.227_228del (p.Val76fs)	TUBB8	Likely pathogenic	criteria provided, single submitter
684762	NM_177987.3(TUBB8):c.735G>C (p.Gln245His)	TUBB8	Likely pathogenic	criteria provided, single submitter
694522	NM_177987.3(TUBB8):c.763G>A (p.Val255Met)	TUBB8	Likely pathogenic	criteria provided, multiple submitters, no conflicts
977653	NM_177987.3(TUBB8):c.394G>T (p.Gly132Cys)	TUBB8	Likely pathogenic	no assertion criteria provided
977654	NM_177987.3(TUBB8):c.422G>C (p.Gly141Ala)	TUBB8	Likely pathogenic	no assertion criteria provided
977655	NM_177987.3(TUBB8):c.1189T>G (p.Trp397Gly)	TUBB8	Likely pathogenic	no assertion criteria provided
977656	NM_177987.3(TUBB8):c.1163T>C (p.Met388Thr)	TUBB8	Likely pathogenic	no assertion criteria provided
977658	NM_177987.3(TUBB8):c.539T>C (p.Val180Ala)	TUBB8	Likely pathogenic	no assertion criteria provided
977659	NM_177987.3(TUBB8):c.550A>G (p.Asn184Asp)	TUBB8	Likely pathogenic	no assertion criteria provided
977660	NM_177987.3(TUBB8):c.1242C>G (p.Asn414Lys)	TUBB8	Likely pathogenic	no assertion criteria provided
977661	NM_177987.3(TUBB8):c.1271A>G (p.Gln424Arg)	TUBB8	Likely pathogenic	no assertion criteria provided
977662	NM_177987.3(TUBB8):c.1178C>A (p.Ala393Asp)	TUBB8	Likely pathogenic	no assertion criteria provided
977663	NM_177987.3(TUBB8):c.629T>A (p.Ile210Lys)	TUBB8	Likely pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
TUBB8	Definitive	Semidominant	oocyte maturation defect 2	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TUBB8	Orphanet:488191	Female infertility due to oocyte meiotic arrest

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TUBB8	HGNC:20773	ENSG00000261456	Q3ZCM7	Tubulin beta-8 chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TUBB8	Tubulin beta-8 chain	Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TUBB8	Other/Unknown	no		Tubulin, Beta_tubulin, Tubulin_FtsZ_GTPase

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TUBB8	107		marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TUBB8	4,732

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TUBB8	Q3ZCM7	91.99

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 77. Enrichment computed across 1 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
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	1	543.8×	0.019	TUBB8
Transport of connexons to the plasma membrane	1	543.8×	0.019	TUBB8
Gap junction trafficking and regulation	1	475.8×	0.019	TUBB8
Gap junction trafficking	1	475.8×	0.019	TUBB8
Activation of AMPK downstream of NMDARs	1	380.7×	0.019	TUBB8
RHO GTPases activate IQGAPs	1	346.1×	0.019	TUBB8
Sealing of the nuclear envelope (NE) by ESCRT-III	1	346.1×	0.019	TUBB8
HCMV Infection	1	326.3×	0.019	TUBB8
Gap junction assembly	1	292.8×	0.019	TUBB8
Nuclear Envelope (NE) Reassembly	1	292.8×	0.019	TUBB8
Selective autophagy	1	278.5×	0.019	TUBB8
Assembly and cell surface presentation of NMDA receptors	1	253.8×	0.019	TUBB8
Cargo trafficking to the periciliary membrane	1	248.3×	0.019	TUBB8
Aggrephagy	1	248.3×	0.019	TUBB8
Carboxyterminal post-translational modifications of tubulin	1	237.9×	0.019	TUBB8
Recycling pathway of L1	1	223.9×	0.019	TUBB8
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.019	TUBB8
Post NMDA receptor activation events	1	203.9×	0.019	TUBB8
Antimicrobial mechanism of IFN-stimulated genes	1	196.9×	0.019	TUBB8
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	193.6×	0.019	TUBB8
Activation of NMDA receptors and postsynaptic events	1	184.2×	0.019	TUBB8
Kinesins	1	178.4×	0.019	TUBB8
The role of GTSE1 in G2/M progression after G2 checkpoint	1	160.8×	0.019	TUBB8
Translocation of SLC2A4 (GLUT4) to the plasma membrane	1	154.3×	0.019	TUBB8
Autophagy	1	148.3×	0.019	TUBB8
PKR-mediated signaling	1	141.0×	0.019	TUBB8
ER to Golgi Anterograde Transport	1	132.8×	0.019	TUBB8
Golgi-to-ER retrograde transport	1	132.8×	0.019	TUBB8
Mitotic G2-G2/M phases	1	126.9×	0.019	TUBB8
G2/M Transition	1	126.9×	0.019	TUBB8

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
spindle assembly involved in female meiosis	1	1872.4×	0.002	TUBB8
oocyte maturation	1	601.9×	0.003	TUBB8
mitotic cell cycle	1	133.8×	0.008	TUBB8
microtubule cytoskeleton organization	1	121.2×	0.008	TUBB8

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
TUBB8	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TUBB8	21	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
COLCHICINE	4	TUBB8
VINBLASTINE	4	TUBB8
LEVOFLOXACIN ANHYDROUS	4	TUBB8
DOCETAXEL	4	TUBB8
NOSCAPINE	4	TUBB8
VINBLASTINE SULFATE	4	TUBB8
PACLITAXEL	4	TUBB8
LEVOFLOXACIN	4	TUBB8
VINORELBINE	4	TUBB8
TIRBANIBULIN	4	TUBB8
PODOFILOX	4	TUBB8
VINCRISTINE	4	TUBB8
DOCETAXEL ANHYDROUS	4	TUBB8
PATUPILONE	3	TUBB8
ABT-751	2	TUBB8
MAYTANSINE	2	TUBB8
DOLASTATIN-10	2	TUBB8
INDIBULIN	2	TUBB8
PARBENDAZOLE	2	TUBB8
NOCODAZOLE	2	TUBB8
COMBRETASTATIN	1	TUBB8

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
TUBB8	1,757	Binding:1717, Functional:34, ADMET:6

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
TUBB8	1,757

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

21 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)
COLCHICINE	4	TUBB8
VINBLASTINE	4	TUBB8
LEVOFLOXACIN ANHYDROUS	4	TUBB8
DOCETAXEL	4	TUBB8
NOSCAPINE	4	TUBB8
VINBLASTINE SULFATE	4	TUBB8
PACLITAXEL	4	TUBB8
LEVOFLOXACIN	4	TUBB8
VINORELBINE	4	TUBB8
TIRBANIBULIN	4	TUBB8
PODOFILOX	4	TUBB8
VINCRISTINE	4	TUBB8
DOCETAXEL ANHYDROUS	4	TUBB8
PATUPILONE	3	TUBB8
ABT-751	2	TUBB8
MAYTANSINE	2	TUBB8
DOLASTATIN-10	2	TUBB8
INDIBULIN	2	TUBB8
PARBENDAZOLE	2	TUBB8
NOCODAZOLE	2	TUBB8
COMBRETASTATIN	1	TUBB8

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	TUBB8
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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: TUBB8