Oocyte/zygote/embryo maturation arrest 16

Summary

Oocyte/zygote/embryo maturation arrest 16 (MONDO:1010200) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	oocyte/zygote/embryo maturation arrest 16
Mondo ID	MONDO:1010200
OMIM	617234
Is cancer (heuristic)	no

Also known as: PADI6 preimplantation embryonic lethality · PADI6-related oocyte/zygote/embryo maturation arrest 16 and maternal-effect disorder · preimplantation embryonic lethality type 2 · PREMBL2

Data availability: 25 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited oocyte maturation defect › oocyte/zygote/embryo maturation arrest 16

Related subtypes (23): female infertility due to zona pellucida defect, oocyte maturation defect 5, oocyte maturation defect 2, oocyte maturation defect 3, oocyte maturation defect 4, oocyte maturation defect 11, oocyte maturation defect 12, oocyte maturation defect 10, oocyte maturation defect 6, oocyte maturation defect 7, oocyte maturation defect 8, oocyte maturation defect 9, oocyte maturation defect 13, oocyte maturation defect 14, oocyte/zygote/embryo maturation arrest 17, oocyte/zygote/embryo maturation arrest 18, oocyte/zygote/embryo maturation arrest 19, oocyte/zygote/embryo maturation arrest 20, oocyte/zygote/embryo maturation arrest 21, oocyte/zygote/embryo maturation arrest 22, oocyte/zygote/embryo maturation arrest 23, oocyte/zygote/embryo maturation arrest 24, oocyte/zygote/embryo maturation arrest 25

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

25 retrieved; paginated sample, class counts are floors:

9 pathogenic, 7 likely pathogenic, 7 uncertain significance, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1308678	NM_207421.4(PADI6):c.559dup (p.Thr187fs)	LOC126805634	Pathogenic	criteria provided, single submitter
372230	NM_207421.4(PADI6):c.633T>A (p.His211Gln)	LOC126805634	Pathogenic	criteria provided, single submitter
372228	NM_207421.4(PADI6):c.1141C>T (p.Gln381Ter)	LOC126805635	Pathogenic	no assertion criteria provided
1308679	NM_207421.4(PADI6):c.1043_1044dup (p.Asp349fs)	PADI6	Pathogenic	criteria provided, single submitter
1308683	NM_207421.4(PADI6):c.707dup (p.Leu237fs)	PADI6	Pathogenic	criteria provided, single submitter
1308687	NM_207421.4(PADI6):c.5dup (p.Ser3fs)	PADI6	Pathogenic	criteria provided, single submitter
1308688	NM_207421.4(PADI6):c.1996dup (p.Cys666fs)	PADI6	Pathogenic	criteria provided, single submitter
372229	NM_207421.4(PADI6):c.2009_2010del (p.Glu670fs)	PADI6	Pathogenic	criteria provided, single submitter
372231	NM_207421.4(PADI6):c.970C>T (p.Gln324Ter)	PADI6	Pathogenic	no assertion criteria provided
1308676	NM_207421.4(PADI6):c.659C>A (p.Ala220Glu)	PADI6	Likely pathogenic	criteria provided, single submitter
1308677	NM_207421.4(PADI6):c.1054C>T (p.Arg352Cys)	PADI6	Likely pathogenic	criteria provided, single submitter
1308681	NM_207421.4(PADI6):c.1894C>A (p.Pro632Thr)	PADI6	Likely pathogenic	criteria provided, single submitter
3075995	NM_207421.4(PADI6):c.721C>T (p.Gln241Ter)	PADI6	Likely pathogenic	criteria provided, single submitter
3382509	NM_207421.4(PADI6):c.19C>T (p.Arg7Ter)	PADI6	Likely pathogenic	criteria provided, single submitter
372232	NM_207421.4(PADI6):c.1618G>A (p.Gly540Arg)	PADI6	Likely pathogenic	criteria provided, single submitter
3780079	NM_207421.4(PADI6):c.1494+1G>T	PADI6	Likely pathogenic	criteria provided, single submitter
1308680	NM_207421.4(PADI6):c.1298C>T (p.Pro433Leu)	LOC126805635	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1308686	NM_207421.4(PADI6):c.1247T>C (p.Ile416Thr)	LOC126805635	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1308682	NM_207421.4(PADI6):c.1756G>A (p.Glu586Lys)	PADI6	Uncertain significance	criteria provided, single submitter
1308684	NM_207421.4(PADI6):c.1006A>C (p.Ser336Arg)	PADI6	Uncertain significance	criteria provided, single submitter
1308685	NM_207421.4(PADI6):c.294+5G>A	PADI6	Uncertain significance	criteria provided, single submitter
1308689	NM_207421.4(PADI6):c.1765C>A (p.Gln589Lys)	PADI6	Uncertain significance	criteria provided, single submitter
2434565	NM_207421.4(PADI6):c.1854dup (p.Arg619fs)	PADI6	Uncertain significance	criteria provided, single submitter
3780080	NM_207421.4(PADI6):c.1690-23CCCA[9]	PADI6	Uncertain significance	criteria provided, single submitter
4796587	NM_207421.4(PADI6):c.1403C>T (p.Pro468Leu)	PADI6	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
PADI6	HGNC:20449	ENSG00000276747	Q6TGC4	Inactive protein-arginine deiminase type-6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PADI6	Inactive protein-arginine deiminase type-6	Structural constituent of cytoplasmic lattices, which plays a key role in early embryonic development.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PADI6	Enzyme (other)	yes	3.5.3.15	PAD, Cupredoxin, PAD_C

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)	1
broad (>20)	0
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	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
PADI6	10		marker	male germ line stem cell (sensu Vertebrata) in testis, granulocyte, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PADI6	392

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PADI6	Q6TGC4	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
M-decay: degradation of maternal mRNAs by maternally stored factors	1	326.3×	0.006	PADI6
Chromatin modifying enzymes	1	72.3×	0.014	PADI6

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of translation by machinery localization	1	16852.0×	4e-04	PADI6
protein storage	1	3370.4×	8e-04	PADI6
cytoplasm organization	1	2808.7×	8e-04	PADI6
epigenetic programming in the zygotic pronuclei	1	1872.4×	8e-04	PADI6
embryonic cleavage	1	1685.2×	8e-04	PADI6
cytoskeleton organization	1	132.7×	0.009	PADI6
in utero embryonic development	1	72.0×	0.014	PADI6

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PADI6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PADI6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PADI6	3.5.3.15	protein-arginine deiminase

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

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	1	PADI6
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PADI6	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.