Premature ovarian failure 12

disease

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Also known as POF12premature ovarian failure 12premature ovarian failure type 12primary ovarian failure caused by mutation in SYCE1SYCE1 primary ovarian failure

Summary

Premature ovarian failure 12 (MONDO:0014844) is a disease caused by SYCE1 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

Causal gene: SYCE1 (GenCC Strong)
Cohort genes: 1
ClinVar variants: 7
Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 12
Mondo ID	MONDO:0014844
OMIM	616947
UMLS	C4310782
MedGen	934749
GARD	0025025
Is cancer (heuristic)	no

Also known as: POF12 · premature ovarian failure 12 · premature ovarian failure 12; POF12 · premature ovarian failure type 12 · primary ovarian failure caused by mutation in SYCE1 · SYCE1 primary ovarian failure

Data availability: 7 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inherited primary ovarian failure › premature ovarian failure 12

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

7 retrieved; paginated sample, class counts are floors:

6 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
226122	NM_001143764.3(SYCE1):c.721C>T (p.Gln241Ter)	SYCE1	Pathogenic	no assertion criteria provided
4796749	SYCE1, IVS4, G-A, +1	SYCE1	Pathogenic	no assertion criteria provided
4796750	SYCE1, 2-BP DEL, 689TT	SYCE1	Pathogenic	no assertion criteria provided
4796751	NM_001143764.3(SYCE1):c.475G>A (p.Glu159Lys)	SYCE1	Pathogenic	no assertion criteria provided
4796753	SYCE1, ARG52TER	SYCE1	Pathogenic	no assertion criteria provided
4796754	SYCE1, 1-BP DEL, NT675	SYCE1	Pathogenic	no assertion criteria provided
4796755	NM_001143764.3(SYCE1):c.271+1G>A	SYCE1	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
SYCE1	Strong	Autosomal recessive	premature ovarian failure 12	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SYCE1	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation

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
SYCE1	HGNC:28852	ENSG00000171772	Q8N0S2	Synaptonemal complex central element protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SYCE1	Synaptonemal complex central element protein 1	Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase.

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)
SYCE1	Other/Unknown	no		SYCE1

Expression context

Cohort genes with no expression data: 0.

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
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SYCE1	162	broad	yes	right testis, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SYCE1	1,334

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SYCE1	Q8N0S2	79.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Meiosis	1	285.5×	0.009	SYCE1
Reproduction	1	190.3×	0.009	SYCE1
Meiotic synapsis	1	141.0×	0.009	SYCE1
Cell Cycle	1	36.0×	0.028	SYCE1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
synaptonemal complex assembly	1	648.1×	0.003	SYCE1
cell division	1	46.2×	0.022	SYCE1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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
SYCE1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SYCE1

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)
SYCE1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation

Cohort genes: SYCE1