Premature ovarian failure 6

disease

On this page

Also known as FIGLA primary ovarian failurePof6premature ovarian failure type 6primary ovarian failure caused by mutation in FIGLA

Summary

Premature ovarian failure 6 (MONDO:0012861) is a disease caused by FIGLA (GenCC Strong), with 1 cohort gene and 2 clinical trials.

At a glance

Causal gene: FIGLA (GenCC Strong)
Cohort genes: 1
ClinVar variants: 32
Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	premature ovarian failure 6
Mondo ID	MONDO:0012861
MeSH	C567351
OMIM	612310
DOID	DOID:0080863
UMLS	C2676742
MedGen	394115
GARD	0024891
Is cancer (heuristic)	no

Also known as: FIGLA primary ovarian failure · Pof6 · premature ovarian failure 6 · premature ovarian failure type 6 · primary ovarian failure caused by mutation in FIGLA

Data availability: 32 ClinVar variants · 4 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 6

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

32 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 9 benign, 4 pathogenic, 3 likely benign, 1 benign/likely benign, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
2137	NM_001004311.3(FIGLA):c.15_36del (p.Gly6fs)	FIGLA	Pathogenic	no assertion criteria provided
2138	NM_001004311.3(FIGLA):c.416ACA[1] (p.Asn140del)	FIGLA	Pathogenic	no assertion criteria provided
3901241	NM_001004311.3(FIGLA):c.339T>G (p.Tyr113Ter)	FIGLA	Pathogenic	no assertion criteria provided
635131	NM_001004311.3(FIGLA):c.2T>C (p.Met1Thr)	FIGLA	Pathogenic	no assertion criteria provided
4292272	NM_001004311.3(FIGLA):c.164C>A (p.Ser55Ter)	FIGLA	Likely pathogenic	criteria provided, single submitter
898224	NM_001004311.3(FIGLA):c.277C>A (p.Pro93Thr)	FIGLA	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1256037	NM_001004311.3(FIGLA):c.326G>A (p.Gly109Asp)	FIGLA	Uncertain significance	criteria provided, single submitter
1256046	NM_001004311.3(FIGLA):c.11C>A (p.Ala4Glu)	FIGLA	Uncertain significance	criteria provided, multiple submitters, no conflicts
336906	NM_001004311.3(FIGLA):c.566G>A (p.Ser189Asn)	FIGLA	Uncertain significance	criteria provided, single submitter
336910	NM_001004311.3(FIGLA):c.384+11A>G	FIGLA	Uncertain significance	criteria provided, single submitter
336913	NM_001004311.3(FIGLA):c.154G>A (p.Gly52Ser)	FIGLA	Uncertain significance	criteria provided, single submitter
3892154	NM_001004311.3(FIGLA):c.345G>C (p.Gln115His)	FIGLA	Uncertain significance	criteria provided, single submitter
3892158	NM_001004311.3(FIGLA):c.92G>A (p.Arg31Gln)	FIGLA	Uncertain significance	criteria provided, single submitter
4257626	NM_001004311.3(FIGLA):c.599C>T (p.Thr200Ile)	FIGLA	Uncertain significance	criteria provided, multiple submitters, no conflicts
898225	NM_001004311.3(FIGLA):c.247C>T (p.Arg83Cys)	FIGLA	Uncertain significance	criteria provided, single submitter
898227	NM_001004311.3(FIGLA):c.73G>A (p.Val25Met)	FIGLA	Uncertain significance	criteria provided, multiple submitters, no conflicts
899335	NM_001004311.3(FIGLA):c.29C>A (p.Pro10His)	FIGLA	Uncertain significance	criteria provided, multiple submitters, no conflicts
899336	NM_001004311.3(FIGLA):c.28C>T (p.Pro10Ser)	FIGLA	Uncertain significance	criteria provided, multiple submitters, no conflicts
899337	NM_001004311.3(FIGLA):c.21C>T (p.Val7=)	FIGLA	Uncertain significance	criteria provided, single submitter
1285270	NM_001004311.3(FIGLA):c.231+24T>C	FIGLA	Benign	criteria provided, multiple submitters, no conflicts
197698	NM_001004311.3(FIGLA):c.*5T>A	FIGLA	Benign	criteria provided, multiple submitters, no conflicts
197699	NM_001004311.3(FIGLA):c.*7A>G	FIGLA	Benign	criteria provided, multiple submitters, no conflicts
336904	NM_001004311.3(FIGLA):c.*53A>C	FIGLA	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
336907	NM_001004311.3(FIGLA):c.552C>T (p.His184=)	FIGLA	Benign	criteria provided, multiple submitters, no conflicts
336908	NM_001004311.3(FIGLA):c.443C>T (p.Ser148Leu)	FIGLA	Likely benign	criteria provided, multiple submitters, no conflicts
336909	NM_001004311.3(FIGLA):c.422G>C (p.Ser141Thr)	FIGLA	Benign	criteria provided, multiple submitters, no conflicts
336911	NM_001004311.3(FIGLA):c.248G>A (p.Arg83His)	FIGLA	Likely benign	criteria provided, single submitter
336912	NM_001004311.3(FIGLA):c.234A>T (p.Ile78=)	FIGLA	Benign	criteria provided, multiple submitters, no conflicts
336914	NM_001004311.3(FIGLA):c.84C>A (p.Asp28Glu)	FIGLA	Benign	criteria provided, single submitter
895185	NM_001004311.3(FIGLA):c.625G>A (p.Val209Ile)	FIGLA	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
FIGLA	Strong	Autosomal recessive	premature ovarian failure 6	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FIGLA	Orphanet:243	46,XX gonadal dysgenesis

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
FIGLA	HGNC:24669	ENSG00000183733	Q6QHK4	Factor in the germline alpha	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FIGLA	Factor in the germline alpha	Germline specific transcription factor implicated in postnatal oocyte-specific gene expression.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FIGLA	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators

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
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FIGLA	75		marker	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FIGLA	1,035

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FIGLA	Q6QHK4	71.67

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
oocyte development	1	936.2×	0.002	FIGLA
developmental process	1	674.1×	0.002	FIGLA
regulation of transcription by RNA polymerase II	1	11.7×	0.086	FIGLA

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
FIGLA	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	FIGLA

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)
FIGLA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials

Cohort genes: FIGLA