Mayer-Rokitansky-Kuster-Hauser syndrome type 1

Summary

Mayer-Rokitansky-Kuster-Hauser syndrome type 1 (MONDO:0010173) is a disease with 3 cohort genes and 4 clinical trials.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide)
• Cohort genes: 3
• ClinVar variants: 11
• Clinical trials: 4

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Worldwide	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Mayer-Rokitansky-Kuster-Hauser syndrome type 1
Mondo ID	MONDO:0010173
OMIM	277000
Orphanet	247775
DOID	DOID:0112178
UMLS	C5566555
MedGen	1797978
GARD	0004737
Is cancer (heuristic)	no

Also known as: congenital absence of the uterus and vagina (CAUV) · congenital absence of uterus and vagina · genital renal ear syndrome · Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) · MRKH syndrome · MRKH syndrome type 1 · Mullerian dysgenesis · Müllerian agenesis · Rokitansky sequence · Rokitansky syndrome

Data availability: 11 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Mayer-Rokitansky-Kuster-Hauser syndrome › Mayer-Rokitansky-Kuster-Hauser syndrome type 1

Related subtypes (1): Mayer-Rokitansky-Küster-Hauser syndrome type 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

11 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1703541	GRCh37/hg19 16p11.2(chr16:29567295-30177916)	ALDOA	Pathogenic	no assertion criteria provided
1333378	NM_001142966.3(GREB1L):c.4576C>T (p.Arg1526Ter)	GREB1L	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2444475	NM_001142966.3(GREB1L):c.3146+1G>A	GREB1L	Pathogenic	criteria provided, single submitter
4755479	NM_001142966.3(GREB1L):c.4344C>A (p.Tyr1448Ter)	GREB1L	Pathogenic	criteria provided, single submitter
3894535	NM_001256706.2(ANAPC10):c.95C>A (p.Ser32Ter)	ANAPC10	Uncertain significance	criteria provided, single submitter
1033328	NM_001142966.3(GREB1L):c.5650C>T (p.Arg1884Cys)	GREB1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2444477	NM_001142966.3(GREB1L):c.3085G>A (p.Asp1029Asn)	GREB1L	Uncertain significance	criteria provided, single submitter
2444478	NM_001142966.3(GREB1L):c.3353G>A (p.Arg1118Gln)	GREB1L	Uncertain significance	criteria provided, single submitter
2444479	NM_001142966.3(GREB1L):c.575G>A (p.Arg192Gln)	GREB1L	Uncertain significance	criteria provided, single submitter
2444487	NM_001142966.3(GREB1L):c.2722T>C (p.Cys908Arg)	GREB1L	Uncertain significance	criteria provided, single submitter
2444488	NM_001142966.3(GREB1L):c.3068G>A (p.Arg1023Gln)	GREB1L	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GREB1L	Orphanet:1848	Renal agenesis, bilateral
GREB1L	Orphanet:93100	Renal agenesis, unilateral
ALDOA	Orphanet:57	Glycogen storage disease due to aldolase A deficiency

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ANAPC10	HGNC:24077	ENSG00000164162	Q9UM13	Anaphase-promoting complex subunit 10	clinvar
GREB1L	HGNC:31042	ENSG00000141449	Q9C091	GREB1-like protein	clinvar
ALDOA	HGNC:414	ENSG00000149925	P04075	Fructose-bisphosphate aldolase A	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANAPC10	Anaphase-promoting complex subunit 10	Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.
GREB1L	GREB1-like protein	Plays a major role in early metanephros and genital development.
ALDOA	Fructose-bisphosphate aldolase A	Catalyzes the reversible conversion of beta-D-fructose 1,6-bisphosphate (FBP) into two triose phosphate and plays a key role in glycolysis and gluconeogenesis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ANAPC10	Other/Unknown	no		APC_su10/DOC_dom, Galactose-bd-like_sf, APC10/Doc1
GREB1L	Other/Unknown	no		GREB1, GREB1_N, GREB1-like_C
ALDOA	Enzyme (other)	yes	4.1.2.13	FBA_I, Aldolase_TIM, Aldolase_I_AS

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	2
calcaneal tendon	1
oocyte	1
secondary oocyte	1
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
hindlimb stylopod muscle	1
skeletal muscle tissue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANAPC10	282	ubiquitous	marker	oocyte, calcaneal tendon, secondary oocyte
GREB1L	184	broad	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius
ALDOA	134	ubiquitous	marker	skeletal muscle tissue, gastrocnemius, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALDOA	3,591
ANAPC10	2,282
GREB1L	637

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ANAPC10	Q9UM13	21
ALDOA	P04075	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GREB1L	Q9C091	72.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 58. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Glucose metabolism	1	439.2×	0.018	ALDOA
Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components	1	317.2×	0.018	ANAPC10
Phosphorylation of the APC/C	1	271.9×	0.018	ANAPC10
Inactivation of APC/C via direct inhibition of the APC/C complex	1	259.6×	0.018	ANAPC10
Conversion from APC/C:Cdc20 to APC/C:Cdh1 in late anaphase	1	259.6×	0.018	ANAPC10
Aberrant regulation of mitotic exit in cancer due to RB1 defects	1	259.6×	0.018	ANAPC10
APC/C:Cdc20 mediated degradation of Cyclin B	1	228.4×	0.018	ANAPC10
Gluconeogenesis	1	219.6×	0.018	ALDOA
APC-Cdc20 mediated degradation of Nek2A	1	211.5×	0.018	ANAPC10
APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint	1	211.5×	0.018	ANAPC10
Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins	1	203.9×	0.018	ANAPC10
Aberrant regulation of mitotic cell cycle due to RB1 defects	1	203.9×	0.018	ANAPC10
Diseases of mitotic cell cycle	1	196.9×	0.018	ANAPC10
APC/C:Cdc20 mediated degradation of mitotic proteins	1	178.4×	0.018	ANAPC10
APC/C-mediated degradation of cell cycle proteins	1	167.9×	0.018	ANAPC10
Regulation of mitotic cell cycle	1	167.9×	0.018	ANAPC10
DNA Replication Pre-Initiation	1	158.6×	0.018	ANAPC10
Regulation of APC/C activators between G1/S and early anaphase	1	154.3×	0.018	ANAPC10
Switching of origins to a post-replicative state	1	150.3×	0.018	ANAPC10
Synthesis of DNA	1	150.3×	0.018	ANAPC10
Immune System	2	13.0×	0.018	ANAPC10, ALDOA
Glycolysis	1	142.8×	0.018	ALDOA
Transcriptional Regulation by VENTX	1	132.8×	0.019	ANAPC10
DNA Replication	1	119.0×	0.020	ANAPC10
Autodegradation of Cdh1 by Cdh1:APC/C	1	95.2×	0.023	ANAPC10
APC/C:Cdc20 mediated degradation of Securin	1	95.2×	0.023	ANAPC10
S Phase	1	90.6×	0.023	ANAPC10
Cdc20:Phospho-APC/C mediated degradation of Cyclin A	1	86.5×	0.023	ANAPC10
APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1	1	85.2×	0.023	ANAPC10
CDK-mediated phosphorylation and removal of Cdc6	1	85.2×	0.023	ANAPC10

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
paramesonephric duct development	1	1404.3×	0.009	GREB1L
mesonephric duct development	1	1123.5×	0.009	GREB1L
cardiac ventricle development	1	802.5×	0.009	GREB1L
fructose 1,6-bisphosphate metabolic process	1	702.2×	0.009	ALDOA
fructose metabolic process	1	561.7×	0.009	ALDOA
ATP biosynthetic process	1	330.4×	0.009	ALDOA
male genitalia development	1	295.6×	0.009	GREB1L
striated muscle contraction	1	280.9×	0.009	ALDOA
protein branched polyubiquitination	1	280.9×	0.009	ANAPC10
uterus development	1	267.5×	0.009	GREB1L
embryonic heart tube development	1	255.3×	0.009	GREB1L
regulation of meiotic cell cycle	1	255.3×	0.009	ANAPC10
anaphase-promoting complex-dependent catabolic process	1	234.1×	0.009	ANAPC10
canonical glycolysis	1	234.1×	0.009	ALDOA
cardiac muscle cell differentiation	1	224.7×	0.009	GREB1L
muscle cell cellular homeostasis	1	216.1×	0.009	ALDOA
retinoic acid receptor signaling pathway	1	216.1×	0.009	GREB1L
ribosome biogenesis	1	208.1×	0.009	GREB1L
metanephros development	1	170.2×	0.010	GREB1L
binding of sperm to zona pellucida	1	140.4×	0.011	ALDOA
protein K11-linked ubiquitination	1	130.6×	0.011	ANAPC10
glycolytic process	1	127.7×	0.011	ALDOA
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	124.8×	0.011	ALDOA
branching involved in ureteric bud morphogenesis	1	122.1×	0.011	GREB1L
morphogenesis of an epithelium	1	114.6×	0.011	GREB1L
outflow tract morphogenesis	1	102.1×	0.012	GREB1L
regulation of mitotic cell cycle	1	80.2×	0.015	ANAPC10
protein homotetramerization	1	79.1×	0.015	ALDOA
protein K48-linked ubiquitination	1	56.2×	0.020	ANAPC10
kidney development	1	46.8×	0.023	GREB1L

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALDOA	1	2
ANAPC10	0	0
GREB1L	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	ALDOA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ALDOA	9	Binding:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALDOA	4.1.2.13	fructose-bisphosphate aldolase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	ALDOA

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	ALDOA
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	ANAPC10, GREB1L

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ANAPC10	0	—
GREB1L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07186764	Not specified	RECRUITING	Evaluation of the Quality of Life and Gynecological Follow-up of Patients Treated for Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome
NCT07321782	Not specified	NOT_YET_RECRUITING	Clinical and Imaging Features in MRKH Syndrome
NCT01911884	Not specified	COMPLETED	Assessment of Quality of Global and Sexual Life and Impact of Surgical and Non Surgical Vaginal Aplasia in Patients With a Rokitansky Syndrome
NCT05415540	Not specified	COMPLETED	Evolution of the Quality of Life and Experience of Young Women With Utero-vaginal Aplasia (MRKHPSY)