Mayer-Rokitansky-Küster-Hauser syndrome type 2

Summary

Mayer-Rokitansky-Küster-Hauser syndrome type 2 (MONDO:0010989) is a disease with 2 cohort genes.

At a glance

• Prevalence: 1-9 / 100 000 (Europe)
• Cohort genes: 2
• ClinVar variants: 9
• Phenotypes (HPO): 12

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Europe	Not yet validated
Prevalence at birth	1-9 / 100 000	1	Europe	Not yet validated

Signs & symptoms

Clinical features (HPO)

12 HPO clinical features (Orphanet curated; top 12 by frequency):

HPO ID	Term	Frequency
HP:0000027	Azoospermia	Very frequent (80-99%)
HP:0000086	Ectopic kidney	Very frequent (80-99%)
HP:0000104	Renal agenesis	Very frequent (80-99%)
HP:0000110	Renal dysplasia	Very frequent (80-99%)
HP:0000470	Short neck	Very frequent (80-99%)
HP:0000813	Bicornuate uterus	Very frequent (80-99%)
HP:0002162	Low posterior hairline	Very frequent (80-99%)
HP:0004322	Short stature	Very frequent (80-99%)
HP:0008684	Aplasia/hypoplasia of the uterus	Very frequent (80-99%)
HP:0000772	Abnormal rib morphology	Frequent (30-79%)
HP:0003422	Vertebral segmentation defect	Frequent (30-79%)
HP:0000365	Hearing impairment	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Mayer-Rokitansky-Küster-Hauser syndrome type 2
Mondo ID	MONDO:0010989
OMIM	601076
Orphanet	2578
DOID	DOID:0112179
ICD-11	1521808255
SNOMED CT	717705004
UMLS	C4305568
MedGen	931237
GARD	0005513
Is cancer (heuristic)	no

Also known as: atypical MRKH syndrome · Mayer-Rokitansky-Küster-Hauser syndrome type 2 · MRKH syndrome type 2 · MULLERIAN duct aplasia, unilateral renal agenesis, and cervicothoracic somite anomalies · MURCS · MURCS association · Müllerian duct aplasia-renal dysplasia-cervical somite anomalies syndrome

Data availability: 9 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Mayer-Rokitansky-Kuster-Hauser syndrome › Mayer-Rokitansky-Küster-Hauser syndrome type 2

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

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

9 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2445432	GRCh37/hg19 18q11.1-11.2(chr18:18856932-19159898)x1	ESCO1	Pathogenic	criteria provided, single submitter
1684664	NM_001142966.3(GREB1L):c.4992T>A (p.Tyr1664Ter)	GREB1L	Pathogenic	criteria provided, single submitter
2444485	NM_001142966.3(GREB1L):c.5396_5397del (p.Lys1799fs)	GREB1L	Pathogenic	criteria provided, single submitter
1328379	NM_001142966.3(GREB1L):c.553G>A (p.Gly185Ser)	GREB1L	Uncertain significance	criteria provided, multiple submitters, no conflicts
2444476	NM_001142966.3(GREB1L):c.5441C>A (p.Ala1814Asp)	GREB1L	Uncertain significance	criteria provided, single submitter
2444482	NM_001142966.3(GREB1L):c.3167T>C (p.Leu1056Pro)	GREB1L	Uncertain significance	criteria provided, single submitter
2444483	NM_001142966.3(GREB1L):c.4054GAG[2] (p.Glu1354del)	GREB1L	Uncertain significance	criteria provided, single submitter
2444484	NM_001142966.3(GREB1L):c.3205T>A (p.Leu1069Met)	GREB1L	Uncertain significance	criteria provided, single submitter
2444486	NM_001142966.3(GREB1L):c.1558G>A (p.Asp520Asn)	GREB1L	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · 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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ESCO1	HGNC:24645	ENSG00000141446	Q5FWF5	N-acetyltransferase ESCO1	clinvar
GREB1L	HGNC:31042	ENSG00000141449	Q9C091	GREB1-like protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ESCO1	N-acetyltransferase ESCO1	Acetyltransferase required for the establishment of sister chromatid cohesion.
GREB1L	GREB1-like protein	Plays a major role in early metanephros and genital development.

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	4.1×	0.455
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ESCO1	Transcription factor	no		AcTrfase_ESCO_Znf_dom, ESCO_Acetyltransf_dom
GREB1L	Other/Unknown	no		GREB1, GREB1_N, GREB1-like_C

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	2
oviduct epithelium	1
tendon of biceps brachii	1
gastrocnemius	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ESCO1	259	ubiquitous	marker	oviduct epithelium, buccal mucosa cell, tendon of biceps brachii
GREB1L	184	broad	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ESCO1	2,427
GREB1L	637

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ESCO1	Q5FWF5	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GREB1L	Q9C091	72.90

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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
Establishment of Sister Chromatid Cohesion	1	1038.2×	1e-03	ESCO1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
post-translational protein acetylation	1	2808.7×	0.003	ESCO1
peptidyl-lysine acetylation	1	2106.5×	0.003	ESCO1
paramesonephric duct development	1	2106.5×	0.003	GREB1L
mesonephric duct development	1	1685.2×	0.003	GREB1L
cardiac ventricle development	1	1203.7×	0.003	GREB1L
mitotic sister chromatid cohesion	1	561.7×	0.005	ESCO1
male genitalia development	1	443.5×	0.005	GREB1L
uterus development	1	401.2×	0.005	GREB1L
sister chromatid cohesion	1	383.0×	0.005	ESCO1
embryonic heart tube development	1	383.0×	0.005	GREB1L
cardiac muscle cell differentiation	1	337.0×	0.005	GREB1L
retinoic acid receptor signaling pathway	1	324.1×	0.005	GREB1L
ribosome biogenesis	1	312.1×	0.005	GREB1L
metanephros development	1	255.3×	0.005	GREB1L
branching involved in ureteric bud morphogenesis	1	183.2×	0.006	GREB1L
regulation of DNA replication	1	183.2×	0.006	ESCO1
morphogenesis of an epithelium	1	172.0×	0.006	GREB1L
outflow tract morphogenesis	1	153.2×	0.007	GREB1L
kidney development	1	70.2×	0.014	GREB1L

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 2 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
ESCO1	0	0
GREB1L	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	ESCO1, 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)
ESCO1	0	—
GREB1L	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.