Ulnar/fibula ray defect-brachydactyly syndrome

Summary

Ulnar/fibula ray defect-brachydactyly syndrome (MONDO:0012063) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 1
• Phenotypes (HPO): 12

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		1	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0001510	Growth delay	Very frequent (80-99%)
HP:0000272	Malar flattening	Frequent (30-79%)
HP:0001156	Brachydactyly	Frequent (30-79%)
HP:0004322	Short stature	Frequent (30-79%)
HP:0006492	Aplasia/Hypoplasia of the fibula	Frequent (30-79%)
HP:0006495	Aplasia/Hypoplasia of the ulna	Frequent (30-79%)
HP:0009237	Short 5th finger	Frequent (30-79%)
HP:0001028	Hemangioma	Occasional (5-29%)
HP:0001631	Atrial septal defect	Occasional (5-29%)
HP:0001762	Talipes equinovarus	Occasional (5-29%)
HP:0001773	Short foot	Occasional (5-29%)
HP:0006210	Postaxial oligodactyly	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	ulnar/fibula ray defect-brachydactyly syndrome
Mondo ID	MONDO:0012063
MeSH	C563905
OMIM	608571
Orphanet	52056
SNOMED CT	719843001
UMLS	C1837830
MedGen	324890
GARD	0016654
Is cancer (heuristic)	no

Also known as: Morava-Mehes syndrome

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › disorder of development or morphogenesis › developmental defect during embryogenesis › congenital limb malformation › ulnar/fibula ray defect-brachydactyly syndrome

Related subtypes (106): Adams-Oliver syndrome, ADULT syndrome, Hypoglossia-hypodactyly syndrome, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, Cooks syndrome, Townes-Brocks syndrome, brachydactyly-arterial hypertension syndrome, brachydactyly-preaxial hallux varus syndrome, fibular aplasia-ectrodactyly syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, femoral-facial syndrome, laurin-Sandrow syndrome, Emery-Nelson syndrome, hand-foot-genital syndrome, IVIC syndrome, Leri pleonosteosis, OSLAM syndrome, pelvis-shoulder dysplasia, phocomelia-ectrodactyly-deafness-sinus arrhythmia syndrome, Poland syndrome, crossed polysyndactyly, postaxial tetramelic oligodactyly, radio-renal syndrome, scalp defects-postaxial polydactyly syndrome, splenogonadal fusion-limb defects-micrognathia syndrome, Karsch-Neugebauer syndrome, symphalangism with multiple anomalies of hands and feet, proximal symphalangism, tarsal-carpal coalition syndrome, extensor tendons of finger anomalies, tetramelic monodactyly, thumb stiffness-brachydactyly-intellectual disability syndrome, tibia, hypoplasia or aplasia of, with polydactyly, Say-field-Coldwell syndrome, triphalangeal thumbs-brachyectrodactyly syndrome, humerus trochlea aplasia, Aphalangy-hemivertebrae-urogenital-intestinal dysgenesis syndrome, camptodactyly syndrome, Guadalajara type 2, Cenani-Lenz syndactyly syndrome, split hand-foot malformation 1 with sensorineural hearing loss, EEM syndrome, ectrodactyly-polydactyly syndrome, lethal faciocardiomelic dysplasia, femur-fibula-ulna complex, Gollop-Wolfgang complex, acromesomelic dysplasia 2B, Fuhrmann syndrome, hallux varus-preaxial polysyndactyly syndrome, Keutel syndrome, absence deformity of leg-cataract syndrome, intellectual disability-spasticity-ectrodactyly syndrome, fibular aplasia, tibial campomelia, and oligosyndactyly syndrome, pelviscapular dysplasia, radioulnar synostosis-developmental delay-hypotonia syndrome, rapadilino syndrome, EEC syndrome, Sugarman brachydactyly, tetraamelia-multiple malformations syndrome, thrombocytopenia-absent radius syndrome, phocomelia, Schinzel type, ulna hypoplasia-intellectual disability syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, Mononen-Karnes-Senac syndrome, absent radius-anogenital anomalies syndrome, ulnar hypoplasia-split foot syndrome, aphalangy-syndactyly-microcephaly syndrome, 2q37 microdeletion syndrome, absent tibia-polydactyly-arachnoid cyst syndrome, skeletal dysplasia-epilepsy-short stature syndrome, autosomal recessive amelia, temtamy preaxial brachydactyly syndrome, radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome, acropectoral syndrome, familial digital arthropathy-brachydactyly, Duane-radial ray syndrome, intellectual disability-brachydactyly-Pierre Robin syndrome, Al-Gazali syndrome, cocoon syndrome, mammary-digital-nail syndrome, syndactyly-camptodactyly and clinodactyly of fifth fingers-bifid toes syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, split-foot malformation-mesoaxial polydactyly syndrome, TELO2-related intellectual disability-neurodevelopmental disorder, arthrogryposis syndrome, radial deficiency-tibial hypoplasia syndrome, camptodactyly-taurinuria syndrome, fibular dimelia-diplopodia syndrome, shoulder and thorax deformity-congenital heart disease syndrome, Cornelia de Lange syndrome, familial clubfoot with or without associated lower limb anomalies, heart-hand syndrome, hyperphosphatasia-intellectual disability syndrome, limb transversal defect-cardiac anomaly syndrome, triphalangeal thumb-polysyndactyly syndrome, multiple synostoses syndrome, hereditary thrombocytosis with transverse limb defect, thalidomide embryopathy, tibial aplasia-ectrodactyly syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, acrofacial dysostosis, caudal regression-sirenomelia spectrum, Rubinstein-Taybi syndrome, acrocephalosyndactyly, congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome, omphalocele-diaphragmatic hernia-cardiovascular anomalies-radial ray defect syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
265995	NM_178857.6(RP1L1):c.328C>T (p.Pro110Ser)	RP1L1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

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
RP1L1	Orphanet:247834	Occult macular dystrophy
RP1L1	Orphanet:791	Retinitis pigmentosa

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
RP1L1	HGNC:15946	ENSG00000183638	Q8IWN7	Retinitis pigmentosa 1-like 1 protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RP1L1	Retinitis pigmentosa 1-like 1 protein	Required for the differentiation of photoreceptor cells.

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)
RP1L1	Other/Unknown	no		Doublecortin_dom, Doublecortin_dom_sf

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
bone marrow cell	1
buccal mucosa cell	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RP1L1	30	tissue_specific	yes	primordial germ cell in gonad, buccal mucosa cell, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RP1L1	1,004

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RP1L1	Q8IWN7	38.97

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
photoreceptor cell development	1	4213.0×	0.002	RP1L1
photoreceptor cell outer segment organization	1	1053.2×	0.003	RP1L1
axoneme assembly	1	543.6×	0.004	RP1L1
photoreceptor cell maintenance	1	358.6×	0.005	RP1L1
retina development in camera-type eye	1	255.3×	0.005	RP1L1
visual perception	1	79.5×	0.015	RP1L1
intracellular signal transduction	1	38.1×	0.026	RP1L1

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
RP1L1	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	RP1L1

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)
RP1L1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.