Brittle cornea syndrome 2

Summary

Brittle cornea syndrome 2 (MONDO:0013605) is a disease caused by PRDM5 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PRDM5 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 58

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brittle cornea syndrome 2
Mondo ID	MONDO:0013605
OMIM	614170
DOID	DOID:0080729
UMLS	C3280011
MedGen	481641
GARD	0015764
Is cancer (heuristic)	no

Also known as: BCS2 · brittle cornea syndrome 2 · brittle cornea syndrome caused by mutation in PRDM5 · brittle cornea syndrome type 2 · PRDM5 brittle cornea syndrome

Data availability: 58 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › corneal disorder › brittle cornea syndrome › brittle cornea syndrome 2

Related subtypes (1): brittle cornea syndrome 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

58 retrieved; paginated sample, class counts are floors:

15 conflicting classifications of pathogenicity, 15 likely pathogenic, 12 uncertain significance, 7 pathogenic, 5 pathogenic/likely pathogenic, 2 benign/likely benign, 1 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1710895	NM_018699.4(PRDM5):c.1513dup (p.Arg505fs)	PRDM5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2053127	NM_018699.4(PRDM5):c.694C>T (p.Arg232Ter)	PRDM5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2627792	NM_018699.4(PRDM5):c.1036C>T (p.Arg346Ter)	PRDM5	Pathogenic	criteria provided, multiple submitters, no conflicts
2780142	NM_018699.4(PRDM5):c.1030G>T (p.Glu344Ter)	PRDM5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2972163	NM_018699.4(PRDM5):c.307G>T (p.Glu103Ter)	PRDM5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31110	NM_018699.3(PRDM5):c.946_1623del	PRDM5	Pathogenic	no assertion criteria provided
31111	NM_018699.4(PRDM5):c.1768C>T (p.Arg590Ter)	PRDM5	Pathogenic	criteria provided, single submitter
31112	NM_018699.4(PRDM5):c.93+1G>A	PRDM5	Pathogenic	no assertion criteria provided
31114	NM_018699.4(PRDM5):c.974del (p.Cys325fs)	PRDM5	Pathogenic	criteria provided, multiple submitters, no conflicts
31115	NM_018699.4(PRDM5):c.93+2T>C	PRDM5	Pathogenic	criteria provided, single submitter
3589784	NM_018699.4(PRDM5):c.1258C>T (p.Gln420Ter)	PRDM5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4531924	NM_018699.4(PRDM5):c.1138_1140delinsTA (p.Leu380fs)	PRDM5	Pathogenic	criteria provided, single submitter
1677171	NM_018699.4(PRDM5):c.1650C>A (p.Cys550Ter)	PRDM5	Likely pathogenic	criteria provided, single submitter
1683364	NM_018699.4(PRDM5):c.1785_1786del (p.His595fs)	PRDM5	Likely pathogenic	criteria provided, single submitter
1704586	NM_018699.4(PRDM5):c.475+2T>C	PRDM5	Likely pathogenic	criteria provided, single submitter
2501236	NM_018699.4(PRDM5):c.658C>T (p.Gln220Ter)	PRDM5	Likely pathogenic	criteria provided, single submitter
2801904	NM_018699.4(PRDM5):c.865+1G>A	PRDM5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
31113	NM_018699.4(PRDM5):c.320A>G (p.Tyr107Cys)	PRDM5	Likely pathogenic	criteria provided, single submitter
3589783	NM_018699.4(PRDM5):c.1282+1G>T	PRDM5	Likely pathogenic	criteria provided, single submitter
3589785	NM_018699.4(PRDM5):c.1131dup (p.Cys378fs)	PRDM5	Likely pathogenic	criteria provided, single submitter
3589786	NM_018699.4(PRDM5):c.911_912del (p.Cys304fs)	PRDM5	Likely pathogenic	criteria provided, single submitter
3589788	NM_018699.4(PRDM5):c.69_70dup (p.Tyr24fs)	PRDM5	Likely pathogenic	criteria provided, single submitter
4077445	NM_018699.4(PRDM5):c.1461_1468del (p.Lys487fs)	PRDM5	Likely pathogenic	criteria provided, single submitter
4537301	NM_018699.4(PRDM5):c.1623+1G>A	PRDM5	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4848735	NM_018699.4(PRDM5):c.1030+1G>A	PRDM5	Likely pathogenic	criteria provided, single submitter
981042	NM_018699.4(PRDM5):c.17T>G (p.Val6Gly)	PRDM5	Likely pathogenic	criteria provided, single submitter
981043	NM_018699.4(PRDM5):c.1858del (p.His620fs)	PRDM5	Likely pathogenic	criteria provided, single submitter
1359408	NM_018699.4(PRDM5):c.740C>T (p.Ser247Leu)	PRDM5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195343	NM_018699.4(PRDM5):c.106G>A (p.Gly36Arg)	PRDM5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2888344	NM_018699.4(PRDM5):c.93+7G>A	PRDM5	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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
PRDM5	Definitive	Autosomal recessive	brittle cornea syndrome 2	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRDM5	Orphanet:90354	Brittle cornea syndrome

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
PRDM5	HGNC:9349	ENSG00000138738	Q9NQX1	PR domain zinc finger protein 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRDM5	PR domain zinc finger protein 5	Sequence-specific DNA-binding transcription factor.

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)
PRDM5	Transcription factor	no		SET_dom, Znf_C2H2_type, Znf_PRDM5-like

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
calcaneal tendon	1
male germ line stem cell (sensu Vertebrata) in testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRDM5	206	ubiquitous	marker	calcaneal tendon, sural nerve, 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
PRDM5	1,303

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRDM5	Q9NQX1	1

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
regulation of extracellular matrix organization	1	1872.4×	0.004	PRDM5
methylation	1	170.2×	0.015	PRDM5
cellular response to leukemia inhibitory factor	1	159.0×	0.015	PRDM5
mitotic cell cycle	1	133.8×	0.015	PRDM5
chromatin organization	1	99.1×	0.016	PRDM5
negative regulation of DNA-templated transcription	1	31.6×	0.042	PRDM5
negative regulation of transcription by RNA polymerase II	1	17.7×	0.064	PRDM5
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	PRDM5

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
PRDM5	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	PRDM5

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)
PRDM5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.