Myopia 27

Summary

Myopia 27 (MONDO:0032941) is a disease caused by CPSF1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CPSF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopia 27
Mondo ID	MONDO:0032941
OMIM	618827
UMLS	C5394215
MedGen	1719756
Is cancer (heuristic)	no

Also known as: MYP27

Data availability: 17 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › myopia › myopia 27

Related subtypes (29): degenerative myopia, myopia 2, autosomal dominant, myopia 18, autosomal recessive, myopia 13, X-linked, myopia 1, X-linked, myopia 3, autosomal dominant, myopia 17, autosomal dominant, myopia 5, autosomal dominant, myopia 6, myopia 7, myopia 8, myopia 9, myopia 10, myopia 11, autosomal dominant, myopia 12, autosomal dominant, myopia 14, myopia 16, autosomal dominant, myopia 15, autosomal dominant, schizophrenia 16, myopia 19, autosomal dominant, myopia 20, autosomal dominant, myopia 21, autosomal dominant, myopia, high, with cataract and vitreoretinal degeneration, myopia 22, autosomal dominant, myopia 23, autosomal recessive, myopia 24, autosomal dominant, myopia 25, autosomal dominant, myopia 28, autosomal recessive, myopia 26, X-linked, female-limited

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

17 retrieved; paginated sample, class counts are floors:

10 uncertain significance, 3 likely pathogenic, 3 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
829510	NM_013291.3(CPSF1):c.4146-2A>G	CPSF1	Pathogenic	no assertion criteria provided
829512	NM_013291.3(CPSF1):c.3823G>T (p.Asp1275Tyr)	CPSF1	Pathogenic	no assertion criteria provided
829514	NM_013291.3(CPSF1):c.1858C>T (p.Gln620Ter)	CPSF1	Pathogenic	no assertion criteria provided
3068158	NM_013291.3(CPSF1):c.539+1G>A	CPSF1	Likely pathogenic	criteria provided, single submitter
3235178	NM_013291.3(CPSF1):c.1258_1259del (p.Lys420fs)	CPSF1	Likely pathogenic	criteria provided, single submitter
4293872	NM_013291.3(CPSF1):c.2156del (p.Asp719fs)	CPSF1	Likely pathogenic	criteria provided, single submitter
829516	NM_013291.3(CPSF1):c.2823_2824del (p.Val943fs)	CPSF1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2688859	NM_013291.3(CPSF1):c.1120-5C>T	CPSF1	Uncertain significance	criteria provided, single submitter
3065967	NM_013291.3(CPSF1):c.1999A>G (p.Met667Val)	CPSF1	Uncertain significance	criteria provided, single submitter
3233327	NM_013291.3(CPSF1):c.1752+4A>T	CPSF1	Uncertain significance	criteria provided, single submitter
3376167	NM_013291.3(CPSF1):c.1119+5G>T	CPSF1	Uncertain significance	criteria provided, single submitter
3496585	NM_013291.3(CPSF1):c.1682C>T (p.Thr561Ile)	CPSF1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3779166	NM_013291.3(CPSF1):c.2401G>T (p.Asp801Tyr)	CPSF1	Uncertain significance	criteria provided, single submitter
3779167	NM_013291.3(CPSF1):c.3953G>C (p.Gly1318Ala)	CPSF1	Uncertain significance	criteria provided, single submitter
3779547	NM_013291.3(CPSF1):c.1882_1895-76del	CPSF1	Uncertain significance	criteria provided, single submitter
3893075	NM_013291.3(CPSF1):c.3096+5G>A	CPSF1	Uncertain significance	criteria provided, single submitter
4533225	NM_013291.3(CPSF1):c.3415-13C>G	CPSF1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 0 · 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
CPSF1	Strong	Autosomal dominant	myopia 27

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
CPSF1	HGNC:2324	ENSG00000071894	Q10570	Cleavage and polyadenylation specificity factor subunit 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CPSF1	Cleavage and polyadenylation specificity factor subunit 1	Component of the cleavage and polyadenylation specificity factor (CPSF) complex that plays a key role in pre-mRNA 3’-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring a…

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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CPSF1	Scaffold/PPI	no		RSE1/DDB1/CPSF1_C, WD40/YVTN_repeat-like_dom_sf, Beta-prop_RSE1/DDB1/CPSF1_1st

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
left testis	1
right hemisphere of cerebellum	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CPSF1	134	ubiquitous	marker	right testis, left testis, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CPSF1	2,771

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CPSF1	Q10570	13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 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
Processing of Intronless Pre-mRNAs	1	571.0×	0.007	CPSF1
Transport of Mature mRNA Derived from an Intronless Transcript	1	271.9×	0.007	CPSF1
RNA Polymerase II Transcription Termination	1	219.6×	0.007	CPSF1
tRNA processing in the nucleus	1	196.9×	0.007	CPSF1
mRNA 3’-end processing	1	196.9×	0.007	CPSF1
mRNA Polyadenylation	1	87.8×	0.013	CPSF1
Dengue Virus-Host Interactions	1	45.7×	0.022	CPSF1

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
co-transcriptional RNA 3’-end processing, cleavage and polyadenylation pathway	1	16852.0×	1e-04	CPSF1
mRNA processing	1	78.8×	0.013	CPSF1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CPSF1	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	CPSF1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CPSF1	7	Binding:7

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

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	CPSF1

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	CPSF1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.