Myopia 22, autosomal dominant

Summary

Myopia 22, autosomal dominant (MONDO:0014177) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopia 22, autosomal dominant
Mondo ID	MONDO:0014177
OMIM	615420
UMLS	C3809464
MedGen	815794
Is cancer (heuristic)	no

Also known as: myopia 22, autosomal dominant · MYP22

Data availability: 4 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 22, autosomal dominant

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 23, autosomal recessive, myopia 24, autosomal dominant, myopia 25, autosomal dominant, myopia 28, autosomal recessive, myopia 27, 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

4 retrieved; paginated sample, class counts are floors:

4 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3892179	NM_152683.4(PRIMPOL):c.1428AGA[3] (p.Glu478_Phe479insGlu)	CENPU	Uncertain significance	criteria provided, single submitter
2222128	NM_152683.4(PRIMPOL):c.292C>T (p.His98Tyr)	PRIMPOL	Uncertain significance	criteria provided, multiple submitters, no conflicts
4293693	NM_152683.4(PRIMPOL):c.844+3A>T	PRIMPOL	Uncertain significance	criteria provided, single submitter
65424	NM_152683.4(PRIMPOL):c.265T>G (p.Tyr89Asp)	PRIMPOL	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
PRIMPOL	Limited	Autosomal dominant	myopia 22, autosomal dominant

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
PRIMPOL	HGNC:26575	ENSG00000164306	Q96LW4	DNA-directed primase/polymerase protein	gencc,clinvar
CENPU	HGNC:21348	ENSG00000151725	Q71F23	Centromere protein U	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRIMPOL	DNA-directed primase/polymerase protein	DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them.
CENPU	Centromere protein U	Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRIMPOL	Enzyme (other)	yes	2.7.7.102	DNA_primase_S, PRIMPOL
CENPU	Other/Unknown	no		CENP-U

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
male germ cell	1
oocyte	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRIMPOL	250	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum
CENPU	242	ubiquitous	marker	sperm, male germ cell, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CENPU	1,939
PRIMPOL	936

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CENPU	Q71F23	18
PRIMPOL	Q96LW4	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 21. 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
Nucleosome assembly	1	475.8×	0.021	CENPU
Chromosome Maintenance	1	211.5×	0.021	CENPU
Amplification of signal from the kinetochores	1	196.9×	0.021	CENPU
Deposition of new CENPA-containing nucleosomes at the centromere	1	158.6×	0.021	CENPU
Mitotic Spindle Checkpoint	1	158.6×	0.021	CENPU
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	1	116.5×	0.021	CENPU
Mitotic Metaphase and Anaphase	1	96.8×	0.021	CENPU
Mitotic Anaphase	1	96.8×	0.021	CENPU
EML4 and NUDC in mitotic spindle formation	1	92.8×	0.021	CENPU
Cell Cycle Checkpoints	1	88.5×	0.021	CENPU
Resolution of Sister Chromatid Cohesion	1	86.5×	0.021	CENPU
RHO GTPases Activate Formins	1	77.7×	0.021	CENPU
Mitotic Prometaphase	1	69.2×	0.021	CENPU
RHO GTPase Effectors	1	68.0×	0.021	CENPU
M Phase	1	66.0×	0.021	CENPU
Separation of Sister Chromatids	1	60.7×	0.022	CENPU
Cell Cycle, Mitotic	1	48.2×	0.026	CENPU
Cell Cycle	1	36.0×	0.031	CENPU
Signaling by Rho GTPases	1	34.2×	0.031	CENPU
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.031	CENPU
Signal Transduction	1	10.2×	0.098	CENPU

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
DNA replication, synthesis of primer	1	1404.3×	0.002	PRIMPOL
chordate embryonic development	1	1404.3×	0.002	CENPU
mitochondrial DNA repair	1	1203.7×	0.002	PRIMPOL
R-loop processing	1	842.6×	0.002	PRIMPOL
mitochondrial DNA replication	1	766.0×	0.002	PRIMPOL
error-prone translesion synthesis	1	766.0×	0.002	PRIMPOL
translesion synthesis	1	468.1×	0.003	PRIMPOL
replication fork processing	1	210.7×	0.006	PRIMPOL
response to UV	1	183.2×	0.006	PRIMPOL
chromosome segregation	1	86.9×	0.011	CENPU

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
PRIMPOL	0	0
CENPU	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PRIMPOL	2.7.7.102	DNA primase AEP

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	1	PRIMPOL
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CENPU

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)
PRIMPOL	0	—
CENPU	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.