Myopia 21, autosomal dominant

Summary

Myopia 21, autosomal dominant (MONDO:0013604) is a disease caused by ZNF644 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ZNF644 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopia 21, autosomal dominant
Mondo ID	MONDO:0013604
OMIM	614167
UMLS	C3279997
MedGen	481627
Is cancer (heuristic)	no

Also known as: myopia (disease) caused by mutation in ZNF644 · myopia 21, autosomal dominant · MYP21 · ZNF644 myopia (disease)

Data availability: 11 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › myopia › myopia 21, 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, 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 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

11 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
31107	NM_201269.3(ZNF644):c.2014A>G (p.Ser672Gly)	ZNF644	Pathogenic	no assertion criteria provided
31108	NM_201269.3(ZNF644):c.1759A>G (p.Ile587Val)	ZNF644	Pathogenic	no assertion criteria provided
31109	NM_201269.3(ZNF644):c.*592G>A	ZNF644	Pathogenic	no assertion criteria provided
1031815	NM_201269.3(ZNF644):c.3494del (p.Lys1165fs)	ZNF644	Uncertain significance	criteria provided, single submitter
2438691	NM_201269.3(ZNF644):c.1100C>T (p.Pro367Leu)	ZNF644	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892940	NM_201269.3(ZNF644):c.2402A>G (p.Lys801Arg)	ZNF644	Uncertain significance	criteria provided, multiple submitters, no conflicts
3892941	NM_201269.3(ZNF644):c.913G>A (p.Glu305Lys)	ZNF644	Uncertain significance	criteria provided, single submitter
4081037	NM_201269.3(ZNF644):c.3083-5dup	ZNF644	Uncertain significance	criteria provided, single submitter
931639	NM_201269.3(ZNF644):c.3683A>G (p.His1228Arg)	ZNF644	Uncertain significance	criteria provided, single submitter
931640	NM_201269.3(ZNF644):c.2168A>G (p.His723Arg)	ZNF644	Uncertain significance	criteria provided, single submitter
4533228	NM_201269.3(ZNF644):c.1988G>A (p.Arg663Gln)	ZNF644	Likely benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
ZNF644	Strong	Autosomal dominant	myopia 21, autosomal dominant	4

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
ZNF644	HGNC:29222	ENSG00000122482	Q9H582	Zinc finger protein 644	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ZNF644	Zinc finger protein 644	May be involved in transcriptional regulation.

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)
ZNF644	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Transcr_Reg_ZincFinger

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
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ZNF644	253	ubiquitous	marker	calcaneal tendon, ventricular zone, ganglionic eminence

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ZNF644	1,970

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ZNF644	Q9H582	46.24

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 transcription by RNA polymerase II	1	11.7×	0.086	ZNF644

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
ZNF644	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	ZNF644

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)
ZNF644	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.